Light-driven 3D droplet manipulation on flexible optoelectrowetting devices fabricated by a simple spin-coating method.
Technical advances in electrowetting-on-dielectric (EWOD) over the past few years have extended our attraction to three-dimensional (3D) devices capable of providing more flexibility and functionality with larger volumetric capacity than conventional 2D planar ones. However, typical 3D EWOD devices require complex and expensive fabrication processes for patterning and wiring of pixelated electrodes that also restrict the minimum droplet size to be manipulated. Here, we present a flexible single-sided continuous optoelectrowetting (SCOEW) device which is not only fabricated by a spin-coating method without the need for patterning and wiring processes, but also enables light-driven 3D droplet manipulations. To provide photoconductive properties, previous optoelectrowetting (OEW) devices have used amorphous silicon (a-Si) typically fabricated through high-temperature processes over 300 °C such as CVD or PECVD. However, most of the commercially-available flexible substrates such as polyethylene terephthalate (PET) and polyethylene naphthalate (PEN) experience serious thermal deformation under such high-temperature processes. Because of this compatibility issue of conventional OEW devices with flexible substrates, light-driven 3D droplet manipulations have not yet been demonstrated on flexible substrates. Our study overcomes this compatibility issue by using a polymer-based photoconductive material, titanium oxide phthalocyanine (TiOPc) and thus SCOEW devices can be simply fabricated on flexible substrates through a low-cost, spin-coating method. In this paper, analytical studies were conducted to understand the effects of light patterns on static contact angles and EWOD forces. For experimental validations of our study, flexible SCOEW devices were successfully fabricated through the TiOPc-based spin-coating method and light-driven droplet manipulations (e.g. transportation, merging, and splitting) have been demonstrated on various 3D terrains such as inclined, vertical, upside-down, and curved surfaces. Our flexible SCOEW technology offers the benefits of device simplicity, flexibility, and functionality over conventional EWOD and OEW devices by enabling optical droplet manipulations on a 3D featureless surface.


Loss of nuclear factor-kappaB is tumor promoting but does not substitute for loss of p53.
Inactivation of apoptotic pathways is a common event in cancer. Two transcription factors that regulate apoptosis during tumorigenesis are p53 and nuclear factor (NF)-kappaB. Although NF-kappaB is generally considered a suppressor of cell death, we showed previously that NF-kappaB can contribute to p53-induced death. Here, we show that loss of p65, a critical subunit of NF-kappaB, can cause resistance to different agents that signal death through p53. Loss of p65 also enhances tumorigenesis induced by E1a and Ras. Unlike loss of p53, however, loss of p65 does not cause anchorage-independent growth or enable tumor development following expression of a single oncogene. These findings reaffirm the role of NF-kappaB in p53-induced death but show that its loss does not substitute for loss of p53 in tumor development. Moreover, this indicates that, although perhaps central to p53 function, loss of the ability to induce programmed cell death does not completely inactivate p53's tumor-suppressive effects.


Potential effects of warmer worms and vectors on onchocerciasis transmission in West Africa.
Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25°C, the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29°C and 34°C, about 3°C and 7°C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 29°C and of savannah flies (Ghana) at 30°C. Small temperature increases (less than 2°C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 33°C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13-41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions.


Potential Effects on Mortality of Replacing Sedentary Time With Short Sedentary Bouts or Physical Activity: A National Cohort Study.
Little is known concerning the type of activity that should be substituted for sedentary time and its potentially most hazardous form (prolonged sedentary bouts) to impart health benefit. We used isotemporal substitution techniques to examine whether 1) replacing total sedentary time with light-intensity or moderate to vigorous physical activity (LIPA or MVPA) or 2) replacing prolonged sedentary bouts with shorter sedentary bouts is associated with reductions in all-cause mortality risk. Participants (n = 7,999) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national cohort of US adults aged ≥45 years, were studied. Sedentary time was measured by accelerometry between 2009 and 2013. There was a beneficial association with mortality risk for replacing total sedentary time with both LIPA (per 30 minutes, hazard ratio (HR) = 0.83; 95% confidence interval (CI): 0.80, 0.87) and MVPA (per 30 minutes, HR = 0.65; 95% CI: 0.50, 0.85). Similarly, there was a beneficial association for replacing prolonged sedentary-bout time with LIPA and MVPA but not for replacement with shorter sedentary bouts (per 30 minutes, HR = 1.00; 95% CI: 0.96, 1.03). These findings suggest short sedentary bouts still carry mortality risk and are not a healthful alternative to prolonged sedentary bouts. Instead, physical activity of any intensity is needed to mitigate the mortality risks incurred by sedentary time.


Dynamic 5-HT2C receptor editing in a mouse model of obesity.
The central serotonergic signalling system has been shown to play an important role in appetite control and the regulation of food intake. Serotonin exerts its anorectic effects mainly through the 5-HT(1B), 5-HT(2C) and 5-HT(6) receptors and these are therefore receiving increasing attention as principal pharmacotherapeutic targets for the treatment of obesity. The 5-HT(2C) receptor has the distinctive ability to be modified by posttranscriptional RNA editing on 5 nucleotide positions (A, B, C, D, E), having an overall decreased receptor function. Recently, it has been shown that feeding behaviour and fat mass are altered when the 5-HT(2C) receptor RNA is fully edited, suggesting a potential role for 5-HT(2C) editing in obesity. The present studies investigate the expression of serotonin receptors involved in central regulation of food intake, appetite and energy expenditure, with particular focus on the level of 5-HT(2C) receptor editing. Using a leptin-deficient mouse model of obesity (ob/ob), we show increased hypothalamic 5-HT(1A) receptor expression as well as increased hippocampal 5-HT(1A), 5-HT(1B), and 5-HT(6) receptor mRNA expression in obese mice compared to lean control mice. An increase in full-length 5-HT(2C) expression, depending on time of day, as well as differences in 5-HT(2C) receptor editing were found, independent of changes in total 5-HT(2C) receptor mRNA expression. This suggests that a dynamic regulation exists of the appetite-suppressing effects of the 5-HT(2C) receptor in both the hypothalamus and the hippocampus in the ob/ob mice model of obesity. The differential 5-HT(1A), 5-HT(1B) and 5-HT(6) receptor expression and altered 5-HT(2C) receptor editing profile reported here is poised to have important consequences for the development of novel anti-obesity therapies.


Sexual dysfunction and male infertility.
Infertility affects up to 12% of all men, and sexual dysfunction occurs frequently in men of reproductive age, causing infertility in some instances. In infertile men, hypoactive sexual desire and lack of sexual satisfaction are the most prevalent types of sexual dysfunction, ranging from 8.9% to 68.7%. Erectile dysfunction and/or premature ejaculation, evaluated with validated tools, have a prevalence of one in six infertile men, and orgasmic dysfunction has a prevalence of one in ten infertile men. In addition, infertile men can experience a heavy psychological burden. Infertility and its associated psychological concerns can underlie sexual dysfunction. Furthermore, general health perturbations can lead to male infertility and/or sexual dysfunction. Erectile dysfunction and male infertility are considered proxies for general health, the former underlying cardiovascular disorders and the latter cancerous and noncancerous conditions. The concept that erectile dysfunction in infertile men might be an early marker of poor general health is emerging. Finally, medications used for general health problems can cause sperm abnormalities and sexual dysfunction. The treatment of some causes of male infertility might improve semen quality and reverse infertility-related sexual dysfunction. In infertile men, an investigation of sexual, general, and psychological health status is advisable to improve reproductive problems and general health.


Catalytic properties of lipoxygenase extracted from different varieties of Pisum sativum and Lens culinaris.
Lipoxygenase (LOX, E.C. 188.8.131.52), among its various roles, catalyzes the degradation of polyunsaturated fatty acids and it is considered to be one of the main causes of undesirable off-flavor developments in legumes. The role of LOX in postharvest physiology is particularly significant in seeds with high values of lipoxygenase and linoleic acid levels. This research aimed to study the biochemical properties of the LOX extracted from green pea (Pisum sativum L. var. Léda, Zeusz, Zsuzsi), dry pea (Pisum sativum L. var. Hanka, Irina, Lutra), and lentil (Lens culinaris L., var. Pinklevi, Rézi, Castelluccio), using linoleic acid as a substrate. The raw extracts showed different catalytic properties, with dry pea (var. Irina) that expressed the highest LOX activity, while lentil (var. Pinklevi) expressed the lowest activity. To complete the biochemical characterization of the crude LOX extracts, their optimal pH and temperature were also examined. The highest value of lipoxygenase activity in the pH range 6-7 was measured in all legumes. The optimal temperature for all extracts fell within the range of 30-60°C given the nutritional importance of legumes. This study will serve as a basis for further detailed investigation of the legumes LOX activity and its roles in food products related to legumes. PRACTICAL APPLICATIONS: This study investigated the biochemical properties of lipoxygenase (LOX) extracted from different varieties of lentil and pea, the two important leguminous crops serving as the main protein source for the population of humans worldwide. The biochemical properties of LOX extracted from legumes showed large differences in terms of kinetic properties. The results of this study revealed that the use of lipoxygenase can be a suitable index for managing stabilization techniques of lentil and pea, in order to inhibit the lipid oxidation in grain legume without compromising its nutritional value.


