Capillary forces between sediment particles and an air-water interface.
In the vadose zone, air-water interfaces play an important role in particle fate and transport, as particles can attach to the air-water interfaces by action of capillary forces. This attachment can either retard or enhance the movement of particles, depending on whether the air-water interfaces are stationary or mobile. Here we use three standard PTFE particles (sphere, circular cylinder, and tent) and seven natural mineral particles (basalt, granite, hematite, magnetite, mica, milky quartz, and clear quartz) to quantify the capillary forces between an air-water interface and the different particles. Capillary forces were determined experimentally using tensiometry, and theoretically assuming volume-equivalent spherical, ellipsoidal, and circular cylinder shapes. We experimentally distinguished between the maximum capillary force and the snap-off force when the air-water interface detaches from the particle. Theoretical and experimental values of capillary forces were of similar order of magnitude. The sphere gave the smallest theoretical capillary force, and the circular cylinder had the largest force due to pinning of the air-water interface. Pinning was less pronounced for natural particles when compared to the circular cylinder. Ellipsoids gave the best agreement with measured forces, suggesting that this shape can provide a reasonable estimation of capillary forces for many natural particles.


Patient-controlled analgesia with remifentanil versus alternative parenteral methods for pain management in labour.
Multiple analgesic strategies for pain relief during labour are available. Recently remifentanil, a short-acting opioid, has recently been used as an alternative analgesic due to its unique pharmacological properties. To systematically assess the effectiveness of remifentanil intravenous patient-controlled analgesia (PCA) for labour pain, along with any potential harms to the mother and the newborn. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (9 December 2015), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), handsearched congress abstracts (November 2015), and reference lists of retrieved studies. Randomised controlled trials (RCTs) and cluster-randomised trials comparing remifentanil (PCA) with another opioid (intravenous (IV)/intramuscular (IM)), or with another opioid (PCA), or with epidural analgesia, or with remifentanil (continuous IV), or with remifentanil (PCA, different regimen), or with inhalational analgesia, or with placebo/no treatment in all women in labour including high-risk groups with planned vaginal delivery. Two review authors independently assessed trials for inclusion, extracted data, and appraised study quality.We contacted study authors for additional information other than incomplete outcome data. We performed random-effects meta-analysis.To reduce the risk of random error in meta-analysis we performed trial sequential analysis. We included total zero event trials and used a constant continuity correction of 0.01 (ccc 0.01) for meta-analysis. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to assess the quality of evidence. Twenty RCTs with 3569 women were included. Of those, 10 trials (2983 participants) compared remifentanil (PCA) to an epidural, four trials (216 participants) to another opioid (IV/IM), three trials (215 participants) to another opioid (PCA), two trials (135 participants) to remifentanil (continuous IV), and one trial (20 participants) to remifentanil (PCA, different regimen). No trials were identified for the remaining comparisons.Methodological quality of studies was moderate to poor. We assessed risk of bias as high for blinding issues and incomplete outcome data in 65% and 45% of the included studies, respectively.There is evidence of effect that women in the remifentanil (PCA) group were more satisfied with pain relief than women in the other opioids (IV/IM) group (standardised mean difference (SMD) 2.11, 95% confidence interval (CI) 0.72 to 3.49, four trials, very low-quality evidence), and that women were less satisfied compared to women in the epidural group (SMD -0.22, 95% CI -0.40 to -0.04, seven trials, very low-quality evidence).There is evidence of effect that remifentanil (PCA) provided stronger pain relief at one hour than other opioids administered IV/IM (SMD -1.58, 95% CI -2.69 to -0.48, three trials, very low-quality evidence) or via PCA (SMD -0.51, 95% CI -1.01 to -0.00, three trials, very low-quality evidence). Pain intensity was higher in the remifentanil (PCA) group compared to the epidural group (SMD 0.57, 95% CI 0.31 to 0.84, six trials, low-quality evidence).Data were limited on safety aspects for both the women and the newborns. Only one study analysed maternal apnoea in a comparison of remifentanil (PCA) versus epidural and reported that half of the women in the remifentanil and none in the epidural group had an apnoea (very low-quality evidence). There is no evidence of effect that remifentanil (PCA) was associated with an increased risk for maternal respiratory depression when compared to epidural analgesia (RR 0.91, 95% CI 0.51 to 1.62, ccc 0.01, three trials, low-quality evidence) and no reliable conclusion might be reached compared to remifentanil (continuous IV) (all study arms included zero events, two trials, low-quality evidence). In one trial of remifentanil (PCA) versus another opioid (IM) three out of 18 women in the remifentanil and none out of 18 in the control group had a respiratory depression (very low-quality evidence).There is no evidence of effect that remifentanil (PCA) was associated with an increased risk for newborns with Apgar scores less than seven at five minutes compared to epidural analgesia (RR 1.26, 95% CI 0.62 to 2.57, ccc 0.01, five trials, low-quality evidence) and no reliable conclusion might be reached compared to another opioid (IV) and compared to remifentanil (PCA, different regimen) both with zero events in all study arms (one trial, very-low quality evidence). In one trial of remifentanil (PCA) versus another opioid (PCA) none out of nine newborns in the remifentanil and three out of eight in the opioid (PCA) group had Apgar scores less than seven (very-low quality evidence).There is evidence that remifentanil (PCA) was associated with a lower risk for the requirement of additional analgesia when compared to other opioids (IV/IM) (RR 0.57, 95% CI 0.40 to 0.81, three trials, moderate-quality evidence) and that it was associated with a higher risk compared to epidural analgesia (RR 9.27, 95% CI 3.73 to 23.03, ccc 0.01, six trials, moderate-quality evidence). There is no evidence of effect that remifentanil (PCA) reduced the requirement for additional analgesia compared to other opioids (PCA) (RR 0.76, 95% CI 0.45 to 1.28, three trials, low-quality evidence).There is evidence that there was no difference in the risk for caesarean delivery between remifentanil (PCA) and other opioids (IV/IM) (RR 0.63, 95% CI 0.30 to 1.32, ccc 0.01, four trials, low-quality evidence) and epidural analgesia (RR 1.0, 95% CI 0.82 to 1.22, ccc 0.01, nine trials, moderate-quality evidence), respectively. Pooled meta-analysis revealed an increased risk for caesarean section under remifentanil (PCA) compared to other opioids (PCA) (RR 2.78, 95% CI 0.99 to 7.82, two trials, very low-quality evidence). However, a wide range of clinically relevant and non-relevant treatment effects is compatible with this result. Based on the current systematic review, there is mostly low-quality evidence to inform practice and future research may significantly alter the current situation. The quality of evidence is mainly limited by poor quality of the studies, inconsistency, and imprecision. More research is needed on maternal and neonatal safety outcomes (maternal apnoea and respiratory depression, Apgar score) and on the optimal mode and regimen of remifentanil administration to provide highest efficacy with reasonable adverse effects for mothers and their newborns.


Oriented properties of the chlorophylls: Electronic absorption spectroscopy of orthorhombic pyrochlorophyllide a-apomyoglobin single crystals.
The orientations of the transition dipole moments in chlorophyll (Chl) are among the most useful spectroscopic properties for determining macromolecular architecture in photosynthetic complexes; however, the relationships between these orientations and the Chl molecular geometry are unknown. In order to solve this problem, we have prepared single crystals of the synthetic 1:1 complex between pyrochlorophyllide a and apomyoglobin. The protein crystallizes readily in the orthorhombic (B) form, space group P2(1)2(1)2(1), and the unit cell dimensions are determined to be within 0.5% of those for native MetMb crystals of the same type. These green crystals are highly dichroic, and the strong absorption along the crystallographic a axis in the Q(y) band is red-shifted by about 9 nm, relative to the corresponding feature in a solution of the protein. Although the crystal structure for native Mb in this space group has not been determined, the direction cosines of the heme normal relative to the crystal axes have been measured. By using these values, an appropriate trigonometric analysis, and the measured polarized single-crystal spectra, the orientation of the Chl transition dipole moment for the Q(y) transition can be specified relative to the crystal axes. With the completion of the protein crystal structure, this result will lead directly to the orientations of the optical transition dipole moments relative to the molecular geometry. The effects of vibronic coupling and the protein environment on the absorption properties of Chl are discussed in detail.


Invader danger: lizards faced with novel predators exhibit an altered behavioral response to stress.
Animals respond to stressors by producing glucocorticoid stress hormones, such as corticosterone (CORT). CORT acts too slowly to trigger immediate behavioral responses to a threat, but can change longer-term behavior, facilitating an individual's survival to subsequent threats. To be adaptive, the nature of an animal's behavior following elevated CORT levels should be matched to the predominant threats that they face. Seeking refuge following a stressful encounter could be beneficial if the predominant predator is a visual hunter, but may prove detrimental when the predominant predator is able to enter these refuge sites. As a result, an individual's behavior when their CORT levels are high may differ among populations of a single species. Invasive species impose novel pressures on native populations, which may select for a shift in their behavior when CORT levels are high. We tested whether the presence of predatory invasive fire ants (Solenopsis invicta) at a site affects the behavioral response of native eastern fence lizards (Sceloporus undulatus) to elevated CORT levels. Lizards from an uninvaded site were more likely to hide when their CORT levels were experimentally elevated; a response that likely provides a survival advantage for lizards faced with native predatory threats (e.g. birds and snakes). Lizards from a fire ant invaded site showed the opposite response; spending more time moving and up on the basking log when their CORT levels were elevated. Use of the basking log likely reflects a refuge-seeking behavior, rather than thermoregulatory activity, as selected body temperatures were not affected by CORT. Fleeing off the ground may prove more effective than hiding for lizards that regularly encounter small, terrestrially-foraging fire ant predators. This study suggests that invasive species may alter the relationship between the physiological and behavioral stress response of native species.


