High HIV incidence in the postpartum period sustains vertical transmission in settings with generalized epidemics: a cohort study in Southern Mozambique.
Acute infection with HIV in the postpartum period results in a high risk of vertical transmission through breastfeeding. A study was done to determine the HIV incidence rate and associated risk factors among postpartum women in Southern Mozambique, where HIV prevalence among pregnant women is 21%. A prospective cohort study was conducted in six rural health facilities in Gaza and Maputo provinces from March 2008 to July 2011. A total of 1221 women who were HIV-negative on testing at delivery or within two months postpartum were recruited and followed until 18 months postpartum. HIV testing, collection of dried blood spot samples and administration of a structured questionnaire to women were performed every three months. Infant testing by DNA-PCR was done as soon as possible after identification of a new infection in women. HIV incidence was estimated, and potential risk factors at baseline were compared using Poisson regression. Data from 957 women were analyzed with follow-up after the enrolment visit, with a median follow-up of 18.2 months. The HIV incidence in postpartum women is estimated at 3.20/100 women-years (95% CI: 2.30-4.46), with the highest rate among 18- to 19-year-olds (4.92 per 100 women-years; 95% CI: 2.65-9.15). Of the new infections, 14 (34%) were identified during the first six months postpartum, 11 (27%) between 6 and 12 months and 16 (39%) between 12 and 18 months postpartum. Risk factors for incident HIV infection include young age, low number of children, higher education level of the woman's partner and having had sex with someone other than one's partner. The vertical transmission was 21% (95% CI: 5-36) among newly infected women. Incidence of HIV is high among breastfeeding women in Southern Mozambique, contributing to increasing numbers of HIV-infected infants. Comprehensive primary prevention strategies targeting women of reproductive age, particularly pregnant and postpartum women and their partners, will be crucial for the elimination of paediatric AIDS in Africa.


Evolutionary origins of ultrasonic hearing and laryngeal echolocation in bats inferred from morphological analyses of the inner ear.
Many mammals have evolved highly adapted hearing associated with ecological specialisation. Of these, bats possess the widest frequency range of vocalisations and associated hearing sensitivities, with frequencies of above 200 kHz in some lineages that use laryngeal echolocation. High frequency hearing in bats appears to have evolved via structural modifications of the inner ear, however, studying these minute features presents considerable challenges and hitherto few such attempts have been made. To understand these adaptations more fully, as well as gain insights into the evolutionary origins of ultrasonic hearing and echolocation in bats, we undertook micro-computed tomography (μCT) scans of the cochleae of representative bat species from 16 families, encompassing their broad range of ecological diversity. To characterise cochlear gross morphology, we measured the relative basilar membrane length and number of turns, and compared these values between echolocating and non-echolocating bats, as well as other mammals. We found that hearing and echolocation call frequencies in bats correlated with both measures of cochlear morphology. In particular, relative basilar membrane length was typically longer in echolocating species, and also correlated positively with the number of cochlear turns. Ancestral reconstructions of these parameters suggested that the common ancestor of all extant bats was probably capable of ultrasonic hearing; however, we also found evidence of a significant decrease in the rate of morphological evolution of the basilar membrane in multiple ancestral branches within the Yangochiroptera suborder. Within the echolocating Yinpterochiroptera, there was some evidence of an increase in the rate of basilar membrane evolution in some tips of the tree, possibly associated with reported shifts in call frequency associated with recent speciation events. The two main groups of echolocating bat were found to display highly variable inner ear morphologies. Ancestral reconstructions and rate shift analyses of ear morphology point to a complex evolutionary history, with the former supporting ultrasonic hearing in the common bat ancestor but the latter suggesting that morphological changes associated with echolocation might have occurred later. These findings are consistent with theories that sophisticated laryngeal echolocation, as seen in modern lineages, evolved following the divergence of the two main suborders.