Comorbidities, anticoagulants, and geriatric-specific physiology for the field triage of injured older adults.
Comorbid conditions and anticoagulants have been considered as field triage criteria to raise the sensitivity for identifying seriously injured older adults, but research is sparse. We evaluated the utility of comorbidities, anticoagulant use, and geriatric-specific physiologic measures to improve the sensitivity of the field triage guidelines for high-risk older adults in the out-of-hospital setting. This was a cohort study of injured adults 65 years or older transported by 44 emergency medical services agencies to 51 trauma and nontrauma hospitals in seven Oregon and Washington counties from January 1, 2011, to December 31, 2011. Out-of-hospital predictors included current field triage criteria, 13 comorbidities, preinjury anticoagulant use, and previously developed geriatric specific physiologic measures. The primary outcome (high-risk patients) was Injury Severity Score of 16 or greater or need for major nonorthopedic surgical intervention. We used binary recursive partitioning to develop a clinical decision rule with a target sensitivity of 95% or greater. There were 5,021 older adults, of which 320 (6.4%) had Injury Severity Score of 16 or greater or required major nonorthopedic surgery. Of the 2,639 patients with preinjury medication history available, 400 (15.2%) were taking an anticoagulant. Current field triage practices were 36.6% sensitive (95% confidence interval [CI], 31.2%-42.0%) and 90.1% specific (95% CI, 89.2%-91.0%) for high-risk patients. Recursive partitioning identified (in order): any current field triage criteria, Glasgow Coma Scale score of 14 or less, geriatric-specific vital signs, and comorbidity count of 2 or more. Anticoagulant use was not identified as a predictor variable. The new criteria were 90.3% sensitive (95% CI, 86.8%-93.7%) and 17.0% specific (95% CI, 15.8%-18.1%). The current field triage guidelines have poor sensitivity for high-risk older adults. Adding comorbidity information and geriatric-specific physiologic measures improved sensitivity, with a decrement in specificity. Prognostic/Epidemiologic, level II.


Tailoring modulation instabilities and four-wave mixing in dispersion-managed composite liquid-core fibers.
We show that the ultrafast nonlinear dynamics in supercontinuum generation can be tailored via mixture-based liquid core fibers. Samples containing mixtures of inorganic solvents allow changing dispersion from anomalous to normal, i.e., shifting zero dispersion across pump laser wavelength. A significant control over modulation instability and four-wave mixing has been demonstrated experimentally in record-long (up to 60 cm) samples in agreement with simulations when using sub-psec pulses at 1.555 µm. The smallest concentration ratio yields indications of soliton-fission based supercontinuum generation at soliton numbers that are beyond the coherence limit. The presented dispersion tuning scheme allows creating unprecedented dispersion landscapes for accessing unexplored nonlinear phenomena and selected laser sources.


An analysis of selected kinematic variables in national and elite male and female 100-m and 200-m breaststroke swimmers.
The kinematic analysis of competition breaststroke swimming has tended to focus on the mean values of swimming speed, stroke rate and stroke length; values in individual lengths, as well as the start, turns and finish, have largely been ignored. This study includes all such variables and aims to improve the coach's holistic understanding of breaststroke racing by determining the relationships and differences between and within these selected kinematic variables. We also compare 100-m events with 200-m events to determine if there are characteristic differences between them. Competitive breaststroke swimming performances in 100-m events (males: n = 159, finishing time = 65.05 +/- 2.62 s; females: n = 158, finishing time = 74.04 +/- 3.66 s) and 200-m events (males: n = 159, finishing time = 141.47 +/- 6.15 s; females: n = 158, finishing time = 158.66 +/- 7.87 s) were collected and analysed from 12 world, international and national championships. The better 100-m and 200-m breaststroke swimmers were found to demonstrate greater competency in the kinematic variables measured, except stroke kinematics, which were unique to each individual. These findings suggest that coaches should place emphasis on all of the kinematic components in training and that they should attempt to identify the stroke rate to stroke length ratio most appropriate for the individual. Finally, characteristic differences do exist between the 100-m and 200-m events, which has implications for how swimmers might train for each event.


C-phycocyanin protects against low fertility by inhibiting reactive oxygen species in aging mice.
Women over 35 have higher rates of infertility, largely due to deterioration of oocyte quality characterized by fragmentation, abnormal meiotic spindle-chromosome complexes, and oxidative stress. C-phycocyanin (PC) is a biliprotein enriched in Spirulina platensis that is known to possess antioxidant, anti-inflammatory, and radical-scavenging properties. D-galactose-induced aging acceleration in mice has been extensively used to study aging mechanisms and for pharmaceutical screening. In this study, adult female B6D2F/1 mice injected with D-galactose were used as a model to test the age-reversing effects of PC on degenerated reproductive ability. Our results show that PC can prevent oocyte fragmentation and aneuploidy by maintaining cytoskeletal integrity. Moreover, PC can reverse the expression of antioxidant genes, increase superoxide dismutase (SOD) activity and decrease methane dicarboxylic aldehyde (MDA) content, and normalize mitochondria distribution. PC exerts its benefit by inhibiting reactive oxygen species (ROS) production, which decreases apoptosis. Finally, we observe a significant increase in litter size after PC administration to D-galactose-induced aging mice. Our study demonstrates for the first time that D-galactose-induced impaired female reproductive capability can be partially rescued by the antioxidant effects of PC.


Nomenclature for factors of the SLA class-I system, 2004.
A systematic nomenclature for the genes and alleles of the swine major histocompatibility complex (MHC) is essential to the development and communication of research in swine immunology. The Swine Leucocyte Antigen (SLA) Nomenclature Committee of the International Society for Animal Genetics has reviewed all of the DNA sequence information for MHC class-I genes, available in GenBank/EMBL/DDBJ databases, and the associated published reports in order to develop such a systematic nomenclature. This report summarizes the proposed nomenclature, which parallels the World Health Organization's nomenclature for factors of the human MHC. The classical class-I SLA genes are designated as SLA-1, SLA-2 and SLA-3; the non-classical as SLA-6, SLA-7 and SLA-8. Nomenclature assignments for all SLA class-I GenBank sequences are now noted. The Committee will add new SLA class-I allele designations, as they are discovered, and will maintain a publicly available list of all recognized genes and alleles by using the International ImMunoGeneTics Project and its Immuno Polymorphism Database/MHC (IPD/MHC) sequence database for MHC sequences in veterinary species.


Early presence of Homo sapiens in Southeast Asia by 86-68 kyr at Tam Pà Ling, Northern Laos.
The timing of the first arrival of Homo sapiens in East Asia from Africa and the degree to which they interbred with or replaced local archaic populations is controversial. Previous discoveries from Tam Pà Ling cave (Laos) identified H. sapiens in Southeast Asia by at least 46 kyr. We report on a recently discovered frontal bone (TPL 6) and tibial fragment (TPL 7) found in the deepest layers of TPL. Bayesian modeling of luminescence dating of sediments and U-series and combined U-series-ESR dating of mammalian teeth reveals a depositional sequence spanning ~86 kyr. TPL 6 confirms the presence of H. sapiens by 70 ± 3 kyr, and TPL 7 extends this range to 77 ± 9 kyr, supporting an early dispersal of H. sapiens into Southeast Asia. Geometric morphometric analyses of TPL 6 suggest descent from a gracile immigrant population rather than evolution from or admixture with local archaic populations.


Subtalar dislocation of the foot.
We studied a series of seventeen cases of subtalar dislocation of the foot. There were on anterior, twelve medial, and four lateral dislocations. Of the seventeen dislocations, fourteen were closed and three, open. Two of the four lateral dislocations were open. Associated fractures involving the talocalcaneal or talonavicular joints were noted in eight feet, including three of the four with a lateral dislocation. In two feet these fractures were noted only on post-reduction polytomography. Associated fractures of the ankle mortise and of the metatarsals were present in seven feet. Associated fractures involving the subtalar or talonavicular joints, open dislocations, and associated injuries requiring immobilization of the foot for more than three weeks produced poor results due to pain and limitation of subtalar motion. Lateral dislocations were particularly prone to poor results, due to the frequency of open injuries and associated fractures. Cast immobilization for three weeks and early range-of-motion exercises of the subtalar joint are recommended for the best results.


List Equivalency and Critical Differences of a Mandarin Bamford-Kowal-Bench Sentence in Babble Noise Test for Adults and Preschool Children With Normal Hearing.
The purpose of this study was to determine the speech recognition equivalence of Mandarin Bamford-Kowal-Bench (BKB) sentence lists with adults and children with normal hearing. A total of 32 lists, each of nine sentences, were compiled from a corpus of BKB-like sentences with paired babble in Mandarin. Interlist equivalence, critical differences, and sensitivity of performance to signal-to-noise ratio (SNR) were examined. Experiment 1 included 64 native Mandarin-speaking adults with normal hearing. Experiment 2 included 54 native Mandarin-speaking children with normal hearing aged 4-6 years. Among the 32 sentence lists, 28 lists were confirmed to be equivalent in adults, with a mean SNR required for 50% correct (SNR50) of -5.9 ± 0.1 dB, a mean slope of 22.3%/dB ± 1.5%/dB, and a grand 95% critical difference subsequently calculated as 27.2% for score. From the 28 equivalent lists, 27 lists were selected and observed to be equivalent in children, with a mean SNR50 threshold of -2.0 ± 0.2 dB, a mean slope of 15.8%/dB ± 1.1%/dB, and a grand 95% critical difference of 24.6% for score. The Mandarin BKB sentences in babble noise test offers an opportunity for clinicians and researchers to assess speech understanding in adults and preschool children in an efficient manner. For comparisons of performance in different test conditions, 28 equivalent lists are available for adults and 27 equivalent lists for preschool children. The 95% critical difference values can be used for total percentage correct or SNR for 50% performance. Future work will examine the clinical utility for school-age children and children who are deaf and hard of hearing. https://doi.org/10.23641/asha.24400066.