Pandemica Panoptica: Biopolitical Management of Viral Spread in the Age of Covid-19.
The current pandemic period has triggered a series of changes in society, at both individual and collective behavioral levels. These changes were perceived as either positive or negative by the impacted bodies, leading to both social change and positive interactions in a tense context. In this paper, the authors will deal with Pandemica Panotpica, subjugation infiltrating all levels of society, and the approach adopted by several countries in trying to find countermeasures to combat the virus' proliferation. Our research scope began at the onset of the pandemic and ended on early January 2021.


Variation in the regulatory region of FZP causes increases in secondary inflorescence branching and grain yield in rice domestication.
Inflorescence branching is a key agronomic trait determining rice yield. The primary branch of the ancestral wild rice (Oryza rufipogon Griff.) bears few grains, due to minimal secondary branching. By contrast, Oryza sativa cultivars have been selected to produce large panicles with more secondary branches. Here we showed that the CONTROL OF SECONDARY BRANCH 1 (COS1) gene, which is identical to FRIZZY PANICLE (FZP), plays an important role in the key transition from few secondary branches in wild rice to more secondary branches in domesticated rice cultivars. A 4-bp tandem repeat deletion approximately 2.7 kb upstream of FZP may affect the binding activities of auxin response factors to the FZP promoter, decrease the expression level of FZP and significantly enhance the number of secondary branches and grain yield in cultivated rice. Functional analyses showed that NARROW LEAF 1 (NAL1), a trypsin-like serine and cysteine protease, interacted with FZP and promoted its degradation. Consistently, downregulating FZP expression or upregulating NAL1 expression in the commercial cultivar Zhonghua 17 increased the number of secondary branches per panicle, grain number per panicle and grain yield per plant. Our findings not only provide insights into the molecular mechanism of increasing grain number and yield during rice domestication, but also offer favorable genes for improving the grain yield of rice.


Chondroitin sulfates in developing mouse tooth germs. An immunohistochemical study with monoclonal antibodies against chondroitin-4 and chondroitin-6 sulfates.
The role of glycosaminoglycans and proteoglycans during ontogenesis is not known. The developing tooth offers a potentially important model for studies of structure-function relationships. In this study, we have analysed the temproal and spatial expression of chondroitins of differing sulfation patterns in embryonic molars and incisors. For this purpose, we have used monoclonal antibodies (Mabs) specific for unsulfated, 4-sulfated, and 6-sulfated forms of chondroitin in conjunction with indirect immunofluorescence or immunoperoxidase labeling. Unsulfated chondroitin was not detected in embryonic teeth. Chondroitin 4- and chondroitin 6-sulfates were present in the stellate reticulum but otherwise they were confined to the dental mesenchyme. The 3B3 and MC21C-epitope, which are markers of 6-sulfated chondroitin, were uniformly distributed in the dental mesenchyme during the bud stage; they disappeared from the dental papilla of the cusps and of the anterior region of the incisor as development proceeded. These epitopes were absent from the basement membrane and from the predentin. In the odontoblastic cell lineage, the 3B3 and MC21C-epitopes were detected only between preodontoblasts at an early stage of differentiation. The monoclonal antibody 2B6 served as a probe to localize chondroitin 4-sulfate. This glycosaminoglycan was detected as early as the dental lamina stage but its expression was restricted to the basement membrane of the teeth until the late bell stage. After the onset of cusp formation, strong staining was also observed over the occlusal region of the dental papilla while the cervical region of the dental papilla remained 2B6-negative. Incisors at the bell stage exhibited a decreasing gradient of immunostaining by 2B6 from their anterior region to their posterior end. The extracellular matrix surrounding preodontoblasts reacted with 2B6 and the predentin, produced by the odontoblasts, was also intensely labeled with this antibody. Comparison between immunostaining with 3B3 and 2B6, on consecutive sections revealed a mutually exclusive pattern of distribution of the corresponding epitopes during odontogenesis. Furthermore, in the continuously growing incisor, a striking positive correlation was found between the immunostaining patterns produced by 3B3 and MC21C and the mitotic indices along the anterior-posterior axis of the tooth. Hence, sulfation of chondroitin seems developmentally regulated. We postulate that changes in the sulfation pattern of chondroitin might play a role in ontogenesis by locally altering the functional properties of the extracellular matrix.


Active dendritic integration of inhibitory synaptic inputs in vivo.
Synaptic integration in vivo often involves activation of many afferent inputs whose firing patterns modulate over time. In spinal motoneurons, sustained excitatory inputs undergo enormous enhancement due to persistent inward currents (PICs) that are generated primarily in the dendrites and are dependent on monoaminergic neuromodulatory input from the brain stem to the spinal cord. We measured the interaction between dendritic PICs and inhibition generated by tonic electrical stimulation of nerves to antagonist muscles during voltage clamp in motoneurons in the lumbar spinal cord of the cat. Separate samples of cells were obtained for two different states of monoaminergic input: standard (provided by the decerebrate preparation, which has tonic activity in monoaminergic axons) and minimal (the chloralose anesthetized preparation, which lacks tonic monoaminergic input). In the standard state, steady inhibition that increased the input conductance of the motoneurons by an average of 38% reduced the PIC by 69%. The range of this reduction, from <10% to >100%, was proportional to the magnitude of the applied inhibition. Thus nearly linear integration of synaptic inhibition may occur in these highly active dendrites. In the minimal state, PICs were much smaller, being approximately equal to inhibition-suppressed PICs in the standard state. Inhibition did not further reduce these already small PICs. Overall, these results demonstrate that inhibition from local spinal circuits can oppose the facilitation of dendritic PICs by descending monoaminergic inputs. As a result, local inhibition may also suppress active dendritic integration of excitatory inputs.


Genes mirror geography in Daphnia magna.
Identifying the presence and magnitude of population genetic structure remains a major consideration in evolutionary biology as doing so allows one to understand the demographic history of a species as well as make predictions of how the evolutionary process will proceed. Next-generation sequencing methods allow us to reconsider previous ideas and conclusions concerning the distribution of genetic variation, and what this distribution implies about a given species evolutionary history. A previous phylogeographic study of the crustacean Daphnia magna suggested that, despite strong genetic differentiation among populations at a local scale, the species shows only moderate genetic structure across its European range, with a spatially patchy occurrence of individual lineages. We apply RAD sequencing to a sample of D. magna collected across a wide swath of the species' Eurasian range and analyse the data using principle component analysis (PCA) of genetic variation and Procrustes analytical approaches, to quantify spatial genetic structure. We find remarkable consistency between the first two PCA axes and the geographic coordinates of individual sampling points, suggesting that, on a continent-wide scale, genetic differentiation is driven to a large extent by geographic distance. The observed pattern is consistent with unimpeded (i.e. no barriers, landscape or otherwise) migration at large spatial scales, despite the fragmented and patchy nature of favourable habitats at local scales. With high-resolution genetic data similar patterns may be uncovered for other species with wide geographic distributions, allowing an increased understanding of how genetic drift and selection have shaped their evolutionary history.


Drug-to-Antibody Ratio Estimation via Proteoform Peak Integration in the Analysis of Antibody-Oligonucleotide Conjugates with Orbitrap Fourier Transform Mass Spectrometry.
The therapeutic efficacy and pharmacokinetics of antibody-drug conjugates (ADCs) in general, and antibody-oligonucleotide conjugates (AOCs) in particular, depend on the drug-to-antibody ratio (DAR) distribution and average value. The DAR is considered a critical quality attribute, and information pertaining to it needs to be gathered during ADC/AOC development, production, and storage. However, because of the high structural complexity of ADC/AOC samples, particularly in the initial drug-development stages, the application of the current state-of-the-art mass spectrometric approaches can be limited for DAR analysis. Here, we demonstrate a novel approach for the analysis of complex ADC/AOC samples, following native size-exclusion chromatography Orbitrap Fourier transform mass spectrometry (FTMS). The approach is based on the integration of the proteoform-level mass spectral peaks in order to provide an estimate of the DAR distribution and its average value with less than 10% error. The peak integration is performed via a truncation of the Orbitrap's unreduced time-domain ion signals (transients) before mass spectra generation via FT processing. Transient recording and processing are undertaken using an external data acquisition system, FTMS Booster X2, coupled to a Q Exactive HF Orbitrap FTMS instrument. This approach has been applied to the analysis of whole and subunit-level trastuzumab conjugates with oligonucleotides. The obtained results indicate that ADC/AOC sample purification or simplification procedures, for example, deglycosylation, could be omitted or minimized prior to the DAR analysis, streamlining the drug-development process.


Concrete floor-bovine claw contact pressures related to floor roughness and deformation of the claw.
The intention of this research was to study the impact of concrete floor surface roughness on a bovine claw model and to assess the deformation of the bovine claw model under load. The pressure distribution between the floor and the claw is the key method in this research. Monitoring foot-to-ground pressure distributions may provide insight into the relation between high local pressures and foot lesions. Concrete floor samples were made with 5 different finishing methods. Their roughness was determined by measuring the heights of the "peaks and the valleys" of the surface with a high-precision laser beam. The smoothest surface was the sample finished with a metal float (surface roughness R(a) = 0.062 mm) and the roughest surface occurred with the heavily sandblasted sample (surface roughness R(a) = 0.488 mm). The roughness of the concrete floor samples was related to the mean and peak contact pressures that can occur in a laboratory test bench between floor and bovine claw. It was found that the claw itself has approximately 2 times more effect on these contact pressures than the surface roughness. Peak pressures found were high enough (up to 111 MPa) to cause damage to the bovine claw sole horn. The strains occurring in the horn wall were measured and related to the floor-finishing method and the load. Strain gauge measurements indicated that it is difficult to predict what kind of deformation of the claw wall will occur at a certain location. Different strains will occur for different floor-finishing methods. The corresponding stresses in the horn wall did not exceed the yield stress (14 and 11 MPa for dorsal and abaxial wall horn, respectively).


