Nicotine does not enhance discrimination performance in a temporal bisection procedure.
Recent reports of selective disruption of stimulus control by drug administration and other disruptive operations in temporal discrimination procedures may be interpreted as a disruption of attention to the temporal sample stimuli. This experiment assessed the effects of nicotine, a compound that has been widely shown to increase measures of attention, on temporal discrimination performance. Pigeons responded under a psychophysical choice procedure in which responses to one key color were correct after presentation of four shorter sample durations and responses to another key color were correct after presentation of four longer sample durations. Performance under nicotine was characterized by using a model that differentiates the effects of nicotine on stimulus control, bias, and sensitivity of temporal discrimination. Nicotine selectively decreased the measure of stimulus control, but did not systematically affect the measures of timing. Mecamylamine (1.0 mg/kg) failed to antagonize the disruptive effects of nicotine. These results suggest that disruption of temporal discrimination performance in this preparation may not have been dependent on the specific pharmacology of nicotine and underscore the importance of quantitative separation of the effects of various manipulations on stimulus control from effects on timing.


Ventilation and oxygen uptake during escape from a civil aircraft.
To help develop a specification for equipment providing personal respiratory protection in the event of aircraft fire a study was carried out to quantify ventilation and oxygen consumption during escape from a Trident aircraft. Data were gathered using the P.K. Morgan 'Oxylog' apparatus after its response time to rapid changes in inspired to expired oxygen concentration difference was assessed using a bench test. The 'Oxylog' had a lag time of 30-32 s and a 5-95% response typified by a half time of 20 s. The data gathered were corrected in the light of these findings. Fourteen male subjects aged 17-38 years were studied under two conditions. Four mass evacuations each involving 40 people; a total of nine subjects escaping from the front rank over eight seats being monitored. Six evacuations each involving only two people escaping from the rear of the cabin; a total of 11 subjects escaping over 14 seats being monitored. Escape was made over the seat backs, down an escape chute to a position 12 m from the base of the chute. Resting minute ventilation (mean 16.7 1 STPD) and oxygen consumption (mean 0.41 min-1 STPD) were similar before both evacuations. There were no significant differences between the two conditions either during, or up to 180 s after escape. Ventilation and oxygen consumption were greatest in the recovery period. The highest oxygen consumption seen was 2.08 l min-1 and maximum minute ventilation was 641. Mean total oxygen consumption for the escape and a 150 s recovery period was 2.41 l (s.d. 0.64, max. 3.11) for the mass evacuation and 2.97 l (s.d. 0.68, max. 4.09) for the two person evacuation. The mean total amount of gas inhaled during the same time period was 89.3 l (s.d. 25.6, max. 121.3) for the mass evacuation and 99.01 (s.d. 26.2, max. 137.3) for the other. These was no correlation between ventilation or oxygen consumption and either escape time, body weight, height or age.


Single-particle imaging reveals intraflagellar transport-independent transport and accumulation of EB1 in Chlamydomonas flagella.
The microtubule (MT) plus-end tracking protein EB1 is present at the tips of cilia and flagella; end-binding protein 1 (EB1) remains at the tip during flagellar shortening and in the absence of intraflagellar transport (IFT), the predominant protein transport system in flagella. To investigate how EB1 accumulates at the flagellar tip, we used in vivo imaging of fluorescent protein-tagged EB1 (EB1-FP) in Chlamydomonas reinhardtii. After photobleaching, the EB1 signal at the flagellar tip recovered within minutes, indicating an exchange with unbleached EB1 entering the flagella from the cell body. EB1 moved independent of IFT trains, and EB1-FP recovery did not require the IFT pathway. Single-particle imaging showed that EB1-FP is highly mobile along the flagellar shaft and displays a markedly reduced mobility near the flagellar tip. Individual EB1-FP particles dwelled for several seconds near the flagellar tip, suggesting the presence of stable EB1 binding sites. In simulations, the two distinct phases of EB1 mobility are sufficient to explain its accumulation at the tip. We propose that proteins uniformly distributed throughout the cytoplasm like EB1 accumulate locally by diffusion and capture; IFT, in contrast, might be required to transport proteins against cellular concentration gradients into or out of cilia.


Gastrodin Protects against Ethanol-Induced Liver Injury and Apoptosis in HepG2 Cells and Animal Models of Alcoholic Liver Disease.
This study aims to investigate the protective effects of gastrodin (GSTD), a natural compound isolated from the root of Gastrodia elata BL., on ethanol-induced liver injury and apoptosis in HepG2 cells and animal models. For in vitro studies, GSTD was used to pre-treat the cells for 4 h followed by 600 mM of ethanol co-administration for 24 h. Alcoholic liver disease (ALD) of Sprague-Dawley (SD) rats was induced by chronic ethanol-feeding plus a single dose (5 g/kg) of acute ethanol administration, GSTD at different doses were co-administered for 8 weeks. For acute liver injury experiment of ICR mice, GSTD (100 mg/kg/d) was pre-treated for 3 d followed by ethanol administration (5 g/kg) for 3 times. The results showed that GSTD protects HepG2 cells from ethanol-induced toxicity, injury, and apoptosis significantly. Co-administered with ethanol, GSTD prevented the loss of mitochondrial membrane potential, reduced the release cytochrome c from mitochondria, and inhibited the activation of caspase-3 in HepG2 cells. In SD rats induced by chronic ethanol-feeding, GSTD significantly restored liver function and ameliorated pathological changes of the liver. In rat liver, GSTD greatly suppressed the activation of caspase-3 and inhibited hepatocellular apoptosis. In ethanol-induced acute liver injury of ICR mice, GSTD reduced liver acetaldehyde and suppressed the up-regulation of alcohol dehydrogenase (ADH) and CYP2E1 significantly. Our results demonstrate that GSTD is efficacious in protecting liver cells from ethanol-induced injury and apoptosis; it may be useful for the development of novel agents for the treatment of ALD in the future.


Functional brain imaging using a blood oxygenation sensitive steady state.
Blood oxygenation level dependent (BOLD) functional MRI (fMRI) is an important method for functional neuroimaging that is sensitive to changes in blood oxygenation related to brain activation. While BOLD imaging has good spatial coverage and resolution relative to other neuroimaging methods (such as positron emission tomography (PET)), it has significant limitations relative to other MRI techniques, including poor spatial resolution, low signal levels, limited contrast, and image artifacts. These limitations derive from the coupling of BOLD functional contrast to sources of image degradation. This work presents an alternative method for fMRI that may over-come these limitations by establishing a blood oxygenation sensitive steady-state (BOSS) that inverts the signal from deoxygenated blood relative to the water signal. BOSS fMRI allows the imaging parameters to be optimized independently of the functional contrast, resulting in fewer image artifacts and higher signal-to-noise ratio (SNR). In addition, BOSS fMRI has greater functional contrast than BOLD. BOSS fMRI requires careful shimming and multiple acquisitions to obtain a precise alignment of the magnetization to the SSFP frequency response.


DMMS: A Decentralized Blockchain Ledger for the Management of Medication Histories.
Access to accurate and complete medication histories across healthcare institutions enables effective patient care. Histories across healthcare institutions currently rely on centralized systems for sharing medication data. However, there is a lack of efficient mechanisms to ensure that medication histories transferred from one institution to another are accurate, secure, and trustworthy. In this article, we introduce a decentralized medication management system (DMMS) that leverages the advantages of blockchain to manage medication histories. DMMS is realized as a decentralized network under the hyperledger fabric framework. Based on the network, we designed an architecture, within which each prescriber can create prescriptions for each patient and perform queries about historical prescriptions accordingly. finally, we analyzed the advantages of DMMS over centralized systems in terms of accuracy, security, trustworthiness, and privacy. We developed a proof of concept to showcase DMMS. In this system, a prescriber prescribes medications for a patient and then encrypts the prescriptions via the patient's public keys. Patients can query their own prescriptions from different histories across healthcare institutions and then decrypt the prescriptions via their private keys. At the same time, a prescriber can query a patient's prescription records across healthcare institutions after approval from the patient. Analytic results show that DMMS can improve security, trustworthiness, and privacy in medication history sharing and exchanging across healthcare institutions. In addition, we discuss the potential for DMMS in e-prescribing markets. This study shows that a distributed secure ledger can enable reliable, interoperable, and accurate medication history sharing.


Cryptic diversity in European bats.
Different species of bat can be morphologically very similar. In order to estimate the amount of cryptic diversity among European bats we screened the intra- and interspecific genetic variation in 26 European vespertilionid bat species. We sequenced the DNA of subunit 1 of the mitochondrial protein NADH dehydrogenase (ND1) from several individuals of a species, which were sampled in a variety of geographical regions. A phylogeny based on the mitochondrial (mt) DNA data is in good agreement with the current classification in the family. Highly divergent mitochondrial lineages were found in two taxa, which differed in at least 11% of their ND1 sequence. The two mtDNA lineages in Plecotus austriacus correlated with the two subspecies Plecotus austriacus austriacus and Plecotus austriacus kolombatovici. The two mtDNA lineages in Myotis mystacinus were partitioned among two morphotypes. The evidence for two new bat species within Europe is discussed. Convergent adaptive evolution might have contributed to the morphological similarity among distantly related species if they occupy similar ecological niches. Closely related species may differ in their ecology but not necessarily in their morphology. On the other hand, two morphologically clearly different species (Eptesicus serotinus and Eptesicus nilssonii) were found to be genetically very similar. Neither morphological nor mitochondrial DNA sequence analysis alone can be guaranteed to identify species.