Evidence of Ongoing Cerebral Microstructural Reorganization in Children With Persisting Symptoms Following Mild Traumatic Brain Injury: A NODDI DTI Analysis.
Approximately 300-550 children per 100,000 sustain a mild traumatic brain injury (mTBI) each year, of whom ∼25-30% have long-term cognitive problems. Following mTBI, free water (FW) accumulation occurs in white matter (WM) tracts. Diffusion tensor imaging (DTI) can be used to investigate structural integrity following mTBI. Compared with conventional DTI, neurite orientation dispersion and density imaging (NODDI) orientation dispersion index (ODI) and fraction of isolated free water (FISO) metrics may allow a more advanced insight into microstructural damage following pediatric mTBI. In this longitudinal study, we used NODDI to explore whole-brain and tract-specific differences in ODI and FISO in children with persistent symptoms after mTBI (n = 80) and in children displaying clinical recovery (n = 32) at 1 and 2-3 months post-mTBI compared with healthy controls (HCs) (n = 21). Two-way repeated measures analysis of variance (ANOVA) and voxelwise two-sample t tests were conducted to compare whole-brain and tract-specific diffusion across groups. All results were corrected at positive false discovery rate (pFDR) <0.05. We also examined the association between NODDI metrics and clinical outcomes, using logistical regression to investigate the value of NODDI metrics in predicting future recovery from mTBI. Whole-brain ODI was significantly increased in symptomatic participants compared with HCs at both 1 and 2 months post-injury, where the uncinate fasciculus (UF) and inferior fronto-occipital fasciculus (IFOF) were particularly implicated. Using region of interest (ROI) analysis in significant WM, bilateral IFOF and UF voxels, symptomatic participants had the highest ODI in all ROIs. ODI was lower in asymptomatic participants, and HCs had the lowest ODI in all ROIs. No changes in FISO were found across groups or over time. WM ODI was moderately correlated with a higher youth-reported post-concussion symptom inventory (PCSI) score. With 87% predictive power, ODI (1 month post-injury) and clinical predictors (age, sex, PCSI score, attention scores) were a more sensitive predictor of recovery at 2-3 months post-injury than fractional anisotropy (FA) and clinical predictors, or clinical predictors alone. FISO could not predict recovery at 2-3 months post-injury. Therefore, we found that ODI was significantly increased in symptomatic children following mTBI compared with HCs at 1 month post-injury, and progressively decreased over time alongside clinical recovery. We found no significant differences in FISO between groups or over time. WM ODI at 1 month was a more sensitive predictor of clinical recovery at 2-3 months post-injury than FA, FISO, or clinical measures alone. Our results show evidence of ongoing microstructural reorganization or neuroinflammation between 1 and 2-3 months post-injury, further supporting delayed return to play in children who remain symptomatic. We recommend future research examining the clinical utility of NODDI following mTBI to predict recovery or persistence of post-concussion symptoms and thereby inform management of mTBI.


3-n-butylphthalide inhibits the apoptosis of nerve cells in rats with cerebral small vessel disease via the PI3K/Akt pathway.
The aim of this study was to investigate the effect of 3-n-butylphthalide (NBP) on the apoptosis of nerve cells in vascular dementia (VaD) model rats caused by cerebral small vessel disease (CSVD), and to explore its regulatory mechanism. The model of VaD was successfully established in rats by carotid artery ligation. All rats were randomly divided into three groups, including the sham operation group, model group and NBP group. The neurobehavioral score was used to verify whether the model was successfully established. The changes in learning and memory abilities of rats were detected via water maze experiment. The levels of Bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase-3 (Caspase-3) in the serum of rats was detected by enzyme-linked immunosorbent assay (ELISA). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was adopted to detect the apoptosis of nerve cells in brain tissues of rats. Moreover, the protein levels of phosphorylated phosphatidylinositol-3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in brain tissues of rats were measured using Western blotting. Compared with the sham operation group, the neurobehavioral score of rats increased significantly, whereas learning and memory abilities decreased markedly in the model group. The levels of Bax and Caspase-3 in rat serum were remarkably up-regulated, and the apoptosis rate of nerve cells in brain tissues of rats increased significantly in the model group as well. Meanwhile, the levels of phosphorylated PI3K and phosphorylated Akt were notably declined. Compared with the model group, the neurobehavioral score decreased markedly, while learning and memory abilities were remarkably improved in the NBP group. The levels of Bax and Caspase-3 in rat serum were significantly down-regulated, and the apoptosis rate of nerve cells in brain tissues of rats were reduced in the NBP group. Furthermore, the protein levels of phosphorylated PI3K and phosphorylated Akt were remarkably elevated in the NBP group. NBP can improve the morphology of brain tissue cells and the learning and memory abilities, and inhibit the apoptosis of nerve cells in VaD model rats with CSVD. The possible underlying mechanism may be related to the activation of the PI3K/Akt signaling pathway.


Atlantooccipital instability in Down syndrome.
Atlantooccipital instability is an uncommon and usually lethal result of major trauma. Nontraumatic cases of instability at this site are rare. We report the findings in two children with Down syndrome who have striking atlantooccipital subluxation demonstrated on flexion and extension radiographs. Since there is increasing radiologic evaluation of cervical spine stability in patients with Down syndrome who wish to participate in athletic activities, the status of the atlantooccipital joint needs careful assessment, especially after cervical fusion for C1-C2 instability.


EF2-kinase targeted cobalt-ferrite siRNA-nanotherapy suppresses BRCA1-mutated breast cancer.
Aim: To investigate the role of EF2K in BRCA1-mutated breast cancer. Materials & methods: We developed silica coated cobalt-ferrite (CoFe) nanoparticles for in vivo delivery of small interfering RNAs (siRNAs) into BRCA1-mutated breast cancer. Results: Expression of EF2K is highly upregulated in the majority (78.5%) of BRCA1-mutated patients and significantly associated with poor patient survival and metastasis. Silencing of EF2K reduced cell proliferation, migration and invasion of the cancer cells. In vivo therapeutic targeting of EF2K by CoFe-siRNA-nanoparticles leads to sustained EF2K gene knockdown and suppressed tumor growth in orthotopic xenograft models of BRCA1-mutated breast cancer. Conclusion: EF2K is a potential novel molecular target in BRCA1-mutated tumors and CoFe-based siRNA nanotherapy may be used as a novel approach to target EF2K.


Antibody response of calves after intranasal inoculation with parainfluenza-3 virus and resistance of inoculated calves to experimental homologous viral infection.
The immunologic response of colostrum-deprived calves to parainfluenza-3 (PI-3) virus given by intranasal inoculation was studied. Inoculation of calves with 3.2 x 10(6) median cell culture infective doses (CCID50) of either virulent (SF-4) virus or a modified strain of PI-3 virus, or with 2.0 x 10(8) CCID50 of SF-4 virus, stimulated development of both serum antibody and nasal secretion (NS) antibody. However, NA antibody decreased in all calves between the 16th and 42nd postinoculation days and was present only at low or moderately low concentrations on the 126th day, when the immunity of the calves was challenged. Generally, calves that were inoculated with 3.2 x 10(6) CCID50 of SF-4 virus developed slightly higher concentrations of serum and NS antibodies than did calves inoculated with modified virus. Calves that were inoculated with 2.0 x 10(8) or 3.2 x 10(6) CCID 50 of SF-4 virus developed comparable concentrations of serum antibody, but large doses of SF-4 virus were less effective than smaller doses of the same virus in stimulating the development of NS antibody. Reinoculation of 3 calves with modified PI-3 virus resulted in a demonstrable increase in serum antibody in 2 calves and an increase and subsequent decrease in NS antibody in all calves. Challenge exposure of inoculated calves to aerosols of SF-4 virus failed to cause clinical signs of disease, and the challenge virus was not isolated from the nasal passages.


Far-red BODIPY-based oxime esters: photo-uncaging and drug delivery.
Far-red BODIPY-based oxime esters for photo-uncaging were designed to release molecules of interest with carboxylic acids. The low power red LED light breaks the N-O oxime ester bond and frees the caged molecules. We studied the mechanism and kinetics of the uncaging procedure using a 1H NMR spectrometer. Moreover, the drug delivery strategy to release valproic acid (VPA) on demand was tested in vitro using this far-red BODIPY photo-uncaging strategy to induce apoptosis in tumor cells.


Stroke risk in women with atrial fibrillation.
Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF. Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care. The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years. Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.


Near-infrared spectroscopic measurement of urea in dialysate samples collected during hemodialysis treatments.
Single-beam spectra were collected over the combination region of the near-infrared spectrum for 80 samples collected from 15 people over a two-week period. Partial least-squares (PLS) regression was used to generate an optimized calibration model for urea. PLS calibration models accurately measure urea in the spent dialysate matrix. Prediction errors are on the order of 0.15 mM, which is sufficient for the clinical assessment of the dialysis process. In addition, the feasibility of a global calibration model is demonstrated by generating a calibration model from samples and spectra obtained from 12 people to predict the level of urea in samples collected from 3 different people. In this case, the standard error of prediction is 0.09 mM. Spectra were modified in order to systematically examine the impact of resolution and noise. Little impact is observed by altering the spectral resolution from 4 to 32 cm-1. Spectral noise, however, plays an important role in the accuracy of these calibration models. Increasing the magnitude of the spectral noise increases the prediction errors and increases the width of the spectral range necessary for extracting the analytical information. The utility of the method is demonstrated by analyzing dialysate samples collected during actual dialysis treatments. In addition, the necessary resolution and spectral quality necessary for reliable on-line urea monitoring is identified. These findings indicate that a dedicated, on-line urea spectrometer must posses a resolution of 16 cm-1 coupled with a sample thickness of 1.5 mm and spectral noise levels on the order of 25 micro-absorbance units when measured as the root-mean-square (RMS) noise of 100% lines.


Risk of rupture of small anterior communicating artery aneurysms is similar to posterior circulation aneurysms.
According to the International Study of Unruptured Intracranial Aneurysms (ISUIA), anterior circulation (AC) aneurysms of <7 mm in diameter have a minimal risk of rupture. It is general experience, however, that anterior communicating artery (AcoA) aneurysms are frequent and mostly rupture at <7 mm. The aim of the study was to assess whether AcoA aneurysms behave differently from other AC aneurysms. Information about 932 patients newly diagnosed with intracranial aneurysms between November 1, 2006, and March 31, 2012, including aneurysm status at diagnosis, its location, size, and risk factors, was collected during the multicenter @neurIST project. For each location or location and size subgroup, the odds ratio (OR) of aneurysms being ruptured at diagnosis was calculated. The OR for aneurysms to be discovered ruptured was significantly higher for AcoA (OR, 3.5 [95% confidence interval, 2.6-4.5]) and posterior circulation (OR, 2.6 [95% confidence interval, 2.1-3.3]) than for AC excluding AcoA (OR, 0.5 [95% confidence interval, 0.4-0.6]). Although a threshold of 7 mm has been suggested by ISUIA as a threshold for aggressive treatment, AcoA aneurysms <7 mm were more frequently found ruptured (OR, 2.0 [95% confidence interval, 1.3-3.0]) than AC aneurysms of 7 to 12 mm diameter as defined in ISUIA. We found that AC aneurysms are not a homogenous group. Aneurysms between 4 and 7 mm located in AcoA or distal anterior cerebral artery present similar rupture odds to posterior circulation aneurysms. Intervention should be recommended for this high-risk lesion group.