The course of anhedonia during 10 years of schizophrenic illness.
Although anhedonia has been proposed to be a trait-like characteristic in schizophrenia patients, its persistence and stability have not been tested using multiple assessments over a multiyear period. Specific definitions of anhedonia vary across studies, and relationships between different types of anhedonia as well as their relationship to schizophrenic symptoms over the course of illness have not been addressed. The current research, using prospectively collected longitudinal data covering a 10-year span for 127 individuals with schizophrenic illness, found that (a) physical, but not depressive, anhedonia is a stable characteristic over a 10-year period; (b) physical anhedonia does not show strong and consistent relationships with psychotic, negative, or depressive symptoms; and (c) the relationship between some premorbid characteristics and physical anhedonia are significant even 10 years into the course of illness.


Identifying stride-to-stride control strategies in human treadmill walking.
Variability is ubiquitous in human movement, arising from internal and external noise, inherent biological redundancy, and from the neurophysiological control actions that help regulate movement fluctuations. Increased walking variability can lead to increased energetic cost and/or increased fall risk. Conversely, biological noise may be beneficial, even necessary, to enhance motor performance. Indeed, encouraging more variability actually facilitates greater improvements in some forms of locomotor rehabilitation. Thus, it is critical to identify the fundamental principles humans use to regulate stride-to-stride fluctuations in walking. This study sought to determine how humans regulate stride-to-stride fluctuations in stepping movements during treadmill walking. We developed computational models based on pre-defined goal functions to compare if subjects, from each stride to the next, tried to maintain the same speed as the treadmill, or instead stay in the same position on the treadmill. Both strategies predicted average behaviors empirically indistinguishable from each other and from that of humans. These strategies, however, predicted very different stride-to-stride fluctuation dynamics. Comparisons to experimental data showed that human stepping movements were generally well-predicted by the speed-control model, but not by the position-control model. Human subjects also exhibited no indications they corrected deviations in absolute position only intermittently: i.e., closer to the boundaries of the treadmill. Thus, humans clearly do not adopt a control strategy whose primary goal is to maintain some constant absolute position on the treadmill. Instead, humans appear to regulate their stepping movements in a way most consistent with a strategy whose primary goal is to try to maintain the same speed as the treadmill at each consecutive stride. These findings have important implications both for understanding how biological systems regulate walking in general and for being able to harness these mechanisms to develop more effective rehabilitation interventions to improve locomotor performance.


Developing and Testing Automatic Models of Patient Communicative Health Literacy Using Linguistic Features: Findings from the ECLIPPSE study.
Patients with diabetes and limited health literacy (HL) may have suboptimal communication exchange with their health care providers and be at elevated risk of adverse health outcomes. These difficulties are generally attributed to patients' reduced ability to both communicate and understand health-related ideas as well as physicians' lack of skill in identifying those with limited HL. Understanding and identifying patients with barriers posed by lower HL to improve healthcare delivery and outcomes is an important research avenue. However, doing so using traditional methods has proven difficult and infeasible to scale. This study using corpus analyses, expert human ratings of HL, and natural language processing (NLP) approaches to estimate HL at the individual patient level. The goal of the study is to better understand HL from a linguistic perspective and to open new research areas to enhance population management and individualized care. Specifically, this study examines HL as a function of patients' demonstrated ability to communicate health-related information to their providers via secure messages. The study develops an NLP-based HL model and validates the model by predicting patient-related events such as medical outcomes and hospitalizations. Results indicate that the developed model predicts human ratings of HL with ~80% accuracy. Validation indicates that lower HL patients are more likely to be nonwhite and have lower educational attainment. In addition, patients with lower HL suffered more negative health outcomes and had higher healthcare service utilization.


ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling.
Immature dendritic cells (DCs) specialize in antigen capture and maintain a highly dynamic pool of intracellular major histocompatibility complex class II (MHCII) that continuously recycles from peptide loading compartments to the plasma membrane and back again. This process facilitates sampling of environmental antigens for presentation to T helper cells. Here, we show that a signaling pathway mediated by the DC immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptors (DAP12 and FcRγ) and Vav family guanine nucleotide exchange factors controls the half-life of surface peptide-MHCII (pMHCII) complexes and is critical for CD4 T-cell triggering in vitro. Strikingly, mice with disrupted DC ITAMs show defective T helper cell priming in vivo and are protected from experimental autoimmune encephalitis. Mechanistically, we show that deficiency in ITAM signaling results in increased pMHCII internalization, impaired recycling, and an accumulation of ubiquitinated MHCII species that are prematurely degraded in lysosomes. We propose a novel mechanism for control of T helper cell priming.


Enzymatic catalyzed synthesis and triggered gelation of ionic peptides.
We investigate the possibility of using the protease thermolysin to drive the synthesis and gelation of ionic-complementary peptides from nongelling precursors. In this system, short peptide fragments are continuously interconverted to form a dynamic peptide library, which eventually favors synthesis of peptides that are thermodynamically stabilized by molecular self-assembly. Thermolysin was added at a fixed concentration (0.3 mg mL(-1)) to solutions (0-300 mg mL(-1)) of the short tetrapeptide FEFK. Initially, the protease partially hydrolyzed the tetrapeptide into dipeptides in all samples. Subsequently, longer peptide sequences were found to form through reverse-hydrolysis. The stability of the different sequences was found to be dependent on their self-assembling properties. The sequences that self-assembled into antiparallel beta-sheet rich fibers became the stable products for the reverse hydrolysis reaction, while the others formed were unstable and disappeared with increasing incubation time. Ultimately, the main product of the system was octapeptide, which suggests that it represents the thermodynamically favored product of this dynamic library. Its concentration dictated the gelation behavior of the sample, and gels with moduli up to 25 kPa where obtained depending on the initial concentration of tetrapeptide.


Experience-driven remodeling of S1 digit representation in awake monkeys: the challenge of comparing active and passive touch.
Many studies have compared active and passive touch to understand how motor action shapes touch perception. Current views emphasize the difficulties in making such a comparison and promote investigating how motor strategies enable the filtering out of sensory inputs to reshape touch perception. Cybulska-Klosowicz et al. (Cybulska-Klosowicz A, Tremblay F, Jiang W, Bourgeon S, Meftah E-M, Chapman CE. J Neurophysiol 123: 1072-1089, 2020) suggest that primary somatosensory (S1) cortical remodeling of digit representation occurs during active touch. Here, alternative interpretations are proposed, and the relevance of studying multidigit scanning is emphasized.


Changes in arterial wall properties during development and maintenance of renal hypertension.
Segments of carotid and tail arteries were used to determine the effects of two-kidney Goldblatt hypertension on mechanical properties and chemical contents. Arteries were obtained after 4 and 12 wk of hypertension. Systolic pressures averaged 129 mmHg in control animals and 150 mmHg in hypertensive ones. Pressure-diameter data were recorded under conditions of active (145 mM K+) and passive (0 Ca2+ and 2 mM EGTA) smooth muscle. Small increases in passive stiffness were found after 4 and 12 wk in the carotid arteries of hypertensive animals, but no significant change occurred in the tail arteries. Small but significant decreases in total connective tissue content of these arteries were found after 12 wk of hypertension. Maximum values of active stress response were significantly larger in carotid arteries from hypertensive animals at both 4 and 12 wk of hypertension. No significant differences were found for the tail arteries. The K+ content of the carotid but not the tail artery was larger for the hypertensive animals. When corrected for differences in relative cell content most of the differences in active force development were eliminated. The differences in passive mechanics can not be explained on the basis of the changes in connective tissue content. The active smooth muscle responses and content changes suggest that they are directly related to the moderate elevation of arterial pressure.


Psychosis and the Control of Lucid Dreaming.
Dreaming and psychosis share important features, such as intrinsic sense perceptions independent of external stimulation, and a general lack of criticism that is associated with reduced frontal cerebral activity. Awareness of dreaming while a dream is happening defines lucid dreaming (LD), a state in which the prefrontal cortex is more active than during regular dreaming. For this reason, LD has been proposed to be potentially therapeutic for psychotic patients. According to this view, psychotic patients would be expected to report LD less frequently, and with lower control ability, than healthy subjects. Furthermore, psychotic patients able to experience LD should present milder psychiatric symptoms, in comparison with psychotic patients unable to experience LD. To test these hypotheses, we investigated LD features (occurrence, control abilities, frequency, and affective valence) and psychiatric symptoms (measure by PANSS, BPRS, and automated speech analysis) in 45 subjects with psychotic symptoms [25 with Schizophrenia (S) and 20 with Bipolar Disorder (B) diagnosis] versus 28 non-psychotic control (C) subjects. Psychotic lucid dreamers reported control of their dreams more frequently (67% of S and 73% of B) than non-psychotic lucid dreamers (only 23% of C; S > C with p = 0.0283, B > C with p = 0.0150). Importantly, there was no clinical advantage for lucid dreamers among psychotic patients, even for the diagnostic question specifically related to lack of judgment and insight. Despite some limitations (e.g., transversal design, large variation of medications), these preliminary results support the notion that LD is associated with psychosis, but falsify the hypotheses that we set out to test. A possible explanation is that psychosis enhances the experience of internal reality in detriment of external reality, and therefore lucid dreamers with psychotic symptoms would be more able to control their internal reality than non-psychotic lucid dreamers. Training dream lucidity is likely to produce safe psychological strengthening in a non-psychotic population, but in a psychotic population LD practice may further empower deliria and hallucinations, giving internal reality the appearance of external reality.