The effect of perioperative blood transfusion on survival after renal cell carcinoma nephrectomy: A systematic review and meta-analysis.
The effect of perioperative blood transfusion (PBT) on postoperative survival in RCC patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) remains controversial. Two meta-analyses in 2018 and 2019 reported the postoperative mortality of PBT patients with RCC, but they did not investigate the effect on the survival of patients. We performed a systematic review and meta-analysis of relevant literature to demonstrate whether PBT affected postoperative survival in RCC patients who received nephrectomy. Pubmed, Web of Science, Cochrane, and Embase databases were searched. Studies comparing RCC patients with or without PBT following either RN or PN were included in this analysis. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included literature, and hazard ratios (HRs) of overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS), as well as 95% confidence intervals, were considered as effect sizes. All data were processed using Stata 15.1. Ten retrospective studies involving 19,240 patients were included in this analysis, with the publication dates ranging from 2014 to 2022. Evidence revealed that PBT was significantly associated with the decline of OS (HR, 2.62; 95%CI: 1,98-3.46), RFS (HR, 2.55; 95%CI: 1.74-3.75), and CSS (HR, 3.15; 95%CI: 2.3-4.31) values. There was high heterogeneity among the study results due to the retrospective nature and the low quality of the included studies. Subgroup analysis findings suggested that the heterogeneity of this study might be caused by different tumor stages in the included articles. Evidence implied that PBT had no significant influence on RFS and CSS with or without robotic assistance, but it was still linked to worse OS (combined HR; 2.54 95% CI: 1.18, 5.47). Furthermore, the subgroup analysis with intraoperative blood loss lower than 800 ML revealed that PBT had no substantial impact on OS and CSS of postoperative RCC patients, whereas it was correlated with poor RFS (1.42, 95% CI: 1.02-1.97). RCC patients undergoing PBT after nephrectomy had poorer survival. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363106.


Pyrimidine salvage in Giardia lamblia.
We have found that the anaerobic protozoan parasite Giardia lamblia is incapable of de novo pyrimidine metabolism, as shown by its inability to incorporate orotate, bicarbonate, and aspartate into the pyrimidine nucleotide pool. Results from high performance liquid chromatography of pyrimidine and pyrimidine nucleoside pulse-labeled nucleotide pools and enzyme assays suggest that the parasite satisfies its pyrimidine nucleotide needs predominantly through salvage of uracil by a cytoplasmic uracil phosphoribosyltransferase. Exogenous uridine and cytidine are primarily converted to uracil by the action of uridine hydrolase and cytidine deaminase before incorporation into nucleotide pools. Direct salvage of cytosine occurs to a relatively limited extent via cytosine phosphoribosyltransferase. G. lamblia relies on salvage of exogenous thymidine for ribosylthymine monophosphate (TMP) synthesis, accomplished primarily through the action of a 100,000 g-pelletable thymidine phosphotransferase.


Automated assessment of bradykinesia and dyskinesia in Parkinson's disease.
There is a need for objective measures of dyskinesia and bradykinesia of Parkinson's disease (PD) that are continuous throughout the day and related to levodopa dosing. The output of an algorithm that calculates dyskinesia and bradykinesia scores every two minutes over 10 days (PKG: Global Kinetics Corporation) was compared with conventional rating scales for PD in PD subjects. The algorithm recognises bradykinesia as movements made with lower acceleration and amplitude and with longer intervals between movement. Similarly the algorithm recognises dyskinesia as having movements of normal amplitude and acceleration but with shorter periods without movement. The distribution of the bradykinesia and dyskinesia scores from PD subjects differed from that of normal subjects. The algorithm predicted the clinical dyskinesia rating scale AIMS with a 95% margin of error of 3.2 units compared with the inter-rater 95% limits of agreement from 3 neurologists of -3.4 to +4.3 units. Similarly the algorithm predicted the UPDRS III score with a margin of error similar to the inter-rater limits of agreement. Improvement in scores in response to changes in medication could be assessed statistically in individual patients. This algorithm provides objective, continuous and automated assessment of the clinical features of bradykinesia and dyskinesia in PD.


Reducing the impact of summer cattle grazing on water quality in the Sierra Nevada Mountains of California: a proposal.
The Sierra Nevada Mountain range serves as an important source of drinking water for the State of California. However, summer cattle grazing on federal lands affects the overall water quality yield from this essential watershed as cattle manure is washed into the lakes and streams or directly deposited into these bodies of water. This organic pollution introduces harmful microorganisms and also provides nutrients such as nitrogen and phosphorus which increase algae growth causing eutrophication of otherwise naturally oligotrophic mountain lakes and streams. Disinfection and filtration of this water by municipal water districts after it flows downstream will become increasingly costly. This will be compounded by increasing surface water temperatures and the potential for toxins release by cyanobacteria blooms. With increasing demands for clean water for a state population approaching 40 million, steps need to be implemented to mitigate the impact of cattle on the Sierra Nevada watershed. Compared to lower elevations, high elevation grazing has the greatest impact on the watershed because of fragile unforgiving ecosystems. The societal costs from non-point pollution exceed the benefit achieved through grazing of relatively few cattle at the higher elevations. We propose limiting summer cattle grazing on public lands to lower elevations, with a final goal of allowing summer grazing on public lands only below 1,500 m elevation in the Central and Northern Sierra and 2,000 m elevation in the Southern Sierra.