Patients Awaiting Heart Transplantation on HVAD Support for Greater Than 2 Years.
Advanced heart failure patients who are classified as bridge to transplant (BTT) often remain on mechanical circulatory support (MCS) for long durations because of the limited supply of donor organs. Here, we present the outcomes of patients who have been supported by the HeartWare ventricular assist device system for more than 2 years. In the HeartWare BTT and continued access protocol trial, 74 of the 382 total patients (19.4%) had more than 2 years of MCS with a mean time of 1,045 days on device. The long-term group was more frequently female, was nonwhite, and had Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7. Postimplant adverse event rates including bleeding, cardiac arrhythmia, infection, stroke, renal dysfunction, and right heart failure were less frequent in the long-term cohort. In addition, the long-term cohort displayed significant improvements in Kansas City Cardiomyopathy Questionnaire Overall Summary Score, EuroQOL-5D Overall Health State Score, and 6 minute walk scores from baseline values. The rate of heart transplantation was lower for the long-term cohort, which may have been a result of their sex and blood type. However, most of these patients are still listed for cardiac transplantation and maintained their quality of life profiles through 3 years of support.


[Benefits, costs and analysis in diagnostic radiology: definitions and glossary].
Cost efficiency analyses in clinical radiology require the application of methods and techniques that are not yet part of the academic qualifications of the specialists. The procedures used are borrowed from economics, decision theory, applied social sciences, epidemiology and statistics. Many expressions hail from the angloamerican literature and are presently not yet germanized unequivocally. This survey is intended to present main terms of cost efficiency analysis in the english version as well as a german translation, to give a clear definition and, if necessary, explanatory notes, and to illustrate their application by means of concrete radiologic examples. The selection of the terms is based on the hierarchical models of health technology assessment resp. clinical outcome research by Fryback & Thornbury resp. Maisey & Hutton. In concrete terms, both the differences between benefit, outcomes, and utility and the differences between effectiveness, efficacy and efficiency and the differences between direct, indirect, intangible, and marginal costs are explained. True cost efficiency analysis is compared with cost effectiveness analysis, cost identification analysis, cost minimization analysis, and cost utility analysis. Applied social sciences are represented by the Medical Outcomes Study Short Form-36 and the QALY conception. From decision theory both the analysis of hypothetical alternatives and the Markov model are taken. Finally, sensitivity analysis and the procedures of combined statistical evaluation of comparable results (meta-analysis) are quoted.


Receptive fields, geometry and conduction block of sensory neurones in the central nervous system of the leech.
1. In segmental ganglia of the leech, the cutaneous mechanosensory neurones responding to to touch innervated the skin of their own segment and of part of the anterior and posterior adjacent segments. Each touch receptive field could be divided into three non-overlapping areas: a central part innervated by the branches of the cell which ran in the nerve roots of the ganglion containing the cell body, and anterior and posterior parts innervated by its branches which ran in the nerve roots of the anterior and posterior adjacent ganglia. 2. Impulses originating from the anterior and posterior parts of the receptive fields were susceptible to conduction block within the central nervous system when the touch cells fired repetitively at frequencies that could readily be elicited with weak mechanical stimulation. In contrast, impulses originating from the central part of the receptive fields were less susceptible to block. 3. The morphology of touch cells revealed by intracellular injection of horseradish peroxidase suggested that conduction block occurred at specific bifurcation points where small cell processes joined the main process. Different physiological experiments supported this conclusion. 4. In some touch cells, bifurcation points with particularly low safety margins of conduction operated as low-pass filters, limiting the frequency of impulses capable of invading certain branches. 5. The results suggest that mechanical stimuli which would likely be encountered by the animal can lead to conduction block within its central nervous system and as a result modify its integrative activities.


SURFEIT-1 gene analysis and two-dimensional blue native gel electrophoresis in cytochrome c oxidase deficiency.
Leigh syndrome, a progressive, often fatal, neurodegenerative disorder, is frequently associated with a deficiency in the activity of cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain. In contrast to NADH:ubiquinone oxidoreductase and succinate dehydrogenase deficiencies, no mutations in nuclear genes encoding COX subunits have been identified thus far. Very recently, however, a Leigh syndrome complementation group has been identified which showed mutations in the SURFEIT-1 (SURF-1) gene. The results of a mutational detection study in 16 new randomly selected COX-deficient patients revealed a new mutation (C688T) in 2 patients and the earlier reported 845delCT mutation in 2 additional patients. In addition, we evaluated the diagnostic value of two-dimensional blue native gel electrophoresis. We show that this technique reveals distinct patterns of both fully and partially assembled COX complexes and is thereby capable of discrimination between COX-deficient SURF-1 and non-SURF-1-mutated patients.


Dealing with the clandestine nature of wildlife-trade market surveys.
Illegal international trade in wildlife (excluding fisheries and timber) has been valued at more than US$20 billion. A more precise figure has not been determined in part because of the clandestine nature of the trade, and for this same reason even regional and local levels of wildlife trade are difficult to assess. The application of recent developments in wildlife field-survey methods (e.g., occupancy) now allows for a more-accurate estimation of wildlife trade occurrence, including its hidden components at a variety of scales (e.g., regional, local) and periods (e.g., single season, 1 year, multiple years). Occupancy models have been applied in wildlife field studies to address the problem of false absences when conducting presence-absence surveys. Occupancy surveys differ from traditional presence-absence surveys because they incorporate repeat surveys, allowing for the likelihood of detecting a species (the probability of detection) to be estimated explicitly (in contrast to traditional surveys that often incorrectly treat this probability as close to one to allow for estimation of presence). Occupancy methods can be applied to a variety of wildlife-trade surveys, including, for example, single-species availability, links between two illegally traded species (i.e., co-occurrence), and disease occurrence in live trade. In addition, free user-friendly software (i.e., PRESENCE) allows even nonstatisticians to adequately address this issue. I simulated a hypothetical wildlife-trade market survey that resulted in an apparent 20% decline in naïve occupancy (proportion of surveyed towns engaged in the trade) over 2 years, but when I accounted for change in probability of detection over the years the difference in occupancy was not statistically significant. As more sophisticated methods, such as occupancy, are applied to wildlife-trade market surveys, results will be more robust and defensible and therefore, theoretically, more powerful when presented to conservation policy and decision makers.


SAMHD1 prevents autoimmunity by maintaining genome stability.
The HIV restriction factor, SAMHD1 (SAM domain and HD domain-containing protein 1), is a triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs). Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), an inflammatory disorder that shares phenotypic similarity with systemic lupus erythematosus, including activation of antiviral type 1 interferon (IFN). To further define the pathomechanisms underlying autoimmunity in AGS due to SAMHD1 mutations, we investigated the physiological properties of SAMHD1. Primary patient fibroblasts were examined for dNTP levels, proliferation, senescence, cell cycle progression and DNA damage. Genome-wide transcriptional profiles were generated by RNA sequencing. Interaction of SAMHD1 with cyclin A was assessed by coimmunoprecipitation and fluorescence cross-correlation spectroscopy. Cell cycle-dependent phosphorylation of SAMHD1 was examined in synchronised HeLa cells and using recombinant SAMHD1. SAMHD1 was knocked down by RNA interference. We show that increased dNTP pools due to SAMHD1 deficiency cause genome instability in fibroblasts of patients with AGS. Constitutive DNA damage signalling is associated with cell cycle delay, cellular senescence, and upregulation of IFN-stimulated genes. SAMHD1 is phosphorylated by cyclin A/cyclin-dependent kinase 1 in a cell cycle-dependent manner, and its level fluctuates during the cell cycle, with the lowest levels observed in G1/S phase. Knockdown of SAMHD1 by RNA interference recapitulates activation of DNA damage signalling and type 1 IFN activation. SAMHD1 is required for genome integrity by maintaining balanced dNTP pools. dNTP imbalances due to SAMHD1 deficiency cause DNA damage, leading to intrinsic activation of IFN signalling. These findings establish a novel link between DNA damage signalling and innate immune activation in the pathogenesis of autoimmunity.


The effect of complete or specific partial acetimidylation on the biological properties of cytochrome c and cytochrome c-T.
The biological consequences of acetimidylation of all 19 epsilon-amino groups of horse cytochrome c are a slight decrease in both the redox potential of the protein and its ability to stimulate oxygen uptake in the cytochrome c-depleted-mitochondria assay. Examination of a number of specific partially acetimidylated analogues and acetimidylated cytochromes c of other species has shown that the changes in biological properties, which are associated with a slight structural change as monitored by n.m.r. spectroscopy [Boswell, Moore, Williams, Harris, Wallace, Bocieck & Welti (1983) Biochem. J. 213, 679-686], appear to stem from modification of residues in a restricted region of the sequence. The failure of the redox potential of Saccharomyces cerevisae cytochrome c to be affected by acetimidylation suggests that it is lysine-53, absent from that species, that is the sensitive residue.


Docking of the Femoral Head Following Closed Reduction for DDH: Does it Really Occur?
It has been suggested that the femoral head can "dock" deeper into the acetabulum after initial closed reduction (CR) for developmental dysplasia of the hip (DDH). The purpose of this study was to quantify the interval change in femoral head position between immediate postoperative magnetic resonance imaging (MRI) and follow-up imaging at ~3 weeks. A retrospective review of 29 patients (30 hips) who underwent CR and spica casting for DDH was conducted. Immediate postoperative and average 3-week follow-up MRI scans in spica were performed on all patients. On both scans, 2 blinded reviewers measured the following indices: the distance between the femoral head and the acetabulum on midcoronal and midaxial images, the displacement of the center of femoral head from Hilgenreiner's line in the coronal and axial plane, and the left-right displacement of the center of femoral head from Perkins line. Measurements were averaged between the 2 reviewers and the interval change in femoral head position between the immediate postoperative and follow-up scans were compared. There were 26 female individuals and 3 male individuals in our series with a mean age of 7.6 months (range, 4 to 13 mo). Follow-up MRI scans were performed at an average of 23.8 days (range, 13 to 46 d). On the basis of the averaged measurements from both readers, the distance between the femoral head and the acetabulum decreased significantly on coronal measurement and on all 3 axial measurements between initial and follow-up MRI. In addition, the position of the femoral head became significantly more medial, more anterior, and more cranial relative to the acetabulum. The interrater correlation coefficient between both readers across all measurements was 0.731. These findings provide evidence that femoral head position within the acetabulum improves even over a short time period following initial CR for DDH, suggesting that the "docking" phenomenon may in fact occur. Level IV-therapeutic study.