[Aging of veins and venules].
There is a distinction between natural ageing and excessive ageing. The problem is not only vascular, it is above all interstitial conjunctival; it is located in the trunk wall and in the initial collector walls; the capillary-venular section is, from this point of view, just a unit of structure and function. The clinical and anatomopathological aspects of venous ageing are known: they are those of phlebosclerosis and deposits of proteoglycanes, the lesions are non-homogenous, dispersed and constantly changing. The elderly patient lives in a state of stasis. Stasis creates exaggerated and uncontrollable histangic neogenesis, it is the backcloth of "micro-angiopathy of senescence", but if the membrane thickens, it is in order to counter the ill effects of stasis; it is a control reaction not one caused by lesion. It is vital to establish an analogy between vascular ageing and "plastic" ageing, the process of polymerization is the same and we shall produce the evidence of this on another occasion.


Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2.
Postmenopausal women with hormone receptor-positive (HR(+)) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR(+) advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest. BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR(+) advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up. Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths. Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+) advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population.


[Frequency of delta F508 mutation in Venezuelan patients with cystic fibrosis].
Cystic Fibrosis (CF) is the most common and severe autosomal recessive disease in Caucasian populations, with an incidence of 1 in 2500 live births. It is characterized by a generalized disturbance in exocrine glands and it is caused by over one thousand mutations at the cystic fibrosis conductance regulator gene (CFTR) mapped at 7q31. AF508 is the most frequent mutation worldwide and it consists in a deletion of the codon that encodes fenilalanine at the 508 protein's position. The aim of this study was to determine the frequency of the delta F508 mutation in Venezuelan patients with CF using the Polymerase Chain Reaction (PCR). We studied thirty patients of twenty eight families who were diagnosed with CF based on their clinical features and sweat chloride level > 60 mEq/l in two determinations. Detection of the mutation was performed from the amplification of a 98 pair of bases (pb) CF gene segment which contains the codon that encodes fenilalanine in the 508 position by PCR. This PCR product is absent in those who have the mutation. The delta F508 allelic frequency was 26.79%, distributed in six homozygous and seven compound heterozygote delta F508/X. The reminder mutations (no delta F508) represent 73.21%. The delta F508 frequency in our sample is less than the reported in European countries. On the other hand, a delta F508 frequency highly heterogeneous has been observed in Latin-American countries. This variation results from mixed populations with a different genetic background influenced by external migration and CF molecular alterations, which exists in the analyzed populations. In this study, the delta F508 mutation comes mainly from grandparents (79.41%) who were born in Mediterranean countries and Colombia, while the no delta F508 mutations come from grandparents who were born in Venezuela (79.27%) and Colombia (17.07%).


Influence of the dielectric property on microwave oven heating patterns: application to food materials.
Patterns of power absorption in a microwave oven for a range of dielectric properties of relevance to food processing were investigated. The governing Maxwell's equations with boundary conditions and a TE10 excitation were solved using a finite element method. Food properties were varied from values at their frozen state to values at high temperatures, as would be typical in a thawing process. For low-loss materials such as frozen foods, the high quality factor makes the heating significantly higher only when the size and shape of the load permit a dielectric cavity resonance in the load. Otherwise, the heating pattern will follow the modal electric field pattern of the oven. For moderate loss materials, the patterns will come from the modes of the dielectric cavity. The bandwidths of these modes are larger than the low-loss situation and their overlap results in a heating pattern that is somewhat more uniform. For high-loss materials, the concept of modes is no longer useful as the very large number of modes strongly overlap. The rapidly decaying field and power loss in the high-loss material can probably be characterized as an exponential decay.


Addressing mental health stigma among young adolescents: evaluation of a youth-led approach.
Stigma around mental illness puts adolescents at risk for not seeking help for themselves or helping peers dealing with mental distress. This program evaluation looks at a youth-led mental health awareness promotion campaign, in which high school students led educational workshops for at-risk middle school students in an after-school program. Pre- and posttests were used to measure knowledge about mental illness as well as social distance; a total of 57 pre- and posttests were analyzed. Analyses revealed statistically significant changes in both the Knowledge and Social Distance scales. The results suggest that salutary results can be realized as a result of very brief intervention with youths around the topic of mental health awareness.


Adaptive Interactions of Achromobacter spp. with Pseudomonas aeruginosa in Cystic Fibrosis Chronic Lung Co-Infection.
In the lungs of patients with cystic fibrosis (CF), the main pathogen Pseudomonas aeruginosa is often co-isolated with other microbes, likely engaging in inter-species interactions. In the case of chronic co-infections, this cohabitation can last for a long time and evolve over time, potentially contributing to the clinical outcome. Interactions involving the emerging pathogens Achromobacter spp. have only rarely been studied, reporting inhibition of P. aeruginosa biofilm formation. To evaluate the possible evolution of such interplay, we assessed the ability of Achromobacter spp. isolates to affect the biofilm formation of co-isolated P. aeruginosa strains during long-term chronic co-infections. We observed both competition and cohabitation. An Achromobacter sp. isolate secreted exoproducts interfering with the adhesion ability of a co-isolated P. aeruginosa strain and affected its biofilm formation. Conversely, a clonal Achromobacter sp. strain later isolated from the same patient, as well as two longitudinal strains from another patient, did not show similar competitive behavior against its P. aeruginosa co-isolates. Genetic variants supporting the higher virulence of the competitive Achromobacter sp. isolate were found in its genome. Our results confirm that both inter-species competition and cohabitation are represented during chronic co-infections in CF airways, and evolution of these interplays can happen even at the late stages of chronic infection.


Does Father Know Best? A Formal Model of the Paternal Influence on Childhood Social Anxiety.
We explore paternal social anxiety as a specific risk factor for childhood social anxiety in a rational optimization model. In the course of human evolution, fathers specialized in external protection (e.g., confronting the external world) while mothers specialized in internal protection (e.g., providing comfort and food). Thus, children may instinctively be more influenced by the information signaled by paternal versus maternal behavior with respect to potential external threats. As a result, if fathers exhibit social anxiety, children interpret it as a strong negative signal about the external social world and rationally adjust their beliefs, thus becoming stressed. Under the assumption that paternal signals on social threats are more influential, a rational cognitive inference leads children of socially anxious fathers to develop social anxiety, unlike children of socially anxious mothers. We show in the model that mothers cannot easily compensate for anxious paternal behavior, but choose to increase maternal care to maintain the child's wellbeing. We discuss research directions to test the proposed model as well as implications for the prevention and treatment of child social anxiety.


Comparison of anticoagulation clinic patient outcomes with outcomes from traditional care in a family medicine clinic.
Giving patients oral anticoagulation therapy in an ambulatory clinic setting is associated with substantial risk of adverse outcomes leading to emergency department visits and unplanned inpatient admissions. This article describes an effectiveness study conducted in a well-characterized family practice setting that compares anticoagulation outcomes in patients managed by a traditional care model with outcomes obtained with an anticoagulation clinic model. All study patients received continuous anticoagulation care at the Family Medicine of Southwest Washington (FMSW) clinic during the 1-year study period. The method was retrospective and used linked record review, including outpatient, inpatient, and emergency department records. Patients were divided into two groups as naturally observed: those treated in the clinic by traditional care compared with those treated in an anticoagulation clinic model. Data analyses compared the two groups in terms of patient demographics, anticoagulation control, and inpatient admissions and emergency department visits that were related to clotting or bleeding events. There were no differences in demographic variables between the anticoagulation clinic and traditional care groups. There was a statistically significant difference in anticoagulation control as measured by international normalized ratio (INR) values. The anticoagulation clinic group had fewer INR values outside the target range, +/- 0.1, than the traditional care group (40.4% vs 47.3% P = .022). The anticoagulation clinic group also had significantly fewer INR tests drawn more than 6 weeks apart than the traditional care group (3.7% vs 8.1% P = .01). There was no statistically significant difference in emergency department visit rates caused by adverse events. Inpatient admission rates for the anticoagulation clinic and traditional care groups were not statistically different; however, they were clinically different (4.7 vs 19.7 admissions per 100 patient years of therapy P = .15). More anticoagulation patients treated by the anticoagulation clinic model at FMSW received an INR test at least every 6 weeks than those treated by the traditional care model, and more of their INR results were within target range +/- 0.1 when compared with the traditional care model.


Influences on the choice of health professionals to practice in rural areas.
Training health care professionals (HCPs) to work in rural areas is a challenge for educationalists. This study aimed to understand how HCPs choose to work in rural areas and how education influences this. Qualitative individual interviews were conducted with 15 HCPs working in rural areas in SA. Themes identified included personal, facilitating, contextual, staying and reinforcing factors. Personal attributes of the HCPs, namely rural origin and/or their value system, determine consideration of rural practice. The decision to 'go rural' is facilitated by exposure to rural practice during training, an understanding of rural needs and exposure to rural role models. Once practising in a rural area, the context and nature of work and the environment influence the decision to remain, supported by the role of family and friends, ongoing training and development, and the style of health service management. Personal motivation is reinforced by a positive relationship with the community, and by being an advocate and role model for the local community. Educational factors were often felt to work against the decision to practise in rural areas. The results show the complexity of the interaction between a large number of factors working together to make HCPs choose to go and stay in rural areas. Factors other than educational ones seem more important. A comprehensive approach is needed to attract and retain HCPs in rural areas. Issues for educationalists to address include helping rural-origin students to connect with their own values and communities.


A retrospective audit of electroconvulsive therapy at King Khalid University Hospital, Saudi Arabia.
The case records of patients receiving ECT at King Khalid University Hospital over a 10-year period were reviewed for all aspects of ethical and technical administration of ECT. The audit of 127 patients showed some deficiencies in the early years: no seizure monitoring, no training or education for staff (particularly psychiatrists and anaesthetists), and the use of atropine as a premedication for all patients. Recently, regular education and staff training have been organized and seizure timing regularly monitored. Use of an ECT machine with EEG monitoring and the systematic and scaled monitoring of complications is recommended. Results show the necessity of ECT auditing, including an unbiased external audit for effective monitoring of the practical administration of ECT. Similar audits in other mental health institutions in Saudi Arabia are recommended.