The cytoskeleton in mRNA localization and cell differentiation.
Asymmetric distribution of cytoplasmic proteins and messenger RNAs has been implicated in several instances of cell differentiation. Microtubules have been suggested to direct mRNA localization in Drosophila and Xenopus oocytes but motor proteins that might transport mRNAs have not yet been identified. Recent data imply that in Drosophila, Caenorhabditis elegans and budding yeast, proteins of the actin cytoskeleton, including unconventional myosins, play active roles in the segregation of differentiation factors and mRNAs.


Nonparaxial propagation and focusing properties of azimuthal-variant vector fields diffracted by an annular aperture.
Based on the vectorial Rayleigh-Sommerfeld integrals, the analytical expressions for azimuthal-variant vector fields diffracted by an annular aperture are presented. This helps us to investigate the propagation behaviors and the focusing properties of apertured azimuthal-variant vector fields under nonparaxial and paraxial approximations. The diffraction by a circular aperture, a circular disk, or propagation in free space can be treated as special cases of this general result. Simulation results show that the transverse intensity, longitudinal intensity, and far-field divergence angle of nonparaxially apertured azimuthal-variant vector fields depend strongly on the azimuthal index, the outer truncation parameter and the inner truncation parameter of the annular aperture, as well as the ratio of the waist width to the wavelength. Moreover, the multiple-ring-structured intensity pattern of the focused azimuthal-variant vector field, which originates from the diffraction effect caused by an annular aperture, is experimentally demonstrated.


Medullary lesions eliminate ACTH responses to hypotensive hemorrhage.
The adrenocorticotropin (ACTH) response to hemorrhage (15 ml . kg-1 . 3 min-1) before and 30 min or 4 days after placement of bilateral electrolytic lesions of the nucleus tractus solitarius (NTS) were examined in anesthetized and in conscious rats. Two groups of rats were anesthetized with pentobarbital sodium (45 mg/kg). Femoral arterial and venous cannulas were placed acutely in the anesthetized group and chronically in the conscious group. Each rat received a hemorrhage 30 min before and 30 min after NTS lesions (in the anesthetized group) and 1 day before and 4 days after NTS lesions (in the conscious group). Plasma ACTH was determined before and 20 min after hemorrhage, and mean arterial blood pressure and heart rate were measured throughout. The baroreceptor reflex (bradycardia caused by a phenylephrine-induced rise in MABP) was determined 5 min before hemorrhage (in the anesthetized group) and 1 day before hemorrhage (in the conscious group) to assess the effectiveness of lesion. Hexamethonium was given to rats that developed hypertension postlesion and to sham-lesioned controls. Plasma ACTH did not increase after hemorrhage 30 min or 4 days after NTS lesions when compared with the other groups (sham, sham with hexamethonium, and missed lesion) and to prelesion controls. Also, lesions of the NTS had no effect on resting ACTH levels 4 days later. Mean arterial pressure and heart rate decreased during hemorrhage to similar extents before and after lesions in all groups. This study demonstrates that lesions of the NTS eliminate the ACTH response to hemorrhage immediately and 4 days after the lesions but have no effect on resting ACTH levels. The result suggests that the NTS is an essential part of the neural pathway for ACTH release after hemorrhage.


Relationship of leg strength and power to ground reaction forces in both experienced and novice jump trained personnel.
There were 14 male soldiers who participated in this study examining the relationship of leg strength and power on landing performance. Subjects were separated into two groups. The first group (E, n = 7) were parachute training instructors and highly experienced in parachute jumping. The second group of subjects (N, n = 7) had no prior parachute training experience and were considered novice jumpers. All subjects were tested for one-repetition maximum (1 RM) squat strength and maximal jump power. Ground reaction forces (GRF) and the time to peak force (TPF) at landing were measured from jumps at four different heights (95 cm, 120 cm, 145 cm, and 170 cm). All jumps were performed from a customized jump platform onto a force plate. No differences were seen between E and N in either IRM squat strength or in MJP. In addition, no differences were seen between the groups for time to peak force at any jump height. However, significantly greater GRF were observed in E compared to N. Moderate to high correlations between maximal jump power and GRF (r values ranging from 0.62-0.93) were observed in E. Although maximal jump power and the TPF was significantly correlated (r = -0.89) at only 120 cm for E, it was interesting to note that the correlations between MJP and the time to peak force in E were all negative and that the correlations between these variables in N were all positive. These results suggest that experienced parachutists may use a different landing strategy than novice jumpers. This difference may be reflected by differences in GRF generated during impact and a more efficient utilization of muscle power during the impact phase of the landing.


Crystallization of hollow mesoporous silica nanoparticles.
Complex 3D macrostructured nanoparticles are transformed from amorphous silica into pure polycrystalline α-quartz using catalytic quantities of alkaline earth metals as devitrifying agent. Walls as thin as 10 nm could be crystallized without losing the architecture of the particles. The roles of cation size and the mol% of the incorporated devitrifying agent in crystallization behavior are studied, with Mg(2+), Ca(2+), Sr(2+) and Ba(2+) all producing pure α-quartz under certain conditions.


"A good collaboration is based on unique contributions from each side": assessing the dynamics of collaboration in stem cell science.
The rise of 'big biology' is bringing academic and industrial scientists together in large consortia to address translational challenges in the life sciences. In order to assess the impact of this change, this paper examines the existing norms and styles of collaboration in one high profile translational domain; stem cell research. Data is drawn from qualitative interviews with academic and industry scientists working in a large European stem cell research project. Respondents discussed what they perceived as the main benefits and risks of collaborative research, what styles of collaboration they were familiar with, and what collaborative work in stem cell science normally involves. A wide range of materials, data, and expertise can be exchanged during collaborative work. Informal collaborations are governed by an ethos of reciprocity and mediated by trust while formal project agreements can provide a safe space for sharing between unfamiliar partners. These characteristics make stem cell research well suited to pre-competitive public-private ventures but translation of new products to market may be more challenging.


Influencing factors on the foot health of captive Asian elephants (Elephas maximus) in European zoos.
Pathological lesions of feet occur frequently in captive elephant populations. To improve foot health, it is important to identify risk factors associated with such pathologies. Several previous studies have analyzed potentially influencing factors but were limited, for example, by small sample sizes. This study analyzed the relationship between 87 independent variables and the foot health score of 204 Asian elephants (Elephas maximus) in European zoos using bivariate correlation, multivariable regression models, and principal component analysis (PCA). Correlation and regression tests revealed significant results for 30 different variables, mainly with small effect sizes. Only three variables were significant in more than one test: sex, time spent indoors, and time spent on hard ground, with lower scores (i.e. less or less severe pathological lesions) in females, and when less time is spent indoors or on hard ground. Due to small effect sizes and differing results of the statistical tests, it is difficult to determine which risk factors are most important. Instead, a holistic consideration appears more appropriate. A biplot of the PCA shows that factors representing more advanced husbandry conditions (e.g. large areas, high proportions of sand flooring) were associated with each other and with decreased foot scores, whereas indicators of more limited conditions (e.g. high proportions of hard ground, much time spent indoors) were also associated with each other but increased the foot score. In conclusion, instead of resulting from just one or two factors, reduced foot health might be an indicator of a generally poorer husbandry system.


Morning vs evening light treatment of patients with winter depression.
According to the phase-shift hypothesis for winter depression, morning light (which causes a circadian phase advance) should be more antidepressant than evening light (which causes a delay). Although no studies have shown evening light to be more antidepressant than morning light, investigations have shown either no difference or morning light to be superior. The present study assesses these light-exposure schedules in both crossover and parallel-group comparisons. Fifty-one patients and 49 matched controls were studied for 6 weeks. After a prebaseline assessment and a light/dark and sleep/wake adaptation baseline week, subjects were exposed to bright light at either 6 to 8 AM or 7 to 9 PM for 2 weeks. After a week of withdrawal from light treatment, they were crossed over to the other light schedule. Dim-light melatonin onsets were obtained 7 times during the study to assess circadian phase position. Morning light phase-advanced the dim-light melatonin onset and was more antidepressant than evening light, which phase-delayed it. These findings were statistically significant for both crossover and parallel-group comparisons. Dim-light melatonin onsets were generally delayed in the patients compared with the controls. These results should help establish the importance of circadian (morning or evening) time of light exposure in the treatment of winter depression. We recommend that bright-light exposure be scheduled immediately on awakening in the treatment of most patients with seasonal affective disorder.


The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis.
Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance.


Planar ventilation-perfusion imaging for pulmonary embolism: the case for "outcomes" medicine.
Single-photon emission computed tomography (SPECT) has been a significant advancement in scintigraphy, impacting many areas of diagnosis. It has begun to find use in ventilation-perfusion (V/Q) scintigraphy. However, its utility has been limited in the United States because of a lack of an optimal and Food and Drug Administration-approved SPECT ventilatory agent. Although SPECT V/Q can show more and smaller mismatches than planar studies, there is persistent debate regarding the clinical significance of these smaller pulmonary emboli (PE); they may be neither clinically significant nor require treatment. Available data suggest that planar V/Q, SPECT V/Q, and computed tomographic pulmonary angiography (CTPA) have similar false-negative rates and thus have a similar impact on outcomes. In most cases, emergency department physicians are the first to encounter patients who may have PE, and they frequently use an imaging study as part of the evaluation. We discuss the rational for triaging patients to different imaging modalities with the use of chest radiography and the strengths and weaknesses of each modality. Detailed anatomy is an advantage of CTPA, breast radiation dose is reduced with scintigraphy, and imaging is quicker and more detailed with SPECT. We also review planar and SPECT V/Q and CTPA from the differing vantage points of diagnostic accuracy vs patient outcomes. Whatever modality their patients require, physicians can be confident that they are all similarly efficacious at diagnosing clinically relevant emboli.