A comparison of immediate serial recall and immediate serial recognition.
In an immediate serial recall task, participants are presented with a list of items that they must subsequently report back in the original presentation order. Although immediate serial recall has long been taken as the standard short-term and working memory task, a growing body of literature has instead made use of immediate serial recognition. In immediate serial recognition, a list of items is presented and subsequently represented, either in the exact same order or with two adjacent items swapped. Participants must decide whether the order of the list items was the same or different across the two presentations. Whereas serial recall and serial recognition are often treated as comparable tasks, with a few differences that make one or the other more suitable for a given experiment, the relationship between them has not been carefully examined. In this article, we report a series of experiments that directly compare the effects of various manipulations using the two tasks. In Experiments 1 and 2 we show an effect of word frequency in serial recall but not serial recognition. In Experiments 3 and 4 we show an effect of semantic relatedness in serial recall but not serial recognition. Experiments 5 and 6 demonstrate that the two tests are similarly affected by word concreteness and acoustic similarity, respectively. We consider the theoretical and methodological implications of these findings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Sequence determinants of the energetics of folding of a transmembrane four-helix-bundle protein.
Although previous studies are beginning to point to the specific types of helix-helix interactions that stabilize the folds of membrane-bound helical proteins, quantitative thermodynamic data on natural membrane proteins has been very limited. Here the database is expanded substantially by adding thermodynamic data for a series of sequence variants of M2 protein from influenza A virus. The M2 protein has a single transmembrane helix that homotetramerizes to form proton-selective channels that are essential to virus function. To determine the contributions of specific residues to the folding of this protein, a series of transmembrane peptides with single-site changes near the core of the protein were studied by using sedimentation equilibrium analytical ultracentrifugation. Remarkably, a large number of the mutations increased the stability of the protein. The free energies of tetramerization of the variants can be understood in terms of current models for the structure of the protein. In general, the energetic consequences of the mutations are smaller than those observed for similar mutations in water-soluble proteins. This observation is consistent with previous studies and hence may represent a general phenomenon.


The effect of imaging modality (magnetic resonance imaging vs. computed tomography) and patient position (supine vs. prone) on target and organ at risk doses in partial breast irradiation.
Conventionally computed tomography (CT) has been used to delineate target volumes in radiotherapy; however, magnetic resonance imaging (MRI) is being continually integrated into clinical practice; therefore, the investigation into targets derived from MRI is warranted. The purpose of this study was to evaluate the impact of imaging modality (MRI vs. CT) and patient positioning (supine vs. prone) on planning target volumes (PTVs) and organs at risk (OARs) for partial breast irradiation (PBI). A retrospective data set, of 35 patients, was accessed where each patient had undergone MRI and CT imaging for tangential whole breast radiotherapy in both the supine and prone position. PTVs were defined from seroma cavity (SC) volumes delineated on each respective image, resulting in 4 PTVs per patient. PBI plans were generated with 6MV external beam radiotherapy (EBRT) using the TROG 06.02 protocol guidelines. A prescription of 38.5Gy in 10 fractions was used for all cases. The impact analysis of imaging modality and patient positioning included dose to PTVs, and OARs based on agreed criteria. Statistical analysis was conducted though Mann-Whitey U, Fisher's exact and chi-squared testing (P < 0.005). Twenty-four patients were eligible for imaging analysis. However, positioning analysis could only be investigated on 19 of these data sets. No statistically significant difference was found in OAR doses based on imaging modality. Supine patient position resulted in lower contralateral breast dose (0.10Gy ± 0.35 vs. 0.33Gy ± 0.78, p = 0.011). Prone positioning resulted in a lower dose to ipsilateral lung volumes (10.85Gy ± 11.37 vs. 3.41Gy ± 3.93, P = <0.001). PBI plans with PTVs derived from MRI exhibited no clinically significant differences when compared to plans created from CT in relation to plan compliance and OAR dose. Patient position requires careful consideration regardless of imaging modality chosen. Although there was no proven superiority of MRI derived target volumes, it indicates that MRI could be considered for PBI target delineation.


The mammalian cone visual cycle promotes rapid M/L-cone pigment regeneration independently of the interphotoreceptor retinoid-binding protein.
Rapid regeneration of the visual pigment following its photoactivation is critical for the function of cone photoreceptors throughout the day. Though the reactions of the visual cycle in the retinal pigment epithelium (RPE) that recycle chromophore for rod pigment regeneration are well characterized, the corresponding mechanisms that enable rapid regeneration of cone pigment are poorly understood. A key remaining question is the relative contribution of the recently discovered cone-specific retina visual cycle and the classic RPE-dependent visual cycle to mammalian cone pigment regeneration. In addition, it is not clear what role, if any, the abundant interphotoreceptor retinoid-binding protein (IRBP) presumed to facilitate the traffic of chromophore, plays in accelerating mammalian cone pigment regeneration. To address these issues, we used transretinal recordings to evaluate M/L-cone pigment regeneration in isolated retinas and eyecups from control and IRBP-deficient mice. Remarkably, the mouse retina promoted M/L-cone dark adaptation eightfold faster than the RPE. However, complete cone recovery required both visual cycles. We conclude that the retina visual cycle is critical for the initial rapid regeneration of mouse M/L-cone pigment during dark adaptation, whereas the slower RPE visual cycle is required to complete the process. While the deletion of IRBP reduced the amplitude and slowed the kinetics of mouse M/L-cone photoresponses, cone adaptation in bright, steady light and the kinetics of cone dark adaptation were not affected in isolated retina or in intact eyecup. Thus, IRBP does not accelerate cone pigment regeneration and is not critical for the function of mouse M/L-cones in bright light.


Procedural, workforce, and reimbursement trends in neuroendovascular procedures.
This study aims to define the proportion of Medicare neuroendovascular procedures performed by different specialists from 2013 to 2019, map the geographic distribution of these specialists, and trend reimbursement for these procedures. The Medicare Provider Utilization Database was queried for recognized neuroendovascular procedures. Data on specialists and their geographic distribution were tabulated. Reimbursement data were gathered using the Physician Fee Schedule Look-Up Tool and adjusted for inflation using the United States Bureau of Labor Statistics' Consumer Price Index Inflation calculator. The neuroendovascular workforce in 2013 and 2019, respectively, was as follows: radiologists (46% vs 44%), neurosurgeons (45% vs 35%), and neurologists (9% vs 21%). Neurologists increased proportionally (p=0.03). Overall procedure numbers increased across each specialty: radiology (360%; p=0.02), neurosurgery (270%; p<0.01), and neurology (1070%; p=0.03). Neuroendovascular revascularization (CPT 61645) increased in all fields: radiology (170%; p<0.01), neurosurgery (280%; p<0.01), neurology (240%; p<0.01); central nervous system (CNS) permanent occlusion/embolization (CPT61624) in neurosurgery (67%; p=0.03); endovascular temporary balloon artery occlusion (CPT61623) in neurology (29%; p=0.04). In 2019, radiologists were the most common neuroendovascular specialists everywhere except in the Northeast where neurosurgeons predominated. Inflation adjusted reimbursement decreased for endovascular temporary balloon occlusion (CPT61623, -13%; p=0.01), CNS transcatheter permanent occlusion or embolization (CPT61624, -13%; p=0.02), non-CNS transcatheter permanent occlusion or embolization (CPT61626, -12%; p<0.01), and intracranial stent placement (CPT61635, -12%; p=0.05). The number of neuroendovascular procedures and specialists increased, with neurologists becoming more predominant. Reimbursement decreased. Coordination among neuroendovascular specialists in terms of training and practice location may maximize access to acute care.


Hydrocarbons in hydrothermal vent fluids: the role of chromium-bearing catalysts.
Fischer-Tropsch type (FTT) synthesis has long been proposed to account for the existence of hydrocarbons in hydrothermal fluids. We show that iron- and chromium-bearing minerals catalyze the abiotic formation of hydrocarbons. In addition to production of methane (CH4aq), we report abiotic generation of ethane (C2H6aq) and propane (C3H8aq) by mineral-catalyzed hydrothermal reactions at 390 degrees C and 400 bars. Results suggest that the chromium component in ultramafic rocks could be an important factor for FTT synthesis during water-rock interaction in mid-ocean ridge hydrothermal systems. This in turn could help to support microbial communities now recognized in the subsurface at deep-sea vents.


Optical imaging of tumor microenvironment.
Tumor microenvironment plays important roles in tumor development and metastasis. Features of the tumor microenvironment that are significantly different from normal tissues include acidity, hypoxia, overexpressed proteases and so on. Therefore, these features can serve as not only biomarkers for tumor diagnosis but also theraputic targets for tumor treatment. Imaging modalities such as optical, positron emission tomography (PET) and magnetic resonance imaging (MRI) have been intensively applied to investigate tumor microenvironment. Various imaging probes targeting pH, hypoxia and proteases in tumor microenvironment were thus well developed. In this review, we will focus on recent examples on fluorescent probes for optical imaging of tumor microenvironment. Construction of these fluorescent probes were based on characteristic feature of pH, hypoxia and proteases in tumor microenvironment. Strategies for development of these fluorescent probes and applications of these probes in optical imaging of tumor cells or tissues will be discussed in this review paper.