[Peculiarities of clinical picture of duodenal ulcer in the population of Northern Europe].
Duodenal ulcer remains a serious challenge to gastroenterology due to the difficulty of its management despite recent progress in this field. The role of melatonin in human body has attracted much attention of researchers in the recent years. Disturbances of its production are widely recognized to be involved in pathogenesis of duodenal ulcer and its exacerbation. This review summarizes results of research on the clinical picture of the disease in the population of European North where circadian and seasonal variations in melatonin production are most strongly pronounced.


Antiphospholipid syndrome and kidney involvement.
Antiphospholipid syndrome is an autoimmune disease characterized by the development of autoantibodies and the impairment of the coagulation system. Knowledge about this syndrome is increasing over time, but kidney involvement, especially APS nephropathy, still represents a challenge for physicians. A "two hit" model has been hypothesized to explain APS pathophysiology, and the role played by some factors, such as the complement system, is becoming more and more clear. From a clinical point of view, along with thrombosis in any site and/or obstetric morbidities, that are the hallmarks of APS, a constellation of several other clinical symptoms is related to APS. These symptoms alone are not sufficient to fulfill Sydney criteria for APS and this could potentially lead to omitting some diagnoses. The mainstay of management of APS is antithrombotic therapy but there are expectations for new drugs that regulate the immune system. APS could affect the kidneys in many ways and among them, APS nephropathy is an intriguing entity that has been overlooked in recent years. Novel studies on APS nephropathy are lacking. In this review we discuss what we currently know about APS and its relationship with the kidney, with an eye towards the future perspectives. Multicenter studies on APS nephropathy are necessary in order to develop targeted therapies.


Magnetic resonance imaging as a tool to examine the neuropathology of multiple sclerosis.
Magnetic resonance imaging (MRI) has significantly extended the understanding of multiple sclerosis (MS), owing to its ability to sensitively depict the dynamics of the disease process in vivo. The subject of this review is the use of MRI in the post-mortem setting, with emphasis on how it may be used to improve the specimen selection process at autopsy. Lesions with active demyelination are highly interesting in the study of MS pathogenesis, but are rare in a typical autopsy material of chronic MS. The yield of MS lesions in autopsy specimen selection can be increased by the use of MRI-guided tissue sampling, as a significant proportion of abnormalities detected by post-mortem MRI are not macroscopically visible/palpable. The majority of these MRI abnormalities have been found to represent either discrete areas of microglial activation with no demyelination (so-called (p)reactive lesions), or active demyelinating MS lesions by further histopathological examination. The presence and extent of MS pathology outside of the focal demyelinated lesions is more readily appreciated by MRI-guided specimen sampling, as has been shown in the study of extensive areas of partial myelin loss in the spinal cord. A further advantage of MRI-guided specimen sampling is the ability to use three-dimensional and quantitative measures. The potential of correlating these with histopathological data may be further exploited in the future. The technical procedure for MRI-guided tissue sampling at autopsy is presented, and the limitations of the technique are discussed.


[Phenotype of patients with gynecomastia].
Gynecomastia, a benign enlargement of the breast glandular tissue in men. The aim of the study was to evaluate the phenotype of patients with gynecomastia, in particular antropometric assessment, breast ultrasound examination and hormonal testing, as well as to estimate possible causes of gynecomastia in studied population. Two hundred-twenty men were enrolled in the study: 126 patients with gynecomastia and 94 healthy volunteers as a control group. Detailed medical examination, breast ultrasound and hormonal assays for T, E2, LH, FSH, SHBG, S-DHEA, PRL and TSH were performed. Calculation of free testosterone concentration was done. The results of clinical and hormonal evaluation enabled to divide the cases into three groups: patients with idiopathic gynecomastia (58 subjects, 46%), with hypogonadism (34 subjects, 27%) and drug-induced or associated with other disorders gynecomastia (34 subjects, 27%). We found that men with gynecomastia, particularly associated with hypogonadism, had significantly higher BMI compared with control group. Ultrasound examination revealed the positive correlation between breast tissue volume and BMI, duration of gynecomastia and estradiol level, while negative correlation with testosterone level. We demonstrated significant differences in LH, T, SHBG, fT and S-DHEA levels between cases and controls. There were no differences in PRL, FSH and TSH levels among groups. Significant elevation of SHBG concentration in all groups of patients, including idiopathic gynecomastia cases, compared with controls, was remarkable. Clinical evaluation and hormonal profile can help to classify patient with gynecomastia into one of three groups: idiopathic gynecomastia, associated with hypogonadism, and drug-induced or associated with other diseases. Idiopathic gynecomastia - of unknown etiology is diagnosed in almost half of all cases (46%). We showed that apart from well known hormonal disturbances leading to gynecomastia, like hypogonadism or hyperestrogenism, also subtle hormonal alterations, such as sex hormone binding globuline (SHBG) level elevation may contribute to breast enlargement.


Hyperactivated sperm motility driven by CatSper2 is required for fertilization.
Elevations of sperm Ca2+ seem to be responsible for an asymmetric form of motility called hyperactivation, which is first seen near the time of fertilization. The mechanism by which intracellular Ca2+ concentrations increase remains unknown despite considerable investigation. Although several prototypical voltage-gated calcium channels are present in spermatozoa, they are not essential for motility. Furthermore, the forward velocity and percentage of motility of spermatozoa are associated with infertility, but their importance relative to hyperactivation also remains unknown. We show here that disruption of the gene for a recently described sperm-specific voltage-gated cation channel, CatSper2, fails to significantly alter sperm production, protein tyrosine phosphorylation that is associated with capacitation, induction of the acrosome reaction, forward velocity, or percentage of motility, yet CatSper2-/- males are completely infertile. The defect that we identify in the null sperm cells is a failure to acquire hyperactivated motility, which seems to render spermatozoa incapable of generating the "power" needed for penetration of the extracellular matrix of the egg. A loss of power is suggested also by experiments in which the viscosity of the medium was increased after incubation of spermatozoa in normal capacitating conditions. In high-viscosity medium, CatSper2-null spermatozoa lost the ability to swim forward, whereas wild-type cells continued to move forward. Thus, CatSper2 is responsible for driving hyperactivated motility, and, even with typical sperm forward velocities, fertilization is not possible in the absence of this highly active form of motility.


GENOMICS: Rat Genome Off to an Early Start.
The National Human Genome Research Institute has jump-started efforts to determine the order of the roughly 3 billion bases in the rat genome. The original plan had been to wait for funding, expected in fiscal year 2001. Instead, two of the 10 centers involved in sequencing the mouse genome are shifting to the rat now.


Stochastic extinction and the selection of the transmission mode in microparasites.
Stochastic fluctuations in the transmission process of microparasites generate a risk of parasite extinction that cannot be assessed by deterministic models, especially in host populations of small size. While this risk of extinction represents a strong selection pressure for microparasites, it is usually not clearly separated from the deterministic ones. We suggest here that this stochastic selection pressure can affect the selection of the transmission mode of microparasites. To avoid extinction, parasites should maximize their inter-population transmission to ensure frequent reintroductions. Since the types of contacts may differ if congeners belong to the same or distinct populations, strains that are mainly transmitted through inter-population contacts might be selected. To examine this assumption, we analyse the issue of the competition between two strains differing in their transmission mode using a stochastic metapopulation model in which hosts may display different behaviours inside and outside their populations. We show that stochastic selection pressures may drive parasite evolution towards a transmission mode that maximizes the persistence of the parasite. We study the conditions under which stochastic selection pressures may surpass the deterministic ones. Our results are illustrated by the cases of feline immunodeficiency virus in cats and of sexually transmitted diseases in mammals.


Combined phenotypic and genotypic analysis of ringed sideroblasts in acquired idiopathic sideroblastic anemia.
Bone marrow from an 81-year-old male with acquired idiopathic sideroblastic anemia was found to be mosaic for 45,X/46,XY cell lines. Analysis of ringed sideroblasts for the presence or absence of a quinicrine fluorescent Y body indicated that all sideroblastic cells had lost the Y chromosome. The demonstration that the ringed sideroblasts were cytogenetically abnormal in this patient provides evidence that the cytogenetic changes often found in patients with sideroblastic anemia may not be due to randomly acquired chromosome aberrations accompanying tissue aging unrelated to the disease process.


Physiologic and clinical significance of myocardial blood flow quantitation: what is expected from these measurements in the clinical ward and in the physiology laboratory?
In this essay we review data on absolute quantitation of myocardial blood flow (MBF) in humans. Earlier work established that coronary heart disease (CAD) can be detected by coronary angiography and that this disease has characteristic features at rest and during stress, which indicate the linkage between regional metabolic needs and myocardial perfusion. In the 1970s myocardial perfusion was mapped in patients with radioxenon, but this method had significant technical limitations. About the same time, radioactive microspheres were introduced for cardiovascular research and investigations; these particles provided insights on MBF in acute infarction and ischemia, myocardial reperfusion, collateral circulation, myocardial blood flow during exercise, coronary flow reserve (CFR), and layer-to-layer distribution of MBF. Studies with microspheres also permitted investigators to establish the presence in the heart of MBF heterogeneity. Currently, there are several techniques that aim at extending these concepts into clinical investigation. Two of these techniques, i.e. Doppler coronary flow velocity and fast magnetic resonance imaging assess epicardial flow dynamics and CFR. Contrast myocardial echocardiography is another novel technique which has been useful in mapping the area at risk, reperfusion, myocardial viability and collateral circulation. This essay also considers the emerging technique of intracoronary ultrasound which has shown evidence of disease underestimation by conventional contrast angiography. Positron emission tomography (PET) is a noninvasive technique that uniquely and quantitatively maps myocardial perfusion and CFR. The latter can be computed before and after angioplasty. PET studies have further demonstrated that chronic myocardial ischemia does not exist as a distinct state in patients with CAD. From the above investigations the concept has arisen that not only is CAD an entity involving epicardial vessels but also, in a significant portion of patients, an abnormal microcirculation plays an important role in the pathogenesis of ischemic syndromes. PET studies have relatively low spatial resolution since they cannot resolve layer-to-layer absolute MBF.