Identification of phenolic compounds, antibacterial and antioxidant activities of raisin extracts.
In this study, antibacterial, antioxidant and phenolic compounds of raisin extracts was evaluated. Different solvent extraction methods were utilized to extract phenolic compounds from raisin. The phenolic compounds of raisin extracts was determined using HPLC and three compounds were found, catechin, quercetin and rutin. The antibacterial activity of the acetonic extract was tested against four bacterial pathogens viz. Staphylococcus aureus, Pseudomonas aeroginosa, Salmonella typhimurium and Escherichia coli using both disk diffusion and minimum inhibitory concentration (MIC) methods. The acetonic extract exhibited the highest activity against Staphylococcus aureus with zone of inhibition of 14mm and the MIC of 25 mg/ml. However, there was a little activity against E. coli and S. typhimurium. The methanolic extract showed good antioxidant activity as indicated by 2,2-diphenyl-1-picrylhydrazyl free radical assay (DPPH). In conclusion, raisin contains potent phenolic compounds and their application might function as promising natural preservative and antimicrobial agents in food industry and also good antioxidant food that helps to minimize the risk of degenerative diseases.


Tackling variability: A multicenter study to provide a gold-standard network approach for frontotemporal dementia.
Biomarkers represent a critical research area in neurodegeneration disease as they can contribute to studying potential disease-modifying agents, fostering timely therapeutic interventions, and alleviating associated financial costs. Functional connectivity (FC) analysis represents a promising approach to identify early biomarkers in specific diseases. Yet, virtually no study has tested whether potential FC biomarkers prove to be reliable and reproducible across different centers. As such, their implementation remains uncertain due to multiple sources of variability across studies: the numerous international centers capable conducting FC research vary in their scanning equipment and their samples' socio-cultural background, and, more troublingly still, no gold-standard method exists to analyze FC. In this unprecedented study, we aim to address both issues by performing the first multicenter FC research in the behavioral-variant frontotemporal dementia (bvFTD), and by assessing multiple FC approaches to propose a gold-standard method for analysis. We enrolled 52 bvFTD patients and 60 controls from three international clinics (with different fMRI recording parameters), and three additional neurological patient groups. To evaluate FC, we focused on seed analysis, inter-regional connectivity, and several graph-theory approaches. Only graph-theory analysis, based on weighted-matrices, yielded consistent differences between bvFTD and controls across centers. Also, graph metrics robustly discriminated bvFTD from the other neurological conditions. The consistency of our findings across heterogeneous contexts highlights graph-theory as a potential gold-standard approach for brain network analysis in bvFTD. Hum Brain Mapp 38:3804-3822, 2017. © 2017 Wiley Periodicals, Inc.


Anthropogenic aerosols and the weakening of the South Asian summer monsoon.
Observations show that South Asia underwent a widespread summertime drying during the second half of the 20th century, but it is unclear whether this trend was due to natural variations or human activities. We used a series of climate model experiments to investigate the South Asian monsoon response to natural and anthropogenic forcings. We find that the observed precipitation decrease can be attributed mainly to human-influenced aerosol emissions. The drying is a robust outcome of a slowdown of the tropical meridional overturning circulation, which compensates for the aerosol-induced energy imbalance between the Northern and Southern Hemispheres. These results provide compelling evidence of the prominent role of aerosols in shaping regional climate change over South Asia.


A model of the upper extremity using FES for stroke rehabilitation.
A model of the upper extremity is developed in which the forearm is constrained to lie in a horizontal plane and electrical stimulation is applied to the triceps muscle. Identification procedures are described to estimate the unknown parameters using tests that can be performed in a short period of time. Examples of identified parameters obtained experimentally are presented for both stroke patients and unimpaired subjects. A discussion concerning the identification's repeatability, together with results confirming the accuracy of the overall representation, is given. The model has been used during clinical trials in which electrical stimulation is applied to the triceps muscle of a number of stroke patients for the purpose of improving both their performance at reaching tasks and their level of voluntary control over their impaired arm. Its purpose in this context is threefold: Firstly, changes occurring in the levels of stiffness and spasticity in each subject's arm can be monitored by comparing frictional components of models identified at different times during treatment. Secondly, the model is used to calculate the moments applied during tracking tasks that are due to a patient's voluntary effort, and it therefore constitutes a useful tool with which to analyze their performance. Thirdly, the model is used to derive the advanced controllers that govern the level of stimulation applied to subjects over the course of the treatment. Details are provided to show how the model is applied in each case, and sample results are shown.


Antimicrobial resistance of enteropathogenic Escherichia coli strains from a nosocomial outbreak in Kenya.
The majority of the 78 enteropathogenic (EPEC) and the 151 non-EPEC Escherichia coli strains isolated from preterm neonates during an outbreak of gastroenteritis in a hospital in Nairobi, Kenya, were resistant to trimethoprim-sulfamethoxaxole, chloramphenicol, oxytetracycline and ampicillin, but only a few strains were resistant to cefazolin, cefamandole, cefotaxime, amikacin and nalidixic acid. Fourteen different antimicrobial resistance patterns were observed in the 229 strains of E. coli analysed. Eighty-two percent of the EPEC strains belonged to two resistance pattern compared with 79% of non-EPEC strains which exhibited three resistance patterns. There was no consistent relationship between plasmid profile group and antimicrobial resistance pattern, although one resistance pattern was more frequently observed in EAF-positive strains belonging to the dominant plasmid profile group. Nine percent of the EPEC strains were resistant to gentamicin compared to 37% in the non-EPEC group. No correlation was observed between administration of gentamicin and percentage of resistant strains isolated. None of the nine neonates receiving gentamicin died during the outbreak. Gentamicin resistance was observed in E. coli strains from six out of these nine neonates. Five out of fourteen neonates who received other antimicrobials, or no antibiotic treatment at all, died.


Climate. Varying planetary heat sink led to global-warming slowdown and acceleration.
A vacillating global heat sink at intermediate ocean depths is associated with different climate regimes of surface warming under anthropogenic forcing: The latter part of the 20th century saw rapid global warming as more heat stayed near the surface. In the 21st century, surface warming slowed as more heat moved into deeper oceans. In situ and reanalyzed data are used to trace the pathways of ocean heat uptake. In addition to the shallow La Niña-like patterns in the Pacific that were the previous focus, we found that the slowdown is mainly caused by heat transported to deeper layers in the Atlantic and the Southern oceans, initiated by a recurrent salinity anomaly in the subpolar North Atlantic. Cooling periods associated with the latter deeper heat-sequestration mechanism historically lasted 20 to 35 years.


Thermodynamics of twisted DNA with solvent interaction.
The imaginary time path integral formalism is applied to a nonlinear Hamiltonian for a short fragment of heterogeneous DNA with a stabilizing solvent interaction term. Torsional effects are modeled by a twist angle between neighboring base pairs stacked along the molecule backbone. The base pair displacements are described by an ensemble of temperature dependent paths thus incorporating those fluctuational effects which shape the multisteps thermal denaturation. By summing over ~10(7)-10(8) base pair paths, a large number of double helix configurations is taken into account consistently with the physical requirements of the model potential. The partition function is computed as a function of the twist. It is found that the equilibrium twist angle, peculiar of B-DNA at room temperature, yields the stablest helicoidal geometry against thermal disruption of the base pair hydrogen bonds. This result is corroborated by the computation of thermodynamical properties such as fractions of open base pairs and specific heat.


Radiological characterisation of alkali-activated construction materials containing red mud, fly ash and ground granulated blast-furnace slag.
Poor storage of industrial wastes has been a cause of land contamination issues. These wastes or by-products have the potential to be used as secondary raw materials in construction, promoting the concept of a circular economy that will avoid land contamination. Here we evaluate radiological environmental impacts when wastes that contain elevated levels of naturally occurring radionuclides (NORs) such as red mud, fly ash and ground granulated blast furnace slag are made into 'green cements' such as geopolymers or alkali-activated materials (AAMs). During the study, three AAM concrete and mortar series with various mixing ratios were prepared and investigated. The NOR content, I-Index, radon emanation and exhalation of the precursor waste materials and their cement products were measured and calculated and the strength of the cement products was compared. The emanation and the exhalation properties were calculated for the final products, weighing the data of the components as a function of their mixing ratio. The I-index alone suggested that the AAMs would be suitable products. AAMs containing ground granulated blast furnace slag exhibited the lowest radon exhalation and higher compressive strength, while the fly ash and red mud AAMs had increased final radon exhalation. In the case of fly ash, alkaline activation of fly ash dramatically increased the radon exhalation; the highest measured fly ash exhalation was 1.49 times of the theoretically calculated exhalation value. This highlights the increased risk of using fly ash as a component in AAMs and the need to carry out testing on the final products as well as individual secondary raw materials.


ABO and Rh Blood Groups and Risk of Myelomeningocele.
To investigate the relationship between the distribution of ABO or Rhesus (Rh) blood group antigens and the incidence of myelomeningocele. A retrospective data was reviewed for all myelomeningocele patients operated at a tertiary academic hospital between years 2014 and 2019. Age, sex, delivery method, physical and neurological examination findings, and radiological findings alongside with blood type of each patient were recorded. The data of blood group distribution among the study patients was compared to the data of healthy individuals in the same region. Patients with group B and AB showed a higher chance of developing myelomeningocele. Rh-positive blood group was associated with high incidence of myelomeningocele (93.5%), whereas Rh-negative blood group showed least association (6.5%). Rh-positive blood group was also found to be more frequent in patients with myelomeningocele with hydrocephalus and Chiari malformation. The findings of this study show that ABO and Rh blood groups have an effect on the development of myelomeningocele under the influence of environmental or genetic factors.