Implementation of quality assurance in national foot and mouth disease laboratories, based on the guidelines of the Office International des Epizooties.
The final act of the Uruguay Round of the General Agreement on Tariffs and Trade, 1994, contains the Agreement on the Application of Sanitary and Phytosanitary Measures, which aims to reduce the negative effects of health barriers on international trade to a minimum. Therefore, the Office International des Epizooties (OIE) Regional Commission for Europe proposed that an accreditation system based on the EN 45000 standard should be applied to achieve international recognition of certificates and testing laboratories. To this end, the OIE Standards Commission published a series of guidelines for the evaluation of laboratory quality and proficiency testing. In 1995, the Food and Agriculture Organization European Commission for the Control of Foot and Mouth Disease recommended that the OIE proposal should be applied in all foot and mouth disease (FMD) diagnostic laboratories in Europe. This review summarises the EN 45001 standard and the OIE guidelines, and proposes that these guidelines should be taken as a basis for the implementation of a quality assurance programme in FMD laboratories.


Standards of care for hypoparathyroidism in adults: a Canadian and International Consensus.
To provide practice recommendations for the diagnosis and management of hypoparathyroidism in adults. Key questions pertaining to the diagnosis and management of hypoparathyroidism were addressed following a literature review. We searched PubMed, MEDLINE, EMBASE and Cochrane databases from January 2000 to March 2018 using keywords 'hypoparathyroidism, diagnosis, treatment, calcium, PTH, calcidiol, calcitriol, hydrochlorothiazide and pregnancy'. Only English language papers involving humans were included. We excluded letters, reviews and editorials. The quality of evidence was evaluated based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. These standards of care for hypoparathyroidism have been endorsed by the Canadian Society of Endocrinology and Metabolism. Hypoparathyroidism is a rare disease characterized by hypocalcemia, hyperphosphatemia and a low or inappropriately normal serum parathyroid hormone level (PTH). The majority of cases are post-surgical (75%) with nonsurgical causes accounting for the remaining 25% of cases. A careful review is required to determine the etiology of the hypoparathyroidism in individuals with nonsurgical disease. Hypoparathyroidism is associated with significant morbidity and poor quality of life. Treatment requires close monitoring as well as patient education. Conventional therapy with calcium supplements and active vitamin D analogs is effective in improving serum calcium as well as in controlling the symptoms of hypocalcemia. PTH replacement is of value in lowering the doses of calcium and active vitamin D analogs required and may be of value in lowering long-term complications of hypoparathyroidism. This manuscript addresses acute and chronic management of hypoparathyroidism in adults. Hypoparathyroidism requires careful evaluation and pharmacologic intervention in order to improve serum calcium and control the symptoms of hypocalcemia. Frequent laboratory monitoring of the biochemical profile and patient education is essential to achieving optimal control of serum calcium.


Presence of psychiatric morbidity and regrets about participation in trauma-related research-a pilot study.
Little is known about the characteristics of individuals who regret their participation in trauma-related research. The aim of this pilot study was to evaluate (1) regret after participating in a longitudinal study after a burn and (2) associations with psychiatric morbidity prior to the burn. Participants were recruited from a longitudinal study after a burn involving interviews, questionnaires, and psychological testing. Forty-two participants answered questions about regret and positive/negative consequences of participation. Thirty-eight participants reported no regret, while 3 reported the lowest level of regret (1 on a scale of 0-4). All 3 patients with slight regret had psychiatric morbidity prior to the burn. Among the 38 patients without regrets, 23 had prior psychiatric morbidity. Two individuals reported negative consequences of participation, both indicating that the study had elicited negative emotions. Regret and perceived negative consequences were infrequent. The results suggest that a longitudinal trauma-related research protocol is well tolerated by most patients with burns, despite the presence of prior psychiatric morbidity.


Distribution and diversity of sulfur-oxidizing Thiomicrospira spp. at a shallow-water hydrothermal vent in the Aegean Sea (Milos, Greece).
A shallow-water hydrothermal vent system in the Aegean Sea close to the island of Milos (Greece) was chosen to study the diversity and distribution of the chemolithoautotrophic sulfur-oxidizing bacterium Thiomicrospira. Cell numbers in samples from different regions around a solitary vent decreased toward the center of the vent (horizontal distribution), as well as with depth (vertical distribution), corresponding to an increase in temperature (from ca. 25 to 60 degrees C) and a decrease in pH (from ca. pH 7 to 5). Thiomicrospira was one of the most abundant culturable sulfur oxidizers and was even dominant in one region. Phylogenetic analysis of Thiomicrospira spp. present in the highest most-probable-number (MPN) dilutions revealed that most of the obtained sequences grouped in two new closely related clusters within the Thiomicrospira branch. Two different new isolates, i.e., Milos-T1 and Milos-T2, were obtained from high-dilution (10(-5)) enrichments. Phylogenetic analysis indicated that isolate Milos-T1 is related to the recently described Thiomicrospira kuenenii and Hydrogenovibrio marinus, whereas isolate Milos-T2 grouped with the MPN sequences of cluster 2. The predominance of strain Milos-T2 was indicated by its identification in several environmental samples by hybridization analysis of denaturing gradient gel electrophoresis (DGGE) patterns and by sequencing of one of the corresponding bands, i.e., ML-1, from the DGGE gel. The results shown in this paper support earlier indications that Thiomicrospira species are important members of hydrothermal vent communities.


Critical Review of Data Analytics Techniques used in the Expanded Program on Immunization (EPI).
Immunization is a significant public health intervention to reduce child mortality and morbidity. However, its coverage, in spite of free accessibility, is still very low in developing countries. One of the primary reasons for this low coverage is the lack of analysis and proper utilization of immunization data at various healthcare facilities. In this paper, the existing machine learning-based data analytics techniques have been reviewed critically to highlight the gaps where this high potential data could be exploited in a meaningful manner. It has been revealed from our review that the existing approaches use data analytics techniques without considering the complete complexity of Expanded Program on Immunization which includes the maintenance of cold chain systems, proper distribution of vaccine and quality of data captured at various healthcare facilities. Moreover, in developing countries, there is no centralized data repository where all data related to immunization is being gathered to perform analytics at various levels of granularities. We believe that the existing non-centralized immunization data with the right set of machine learning and Artificial Intelligence-based techniques will not only improve the vaccination coverage but will also help in predicting the future trends and patterns of its coverage in different geographical locations.


Orangutans show active voicing through a membranophone.
Active voicing - voluntary control over vocal fold oscillation - is essential for speech. Nonhuman great apes can learn new consonant- and vowel-like calls, but active voicing by our closest relatives has historically been the hardest evidence to concede to. To resolve this controversy, a diagnostic test for active voicing is reached here through the use of a membranophone: a musical instrument where a player's voice flares a membrane's vibration through oscillating air pressure. We gave the opportunity to use a membranophone to six orangutans (with no effective training), three of whom produced a priori novel (species-atypical) individual-specific vocalizations. After 11 and 34 min, two subjects were successful by producing their novel vocalizations into the instrument, hence, confirming active voicing. Beyond expectation, however, within <1 hour, both subjects found opposite strategies to significantly alter their voice duration and frequency to better activate the membranophone, further demonstrating plastic voice control as a result of experience with the instrument. Results highlight how individual differences in vocal proficiency between great apes may affect performance in experimental tests. Failing to adjust a test's difficulty level to individuals' vocal skill may lead to false negatives, which may have largely been the case in past studies now used as "textbook fact" for great ape "missing" vocal capacities. Results qualitatively differ from small changes that can be caused in innate monkey calls by intensive months-long conditional training. Our findings verify that active voicing beyond the typical range of the species' repertoire, which in our species underpins the acquisition of new voiced speech sounds, is not uniquely human among great apes.


Astrocytic Ephrin-B1 Controls Synapse Formation in the Hippocampus During Learning and Memory.
Astrocytes play a fundamental role in synapse formation, pruning, and plasticity, which are associated with learning and memory. However, the role of astrocytes in learning and memory is still largely unknown. Our previous study showed that astrocyte-specific ephrin-B1 knock-out (KO) enhanced but ephrin-B1 overexpression (OE) in hippocampal astrocytes impaired contextual memory recall following fear conditioning. The goal of this study was to understand the mechanism by which astrocytic ephrin-B1 influences learning; specifically, learning-induced remodeling of synapses and dendritic spines in CA1 hippocampus using fear-conditioning paradigm. While we found a higher dendritic spine density and clustering on c-Fos-positive (+) neurons activated during contextual memory recall in both wild-type (WT) and KO mice, overall spine density and mEPSC amplitude were increased in CA1 neurons of KO compared to WT. In contrast, ephrin-B1 OE in hippocampal astrocytes impaired dendritic spine formation and clustering, specifically on c-Fos(+) neurons, coinciding with an overall decrease in vGlut1/PSD95 co-localization. Although astrocytic ephrin-B1 influenced learning-induced spine formation, the changes in astrocytic ephrin-B1 levels did not affect spine enlargement as no genotype differences in spine volume were observed between trained WT, KO, and OE groups. Our results suggest that a reduced formation of new spines rather than spine maturation in activated CA1 hippocampal neurons is most likely responsible for impaired contextual learning in OE mice due to abundantly high ephrin-B1 levels in astrocytes. The ability of astrocytic ephrin-B1 to negatively influence new spine formation during learning can potentially regulate new synapse formation at specific dendritic domains and underlie memory encoding.