Distance from the chromosome end determines the efficiency of double strand break repair in subtelomeres of haploid yeast.
Double strand break (DSB) repair plays an important role in chromosome evolution. We have investigated the fate of DSBs as a function of their location along the yeast chromosome XI, in a system where no conventional homologous recombination can occur. We report that the relative frequency of non-homologous endjoining (NHEJ), which is the exclusive mode of DSB repair in the internal chromosomal portion, decreases gradually towards the telomere, keeping the absolute frequency nearly constant, and that other repair mechanisms, which generally involve the loss of the distal chromosomal fragment, appear in subtelomeric regions. Distance of the DSB from chromosome ends plays a critical role in the global frequency of these repair mechanisms. Direct telomere additions are rare, and other events such as break-induced replication, plasmid incorporation, and gene conversion, involve acquisition of heterologous sequences. Therefore, in subtelomeric regions, cell survival to DSBs is higher and alternative modes of repair allow new genomic combinations to be generated. Furthermore, subtelomeric rearrangements depend on the recombination process, which, unexpectedly, also promotes the joining of heterologous sequences. Finally, we report that the Rad52 protein increases the efficiency of NHEJ.


Towards unconventional computing through simulated evolution: control of nonlinear media by a learning classifier system.
We propose that the behavior of nonlinear media can be controlled automatically through evolutionary learning. By extension, forms of unconventional computing (viz., massively parallel nonlinear computers) can be realized by such an approach. In this initial study a light-sensitive subexcitable Belousov-Zhabotinsky reaction in which a checkerboard image, composed of cells of varying light intensity projected onto the surface of a thin silica gel impregnated with a catalyst and indicator, is controlled using a learning classifier system. Pulses of wave fragments are injected into the checkerboard grid, resulting in rich spatiotemporal behavior, and a learning classifier system is shown to be able to direct the fragments to an arbitrary position through dynamic control of the light intensity within each cell in both simulated and real chemical systems. Similarly, a learning classifier system is shown to be able to control the electrical stimulation of cultured neuronal networks so that they display elementary learning. Results indicate that the learned stimulation protocols identify seemingly fundamental properties of in vitro neuronal networks. Use of another learning scheme presented in the literature confirms that such fundamental behavioral characteristics of a given network must be considered in training experiments.


A cross-cultural comparison of sleep duration between US And Australian adolescents: the effect of school start time, parent-set bedtimes, and extracurricular load.
To test whether sleep duration on school nights differs between adolescents in Australia and the United States and, if so, whether this difference is explained by cultural differences in school start time, parental involvement in setting bedtimes, and extracurricular commitments. Three hundred eighty-five adolescents aged 13 to 18 years (M = 15.57, SD = 0.95; 60% male) from Australia and 302 adolescents aged 13 to 19 years (M = 16.03, SD = 1.19; 35% male) from the United States. Adolescents completed the School Sleep Habits Survey during class time, followed by an 8-day sleep diary. After controlling for age and gender, Australian adolescents obtained an average of 47 minutes more sleep per school night than those in the United States. Australian adolescents were more likely to have a parent-set bedtime (17.5% vs. 6.8%), have a later school start time (8:32 a.m. vs. 7:45 a.m.), and spend less time per day on extracurricular commitments (1 h 37 min vs. 2 h 41 min) than their U.S. peers. The mediating factors of parent-set bedtimes, later school start times, and less time spent on extracurricular activities were significantly associated with more total sleep. In addition to biological factors, extrinsic cultural factors significantly affect adolescent sleep. The present study highlights the importance of a cross-cultural, ecological approach and the impact of early school start times, lack of parental limit setting around bedtimes, and extracurricular load in limiting adolescent sleep.


Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers.
To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States. Cross sectional analysis. Academic medical centers in the United States. Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov. Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on ClinicalTrials.gov with a primary completion date between October 2007 and September 2010 and with a lead investigator affiliated with an academic medical center. The proportion of trials that disseminated results, defined as publication or reporting of results on ClinicalTrials.gov, overall and within 24 months of study completion. We identified 4347 interventional clinical trials across 51 academic medical centers. Among the trials, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double blind, and 2169 (50%) were phase II through IV. Overall, academic medical centers disseminated results for 2892 (66%) trials, with 1560 (35.9%) achieving this within 24 months of study completion. The proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16.2% (6/37) to 55.3% (57/103) across academic medical centers. The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic medical centers, whereas results reporting on ClinicalTrials.gov ranged from 1.6% (2/122) to 40.7% (72/177). Despite the ethical mandate and expressed values and mission of academic institutions, there is poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centers.


Features of effective primary health care models in rural and remote Australia: a case-study analysis.
To describe the factors and processes that facilitate or inhibit implementation, sustainability and generalisation of effective models of primary health care (PHC) service delivery in rural and remote Australia. Case-study approach, including review of relevant literature, interviews with key informants, site visits and direct observation. Thematic analysis and template analysis were used with interview transcripts. An expert reference group provided feedback and advice on policy relevance. Six PHC services in small communities across rural and remote Australia were selected based on results of a previous systematic review; they reflected diverse rural and remote settings and PHC models, and the multidisciplinary nature of PHC. Sites were visited, and 55 individuals associated with the establishment and operation of these services were interviewed between July 2006 and December 2007. Independent and template analysis confirmed the usefulness of a conceptual framework, which identified three key "environmental enablers" - supportive policy; federal and state/territory relations; and community readiness - and five essential service requirements - governance, management and leadership; funding; linkages; infrastructure; and workforce supply. Systematically addressing each of these factors improves effectiveness and lessens the threat to service sustainability. Evidence from existing effective rural and remote PHC services can inform the health care reform agenda, in Australia and other countries. The evidence highlights the need for improved governance, management and community involvement, as well as strong, visionary political leadership to achieve a more responsive and better coordinated health system which could help eliminate existing health status differentials between cities and rural areas. In Australia, establishment of a single national health system, operationalised at a regional level, would obviate much of the current inefficiency and poor coordination.


Characterization of the adhesive holdfast of marine and freshwater caulobacters.
Caulobacters are prosthecate (stalked) bacteria that elaborate an attachment organelle called a holdfast at the tip of the cellular stalk. We examined the binding of lectins to the holdfasts of 16 marine Caulobacter strains and 10 freshwater species or strains by using a panel of fluorescein-conjugated lectins and fluorescence microscopy. The holdfasts of all the marine isolates bound to only wheat germ agglutinin (WGA) and other lectins that bind N-acetylglucosamine (GlcNac) residues. The freshwater caulobacters showed more variability in holdfast composition. Some bound only to WGA and comparable lectins as the marine strains did. Others bound additional or other lectins, and some did not bind to the lectins tested. The binding of WGA appeared to involve the regions of the holdfast involved with adhesion; a holdfast bound to WGA was significantly less adhesive to glass. Competition experiments with WGA-binding holdfasts and oligomers of GlcNac demonstrated that trimers of GlcNac (the preferred substrate for WGA binding) were more effective than dimers or monomers in preventing WGA binding to holdfasts, suggesting that stretches of contiguous GlcNac residues occur in the WGA-binding holdfasts. In addition, differences between freshwater and marine holdfasts in the strength of WGA binding were noted. The effect of a number of proteolytic and glycolytic enzymes on holdfast integrity was examined; the proteases had no effect for all caulobacters. None of the glycolytic enzymes had an effect on marine caulobacter holdfasts, but chitinase and lysozyme (both attack oligomers of GlcNac) disrupted the holdfasts of those freshwater caulobacters that bound WGA. Despite some similarity to chitin, holdfasts did not bind Calcofluor and no measurable effects on holdfast production were detectable after cell growth in the presence of diflubenzuron or polyoxin D, inhibitors of chitin synthesis in other systems. Finally, the holdfasts of all caulobacters bound to colloidal gold particles, without regard to the coating used to stabilize the gold particles. This binding was stronger or more specific than WGA binding; treatment with colloidal gold particles prevented WGA binding, but the reverse was not the case.


Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat.
Curcumin, the principal curcuminoid of turmeric, exhibits beneficial role in several neurodegenerative disorders such as dementia of Alzheimer type. Recent evidences suggest the involvement of brain insulin receptors (IRs) in the pathophysiology of dementia disorders. Therefore, the present study was undertaken to investigate the effect of curcumin on memory functions, brain IRs, acetylcholinesterase (AChE) activity and oxidative stress in intracerebroventricular (ICV) administered streptozotocin (STZ) induced dementia in rats. Rats were injected with STZ (3 mg/kg, ICV) bilaterally twice, on day 1 and 3 and curcumin (200 mg/kg, po) was administered in pre- and post-treatment schedules. STZ (ICV) treated group had shown memory deficit as indicated by no significant decrease in latency time in Morris water maze test and significant decrease in IR protein level in both hippocampus and cerebral cortex. Pre- and post-treatment of curcumin in STZ (ICV) treated rats significantly restored the memory deficit and IR protein level in both the regions. Furthermore, STZ (ICV) resulted into enhanced AChE activity in hippocampus and cerebral cortex which was normalized by curcumin pre- and post-treatment. An increase in MDA level and decrease in GSH level were obtained in both hippocampus and cerebral cortex in STZ treated group, indicating state of oxidative stress, which was also attenuated by pre- and post-treatment of curcumin. The results suggest that besides the anticholinesterase and antioxidant activity, effect on brain IR may also be an important factor for protective effect of curcumin against STZ induced dementia model.


Role of purine N-3 in the biologic activities of poly(A) and poly(I).
Poly(c3A) (poly 3-deazaadenylic acid) and poly(c3I) (poly 3-deazainosinic acid) differ in biological reactivity from their parent compounds poly(A) and poly(I) and from their 7-deaza counterparts poly(c7A) and poly(c7I). Three parameters of biological reactivity were evaluated : (1 degree) interferon induction, (2 degrees) anti-complement activity, (3 degrees) reverse transcriptase inhibition. Unlike poly(A)-poly(U), poly(I)-poly(C) and poly(I)-poly(br5C), the mixtures of poly(c3A) + POLY(U), poly(c3I) + poly(C), and poly(c3I) + poly(br5C) failed to elicit an interferon response in "super-induced" primary rabbit kidney cells; Poly(I) and its analogs poly(c3I) and poly(c7I) inhibited hemolytic complement activity, whereas poly(A) and its analogs poly(c3A) and poly(c7A) failed to do so. Both poly(I) and poly(c7I), but not poly(c3I), lost their anti-complement potency when annealed to either poly(C) or poly(A)-poly(U). Similarly, poly(I) and poly(c7I), but not poly(c3I), suppressed the interferon inducing ability of poly(A)-poly(U), suggesting that both poly(I) and poly(c7I), but not poly(c3I), added to poly(A)-poly(U) to form a triple-helical structure. Poly(I), poly(C7I) and poly(c7A)exerted a distinct inhibitory effect on turine leukemia virus, while under the same conditions poly(c3I) and poly(c3A) showed little, if any, inhibitory effect.


Effect of Cholesterol on Membrane Fluidity and Association of Aβ Oligomers and Subsequent Neuronal Damage: A Double-Edged Sword.
Background: The beta-amyloid peptide (Aβ) involved in Alzheimer's disease (AD) has been described to associate/aggregate on the cell surface disrupting the membrane through pore formation and breakage. However, molecular determinants involved for this interaction (e.g., some physicochemical properties of the cell membrane) are largely unknown. Since cholesterol is an important molecule for membrane structure and fluidity, we examined the effect of varying cholesterol content with the association and membrane perforation by Aβ in cultured hippocampal neurons. Methods: To decrease or increase the levels of cholesterol in the membrane we used methyl-β-cyclodextrin (MβCD) and MβCD/cholesterol, respectively. We analyzed if membrane fluidity was affected using generalized polarization (GP) imaging and the fluorescent dye di-4-ANEPPDHQ. Additionally membrane association and perforation was assessed using immunocytochemistry and electrophysiological techniques, respectively. Results: The results showed that cholesterol removal decreased the macroscopic association of Aβ to neuronal membranes (fluorescent-puncta/20 μm: control = 18 ± 2 vs. MβCD = 10 ± 1, p < 0.05) and induced a facilitation of the membrane perforation by Aβ with respect to control cells (half-time for maximal charge transferred: control = 7.2 vs. MβCD = 4.4). Under this condition, we found an increase in membrane fluidity (46 ± 3.3% decrease in GP value, p < 0.001). On the contrary, increasing cholesterol levels incremented membrane rigidity (38 ± 2.7% increase in GP value, p < 0.001) and enhanced the association and clustering of Aβ (fluorescent-puncta/20 μm: control = 18 ± 2 vs. MβCD = 10 ± 1, p < 0.01), but inhibited membrane disruption. Conclusion: Our results strongly support the significance of plasma membrane organization in the toxic effects of Aβ in hippocampal neurons, since fluidity can regulate distribution and insertion of the Aβ peptide in the neuronal membrane.