Accuracy of official suicide mortality data in Queensland.
The purpose is to answer the following research question: are the time-series data published by the Australian Bureau of Statistics for Queensland statistically the same as those of the Queensland Suicide Register? This question was answered by first modelling statistically, for males and females, the time series suicide data from these two sources for the period of data availability, 1994 to 2007 (14 observations). Fitted values were then derived from the 'best fit' equations, after rigorous diagnostic testing. The outliers in these data sets were addressed with pulse dummy variables. Finally, by applying the Wald test to determine whether or not the fitted values are the same, we determined whether, for males and females, these two data sets are the same or different. The study showed that the Queensland suicide rate, based on Queensland Suicide Register data, was greater than that based on Australian Bureau of Statistics data. Further statistical testing showed that the differences between the two data sets are statistically significant for 24 of the 28 pair-wise comparisons. The quality of Australia's official suicide data is affected by various practices in data collection. This study provides a unique test of the accuracy of published suicide data by the Australian Bureau of Statistics. The Queensland Suicide Register's definition of suicide applies a more suicidological, or medical/health, conception of suicide, and applies different practices of coding suicide cases, timing of data collection processes, etc. The study shows that 'difference' between the two data sets predominates, and is statistically significant; thus the extent of the under-reporting of suicide is not trivial. Given that official suicide data are used for many purposes, including policy evaluation of suicide prevention programmes, it is suggested that the system used in Queensland should be adopted by the rest of Australia too.


Continuous-wave, pump-enhanced optical parametric oscillator based on periodically-poled RbTiOAsO4.
The operation of a continuous-wave optical parametric oscillator (OPO) based on periodically-poled RbTiOAsO4 (PPRTA) and using a pump-enhanced cavity configuration is described. The OPO was pumped by a single-frequency Nd:YVO4 laser and temperature tuning ranges of 1.525-1.583ìm and 3.245-3.520ìm were achieved at the signal and idler, respectively. The external threshold was 250mW and up to 87mW of idler was generated. Fine-tuning behavior of the OPO and material quality of the PPRTA were investigated. We believe this to be the first reported example of an externally-pumped cw OPO based on PPRTA.


A walking behavior generates functional overland movements in the tidepool sculpin, Oligocottus maculosus.
Tidepool sculpins (Oligocottus maculosus) have been observed moving overland in the rocky intertidal, and we documented the terrestrial walking behavior that they use to accomplish this. We quantified the terrestrial movements of O. maculosus and compared them to (1) their aquatic locomotion, (2) terrestrial locomotion of closely-related subtidal species (Leptocottus armatus and Icelinus borealis), and (3) terrestrial movements of walking catfishes (Clarias spp.). We recorded sculpin movements (210 fps) on a terrestrial platform and in a water tank and tracked body landmarks for kinematic analysis. The axial-appendage-based terrestrial locomotion of O. maculosus is driven by cyclic lateral oscillations of the tail, synchronized with alternating rotations about the base of the pectoral fins, a behavior that appears similar to a military "army crawl." The pectoral fins do not provide propulsion, but act as stable points for the body to rotate around. In contrast, individuals of O. maculosus use primarily axial undulation during slow-speed swimming. The army crawl is a more effective terrestrial behavior (greater distance ratio) than the movements produced by L. armatus and I. borealis, which use rapid, cyclic oscillations of the tail, without coordinated pectoral fin movements. Relative to Clarias spp., O. maculosus rotated the body about the base of the pectoral fin, rather than the tip of the fin, which may cause O. maculosus to have a lower distance ratio. Since O. maculosus lack major morphological adaptations for terrestrial locomotion, instead relying on behavioral adaptations, we propose behavioral adaptations may evolutionarily predate morphological adaptations for terrestrial locomotion in vertebrates.


Genetic variation in the zebrafish.
Although zebrafish was introduced as a laboratory model organism several decades ago and now serves as a primary model for developmental biology, there is only limited data on its genetic variation. An establishment of a dense polymorphism map becomes a requirement for effective linkage analysis and cloning approaches in zebrafish. By comparing ESTs to whole-genome shotgun data, we predicted >50,000 high-quality candidate SNPs covering the zebrafish genome with average resolution of 41 kbp. We experimentally validated approximately 65% of a randomly sampled subset by genotyping 16 samples from seven commonly used zebrafish strains. The analysis reveals very high nucleotide diversity between zebrafish isolates. Even with the limited number of samples that we genotyped, zebrafish isolates revealed considerable interstrain variation, ranging from 7% (inbred) to 37% (wild-derived) of polymorphic sites being heterozygous. The increased proportion of polymorphic over monomorphic sites results in five times more frequent observation of a three allelic variant compared with human or mouse. Phylogenetic analysis shows that comparisons between even the least divergent strains used in our analysis may provide one informative marker approximately every 500 nucleotides. Furthermore, the number of haplotypes per locus is relatively large, reflecting independent establishment of the different lines from wild isolates. Finally, our results suggest the presence of prominent C-to-U and A-to-I RNA editing events in zebrafish. Overall, the levels and organization of genetic variation between and within commonly used zebrafish strains are markedly different from other laboratory model organisms, which may affect experimental design and interpretation.


Establishing evidence-based criteria for directly observed hand hygiene compliance monitoring programs: a prospective, multicenter cohort study.
Hand hygiene surveillance programs that rely on direct observations of healthcare worker activity may be limited by the Hawthorne effect. In addition, comparing compliance rates from period to period requires adequately sized samples of observations. We aimed to statistically determine whether the Hawthorne effect is stable over an observation period and statistically derive sample sizes of observations necessary to compare compliance rates. Prospective multicenter cohort study. Five intensive care units and 6 medical/surgical wards in 3 geographically distinct acute care hospitals. Trained observers monitored hand hygiene compliance during routine care in fixed 1-hour periods, using a standardized collection tool. We estimated the impact of the Hawthorne effect using empirical fluctuation processes and F tests for structural change. Standard sample-size calculation methods were used to estimate how many hand hygiene opportunities are required to accurately measure hand hygiene across various levels of baseline and target compliance. Exit hand hygiene compliance increased after 14 minutes of observation (from 56.2% to 60.5%; P < .001) and increased further after 50 minutes (from 60.5% to 66.0%; P < .001). Entry compliance increased after 38 minutes (from 40.4% to 43.4%; P = .005). Between 79 and 723 opportunities are required during each period, depending on baseline compliance rates (range, 35%-90%) and targeted improvement (5% or 10%). Limiting direct observation periods to approximately 15 minutes to minimize the Hawthorne effect and determining required number of hand hygiene opportunities observed per period on the basis of statistical power calculations would be expected to improve the validity of hand hygiene surveillance programs.


High prevalence and antimicrobial resistance of urinary tract infection isolates in febrile young children without localizing signs in Taiwan.
Antimicrobial susceptibility and prevalence of pediatric urinary tract infection (UTI) is very useful for pediatricians in selecting effective antibiotics in time to improve outcomes in patients. This study aimed to determine the prevalence rate, bacterial distribution, and antimicrobial susceptibility of UTI in febrile young children at a teaching hospital in northern Taiwan. From January 2011 to December 2011, all urinary isolates from suspected cases of UTI in febrile young children aged from 1 day to 36 months visiting the Pediatric Emergency Room of Chang Gung Children's Hospital, Taoyuan, Taiwan were identified by conventional methods. Antibiotic susceptibility was determined according to the Clinical and Laboratory Standards Institute. A total of 5470 (78%) from 7009 eligible children were enrolled in the study, and 619 (11.3%) had a diagnosis of UTI. The most prevalent bacterium was Escherichia coli (68%) followed by Klebsiella pneumoniae (8.1%) and Proteus mirabilis (6.8%). Ampicillin, piperacillin, and trimethoprim-sulfamethoxazole (TMP-SMX) showed a higher resistance rate in the three predominant bacteria. All tested bacteria showed higher resistance to ampicillin (79.3%) and TMP-SMX (44.1%), and lower resistance to cefazolin (17.7%) and gentamicin (13.0%). Fourteen percent of the isolates produced extended spectrum β-lactamase (ESBL), among which 93.33% were E. coli isolates. The overall prevalence of UTI in this study was higher than previously reported in febrile children. Higher antimicrobial resistance was found in ampicillin and TMP-SMX. Among commonly used antibiotics, cefazolin and gentamicin are recommended to treat UTI in febrile children aged < 3 years without localizing signs.


Realigning government action with public health evidence: the legal and policy environment affecting sex work and HIV in Asia.
The HIV epidemic has shed light on how government regulation of sex work directly affects the health and well-being of sex workers, their families and communities. A review of the public health evidence highlights the need for supportive legal and policy environments, yet criminalisation of sex work remains standard around the world. Emerging evidence, coupled with evolving political ideologies, is increasingly shaping legal environments that promote the rights and health of sex workers but even as new legislation is created, contradictions often exist with standing problematic legislation. As a region, Asia provides a compelling example in that progressive HIV policies often sit side by side with laws that criminalise sex work. Data from the 21 Asian countries reporting under the UN General Assembly Special Session on HIV in 2010 were analysed to provide evidence of how countries' approach to sex-work regulation might affect HIV-related outcomes. Attention to the links between law and HIV-related outcomes can aid governments to meet their international obligations and ensure appropriate legal environments that cultivate the safe and healthy development and expression of sexuality, ensure access to HIV and other related services and promote and protect human rights.


High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma.
PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit.