Interventions for cisplatin-induced hearing loss in children and adolescents with cancer.
The identification of preventive interventions that are safe and effective for cisplatin-induced ototoxicity is important, especially in children because hearing loss can impair speech-language acquisition development. Previous randomised trials assessed systemic drugs such as amifostine, sodium diethyldithiocarbamate or disulfiram, and sodium thiosulfate. Amifostine, sodium diethyldithiocarbamate, and disulfiram did not show hearing preservation. Paediatric trials assessing sodium thiosulfate showed efficacy in terms of hearing protection. The SIOPEL 6 trial consisted solely of patients with localised hepatoblastoma and no effects on survival were shown. In the ACCL0431 trial, which included heterogeneous patients, a post-hoc analysis showed significantly worse overall survival among patients who had disseminated disease receiving sodium thiosulfate than among controls, but not among those with localised disease. Intratympanically administered drugs have mainly been assessed in adults and include N-acetylcysteine and dexamethasone. Inconsistent effects of these drugs were identified but these studies were limited by design, small sample size, and statistical approach. Future studies of systemic drugs will need to consider the measurement of disease outcomes through study design and sample size, and ototoxicity endpoints should be harmonised to enhance comparability between trials.


Phylodynamic analysis of the emergence and epidemiological impact of transmissible defective dengue viruses.
Intra-host sequence data from RNA viruses have revealed the ubiquity of defective viruses in natural viral populations, sometimes at surprisingly high frequency. Although defective viruses have long been known to laboratory virologists, their relevance in clinical and epidemiological settings has not been established. The discovery of long-term transmission of a defective lineage of dengue virus type 1 (DENV-1) in Myanmar, first seen in 2001, raised important questions about the emergence of transmissible defective viruses and their role in viral epidemiology. By combining phylogenetic analyses and dynamical modeling, we investigate how evolutionary and ecological processes at the intra-host and inter-host scales shaped the emergence and spread of the defective DENV-1 lineage. We show that this lineage of defective viruses emerged between June 1998 and February 2001, and that the defective virus was transmitted primarily through co-transmission with the functional virus to uninfected individuals. We provide evidence that, surprisingly, this co-transmission route has a higher transmission potential than transmission of functional dengue viruses alone. Consequently, we predict that the defective lineage should increase overall incidence of dengue infection, which could account for the historically high dengue incidence reported in Myanmar in 2001-2002. Our results show the unappreciated potential for defective viruses to impact the epidemiology of human pathogens, possibly by modifying the virulence-transmissibility trade-off, or to emerge as circulating infections in their own right. They also demonstrate that interactions between viral variants, such as complementation, can open new pathways to viral emergence.


Molecular dynamics investigation of reduced ethylene carbonate aggregation at the onset of solid electrolyte interphase formation.
Formation of the solid electrolyte interphase (SEI) at the anode surface during the initial charge cycles is critical to lithium ion battery operability. Reduction of electrolyte components must ultimately result in the formation of this ionically conducting and electronically insulating layer to compensate for the limited electrochemical stability window of conventional liquid electrolytes. One important reaction in SEI formation is the bimolecular combination of radical anions to form more stable products. Molecular dynamics simulations illustrate the nature and dynamics of the intermolecular interactions between the reactive intermediates produced from one-electron reduction in ethylene carbonate-based electrolytes. A clear concentration dependence is shown for this interaction, and its ramifications for SEI formation are discussed.


Association between estrogen receptor alpha gene variation and cardiovascular disease.
Estrogen and related hormone therapies activate estrogen receptors, which in turn regulate genes for several cardiovascular disease (CVD) risk factors. Relatively little is known, however, about the impact of genetic variation in estrogen receptor alpha (ESR1) on CVD risk. To investigate whether the ESR1 c.454-397T>C polymorphism is associated with CVD risk. Prospective study of 1739 unrelated men and women from the population-based offspring cohort of the Framingham Heart Study, who were followed up from 1971 to 1998. Total atherosclerotic CVD events, defined as recognized or unrecognized myocardial infarction (MI), angina pectoris, coronary insufficiency, intermittent claudication, coronary heart disease death, or atherothrombotic stroke (n = 178); major atherosclerotic CVD, defined as recognized acute MI, coronary insufficiency, coronary heart disease death, or atherothrombotic stroke (n = 83); and recognized acute MI (n = 59). Twenty percent of participants (n = 352) were homozygous for the ESR1 c.454-397C allele. After adjustment for covariates (age, sex, body mass index, hypertension, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and cigarette smoking), the CC genotype was significantly associated with major atherosclerotic CVD, with an odds ratio of 2.0 (95% confidence interval [CI], 1.3-3.2; P =.004) compared with individuals with the CT or TT genotypes. Participants with the CC genotype had 3.0-fold greater odds of MI (95% CI, 1.7-5.2; P<.001) compared with those with the CT or TT genotype. The results remained significant when analyses were restricted to men; too few women had events to study them separately. Individuals with the common ESR1 c.454-397CC genotype have a substantial increase in risk of MI. Whether ESR1 c.454-397T>C is causally related to MI risk or in linkage disequilibrium with 1 or more causal variants remains to be determined. These findings support the importance of estrogen receptors in CVD susceptibility, especially in men. Estrogen receptor variation also has potential to explain recent conflicting data regarding the effects of hormone therapy on CVD susceptibility in women.


M2 receptor activation inhibits cell cycle progression and survival in human glioblastoma cells.
Muscarinic receptors, expressed in several primary and metastatic tumours, appear to be implicated in their growth and propagation. In this work we have demonstrated that M2 muscarinic receptors are expressed in glioblastoma human specimens and in glioblastoma cell lines. Moreover, we have characterized the effects of the M2 agonist arecaidine on cell growth and survival both in two different glioblastoma cell lines (U251MG and U87MG) and in primary cultures obtained from different human biopsies. Cell growth analysis has demonstrated that the M2 agonist arecaidine strongly decreased cell proliferation in both glioma cell lines and primary cultures. This effect was dose and time dependent. FACS analysis has confirmed cell cycle arrest at G1/S and at G2/M phase in U87 cells and U251 respectively. Cell viability analysis has also shown that arecaidine induced severe apoptosis, especially in U251 cells. Chemosensitivity assays have, moreover, shown arecaidine and temozolomide similar effects on glioma cell lines, although IC50 value for arecaidine was significantly lower than temozolomide. In conclusion, we report for the first time that M2 receptor activation has a relevant role in the inhibition of glioma cell growth and survival, suggesting that M2 may be a new interesting therapeutic target to investigate for glioblastoma therapy.


Apoptosis of pancreatic β-cells in Type 1 diabetes.
Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of pancreatic β-cells after an asymptomatic period over years. Insulitis activates antigen presenting cells, which trigger activating CD4+ helper-T cells, releasing chemokines/cytokines. Cytokines activate CD8+ cytotoxic-T cells, which lead to β-cell destruction. Apoptosis pathway consists of extrinsic (receptor-mediated) and intrinsic (mitochondria-driven) pathway. Extrinsic pathway includes Fas pathway to CD4+-CD8+ interaction, whereas intrinsic pathway includes mitochondria-driven pathway at a balance between anti-apoptotic B-cell lymphoma (Bcl)-2 and Bcl-xL and pro-apoptotic Bad, Bid, and Bik proteins. Activated cleaved caspse-3 is the converging point between extrinsic and intrinsic pathway. Apoptosis takes place only when pro-apoptotic proteins exceed anti-apoptotic proteins. Since the concordance rate of T1DM in identical twins is about 50%, environmental factors are involved in the development of T1DM, opening a door to find means to detect and prevent further development of autoimmune β-cell destruction for a therapeutic application.


Generation of Coherent Light by a Moving Medium.
We show that steady nonuniform motion of a medium through an optical resonator can yield light amplification at the resonator frequency. High gain can be achieved if at the generated frequency the medium refractive index is close to zero or the medium has a very strong frequency dispersion. We also discuss an analogy between light amplification by a moving medium and the generation of sound waves when gas flows along a tube with acoustically closed-open boundaries.


Characterization of white spot syndrome virus envelope protein VP51A and its interaction with viral tegument protein VP26.
In this study, we characterize a novel white spot syndrome virus (WSSV) structural protein, VP51A (WSSV-TW open reading frame 294), identified from a previous mass spectrometry study. Temporal-transcription analysis showed that vp51A is expressed in the late stage of WSSV infection. Gene structure analysis showed that the transcription initiation site of vp51A was 135 bp upstream of the translation start codon. The poly(A) addition signal overlapped with the translation stop codon, TAA, and the poly(A) tail was 23 bp downstream of the TAA. Western blot analysis of viral protein fractions and immunoelectron microscopy both suggested that VP51A is a viral envelope protein. Western blotting of the total proteins extracted from WSSV virions detected a band that was close to the predicted 51-kDa mass, but the strongest signal was around 72 kDa. We concluded that this 72-kDa band was in fact the full-length VP51A protein. Membrane topology assays demonstrated that the VP51A 72-kDa protein is a type II transmembrane protein with a highly hydrophobic transmembrane domain on its N terminus and a C terminus that is exposed on the surface of the virion. Coimmunoprecipitation, colocalization, and yeast two-hybrid assays revealed that VP51A associated directly with VP26 and indirectly with VP28, with VP26 acting as a linker protein in the formation of a VP51A-VP26-VP28 complex.