Molecular physics of a polymer engineering instability: experiments and computation.
Entangled polymer melts exhibit a variety of flow instabilities that limit production rates in industrial applications. We present both experimental and computational findings, using flow of monodisperse linear polystyrenes in a contraction-expansion geometry, which illustrate the formation and development of one such flow instability. This viscoelastic disturbance is observed at the slit outlet and subsequently produces large-scale fluid motions upstream. A numerical linear stability study using the molecular structure based Rolie-Poly model confirms the instability and identifies important parameters within the model, which gives physical insight into the underlying mechanism. Chain stretch was found to play a critical role in the instability mechanism, which partially explains the effectiveness of introducing a low-molecular weight tail into a polymer blend to increase its processability.


The influence of anxiety and depressive symptoms during pregnancy on birth size.
Mental health problems during pregnancy can influence fetal growth. However, studies examining the influence of maternal mental health across the normal range of birth outcomes are uncommon. This study examined the associations between symptoms of maternal depression and anxiety during pregnancy on birth size among term Asian infants. One thousand forty-eight Asian pregnant women from a cohort Growing Up in Singapore Towards Healthy Outcomes were recruited between 2009 to 2010 at two Singaporean maternity hospitals. At 26 weeks gestation, depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory II (BDI-II), and anxiety was measured with the Spielberger State-Trait Anxiety Inventory (STAI). Health personnel recorded birthweight, birthlength, gestational age, and head circumference at birth. Nine hundred forty-six women who delivered term infants had complete data. For this sample, the mean birthweight was 3146.6 g [standard deviation (SD) 399.0], the mean birthlength was 48.9 cm (SD 2.0). After controlling for several potential confounders, there was a significant negative association between STAI and birthlength [β = -0.248, confidence interval (CI) [-0.382, -0.115], P < 0.001] and a small negative association between EPDS and birthlength (β = -0.169, CI [-0.305, -0.033], P = 0.02). No associations were found between scores on the EPDS, BDI-II, and STAI with birthweight or head circumference. Our preliminary data suggest that among term infants, anxiety and depressive symptoms are not associated with birthweight, while anxiety and depressive symptoms are associated with a shorter birthlength.


Are per-incident rape-pregnancy rates higher than per-incident consensual pregnancy rates?
Is a given instance of rape more likely to result in pregnancy than a given instance of consensual sex? This paper undertakes a review and critique of the literature on rape-pregnancy. Next, it presents our own estimation, from U.S. government data, of pregnancy rates for reproductive age victims of penile-vaginal rape. Using data on birth control usage from the Statistical Abstract of the United States, we then form an estimate of rapepregnancy rates adjusted for the substantial number of women in our sample who would likely have been protected by oral contraception or an IUD. Our analysis suggests that per-incident rape-pregnancy rates exceed per-incident consensual pregnancy rates by a sizable margin, even before adjusting for the use of relevant forms of birth control. Possible explanations for this phenomenon are discussed, as are its implications to ongoing debates over the ultimate causes of rape.


[Reduction of HBV and HDV infection in two indigenousmpeoples of Peruvian Amazon after the vaccination against hepatitis B].
To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. The prevalence rates of HBsAg, anti-HBc total, anti- HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). These findings show the elimination of HBVmcarriers in children <11 years, eight years following introduction of the vaccination against HBV.


Human papillomavirus infection and anxiety: analyses in women with low-grade cervical cytological abnormalities unaware of their infection status.
Women testing positive for human papillomavirus (HPV) infection experience increased levels of anxiety that have been attributed to fears of stigmatization and developing cervical cancer. The objective of this study was to investigate the association between HPV infection and anxiety in women who were unaware they had been tested specifically for HPV, to determine if any anxiety experienced by HPV-positive women could be due to causes other than learning of test results. This study was nested within a randomised controlled trial of management of women with abnormal cervical cytology conducted in the United Kingdom with recruitment between 1999 and 2002. At baseline, prior to having a sample taken for HPV testing, the results of which were not disclosed, women were assessed for anxiety using the Hospital Anxiety and Depression Scale and asked about fears of developing cervical cancer ("cancer worries"); this assessment was repeated at 12, 18, 24, and 30 months of follow-up. Logistic regression and generalized estimating equations were used for the cross-sectional (baseline) and longitudinal analyses, respectively. Among the 2842 participants, there was no association between HPV status and anxiety among white women. Among non-white women, however, anxiety was less common among HPV-positive than HPV-negative women (adjusted odds ratio 0.41, 95% confidence interval 0.22 to 0.77). Among non-smokers, cancer worry was more common in HPV-positive than HPV-negative women; the opposite association was observed among ex-smokers. Associations between HPV status and anxiety may be explained by factors other than learning of test results and may vary by ethnicity and lifestyle factors.