Vorapaxar in the secondary prevention of atherothrombosis.
Dual antiplatelet therapy with aspirin, a platelet cyclooxygenase-1 inhibitor and P2Y12 receptor blockers, remains the major drug strategy to prevent ischemic event occurrence in patients with acute coronary syndromes and in patients undergoing coronary stenting, but there some limitations that can be overcome by targeting novel targets. Unlike direct thrombin inhibitors that bind directly to thrombin, targeting the platelet thrombin receptor, protease activated receptor (PAR)-1, may offer a better choice for the attenuation of atherosclerosis progression, thrombus-mediated ischemic events and restenosis without interfering with primary hemostasis. Vorapaxar - a synthetic analogue of himbacine, is a high affinity and highly selective PAR-1 antagonist that can effectively inhibit thrombin-induced platelet aggregation. In the TRACER trial, the addition of vorapaxar to standard therapy in patients with non-stent thrombosis-elevation- acute coronary syndromes did not significantly reduce the primary composite end point occurrence of cardiovascular (CV) death, myocardial infarction (MI), stroke, hospitalization for ischemia, or urgent revascularization, but significantly increased the GUSTO moderate and severe bleeding (p < 0.001) and intracranial hemorrhage (ICH). In the TRA 2°P-TIMI 50 trial, in patients with a history of MI and peripheral arterial disease (PAD) (67% of the total population), the end point of CV death, MI, or stroke was significantly (20%) reduced with vorapaxar whereas GUSTO moderate or severe bleeding was increased (1.5-fold), but not ICH or fatal bleeding and the net clinical outcome favoring the vorapaxar therapy. Based on these favorable results, the FDA approved vorapaxar for the reduction of thrombotic cardiovascular events in patients with prior MI or with PAD for long term therapy. A careful patient selection is needed to balance efficacy versus safety. At this time, patients with high risk for recurrent ischemic event occurrence such as patients with diabetes mellitus and previous MI can be safely treated with vorapaxar for long-term therapy.


The future burden of CKD in the United States: a simulation model for the CDC CKD Initiative.
Awareness of chronic kidney disease (CKD), defined by kidney damage or reduced glomerular filtration rate, remains low in the United States, and few estimates of its future burden exist. We used the CKD Health Policy Model to simulate the residual lifetime incidence of CKD and project the prevalence of CKD in 2020 and 2030. The simulation sample was based on nationally representative data from the 1999 to 2010 National Health and Nutrition Examination Surveys. Current US population. Simulation model following up individuals from current age through death or age 90 years. Residual lifetime incidence represents the projected percentage of persons who will develop new CKD during their lifetimes. Future prevalence is projected for 2020 and 2030. Development and progression of CKD are based on annual decrements in estimated glomerular filtration rates that depend on age and risk factors. For US adults aged 30 to 49, 50 to 64, and 65 years or older with no CKD at baseline, the residual lifetime incidences of CKD are 54%, 52%, and 42%, respectively. The prevalence of CKD in adults 30 years or older is projected to increase from 13.2% currently to 14.4% in 2020 and 16.7% in 2030. Due to limited data, our simulation model estimates are based on assumptions about annual decrements in estimated glomerular filtration rates. For an individual, lifetime risk of CKD is high, with more than half the US adults aged 30 to 64 years likely to develop CKD. Knowing the lifetime incidence of CKD may raise individuals' awareness and encourage them to take steps to prevent CKD. From a national burden perspective, we estimate that the population prevalence of CKD will increase in coming decades, suggesting that development of interventions to slow CKD onset and progression should be considered.


Survival after HIV infection in the pre-antiretroviral therapy era in a rural Tanzanian cohort.
Survival patterns after HIV infection in African populations in the era before antiretroviral therapy (ART) form an important baseline for measuring future successes of treatment programmes. Few studies have followed seroconverters for 10 or more years to describe such patterns. The Kisesa open cohort study conducted four rounds of village-based HIV testing and 20 rounds of household-based demographic surveillance between 1994 and 2006. Approximate infection dates were established for individual seroconverters by allocating a date between the last negative and first positive test. Person-years lived post-infection were computed, allowing for left truncation and right censoring, and Kaplan-Meier survival functions were constructed, truncating the analysis at the start of 2005 when ART first became available in the community. Weibull models were fitted to estimate median survival time, and parametric regression methods were used to investigate the influence of sex and age at infection. A total of 369 seroconverters were identified, providing 890 person-years of follow-up during which 44 deaths were observed. The Kaplan-Meier function showed 67% surviving 9 years post-infection, and the overall predicted median survival was 11.5 years. Survival was strongly related to age at infection (hazard ratio 1.06 for each additional year of age, and weakly to sex. A strong effect of age was evident even after allowing for mortality from non-HIV-related causes using cause deletion methods to estimate net mortality. The survival of HIV-infected individuals was comparable to that reported in developed country studies before the introduction of HAART. Survival patterns in Kisesa are marginally more favourable than those reported in cohort studies in Uganda.


Comorbidities in children and adolescents with AIDS acquired by HIV vertical transmission in Vitória, Brazil.
Studying diseases associated with AIDS is essential for establishing intervention strategies because comorbidities can lead to death. The objectives were to describe the frequency of comorbidities and verify their distribution according to demographic, epidemiological and clinical data as well as to classify diseases in children and adolescents with AIDS in Vitória, Brazil. A retrospective cohort study was conducted among children with AIDS, as defined according to the criteria established by the Ministry of Health, who acquired HIV via vertical transmission, were aged 0 to 18 years, and were monitored at a referral hospital from January 2001 to December 2011. A total of 177 patients were included, of whom 97 were female (55%). There were 60 patients (34%) <1 year old, 67 patients (38%) between the ages of 1 and 5, and 50 patients (28%) ≥6 years of age included at the time of admission to the Infectious Diseases Ward. Regarding clinical-immunological classification, 146 patients (82.5%) showed moderate/severe forms of the disease at the time of admission into the Ward, and 26 patients (14.7%) died during the study. The most common clinical signs were hepatomegaly (81.62%), splenomegaly (63.8%), lymphadenopathy (68.4%) and persistent fever (32.8%). The most common comorbidities were anaemia (67.2%), pneumonia/septicaemia/acute bacterial meningitis (ABM) (64.2%), acute otitis media (AOM)/recurrent sinusitis (55.4%), recurrent severe bacterial infections (47.4%) and dermatitis (43.1%). An association between severe clinical-immunological classification and admission to the Ward for children aged less than one year old was found for several comorbidities (p<0.001). Delayed diagnosis was observed because the majority of patients were admitted to the Infectious Diseases Ward at ≥1 year of age and were already presenting with serious diseases. The general paediatrician should be alert to this possibility to make an early diagnosis in children infected with HIV.


The present status of off-pump coronary artery bypass grafting.
Coronary revascularisation using cardiopulmonary bypass remains the gold standard treatment for coronary artery disease. Over the past decade, techniques of revascularisation on the beating heart without the use of cardiopulmonary bypass (off-pump surgery) have evolved with an attempt to reduce the potential deleterious effects of extracorporeal circulation. Several trials have reported a significant reduction in morbidity with avoidance of cardiopulmonary bypass, while large observational studies have also reported a reduction in mortality. Complete avoidance of aortic manipulation by using off-pump techniques and composite grafts may add an additional benefit particularly in patients at highest risk of stroke. The impact of this mode of revascularisation has probably been underestimated especially in an era where surgical revascularisation is being increasingly undertaken in older patients with significant comorbidities. In this contribution, the current evidence from randomised trials, meta-analyses and observational studies is critically reviewed.


Outcomes in patients with esotropic duane retraction syndrome and a partially accommodative component.
The management of Duane retraction syndrome (DRS) is challenging and may become more difficult if an associated accommodative component due to high hyperopia is present. The purpose of this study is to review clinical features and outcomes in patients with partially accommodative esotropia and DRS. Retrospective, non-comparative case series. Six cases of DRS with high hyperopia were reviewed. Of the patients studied, the mean age of presentation was 1.3 years (range: 0.5-2.5 years). The mean amount of hyperopia was + 5D (range: 3.50-8.50) in both eyes. The mean follow up period was 7 years (range: 4 months-12 years). Five cases were unilateral while one was bilateral. Four cases underwent vertical rectus muscle transposition (VRT) and one had medial rectus recession prior to presentation; all were given optical correction. Two (50%) of the four patients who underwent vertical rectus transposition cases developed consecutive exotropia, one of whom did not have spectacles prescribed pre-operatively. All other cases (four) had minimal residual esotropia and face turn at the last follow-up with spectacle correction. Patients with Duane syndrome can have an accommodative component to their esotropia, which is crucial to detect and correct prior to surgery to decrease the risk of long-term over-correction. Occasionally, torticollis in Duane syndrome can be satisfactorily corrected with spectacles alone.


Semantically linking in silico cancer models.
Multiscale models are commonplace in cancer modeling, where individual models acting on different biological scales are combined within a single, cohesive modeling framework. However, model composition gives rise to challenges in understanding interfaces and interactions between them. Based on specific domain expertise, typically these computational models are developed by separate research groups using different methodologies, programming languages, and parameters. This paper introduces a graph-based model for semantically linking computational cancer models via domain graphs that can help us better understand and explore combinations of models spanning multiple biological scales. We take the data model encoded by TumorML, an XML-based markup language for storing cancer models in online repositories, and transpose its model description elements into a graph-based representation. By taking such an approach, we can link domain models, such as controlled vocabularies, taxonomic schemes, and ontologies, with cancer model descriptions to better understand and explore relationships between models. The union of these graphs creates a connected property graph that links cancer models by categorizations, by computational compatibility, and by semantic interoperability, yielding a framework in which opportunities for exploration and discovery of combinations of models become possible.