Comparative analysis of methane-oxidizing archaea and sulfate-reducing bacteria in anoxic marine sediments.
The oxidation of methane in anoxic marine sediments is thought to be mediated by a consortium of methane-consuming archaea and sulfate-reducing bacteria. In this study, we compared results of rRNA gene (rDNA) surveys and lipid analyses of archaea and bacteria associated with methane seep sediments from several different sites on the Californian continental margin. Two distinct archaeal lineages (ANME-1 and ANME-2), peripherally related to the order Methanosarcinales, were consistently associated with methane seep marine sediments. The same sediments contained abundant (13)C-depleted archaeal lipids, indicating that one or both of these archaeal groups are members of anaerobic methane-oxidizing consortia. (13)C-depleted lipids and the signature 16S rDNAs for these archaeal groups were absent in nearby control sediments. Concurrent surveys of bacterial rDNAs revealed a predominance of delta-proteobacteria, in particular, close relatives of Desulfosarcina variabilis. Biomarker analyses of the same sediments showed bacterial fatty acids with strong (13)C depletion that are likely products of these sulfate-reducing bacteria. Consistent with these observations, whole-cell fluorescent in situ hybridization revealed aggregations of ANME-2 archaea and sulfate-reducing Desulfosarcina and Desulfococcus species. Additionally, the presence of abundant (13)C-depleted ether lipids, presumed to be of bacterial origin but unrelated to ether lipids of members of the order Desulfosarcinales, suggests the participation of additional bacterial groups in the methane-oxidizing process. Although the Desulfosarcinales and ANME-2 consortia appear to participate in the anaerobic oxidation of methane in marine sediments, our data suggest that other bacteria and archaea are also involved in methane oxidation in these environments.


Comparison of the effect of 1-day and 2-day low residue diets on the quality of bowel preparation before colonoscopy.
Low residue diet (LRD) has a similar quality of bowel preparation with clear liquid diet before colonoscopy, but improved patient tolerance. However, the optimal LRD duration is still controversial. In this study, we have compared the effect of a 1-day LRD and 2-day LRD on the quality of bowel preparation and patient tolerance. Our prospective, randomized, single-blind trial, single-blind, trial compared two dietary regimens administered the day before colonoscopy. All patients were administered PEG-ES and simethicone for bowel preparation. The primary outcome measure was bowel preparation quality. The secondary outcome measures were insertion time, withdrawal time, polyp detection rate, patient tolerance, and willingness to use the same diet for bowel preparation again. Bowel preparation quality was evaluated using the Boston bowel preparation scale (BBPS). Patient tolerance was evaluated using a hunger-comfort scale. There was no significant difference in bowel preparation quality between the 2 groups. The 1-day LRD group had a BBPS score of 6.48 ± 1.59 points, while the 2-day LRD group had a score of 6.42 ± 1.06 points (P > 0.05). The groups reported similar colonoscope insertion times, withdrawal times, polyp detection rates and patient tolerance scores (hunger-comfort scores). The numbers of patients who reported that compliance as easy or very easy were 126 (78.2%) in the 1-day group versus 88 (55.0%) in the 2 day group (P < 0.05) and the numbers who were willing to use the diet again in the future were 154 (95.7%) in the 1-day group versus 131 (81.9%) in the 2 day group (P < 0.05). LRD duration (1 day or 2 days) had no significant effect on bowel preparation quality. Patients in the 1-day LRD group had higher tolerance and satisfaction levels than patients in the 2-day LRD group. However, overall satisfaction was higher with the 1-day LRD group than with the 2-day LRD group.


Multiple comparisons for survival data with propensity score adjustment.
This article considers the practical problem in clinical and observational studies where multiple treatment or prognostic groups are compared and the observed survival data are subject to right censoring. Two possible formulations of multiple comparisons are suggested. Multiple Comparisons with a Control (MCC) compare every other group to a control group with respect to survival outcomes, for determining which groups are associated with lower risk than the control. Multiple Comparisons with the Best (MCB) compare each group to the truly minimum risk group and identify the groups that are either with the minimum risk or the practically minimum risk. To make a causal statement, potential confounding effects need to be adjusted in the comparisons. Propensity score based adjustment is popular in causal inference and can effectively reduce the confounding bias. Based on a propensity-score-stratified Cox proportional hazards model, the approaches of MCC test and MCB simultaneous confidence intervals for general linear models with normal error outcome are extended to survival outcome. This paper specifies the assumptions for causal inference on survival outcomes within a potential outcome framework, develops testing procedures for multiple comparisons and provides simultaneous confidence intervals. The proposed methods are applied to two real data sets from cancer studies for illustration, and a simulation study is also presented.


Proteus mirabilis flagella and MR/P fimbriae: isolation, purification, N-terminal analysis, and serum antibody response following experimental urinary tract infection.
Urinary tract infection with Proteus mirabilis may lead to serious complications, including cystitis, acute pyelonephritis, fever, bacteremia, and death. In addition to the production of hemolysin and the enzyme urease, fimbriae and flagellum-mediated motility have been postulated as virulence factors for this species. We purified mannose-resistant/proteuslike (MR/P) fimbriae and flagella from strains CFT322 and HU2450, respectively. Electron microscopy revealed highly concentrated preparations of fimbriae and flagella. Fimbrial and flagellar structural subunits were estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 18.5 and 41 kDa, respectively. N-terminal sequencing revealed that 10 of the first 20 amino acids of the major MR/P subunit matched the sequence of the P. mirabilis uroepithelial cell adhesin N terminus and 11 of 20 amino acids matched the predicted amino acid sequence of the Escherichia coli P fimbriae structural subunit, PapA. In addition, 90 and 80% homologies were found between the first 20 amino acids of P. mirabilis flagellin and those of Salmonella typhimurium phase-1 flagellin and the E. coli hag gene product, respectively. An enzyme-linked immunosorbent assay using purified antigens showed a strong reaction between the MR/P fimbriae or flagella and sera of CBA mice challenged transurethrally with P. mirabilis. A possible role for MR/P fimbriae in the pathogenesis of urinary tract infection is supported by (i) a strong immune response to the antigen in experimentally infected animals, (ii) amino acid sequence similarity to other enteric surface structure, and (iii) our previously reported observation that MR/P fimbriae are expressed preferentially as the sole fimbrial type in human pyelonephritis isolates.


A new system for the measurement of displacements of the human body with widespread applications in human movement studies.
This paper reports the development, construction and use of a new system for the measurement of linear kinematics in one, two or three dimensions. The system uses a series of rotary shaft encoders and inelastic tensioned strings to measure the linear displacement of key anatomical points in space. The system is simple, inexpensive, portable, accurate and flexible. It is therefore suitable for inclusion in a variety of motion analysis studies. Details of the construction, calibration and interfacing of the device to an IBM PC computer are given as is a full mathematical description of the appropriate measurement theory for one, two and three dimensions. Examples of the results obtained from the device during gait, running, rising to stand, sitting down and pointing with the upper limb are given. Finally it is proposed that, provided the constraints of the system are considered, this method has the potential to measure a variety of functional human movements simply and inexpensively and may therefore be a valuable addition to the methods available to the motion scientist.


Photonic-integrated circuit for continuous-wave THz generation.
We demonstrate a photonic-integrated circuit for continuous-wave (cw) terahertz (THz) generation. By comprising two lasers and an optical phase modulator on a single chip, the full control of the THz signal is enabled via a unique bidirectional operation technique. Integrated heaters allow for continuous tuning of the THz frequency over 570 GHz. Applied to a coherent cw THz photomixing system operated at 1.5 μm optical wavelength, we reach a signal-to-noise ratio of 44 dB at 1.25 THz, which is identical to the performance of a standard system based on discrete components.


18F-FDG PET/CT image of pericardial inflammatory myofibroblastic tumor.
Pericardial inflammatory myofibroblastic tumor (IMT) is very rare. Herein, we report fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings of pericardial IMT in a 57-year-old woman. On conventional image, it presented as a pericardial mass with heterogeneous delay enhancement. On 18F-FDG PET/CT image, this lesion had mild 18F-FDG uptake with a maximum standardized uptake value (SUVmax) of 1.84. The postoperative pathology supported a diagnosis of IMT. Our case hints us that IMT should be regarded as a differential diagnosis when we meet a solitary pericardial mass with 18F-FDG uptake.


Outcome-based providing and commissioning: pathways and standards.
Aims and methodImplementation of evidence-based psychosocial interventions in accordance with National Institute of Health and Care Excellence guidelines and quality standards has been incomplete. This project involved allocation of adults under mental health services to six guideline categories, completion of a clinician- and patient-rated outcome measure, and individual assessment against clinical standards. RESULTS: In the first 3 months of the project, 5048 patients were allocated to a pathway and 3734 (73%) were assessed against at least one of the relevant standards. All were assessed using the Health of the Nation Outcome Scales (91-93% of scales completed) and 1866 (36%) completed the patient-rated outcome measure, DIALOG.Clinical implicationsClinicians will allocate patients to pathways, complete outcome measures and assess against standards, providing data to guide practice, service design and costing of mental health systems with supporting technology to assist data entry and presentation. This has the potential to provide much improved and readily accessible information about individual outcomes and standards for people with mental health problems and those working with them. It could also provide a method for payment for services which directly support good clinical practice.Declaration of interestNone.


The association between dietary patterns derived by reduced rank regression and depressive symptoms over time: the Invecchiare in Chianti (InCHIANTI) study.
This study aimed to identify dietary patterns using reduced rank regression (RRR) and to explore their associations with depressive symptoms over 9 years in the Invecchiare in Chianti study. At baseline, 1362 participants (55·4 % women) aged 18-102 years (mean age 68 (sd 15·5) years) were included in the study. Baseline data collection started in 1998 and was repeated after 3, 6 and 9 years. Dietary intake information was obtained using a country-specific, validated FFQ with 188 food items. For baseline diet, dietary pattern scores in quartiles (Q) were derived using RRR with the nutrients EPA+DHA, folate, Mg and Zn as response variables. Continuous depression scores from the Centre for Epidemiologic Studies Depression (CES-D) scale were used for assessing depressive symptoms. The derived dietary pattern was rich in vegetables, olive oil, grains, fruit, fish and moderate in wine and red and processed meat, and was labelled as 'typical Tuscan dietary pattern'. After full adjustment, an inverse association was observed between this dietary pattern and depressive symptoms at baseline (Q1 v. Q4, B -2·77; 95 % CI -4·55, -0·98). When examining the relationship between the above-mentioned dietary pattern at baseline and depressive symptoms over 9 years, a similar association was found after full adjustment for confounding factors (Q1 v. Q4, B -1·78; 95 % CI -3·17, -0·38). A diet rich in vegetables, olive oil, grains, fruits, fish and moderate in wine and red and processed meat was consistently associated with lower CES-D scores over a 9-year period in the Tuscan population.