Blood oxygen level-dependent activation of the primary visual cortex predicts size adaptation illusion.
In natural scenes, objects rarely occur in isolation but appear within a spatiotemporal context. Here, we show that the perceived size of a stimulus is significantly affected by the context of the scene: brief previous presentation of larger or smaller adapting stimuli at the same region of space changes the perceived size of a test stimulus, with larger adapting stimuli causing the test to appear smaller than veridical and vice versa. In a human fMRI study, we measured the blood oxygen level-dependent activation (BOLD) responses of the primary visual cortex (V1) to the contours of large-diameter stimuli and found that activation closely matched the perceptual rather than the retinal stimulus size: the activated area of V1 increased or decreased, depending on the size of the preceding stimulus. A model based on local inhibitory V1 mechanisms simulated the inward or outward shifts of the stimulus contours and hence the perceptual effects. Our findings suggest that area V1 is actively involved in reshaping our perception to match the short-term statistics of the visual scene.


Early Discontinuation of Buprenorphine Therapy for Opioid Use Disorder Among Privately Insured Adults.
This study examined the temporal relationship between early discontinuation of buprenorphine treatment and health care expenditures before and after treatment initiation. MarketScan commercial claims for patients who initiated buprenorphine for opioid use disorder in 2013 and had continuous insurance for the subsequent 12 months (N=6,444) were used to examine the relationship between treatment retention and health care expenditures before and after buprenorphine initiation. Analysis of covariance and generalized linear models (with gamma distribution/log link) were used to compare expenditures across four buprenorphine-retention groups (0-3, 3-6, 6-12, and 12 or more months). Average total health care expenditures in the 3 months prior to buprenorphine initiation ranged from a high of $7,588 among those with the shortest retention to $4,929 among those with the longest retention (p<0.001). In the 12 months after buprenorphine initiation, total health care expenditures averaged $26,332 per year, with $2,916 (11.1%) in out-of-pocket expenditures. Average annual expenditures for medication were highest among patients with the longest buprenorphine retention, and total health care expenditures were highest among those with the shortest retention. Expenditures for health care services other than medication were highest among those with early discontinuation both before the initiation of buprenorphine and during the initial period after initiation but not in subsequent quarters. Poorer treatment retention among privately insured adults was associated with greater clinical and financial burdens that preceded and continued during the period shortly following treatment initiation, suggesting that cost burdens may contribute to poor retention among privately insured adults.


The impact of increasing levels of blood C-reactive protein on the inflammatory loci SPI1 and CD33 in Alzheimer's disease.
Apolipoprotein ε4 (APOE ε4) is the most significant genetic risk factor for late-onset Alzheimer's disease (AD). Elevated blood C-reactive protein (CRP) further increases the risk of AD for people carrying the APOE ε4 allele. We hypothesized that CRP, as a key inflammatory element, could modulate the impact of other genetic variants on AD risk. We selected ten single nucleotide polymorphisms (SNPs) in reported AD risk loci encoding proteins related to inflammation. We then tested the interaction effects between these SNPs and blood CRP levels on AD incidence using the Cox proportional hazards model in UK Biobank (n = 279,176 white participants with 803 incident AD cases). The five top SNPs were tested for their interaction with different CRP cutoffs for AD incidence in the Framingham Heart Study (FHS) Generation 2 cohort (n = 3009, incident AD = 156). We found that for higher concentrations of serum CRP, the AD risk increased for SNP genotypes in 3 AD-associated genes (SPI1, CD33, and CLU). Using the Cox model in stratified genotype analysis, the hazard ratios (HRs) for the association between a higher CRP level (≥10 vs. <10 mg/L) and the risk of incident AD were 1.94 (95% CI: 1.33-2.84, p < 0.001) for the SPI1 rs1057233-AA genotype, 1.75 (95% CI: 1.20-2.55, p = 0.004) for the CD33 rs3865444-CC genotype, and 1.76 (95% CI: 1.25-2.48, p = 0.001) for the CLU rs9331896-C genotype. In contrast, these associations were not observed in the other genotypes of these genes. Finally, two SNPs were validated in 321 Alzheimer's Disease Neuroimaging (ADNI) Mild Cognitive Impairment (MCI) patients. We observed that the SPI1 and CD33 genotype effects were enhanced by elevated CRP levels for the risk of MCI to AD conversion. Furthermore, the SPI1 genotype was associated with CSF AD biomarkers, including t-Tau and p-Tau, in the ADNI cohort when the blood CRP level was increased (p < 0.01). Our findings suggest that elevated blood CRP, as a peripheral inflammatory biomarker, is an important moderator of the genetic effects of SPI1 and CD33 in addition to APOE ε4 on AD risk. Monitoring peripheral CRP levels may be helpful for precise intervention and prevention of AD for these genotype carriers.


A tobacco NtMET1 cDNA encoding a DNA methyltransferase: molecular characterization and abnormal phenotypes of transgenic tobacco plants.
A cDNA encoding a DNA methyltransferase, with a predicted polypeptide of 1556 amino acid residues containing all motifs conserved in this enzyme family, was isolated from tobacco plants, and the corresponding gene was designated as NtMET1. RNA blot analysis indicated NtMET1 transcripts to accumulate in dividing tissues of tobacco plants, and they could be detected during the S phase in synchronized dividing BY2 cells. In situ hybridization revealed the transcripts to be localized exclusively in actively proliferating tissues around axillary apical meristem. In order to ascertain physiological roles, transgenic tobacco plants that had the antisense construct were made and examined for phenotypes. Methylation levels of genomic DNA from transgenic plants significantly decreased in comparison with wild-type levels, and distinct phenotypic changes including small leaves, short internodes and abnormal flower morphology were noted. Microscopic observation revealed that leaf structure differed between transgenic and wild-type plants. These results suggest that NtMET1 functions during DNA replication, and that DNA methylation plays an important role in plant morphogenesis.


The effect of transparency on recognition of overlapping objects.
Are overlapping objects easier to recognize when the objects are transparent or opaque? It is important to know whether the transparency of X-ray images of luggage contributes to the difficulty in searching those images for targets. Transparency provides extra information about objects that would normally be occluded but creates potentially ambiguous depth relations at the region of overlap. Two experiments investigated the threshold durations at which adult participants could accurately name pairs of overlapping objects that were opaque or transparent. In Experiment 1, the transparent displays included monocular cues to relative depth. Recognition of the back object was possible at shorter durations for transparent displays than for opaque displays. In Experiment 2, the transparent displays had no monocular depth cues. There was no difference in the duration at which the back object was recognized across transparent and opaque displays. The results of the two experiments suggest that transparent displays, even though less familiar than opaque displays, do not make object recognition more difficult, and possibly show a benefit. These findings call into question the importance of edge junctions in object recognition. (PsycINFO Database Record (c) 2013 APA, all rights reserved).


Recycling Graphite from Spent Lithium Batteries for Efficient Solar-Driven Interfacial Evaporation to Obtain Clean Water.
Solar-driven interfacial evaporation technology is regarded as an attracting sustainable strategy for obtaining portable water from seawater and wastewater, and the recycle of waste materials to fabricate efficient photothermal materials as evaporator to efficiently utilize solar energy is very critical, but still difficult. To this purpose, graphite recovered from spent lithium-ion batteries (SLIBs) was realized using a simple acid leaching method, and a reconstructed graphite-based porous hydrogel (RG-PH) was subsequently fabricated by crosslinking foaming method. The incorporation of reconstructed graphite (RG) improves the mechanical characteristics of hydrogels and the light absorption performance significantly. The evaporation rate of optimized RG-PH can constantly reach 3.4278 kg m-2 h-1 for desalination under a one solar irradiation, and it also showed the excellent salt resistance in various salty water. Moreover, RG-PH has a strong elimination of a variety of organic contaminants in wastewater, including the typical volatile organic compound of phenol. This research shows the potential application of flexible and durable solar evaporators made from waste materials in purifying seawater and wastewater, not only contributing to carbon neutrality by recycling graphite from SLIBs, but also ensuring the cost-effectiveness harvest of solar energy for constantly obtaining clean water.


Role of silicon in diatom metabolism. Messenger RNA and polypeptide accumulation patterns in synchronized cultures of Cylindrotheca fusiformis.
Patterns of in vitro translation products from isolated mRNA and in vivo polypeptide accumulation in synchronized cultures of Cylindrotheca fusiformis were analysed by two-dimensional gel electrophoresis. The way in which the availability of silicon, the specific cell cycle stage, or the illumination conditions affected the pattern of gene expression was distinguished by comparing the timing of polypeptide and mRNA accumulation in cultures synchronized by two different methods. A rapid and dramatic shift in the relative abundance of in vitro translation products from mRNA followed either the removal or the readdition of silicate to the media as well as the transition from dark to light. Eleven mRNAs appeared to be expressed specifically between mid-S phase and cell separation, as their increase was observed at this stage in both synchronies. In addition, three mildly acidic polypeptides from the soluble protein fraction of C. fusiformis, each representing about 0.05% of the total protein, increased several-fold between mid-S and cell separation. Thus, silicon appears to affect gene expression both directly and, due to its effect on cell cycle progression, indirectly. Both effects are primarily at a level before translation.


Transthoracic echocardiography is adequate for the diagnosis of right coronary artery aneurysms.
Coronary artery aneurysms (CAA) are rare but potentially fatal pathologies. This case was referred to our Unit after occasional echocardiographic finding of an intracardiac mass. A new detailed transthoracic echocardiogram was decisive for a diagnosis of a large CAA of the right coronary artery, compressing and dislocating the right atrium. Transesophageal echocardiography was not performed because of the data obtained. The diagnosis was confirmed by cardiac catheterization. The patient was managed with a surgical procedure.