A conceptual framework for clinicians working with artificial intelligence and health-assistive Smart Homes.
The Smart Home designed to extend older adults independence is emerging as a clinical solution to the growing ageing population. Nurses will and should play a key role in the development and application of Smart Home technology. Accordingly, conceptual frameworks are needed for nurse scientists who are collaborating with multidisciplinary research teams in developing an intelligent Smart Home that assists with managing older adults' health. We present a conceptual framework that is grounded in critical realism and pragmatism, informing a unique mixed methodological approach to generating, analyzing, and contextualizing sensor data for clinician-based machine learning. This framework can guide nurse scientists in knowledge construction as they participate in multidisciplinary health-assistive Smart Home and artificial intelligence research. In this paper, we review philosophical underpinnings and explicate how this framework can guide nurse scientists collaborating with engineers to develop intelligent health-assistive Smart Homes. It is critical that clinical nursing knowledge is integrated into Smart Home and artificial intelligence features. A conceptual framework and practical method will provide needed structure for knowledge construction by nurse scientists.


Prevalence of Appendiceal Lesions in Appendicectomies Performed During Surgery for Mucinous Ovarian Tumors: A Retrospective Study.
The aim of this study was to assess the frequency of appendiceal pathology in women undergoing surgery for mucinous ovarian neoplasm and to evaluate whether appendicectomy is necessary. This single-institution retrospective study reviewed prevalence of appendiceal lesions in all patients operated on at our institution from 2002 to 2013 with the final diagnosis of mucinous tumor of the ovary. Clinicopathological data were analyzed. One hundred twenty-three cases were identified. These included 45 (37%) benign mucinous ovarian neoplasms, 63 (51%) borderline, and 11 (9%) invasive mucinous ovarian tumors. In addition, 4 (3%) cases of metastatic tumors to the ovary were also identified. Appendiceal pathology was found in association with all types of mucinous ovarian tumors (benign, borderline, and malignant). In 24% of cases, appendix was macroscopically abnormal at the time of the surgery, prompting the surgical removal. Regardless of the gross findings, microscopic abnormality in the appendix was seen in 24% of all cases. The prevalence of significant occult microscopic appendiceal pathology, that is, when the appendix was grossly normal, was 6%. Given the prevalence of coexisting appendiceal pathology found in this study and the reported low rates of complications associated with the procedure, an appendicectomy is recommended in the management of all mucinous ovarian neoplasms.


Plant Hsp90 and its co-chaperones.
Molecular chaperones, central to cellular protein homeostasis, are conserved within species. Hsp90 and its cochaperones participate in major cellular functions such as cell growth, response to biotic and abiotic stresses and differentiation, and are critical to the regulation of these functions. Regulation is done through their interacting with client proteins in various cellular compartments under specific conditions. Plant Hsp90 and its co-chaperones resemble their mammalian counterparts in their structure. They were shown to participate in diverse and unique pathways such as defense mechanism against pathogens, regulation of gene expression by regulation of the silencing of RNAs, transport of pre-proteins into chloroplasts and response to heat stress. In many cases, the Hsp90 interaction with the co-chaperone is a prerequisite to interaction with client proteins and regulation of their function. While our understanding of the interaction of plant Hsp90 and its co-chaperones has been greatly enhanced, the large number of isoforms in plants and the diverse molecular pathways specific to plants still leave many open questions about the regulation, specificity, and biophysical characteristics of the complexes formed and their contribution to the cellular homeostasis.


"Picking up the pieces" - Meanings of receiving home nursing care when being old and living with advanced cancer in a rural area.
Rural home nursing care is a neglected area in the research of palliative care offered to older cancer patients. Because access to specialized services is hampered by long distances and fragmented infrastructure, palliative care is often provided through standard home nursing services and delivered by general district nurses. This study aimed to illuminate the lived experience and to interpret the meaning of receiving home nursing care when being old and living with advanced cancer in a rural area in Norway. Narrative interviews were conducted with nine older persons, and a phenomenological hermeneutic approach was used to interpret the meaning of the lived experience. The analysis revealed three themes, each with subthemes: being content with what one gets, falling into place, and losing one's place. The phrase picking up the pieces was found useful to sum up the meaning of this lived experience. The three respective themes refer to how the pieces symbolize the remaining parts of life or available services in their environment, and how the older persons may see themselves as pieces or bricks in a puzzle. A strong place attachment (physical insideness, social insideness, and autobiographical insideness) is demonstrated by the informants in this study and suggests that the rural context may provide an advantageous healthcare environment. Its potential to be a source of comfort, security, and identity concurs with cancer patients' strong desire for being seen as unique persons. The study shows that district nurses play an essential role in the provision of palliative care for older rural patients. However, the therapeutic value of being in one's familiar landscape seems to depend on how homecare nurses manage to locate it and use it in a more or less person-centred manner. Communication skills and attentiveness to psychosocial aspects of patient care stand out as important attributes for nursing in this context.


Optical rectification effect due to surface plasmon polaritons at normal incidence in a nondiffraction regime.
We carried out an experimental and numerical investigation of photoinduced voltage at normal incidence in the nondiffraction regime, which was not predicted to occur by the simple momentum conservation model. We prepared two samples: one having space inversion symmetry and the other without this feature. At normal incidence in the nondiffraction regime, we observed a finite signal only for the asymmetric structure. We found that surface plasmon polaritons (SPPs) are excited by the signal and are attributed to the origin of the voltage. We also evaluated the radiation force of light by using the Maxwell stress tensor and found that pressure of light and not shear force is mainly induced in the structure due to the asymmetric excitation of SPPs.


A stereotactic method for the three-dimensional registration of multi-modality biologic images in animals: NMR, PET, histology, and autoradiography.
The objective of this work was to develop and then validate a stereotactic fiduciary marker system for tumor xenografts in rodents which could be used to co-register magnetic resonance imaging (MRI), PET, tissue histology, autoradiography, and measurements from physiologic probes. A Teflon fiduciary template has been designed which allows the precise insertion of small hollow Teflon rods (0.71 mm diameter) into a tumor. These rods can be visualized by MRI and PET as well as by histology and autoradiography on tissue sections. The methodology has been applied and tested on a rigid phantom, on tissue phantom material, and finally on tumor bearing mice. Image registration has been performed between the MRI and PET images for the rigid Teflon phantom and among MRI, digitized microscopy images of tissue histology, and autoradiograms for both tissue phantom and tumor-bearing mice. A registration accuracy, expressed as the average Euclidean distance between the centers of three fiduciary markers among the registered image sets, of 0.2 +/- 0.06 mm was achieved between MRI and microPET image sets of a rigid Teflon phantom. The fiduciary template allows digitized tissue sections to be co-registered with three-dimensional MRI images with an average accuracy of 0.21 and 0.25 mm for the tissue phantoms and tumor xenografts, respectively. Between histology and autoradiograms, it was 0.19 and 0.21 mm for tissue phantoms and tumor xenografts, respectively. The fiduciary marker system provides a coordinate system with which to correlate information from multiple image types, on a voxel-by-voxel basis, with sub-millimeter accuracy--even among imaging modalities with widely disparate spatial resolution and in the absence of identifiable anatomic landmarks.


Effects of aerosol-vapor JP-8 jet fuel on the functional observational battery, and learning and memory in the rat.
To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.


Involvement of cathepsin B in the plant disease resistance hypersensitive response.
A diverse range of plant proteases are implicated in pathogen perception and in subsequent signalling and execution of disease resistance. We demonstrate, using protease inhibitors and virus-induced gene silencing (VIGS), that the plant papain cysteine protease cathepsin B is required for the disease resistance hypersensitive response (HR). VIGS of cathepsin B prevented programmed cell death (PCD) and compromised disease resistance induced by two distinct non-host bacterial pathogens. It also suppressed the HR triggered by transient co-expression of potato R3a and Phytophthora infestans Avr3a genes. However, VIGS of cathepsin B did not compromise HR following recognition of Cladosporium fulvum AVR4 by tomato Cf-4, indicating that plant PCD can be independent of cathepsin B. The non-host HR to Erwinia amylovora was accompanied by a transient increase in cathepsin B transcript level and enzymatic activity and induction of the HR marker gene Hsr203. VIGS of cathepsin B significantly reduced the induction of Hsr203 following E. amylovora challenge, further demonstrating a role for this protease in PCD. Whereas cathepsin B is often relocalized from the lysosome to the cytosol during animal PCD, plant cathepsin B is secreted into the apoplast, and is activated upon secretion in the absence of pathogen challenge.


Blueberry phenolics are associated with cognitive enhancement in supplemented healthy older adults.
Blueberries (BB) contain an array of bioactive phenolic compounds that may play a protective role against various age-related diseases. Here we explored the metabolic fate of BB phenolics and their relationship to cognitive function after chronic (90 days) supplementation of freeze-dried BB (24 g d-1, equivalent to 1 cup of fresh BB) or control in a randomized, double-blind, parallel study with 38 healthy older adults (60-75 years). Blood samples were collected at fasting (t = 0 h) and 2 h after a breakfast meal on days 0 (no treatment), 45, and 90, and a battery of cognitive tests was also conducted on these days. Hippuric acid, phloroglucinaldehyde, syringic acid, ferulic acid-glucuronide, cyanidin-3-O-galactoside, cyanidin-3-O-glucoside, malvidin-3-O-galactoside, malvidin-3-O-glucoside, peonidin-3-O-xyloside, peonidin glucuronide, and petunidin-3-O-glucoside concentrations were significantly altered after 90 days of BB consumption compared to control. Stepwise regression was used to assess the relationship between significantly altered concentrations of plasma phenolics and observed improvements in cognition. Among participants in the BB group, changes in switch errors on the task-switching test (TST) from day 0 to 90 were associated with changes in postprandial levels of plasma ferulic acid-glucuronide, syringic acid, and malvidin-3-galactoside (R2 = 0.521, p < 0.05). Changes in repetition errors on the California Verbal Learning Test (CVLT-II) from day 0 to 90 were associated with changes in postprandial levels of ferulic acid-glucuronide, syringic acid, and hippuric acid (R2 = 0.807, p < 0.001). These findings demonstrate that the addition of easily achievable quantities of BB to the diets of older adults significantly alters levels of circulating phenolic compounds which are related to improvements in cognition.