Effect of the growth hormone-secreting tumor StW5 on pituitary and adrenal gland function in rats.
A growth hormone-secreting tumor (StW5 was implanted into male rats and resulted in a tripling of adrenal weight concomitant with a 30% decrement in pituitary weight. Plasma concentrations of corticosterone in tumor-bearing (TB) rats were significantly elevated at rest or after ACTH injections or the stress of either anesthesia. The rise in plasma concentrations of corticosterone was due mainly to the large increment in adrenal size although a significant increase in adrenal responsiveness to ACTH was demonstrated in vitro. In addition, plasma corticosterone concentrations were higher in TB rats despite both a doubling of the blood volume and a 50% increase in liver capacity to metabolize corticosterone. Pituitary ACTH content was significantly lower in TB rats, but these pituitary glands could still release near-normal quantities of ACTH as shown both by in vitro incubations and adrenal corticosterone output following ether stress.


To pass or to fail? Understanding the factors considered by faculty in the clinical evaluation of nursing students.
Making the decision to pass or to fail a nursing student is difficult for nurse educators, yet one that all educators face at some point in time. To make this decision, nurse educators draw from their past experiences and personal reflections on the situation. Using the qualitative method of critical incident technique, the authors asked educators to describe a time when they had to make a decision about whether to pass or fail a student in the clinical setting. The findings describe student and faculty factors important in clinical evaluation decisions, demonstrate the benefits of reflective practice to nurse educators, and support the utility of critical incident technique not only as research methodology, but also as a technique for reflective practice.


Reduction of area and influence of the deposit layer in the first stage of a full-scale French system of vertical flow constructed wetlands in a tropical area.
Utilization of the French system of vertical wetlands for treating raw sewage keeps increasing, but there is still limited consolidated information on their long term use in tropical countries. Under these conditions, there are indications that surface area requirements can decrease, whilst still keeping a satisfactory performance. However, variations in the operational mode and the role of the surface organic deposit layer under warm climatic conditions have not been fully investigated. The goal of this work was to evaluate the performance of a system comprised of only the first stage of the French system, with a further reduction of 1/3 of the area (utilization of only two units in parallel, instead of three) in terms of organic matter removal and nitrogen conversion, with one unit with a deposit layer accumulated over 9 years of operation, and the other unit without sludge layer, under Brazilian tropical conditions. The system was originally designed according to Cemagref/Irstea recommendations for the first-stage of the French system for the treatment of raw sewage generated by an equivalent population of 100 inhabitants. However, it was later on changed, and operated with only two units, using only 0.6 m2·pe-1. Feeding and resting periods were of 7 days each. In order to evaluate the influence of the sludge layer, the top sludge from one of the units was removed, and the performance of both units was compared by the Mann-Whitney test. The database comprises the wetland performance values in terms of dissolved oxygen (DO), redox potential (Eh), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total suspended solids (TSS), total Kjeldahl nitrogen (TKN), NH4 +-N and NO3 +-N, covering a monitoring period of 15 months. The effluent DO concentrations were significantly lower in the unit with top sludge, but still sufficiently high in both units. Although there were some variations between both units, effluent concentrations of the major pollutants were not significantly different in the units with and without sludge, and removal efficiencies based on mean values were considered good, given the reduced area of the system: BOD (80% and 79%), TSS (85% and 82%), TKN (60% and 63%) for the units with and without sludge, respectively. Under Brazilian climatic conditions, with the reduced area and employing longer feeding cycles (7 days), the sludge accumulation rate (less than 1 cm·year-1) was lower compared to the French mean values.


ME3183, a novel phosphodiesterase-4 inhibitor, exhibits potent anti-inflammatory effects and is well tolerated in a non-clinical study.
Phosphodiesterase 4 (PDE4) inhibitors are expected to exhibit efficacy against inflammatory diseases due to their broad pharmacological activity. The launched PDE4 inhibitors apremilast, crisaborole, and roflumilast have not exhibited sufficient inhibitory potential due to poor margins of effectiveness and tolerability. In this report, we describe the non-clinical efficacy, brain translocation, and vomit-inducing effects of ME3183 compared with apremilast. ME3183 showed extensive cytokine suppression in vitro studies using human peripheral blood mononuclear cells and T cells. ME3183 also significantly suppressed skin inflammation in a chronic oxazolone-induced dermatitis model and showed antipruritic effects in a substance P-induced mouse pruritus model. In these in vitro and in vivo studies, ME3183 also significantly suppressed cytokines, and focusing on tumor necrosis factor-α as a psoriasis-related cytokine and interleukin-4 as an atopic dermatitis-related cytokine, ME3183 potently inhibited both cytokines. ME3183 showed in vivo efficacy at lower doses than apremilast. The brain distribution of ME3183 was sufficiently low in mice and rats. The effective dose of ME3183 for emesis was similar to that of apremilast in ferrets. Given its high-potency inhibitory effects, ME3183 would have a wide margin of efficacy and tolerability. These wide margins demonstrate the effectiveness of ME3183 in treating many inflammatory diseases, such as psoriasis and atopic dermatitis. An on-going phase 2 trial is expected to further demonstrate the efficacy and safety of ME3183.


Hepatic malignant mesenchymoma in a dog.
Hepatic malignant mesenchymoma was diagnosed in a dog with a history of gradual abdominal distension of 2 months' duration. The tumor was polycystic and attached to the caudal border of the left lateral liver lobe. The dog was euthanatized 16 weeks after surgical excision. Necropsy revealed tumor metastasis throughout the liver.


RNA∶DNA hybrids initiate quasi-palindrome-associated mutations in highly transcribed yeast DNA.
RNase H enzymes promote genetic stability by degrading aberrant RNA:DNA hybrids and by removing ribonucleotide monophosphates (rNMPs) that are present in duplex DNA. Here, we report that loss of RNase H2 in yeast is associated with mutations that extend identity between the arms of imperfect inverted repeats (quasi-palindromes or QPs), a mutation type generally attributed to a template switch during DNA synthesis. QP events were detected using frameshift-reversion assays and were only observed under conditions of high transcription. In striking contrast to transcription-associated short deletions that also are detected by these assays, QP events do not require Top1 activity. QP mutation rates are strongly affected by the direction of DNA replication and, in contrast to their elevation in the absence of RNase H2, are reduced when RNase H1 is additionally eliminated. Finally, transcription-associated QP events are limited by components of the nucleotide excision repair pathway and are promoted by translesion synthesis DNA polymerases. We suggest that QP mutations reflect either a transcription-associated perturbation of Okazaki-fragment processing, or the use of a nascent transcript to resume replication following a transcription-replication conflict.


Foreign body granulomatosis. Clinical and immunologic findings.
We studied the clinical and immunologic features of 10 patients with foreign body granulomatosis associated with injection of pentazocine. Five had typical micronodules on chest radiographs, 9 had abnormal 67Ga lung images, and 9 had elevated serum angiotensin-converting enzyme levels. Pulmonary function tests showed significant decreases in diffusing capacity in 8 subjects, but were otherwise normal. Bronchoalveolar lavage fluid had significantly (p less than 0.02) increased total cell numbers (13.8 +/- 7.5 x 10(7) and significantly lower percentages of lymphocytes (2 +/- 1) and neutrophils (2 +/- 1) (p less than 0.02) when compared with that from control subjects. Peripheral blood lymphocytes were normal when expressed as percentages of total leukocytes or as percent T-lymphocytes. Monoclonal antibody determinations of T-lymphocyte subsets (helper and suppressor) were similar to those in control subjects (p = NS). Lymphocyte transformation responses to a variety of antigens and skin test reactivity were normal. Foreign body granulomatosis contrasts with other interstitial lung diseases in its bronchoalveolar lavage cellular profile and in the absence of altered peripheral immunologic indexes.


Characterization of addressability by simultaneous randomized benchmarking.
The control and handling of errors arising from cross talk and unwanted interactions in multiqubit systems is an important issue in quantum information processing architectures. We introduce a benchmarking protocol that provides information about the amount of addressability present in the system and implement it on coupled superconducting qubits. The protocol consists of randomized benchmarking experiments run both individually and simultaneously on pairs of qubits. A relevant figure of merit for the addressability is then related to the differences in the measured average gate fidelities in the two experiments. We present results from two similar samples with differing cross talk and unwanted qubit-qubit interactions. The results agree with predictions based on simple models of the classical cross talk and Stark shifts.


An ANNEXIN-like protein from the cereal cyst nematode Heterodera avenae suppresses plant defense.
Parasitism genes encoding secreted effector proteins of plant-parasitic nematodes play important roles in facilitating parasitism. An annexin-like gene was isolated from the cereal cyst nematode Heterodera avenae (termed Ha-annexin) and had high similarity to annexin 2, which encodes a secreted protein of Globodera pallida. Ha-annexin encodes a predicted 326 amino acid protein containing four conserved annexin domains. Southern blotting revealed that there are at least two homologies in the H. avenae genome. Ha-annexin transcripts were expressed within the subventral gland cells of the pre-parasitic second-stage juveniles by in situ hybridization. Additionally, expression of these transcripts were relatively higher in the parasitic second-stage juveniles by quantitative real-time RT-PCR analysis, coinciding with the time when feeding cell formation is initiated. Knockdown of Ha-annexin by method of barley stripe mosaic virus-based host-induced gene silencing (BSMV-HIGS) caused impaired nematode infections at 7 dpi and reduced females at 40 dpi, indicating important roles of the gene in parasitism at least in early stage in vivo. Transiently expression of Ha-ANNEXIN in onion epidermal cells and Nicotiana benthamiana leaf cells showed the whole cell-localization. Using transient expression assays in N. benthamiana, we found that Ha-ANNEXIN could suppress programmed cell death triggered by the pro-apoptotic mouse protein BAX and the induction of marker genes of PAMP-triggered immunity (PTI) in N. benthamiana. In addition, Ha-ANNEXIN targeted a point in the mitogen-activated protein kinase (MAPK) signaling pathway downstream of two kinases MKK1 and NPK1 in N. benthamiana.