[Prevalence and comorbidity of body dysmorphic disorder in psychiatric outpatients].
Body dysmorphic disorder (BDD) is a somatoform disorder, characterized by a patient's preoccupation with the belief that some aspect of his/her physical appearance is abnormal. The prevalence of BDD in the general population is 0.7 - 1.7%. The prevalence of BDD in patients attending a Dutch general outpatient clinic has never been examined. Examine the prevalence of BDD in patients attending a Dutch general outpatient clinic. All patients aged 18 to 65 who were referred between September 2003 and July 2007 to six general outpatients clinics for treatment of a depressive disorder, an anxiety disorder, or a somatoform disorder were assessed with the Mini International Neuropsychiatric Interview (mini). Patients with BDD were also assessed by means of the Body Dysmorphic Disorder - Yale- Brown Obsessive Compulsive Scale (BDD-YBOCS). results BDD was diagnosed in 45 out of 5848 patients (0.8% (0.6-1.0%)). The average age of these patients was 31.1. years and 69% were female. A comorbid depressive disorder was present in 35 patients (78%) and a comorbid anxiety disorder in 26 patients (58%). Of the anxiety disorders, social phobia was the most common, with a prevalence of 27%. The average score on the BDD-YBOCS was 22.5 points. The BDD-YBOCS score was significantly higher in patients with a comorbid obsessive-compulsive disorder (35.7 points; p = 0.01). The prevalence of BDD in psychiatric outpatients who were referred for treatment of a depressive disorder, an anxiety disorder, or a somatoform disorder was 0.8%. There was a high comorbidity of BDD with depressive and anxiety disorders.


Antipeptide antiserum identifies a widely distributed cellular tyrosine kinase related to but distinct from the c-fps/fes-encoded protein.
We raised antibodies directed against a synthetic peptide representing an amino acid sequence of the conserved kinase domain of the transforming protein of Fujinami sarcoma virus (FSV) (P140). The antiserum obtained specifically recognized FSV-P140 and its cellular homolog and in addition, it recognized a new cellular protein of 94,000 daltons (NCP94) in avian and mammalian cells. NCP94 was found to be associated with a cyclic nucleotide-independent protein kinase activity that was specific for tyrosine residues. Although NCP94 and FSV-P140 share antigenic determinants, NCP94 is not a cellular homolog of FSV-P140: NCP94 and the previously identified c-fps/fes product were different in their tryptic fingerprints and in their tissue specificities. Thus, the function of NCP94 in normal cells is probably different than that of the c-fps/fes product. NCP94 was expressed in every tissue and cell line that was examined. In chickens, NCP94 levels were highest during embryonic development and NCP94 expression was high in gizzard, brain, and spleen throughout embryonic and adult life. The universal expression of NCP94 suggests that this protein may be involved in an essential function of normal cells. NCP94 may be a new cellular tyrosine kinase of the src gene family.


Luminescence characteristics for identifying irradiated black soybeans.
Considering the commercial use of food irradiation and the prevalence of international trade of irradiated food and agricultural commodities, black soybeans originating from China or Korea were irradiated at 0-5 kGy. Photostimulated luminescence (PSL) and thermoluminescence (TL) were investigated for their ability to identify characteristics that would distinguish irradiated from non-irradiated samples. Dried black soybeans [Glycine max (L.) Merr.] were irradiated using a Co-60 gamma irradiator or an electron-beam accelerator and then analysed by PSL and TL. PSL photon counts were higher in irradiated samples than in non-irradiated ones and increased with applied doses, making it possible to distinguish irradiated from non-irradiated samples. The TL analysis revealed glow curves (TL₁) with low intensity for non-irradiated samples but a higher intensity (approximately 200°C) for irradiated samples, showing increased intensities with radiation dose. The minerals were re-irradiated at 1 kGy and the second TL glow curve (TL₂) was measured. Based on the calculated TL ratios (TL₁/TL₂) and the shape of TL₁ glow curves, the irradiated samples could be distinguished from non-irradiated ones. PSL and TL are effective screening and reference methods for distinguishing gamma ray or electron beam irradiated black soybeans from non-irradiated black soybeans.


Effect of injecting with dexamethasone and progestagen-PMSG on reproduction and rearing of lambs in semi-intensive conditions.
The aim of the present study was to evaluate the effect of different doses dexamethasone and progestagen-PMSG on fertility and prolificacy in Kivircik ewes during the breeding season. For the experiment, 100 ewes were divided into four groups, with 25 females in each group. Groups were fluorgestone acetate (FGA, 30 mg), administered via intravaginal sponges. Experimental groups 2, 3 and 4 mL dexamethasone injection were given 72 h before mating season. The fertility rates control, 2, 3 and 4 mL were 88.0, 92.0, 100.0 and 100.0%, respectively (p<0.05). The prolificacy rates for the same groups were 122.7, 130.4, 144.0 and 156.0%, respectively (p<0.01). The injections dexamethasone significantly increased lamb birth weight and daily weight gain for 60 days (p<0.05).


Effects of prosthetic acetabular replacement on strains in the pelvis.
The effects of cemented acetabular components on the strains in the pelvis were determined experimentally. Four components were tested: A plain metal hemisphere; a metal hemisphere with a triflange; a hemisphere with an iliac peg; and a hemisphere with a complete flange and a peg. Loading was carried out in neutral, flexion, and extension directions. The subchondral bone was only slightly reamed, and components were cemented and tested successively. For the intact hip joint, the strains on the superior acetabular rim were much lower than those on the posterior rim. After placement of the components, the tensile strains on the rim decreased by 22-54% while the compressive strains increased by 0-25%. The bone on the medial inferior surface was subjected to 65% less tensile strain and 48% more compressive strain in neutral and extension loading. There were no great differences between the four styles of acetabular component.


Formation of extracellular polymeric substances corona on TiO2 nanoparticles: Roles of crystalline phase and exposed facets.
Nanoparticles (NPs) in the environment can interact with macromolecules in the surrounding environment to form eco-corona on their surfaces, which in turn affects the environmental fate and toxicity of nanoparticles. Wastewater treatment plants containing large amounts of microbial extracellular polymeric substances (EPS) are an important source of NPs into the environment, where the formation of EPS coronas on NPs is critical. However, it remains unclear how the crystalline phase and exposed facets, which are intrinsic properties of NPs, affect the formation of EPS coronas on NPs. This study investigated the formation of EPS corona on three TiO2 NPs (representing the most widely used engineered NPs) with different crystalline phases and exposed facets. The protein type and abundance in EPS coronas on TiO2 NPs varied depending on the crystalline phase and exposed facets. Anatase with {101} facets and {001} facets preferred to adsorb proteins with lower molecular weights and higher H-bonding relevant amino acids, respectively, while EPS corona on rutile with {110} facets had proteins with higher hydrophobicity. In addition, the selective adsorption of proteins was primarily determined by steric hindrance, hydrogen bonding, and hydrophobic interaction between TiO2 NPs and proteins, which were affected by changes in aggregation state, surface hydroxyl density, and hydrophobicity of TiO2 NPs induced by crystalline phase and exposed facets. Moreover, crystalline phase and exposed facets-induced EPS corona changes altered the aggregation state and oxidation potential of TiO2-EPS corona complexes. These findings emphasize the important role of crystalline phase and exposed facets in the environmental behavior of nanoparticles and may provide insights into the safe design of nanoparticles.


Valuing Mortality Risk Reductions in Global Benefit-Cost Analysis.
The estimates used to value mortality risk reductions are a major determinant of the benefits of many public health and environmental policies. These estimates (typically expressed as the value per statistical life, VSL) describe the willingness of those affected by a policy to exchange their own income for the risk reductions they experience. While these values are relatively well studied in high-income countries, less is known about the values held by lower-income populations. We identify 26 studies conducted in the 172 countries considered low- or middle-income in any of the past 20 years; several have significant limitations. Thus there are few or no direct estimates of VSL for most such countries. Instead, analysts typically extrapolate values from wealthier countries, adjusting only for income differences. This extrapolation requires selecting a base value and an income elasticity that summarizes the rate at which VSL changes with income. Because any such approach depends on assumptions of uncertain validity, we recommend that analysts conduct a standardized sensitivity analysis to assess the extent to which their conclusions change depending on these estimates. In the longer term, more research on the value of mortality risk reductions in low- and middle-income countries is essential.


Crystal structure solution for the A6B2O17 (A = Zr, Hf; B = Nb, Ta) superstructure.
Zr6Ta2O17, Hf6Nb2O17 and Hf6Ta2O17 crystal structure solutions have been solved using synchrotron X-ray powder diffraction and neutron powder diffraction in conjunction with simulated annealing, charge flipping and Rietveld refinement. These structures have been shown to be isomorphous with the Zr6Nb2O17 superstructure, leading to the classification of the A6B2O17 (A = Zr, Hf; B = Nb, Ta) orthorhombic compound family with symmetry Ima2 (No. 46). The asymmetrical structural units of cation-centred oxygen polyhedra used to build the structure are as follows: (i) one set of symmetry-equivalent six-coordinated polyhedra, (ii) three sets of symmetry-equivalent seven-coordinated polyhedra and (iii) one set of symmetry-equivalent eight-coordinated polyhedra. The potential for cation order and disorder was discussed in terms of cation atomic number contrast in X-ray and neutron powder diffraction as well as the bond valence method. In addition, the structural mechanisms for experimentally observed compositional variations within the solid solution range can be attributed to the addition or removal of a set of symmetry-equivalent seven-coordinated polyhedra accompanied by corresponding oxygen tilts within the A6B2O17 structure.


The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients.
The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. Secondary analysis of two clinical trials of early septic shock resuscitation. Large academic emergency departments in the United States. Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p < 0.001) and mortality (29% vs 14%; p < 0.001). Subgroup analysis of 127 patients meeting only the old definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006). In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.