The Association Between Diet and Obesity in Specific European Cohorts: DiOGenes and EPIC-PANACEA.
This review summarizes evidence from two projects embedded within the European Prospective Investigation into Cancer and Nutrition (EPIC) on the association between dietary factors and obesity risk, in particular change in weight and waist circumference. A total of 12 publications from DiOGenes and six from EPIC-PANACEA were reviewed. The results show that dietary fiber, especially cereal fiber, was inversely associated with weight or waist change, as well as fruit/vegetable intake and the Mediterranean dietary pattern. Energy density and meat consumption were positively associated with the anthropometric changes, as was glycemic index with waist change. Clear associations with macronutrient composition were not observed. In additional studies, interactions with genetic polymorphism were investigated and shown to be present for protein intake and GI, although effect estimates were small. These interactions require replication. These results show that in European populations dietary factors are independently associated with weight/waist change. The findings provide further clues for the prevention of obesity.


Increases in regimen durability associated with the introduction of tenofovir at a large public-sector clinic in Johannesburg, South Africa.
In April 2010, tenofovir replaced stavudine in public-sector first-line antiretroviral therapy (ART) in South Africa. The association of tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir-based regimens. We evaluated changes over time in regimen durability at the Themba Lethu Clinic, Johannesburg, South Africa. This was a cohort analysis of treatment-naïve, non-pregnant adult patients initiated on ART between April 2004 and December 2011. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir was substituted for stavudine after April 2010. We evaluated the frequency and type of single-drug substitutions (excluding switches to second-line therapy). Cox models were used to evaluate the association of ART initiation year and antiretroviral drug type with single-drug substitutions in the first 12 months on treatment. One thousand nine hundred and sixty-four (10%) substitutions occurred amongst 19,699 patients. Excluding 2004 (year of treatment roll-out), before 2010 one-year single-drug substitutions ranged from 10.0 to 13.1%. In 2011, well after integration of tenofovir, substitutions decreased to 5.6%. Single-drug substitution was lowest amongst patients on tenofovir (5.1%) versus zidovudine (11.3%), 30 mg stavudine (10.5%) or 40 mg stavudine (14.4%). Adjusted Cox models showed that patients initiating treatment between 2005 and 2010 (vs. 2011) had a twofold increased hazard of single-drug substitution, while those on zidovudine or stavudine had a two to threefold increase in single-drug substitution versus tenofovir patients in the first 12 months on ART. The decline in single-drug substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.


Flexible fabrication of three-dimensional optical-domain photonic crystals using a combination of single-laser-exposure diffractive-optics lithography and template inversion.
We demonstrate inversion of three-dimensional photonic crystal templates fabricated in a large area with diffractive-optics lithography. A custom-designed two-dimensional diffractive optical element was used to generate highly uniform, bicontinuous, three-dimensional photonic crystal templates in a single-laser exposure. Chemical vapor deposition successfully infiltrated the thick periodic polymer structure to deposit amorphous silica and thereby define an all-silica inverted photonic crystal after polymer removal, as confirmed by focused ion-beam milling and energy-dispersive x-ray spectroscopy. The diffractive-optics lithography permitted a large number of uniform layers to form that manifested in the recording of a strong -28 dB stopband in the telecom band.


Risks associated with fresh whole blood and red blood cell transfusions in a combat support hospital.
Fresh whole blood (FWB) and red blood cells (RBCs) are transfused to injured casualties in combat support hospitals. We evaluated the risks of FWB and RBCs transfused to combat-related casualties. Retrospective chart review. Deployed U.S. Army combat support hospitals. Donors of FWB and recipients of FWB and RBCs. The storage age of RBCs at transfusion was measured as an indicator of overall risk associated with the storage lesion of RBCs between January 2004 and December 2004 at one combat support hospital. Between April 2004 and December 2004, FWB was prescreened only at one combat support hospital for human immunodeficiency virus, hepatitis C virus, and hepatitis B surface antigen before transfusion. To estimate the general incidence of infectious agent contamination in FWB units, samples collected between May 2003 and February 2006 were tested retrospectively for human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus, and human lymphotropic virus. Results were compared between FWB samples prescreened and not prescreened for infectious agents before transfusion. At one combat support hospital in 2004, 87 patients were transfused 545 units of FWB and 685 patients were transfused 5,294 units of RBCs with a mean age at transfusion of 33 days (+/- 6 days). Retrospective testing of 2,831 samples from FWB donor units transfused in Iraq and Afghanistan between May 2003 and February 2006 indicated that three of 2,831 (0.11%) were positive for hepatitis C virus recombinant immunoblot assay, two of 2,831 (0.07%) were positive for human lymphotropic virus enzyme immunoassay, and none of 2,831 were positive for both human immunodeficiency virus 1/2 and hepatitis B surface antigen by Western blot and neutralization methods, respectively. The differences in the incidence of hepatitis C virus contamination of FWB donor units between those prescreened for hepatitis C virus (zero of 406; 0%) and not prescreened (three of 2,425; 0.12%) were not significant (p = .48). The risk of infectious disease transmission with FWB transfusion can be minimized by rapid screening tests before transfusion. Because of the potential adverse outcomes of transfusing RBCs of increased storage age to combat-related trauma patients, the risks and benefits of FWB transfusions must be balanced with those of transfusing old RBCs in patients with life-threatening traumatic injuries.


Proximal tubule Na+/H+ exchanger activity in adult NHE8-/-, NHE3-/-, and NHE3-/-/NHE8-/- mice.
NHE3 is the predominant Na(+)/H(+) exchanger on the brush-border membrane (BBM) of the proximal tubule in adults. However, NHE3 null mice still have significant renal BBM Na(+)/H(+) activity. NHE8 has been localized to the BBM of proximal tubules and is more highly expressed in neonates than adult animals. The relative role of NHE8 in adult renal H(+) transport is unclear. This study examined whether there was compensation by NHE8 in NHE3(-/-) mice and by NHE3 in NHE8(-/-) mice. NHE3(-/-) mice had significant metabolic acidosis, and renal BBM NHE8 protein abundance was greater in NHE3(-/-) mice than control mice, indicating that there may be compensation by NHE8 in NHE3(-/-) mice. NHE8(-/-) mice had serum bicarbonate levels and pH that were not different from controls. NHE3 protein expression on the BBM was greater in NHE8(-/-) mice than in wild-type mice, indicating that there may be compensation by NHE3 in NHE8(-/-) mice. Both BBM NHE3 and NHE8 protein abundance increased in response to acidosis. Blood pressure and Na(+)/H(+) exchanger activity were comparable in NHE8(-/-) mice to that of controls, but both were significantly lower in NHE3(-/-) mice compared with control mice. Compared with NHE3(-/-) mice, NHE3(-/-)/NHE8(-/-) mice had lower blood pressures. While serum bicarbonate was comparable in NHE3(-/-) mice and NHE3(-/-)/NHE8(-/-) mice, proximal tubule Na(+)/H(+) exchange activity was less in NHE3(-/-)/NHE8(-/-) mice compared with NHE3(-/-) mice. In conclusion, NHE3 is the predominant Na(+)/H(+) exchanger in adult mice. NHE8 may play a compensatory role in renal acidification and blood pressure regulation in NHE3(-/-) mice.


Comorbidities in Perthes' disease: a case control study using the General Practice Research database.
Perthes' disease is an osteonecrosis of the juvenile hip, the aetiology of which is unknown. A number of comorbid associations have been suggested that may offer insights into aetiology, yet the strength and validity of these are unclear. This study explored such associations through a case control study using the United Kingdom General Practice Research database. Associations investigated were those previously suggested within the literature. A total of 619 cases of Perthes' disease were included, as were 2544 controls. The risk of Perthes' disease was significantly increased with the presence of congenital anomalies of the genitourinary and inguinal region, such as hypospadias (odds ratio (OR) 4.04 (95% confidence interval (CI) 1.41 to 11.58)), undescended testis (OR 1.83 (95% CI 1.12 to 3.00)) and inguinal herniae (OR 1.79 (95% CI 1.02 to 3.16)). Attention deficit hyperactivity disorder was not associated with Perthes' disease (OR 1.01 (95% CI 0.48 to 2.12)), although a generalised behavioural disorder was (OR 1.55 (95% CI 1.10 to 2.17)). Asthma significantly increased the risk of Perthes' disease (OR 1.44 (95% CI 1.17 to 1.76)), which remained after adjusting for oral/parenteral steroid use. Perthes' disease has a significant association with congenital genitourinary and inguinal anomalies, suggesting that intra-uterine factors may be critical to causation. Other comorbid associations may offer insight to support or refute theories of pathogenesis.