Coherence estimation in synthetic aperture radar data based on speckle noise modeling.
In the past we proposed a multidimensional speckle noise model to which we now include systematic phase variation effects. This extension makes it possible to define what is believed to be a novel coherence model able to identify the different sources of bias when coherence is estimated on multidimensional synthetic radar aperture (SAR) data. On the one hand, low coherence biases are basically due to the complex additive speckle noise component of the Hermitian product of two SAR images. On the other hand, the availability of the coherence model permits us to quantify the bias due to topography when multilook filtering is considered, permitting us to establish the conditions upon which information may be estimated independently of topography. Based on the coherence model, two coherence estimation approaches, aiming to reduce the different biases, are proposed. Results with simulated and experimental polarimetric and interferometric SAR data illustrate and validate both, the coherence model and the coherence estimation algorithms.


An intellectual virtue "vaccination" for physician-pharmaceutical industry interactions.
The pharmaceutical industry's wide range of interactions with physicians, trainees, and other medical professionals--interactions that include information transfer and financial incentives--has been the source of undue influences, especially on physicians' prescription behavior. Current literature has mainly been focused on the financial element of these influences, and the problems in medical professional-pharmaceutical industry interactions are mainly viewed in terms of conflicts of interest. There is often the assumption that physicians are intellectually competent but biased because of financial incentives.The author rejects that assumption and proposes an alternative explanation for the observed influence of the pharmaceutical industry on physicians' behavior by emphasizing the importance of the information-transfer side of the interactions and maintaining that physicians and other medical professionals need certain intellectual virtues (i.e., competencies) to properly assess the information, which is often unreliable and biased. These virtues are necessary for the practice of modern medicine and include mindfulness, the ability to understand practical implications of newly found evidence, to consider alternative explanations of data, to recognize and correct errors, to decide on the best available evidence, and to tailor that to the needs and values of individual patients. On the basis of this view, the author recommends that the best solution for the observed problems in physician-pharmaceutical industry interactions is to "vaccinate" physicians and other medical professionals by increasing efforts to inculcate the necessary intellectual virtues early in medical education and fostering them throughout those individuals' professional lives.


What the interventionalist should know about renal denervation in hypertensive patients: a position paper by the ESH WG on the interventional treatment of hypertension.
Percutaneous catheter-based transluminal renal denervation (RDN) has emerged as a new approach to achieve sustained blood pressure reduction in patients with drug-resistant hypertension. Experts from ESH and ESC in their recently released position papers and consensus document have summarised the current evidence, unmet needs and practical recommendations for the application of this therapeutic strategy in clinical practice. Experts of the ESH Working Group for the interventional treatment of hypertension prepared this position paper in order to provide interventionalists with guidance through the procedure of RDN. Given that there is no established intraprocedural control of ablation success, interventionalists have to be familiar with the aspects related to the anatomy and imaging of the renal arteries, the distribution of renal sympathetic fibres, the special equipment necessary for RDN and the procedural details in order to maximise the success and minimise potential complications.


On the role of long incubation periods in the dynamics of acquired immunodeficiency syndrome (AIDS). Part 1: Single population models.
In this study, we investigate systematically the role played by the reproductive number (the number of secondary infections generated by an infectious individual in a population of susceptibles) on single group populations models of the spread of HIV/AIDS. Our results for a single group model show that if R less than or equal to 1, the disease will die out, and strongly suggest that if R greater than 1 the disease will persist regardless of initial conditions. Our extensive (but incomplete) mathematical analysis and the numerical simulations of various research groups support the conclusion that the reproductive number R is a global bifurcation parameter. The bifurcation that takes place as R is varied is a transcritical bifurcation; in other words, when R crosses 1 there is a global transfer of stability from the infection-free state to the endemic equilibrium, and vice versa. These results do not depend on the distribution of times spent in the infectious categories (the survivorship functions). Furthermore, by keeping all the key statistics fixed, we can compare two extremes: exponential survivorship versus piecewise constant survivorship (individuals remain infectious for a fixed length of time). By choosing some realistic parameters we can see (at least in these cases) that the reproductive numbers corresponding to these two extreme cases do not differ significantly whenever the two distributions have the same mean. At any rate a formula is provided that allows us to estimate the role played by the survivorship function (and hence the incubation period) in the global dynamics of HIV. These results support the conclusion that single population models of this type are robust and hence are good building blocks for the construction of multiple group models. Our understanding of the dynamics of HIV in the context of mathematical models for multiple groups is critical to our understanding of the dynamics of HIV in a highly heterogeneous population.