Mechanisms of actin rearrangements mediating platelet activation.
The detergent-insoluble cytoskeleton of the resting human blood platelet contains approximately 2,000 actin filaments approximately 1 micron in length crosslinked at high angles by actin-binding protein and which bind to a spectrin-rich submembrane lamina (Fox, J., J. Boyles, M. Berndt, P. Steffen, and L. Anderson. 1988. J. Cell Biol. 106:1525-1538; Hartwig, J., and M. DeSisto. 1991. J. Cell Biol. 112:407-425). Activation of the platelets by contact with glass results within 30 s in a doubling of the polymerized actin content of the cytoskeleton and the appearance of two distinct new actin structures: bundles of long filaments within filopodia that end at the filopodial tips (filopodial bundles) and a circumferential zone of orthogonally arrayed short filaments within lamellipodia (lamellipodial network). Neither of these structures appears in cells exposed to glass with cytochalasin B present; instead the cytoskeletons have numerous 0.1-0.3-microns-long actin filament fragments attached to the membrane lamina. With the same time course as the glass-induced morphological changes, cytochalasin-sensitive actin nucleating activity, initially low in cytoskeletons of resting platelets, increases 10-fold in cytoskeletons of thrombin-activated platelets. This activity decays with a time course consistent with depolymerization of 0.1-0.3-microns-long actin filaments, and phalloidin inhibits this decay. Cytochalasin-insensitive and calcium-dependent nucleation activity also increases markedly in platelet extracts after thrombin activation of the cells. Prevention of the rise in cytosolic Ca2+ normally associated with platelet activation with the permeant Ca2+ chelator, Quin-2, inhibits formation of lamellipodial networks but not filopodial bundles after glass contact and reduces the cytochalasin B-sensitive nucleation activity by 60% after thrombin treatment. The filopodial bundles, however, are abnormal in that they do not end at the filopodial tips but form loops and return to the cell body. Addition of calcium to chelated cells restores lamellipodial networks, and calcium plus A23187 results in cytoskeletons with highly fragmented actin filaments within seconds. Immunogold labeling with antibodies against gelsolin reveals gelsolin molecules at the ends of filaments attached to the submembrane lamina of resting cytoskeletons and at the ends of some filaments in the lamellipodial networks and filopodial bundles of activated cytoskeletons. Addition of monomeric actin to myosin subfragment 1-labeled activated cytoskeletons leads to new (undecorated) filament growth off the ends of filaments in the filopodial bundles and the lamellipodial network. The simplest explanation for these findings is that gelsolin caps the barbed ends of the filaments in the resting platelet. Uncapping some of these filaments after activation leads to filopodial bundles.(ABSTRACT TRUNCATED AT 400 WORDS)


Delineating the role of CD4+ T cells in the activation of human cytomegalovirus-specific immune responses following immunization with Ad-gBCMVpoly vaccine: implications for vaccination of immunocompromised individuals.
Reconstitution of the virus-specific CD8(+) T-cell response is crucial for the prevention of human cytomegalovirus (CMV)-associated pathogenesis in transplant patients and human immunodeficiency virus-infected individuals. Although adoptive T-cell immunotherapy has been used successfully in various clinical settings, prophylactic vaccination remains the most amenable strategy to prevent CMV disease. However, vaccination in clinical settings where the host is severely immunocompromised due to the loss of CD4(+) T cells remains a significant challenge. This study investigated the efficacy of a chimeric CMV vaccine in a model setting that allowed studies on the generation of CD8(+) T-cell memory responses in a transient CD4(+) T-cell-deficient setting similar to that seen in immunocompromised patients. Immunization with an adenoviral CMV vaccine under transient helpless (complete CD4(+) T-cell depletion) or help-deficient (partial CD4(+) T-cell depletion) conditions demonstrated that induction of the effector CD8(+) T-cell and humoral responses was almost completely eliminated under helpless conditions, and was gradually regained with the recovery of CD4(+) T cells. However, this response failed to protect the host from viral infection, suggesting that lack of CD4(+) T cells during vaccination can significantly impair the priming and maturation of CMV-specific immune responses. Furthermore, although the induction of CMV-specific immune responses was also significantly reduced in a help-deficient environment, these primed effector cells could mature normally and generate long-term polyfunctional memory responses capable of restricting virus replication in vivo. These results highlight the importance of monitoring CD4(+) T-cell numbers before vaccination for the successful implementation of a CMV vaccine in an immunocompromised setting.


CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination.
Cytomegalovirus (CMV) is a globally ubiquitous pathogen with a seroprevalence of approximately 50% in the United Kingdom. CMV infection induces expansion of immunosenescent T cell and NK cell populations, with these cells demonstrating lower responsiveness to activation and reduced functionality upon infection and vaccination. In this study, we found that CMV+ participants had normal T cell responses after a single-dose or homologous vaccination with the viral vector chimpanzee adenovirus developed by the University of Oxford (ChAdOx1). CMV seropositivity was associated with reduced induction of IFN-γ-secreting T cells in a ChAd-Modified Vaccinia Ankara (ChAd-MVA) viral vector vaccination trial. Analysis of participants receiving a single dose of ChAdOx1 demonstrated that T cells from CMV+ donors had a more terminally differentiated profile of CD57+PD1+CD4+ T cells and CD8+ T cells expressing less IL-2Rα (CD25) and fewer polyfunctional CD4+ T cells 14 days after vaccination. NK cells from CMV-seropositive individuals also had a reduced activation profile. Overall, our data suggest that although CMV infection enhances immunosenescence of T and NK populations, it does not affect antigen-specific T cell IFN-γ secretion or antibody IgG production after vaccination with the current ChAdOx1 nCoV-19 vaccination regimen, which has important implications given the widespread use of this vaccine, particularly in low- and middle-income countries with high CMV seroprevalence.


Glioblastoma therapy in the elderly and the importance of the extent of resection regardless of age.
The objective of this study was to analyze whether age influences the outcome of patients with glioblastoma and whether elderly patients with glioblastoma can tolerate the same aggressive treatment as younger patients. Data from 361 consecutive patients with newly diagnosed cerebral glioblastoma (2000-2006) who underwent regular follow-up evaluation from initial diagnosis until death were prospectively entered into a database. Patients underwent resection (complete, subtotal, or partial) or biopsy, depending on tumor size, location, and Karnofsky Performance Scale score. Following surgery, all patients underwent adjuvant treatment consisting of radiotherapy, chemotherapy, or combined treatment. Patients older than 65 years of age were defined as elderly (146 total). Two hundred thirty-four patients underwent tumor resection (complete 26%, subtotal 29%, and partial 45%). One hundred twenty-seven underwent biopsy. Mean patient age was 61 years, and overall survival was 11.6 ± 12.1 months. The overall survival of elderly patients (9.1 ± 11.6 months) was significantly lower than that of younger patients (14.9 ± 16.7 months; p = 0.0001). Stratifying between resection or biopsy, age was a negative prognostic factor in patients undergoing biopsy (4.0 ± 7.1 vs 7.9 ± 8.7 months; p = 0.007), but not in patients undergoing tumor resection (13.0 ± 8.5 vs 13.3 ± 14.5 months; p = 0.86). Survival of elderly patients undergoing complete tumor resection was 17.7 ± 8.1 months. In this series of patients with glioblastoma, age was a prognostic factor in patients undergoing biopsy, but not in patients undergoing resection. Tumor location and patient clinical status may prohibit extensive resection, but resection should not be withheld from patients only on the basis of age. In elderly patients with glioblastoma, undergoing resection to the extent feasible, followed by adjuvant therapies, is warranted.


Experimental study of the effect of surface defects on the finesse and contrast of a Fabry-Perot interferometer.
While investigating the instrumental function of a Fabry-Perot interferometer [Appl. Opt. 34, 58 (1995), we noticed some variation in finesse and contrast in the measured spectra when a 1.5-mm-diameter aperture was used at various spots within the standard 8-mm aperture. By comparing experimentally determined finesse versus contrast plots for many such spectra with calculated plots, we found spots on the plates that gave non-Airy-function line shapes over the entire order of interference, unlike the Airy line shape we determined previously by using the entire 8-mm aperture. We have reviewed several models that describe the effects of various types of surface defects, such as Gaussian-height distribution of roughness, curvature and tilt of plates, sinusoidal roughness, and asymmetrical roughness on the finesse and contrast. Our experimental results can be accounted for if we assume that the reflectivity is nonuniform over the Fabry-Perot plates and that there is some reasonable contribution that is due to Gaussian roughness, curvature, or tilt.


A comparison of adolescent moderate-to-vigorous physical activity participation in relation to a sustained or accumulated criterion.
Contemporary guidelines for young people advocate both a sustained and accumulative approach to moderate-to-vigorous physical activity (MVPA) participation. In order to investigate the behavioural significance of applying these approaches, this study assessed if differences in adolescent MVPA occurred when either a sustained or accumulated criterion was adopted. Using heart rate thresholds indicative of intensity, the physical activity of 25 adolescents was assessed by monitoring heart rate over 3 days. Results indicated that differences in MVPA participation did exist when different approaches were used, in that the majority of adolescents were active with respect to an accumulated criterion yet inactive with respect to a sustained criterion. Such a disparity may be due to accumulative MVPA being more characteristic of young people's natural activity behaviour. Such findings have strong implications for practitioners seeking to counter young people's inactivity, in that the application of an accumulative approach may be more effective at initiating and establishing an habitual activity behaviour than that of a sustained approach.


Interspecific social networks promote information transmission in wild songbirds.
Understanding the functional links between social structure and population processes is a central aim of evolutionary ecology. Multiple types of interactions can be represented by networks drawn for the same population, such as kinship, dominance or affiliative networks, but the relative importance of alternative networks in modulating population processes may not be clear. We illustrate this problem, and a solution, by developing a framework for testing the importance of different types of association in facilitating the transmission of information. We apply this framework to experimental data from wild songbirds that form mixed-species flocks, recording the arrival (patch discovery) of individuals to novel foraging sites. We tested whether intraspecific and interspecific social networks predicted the spread of information about novel food sites, and found that both contributed to transmission. The likelihood of acquiring information per unit of connection to knowledgeable individuals increased 22-fold for conspecifics, and 12-fold for heterospecifics. We also found that species varied in how much information they produced, suggesting that some species play a keystone role in winter foraging flocks. More generally, these analyses demonstrate that this method provides a powerful approach, using social networks to quantify the relative transmission rates across different social relationships.