Genome-wide association study of suicide attempts in mood disorder patients.
Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.


Does Abatacept Increase Postoperative Adverse Events in Rheumatoid Arthritis Compared with Conventional Synthetic Disease-modifying Drugs?
To investigate whether abatacept (ABA) causes more adverse events (AE) than conventional synthetic disease-modifying antirheumatic drugs (csDMARD) after orthopedic surgery in patients with rheumatoid arthritis (RA). A retrospective multicenter nested case-control study was performed in 18 institutions. Patients receiving ABA (ABA group) were matched individually with patients receiving csDMARD and/or steroids (control group). Postoperative AE included surgical site infection, delayed wound healing, deep vein thrombosis or pulmonary embolism, flare, and death. The incidence rates of the AE in both groups were compared with the Mantel-Haenszel test. Risk factors for AE were analyzed by logistic regression model. A total of 3358 cases were collected. After inclusion and exclusion, 2651 patients were selected for matching, and 194 patients in 97 pairs were chosen for subsequent comparative analyses between the ABA and control groups. No between-group differences were detected in the incidence rates of each AE or in the incidence rates of total AE (control vs ABA: 15.5% vs 20.7% in total, 5.2% vs 3.1% in death). Compared with csDMARD and/or steroids without ABA, adding ABA to the treatment does not appear to increase the incidence rates of postoperative AE in patients with RA undergoing orthopedic surgery. Large cohort studies should be performed to add evidence for the perioperative safety profile of ABA.


Local heroes or villains: tissue-resident memory T cells in human health and disease.
Tissue-resident memory T (TRM) cells are increasingly associated with the outcomes of health and disease. TRM cells can mediate local immune protection against infections and cancer, which has led to interest in TRM cells as targets for vaccination and immunotherapies. However, these cells have also been implicated in mediating detrimental pro-inflammatory responses in autoimmune skin diseases such as psoriasis, alopecia areata, and vitiligo. Here, we summarize the biology of TRM cells established in animal models and in translational human studies. We review the beneficial effects of TRM cells in mediating protective responses against infection and cancer and the adverse role of TRM cells in driving pathology in autoimmunity. A further understanding of the breadth and mechanisms of TRM cell activity is essential for the safe design of strategies that manipulate TRM cells, such that protective responses can be enhanced without unwanted tissue damage, and pathogenic TRM cells can be eliminated without losing local immunity.


Comparative efficacy of individual renin-angiotensin system inhibitors on major renal outcomes in diabetic kidney disease: a network meta-analysis.
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are two drug classes with well-documented renal protective effects. However, whether there is any difference among individual drugs remains unknown. In this study, we aimed to compare the efficacy of individual ACEIs/ARBs on major renal outcomes in adults with diabetic kidney disease (DKD). We conducted a Bayesian-framework network meta-analysis with a random effects model. We searched PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for clinical trials of ACEIs or ARBs as monotherapy compared with other conventional antihypertensive drugs or placebo. Primary outcomes were end-stage renal disease (ESRD) and albuminuria/proteinuria (including change in albuminuria/proteinuria, progression to macroalbuminuria and remission to normoalbuminuria). Secondary outcome was doubling of serum creatinine levels. We also assessed for hyperkalemia, cough and angioedema/edema. International prospective register of systematic reviews (PROSPERO) registration CRD42016036997. A total of 100 studies with data for 22 365 DKD patients, the majority of whom had type 2 diabetes, were included. Individual ACEIs and ARBs at goal doses showed no significant differences in ESRD and doubling of serum creatinine levels. They also shared similar effects on albuminuria/proteinuria reduction and progression or remission of albuminuria. When combining three outcomes of albuminuria/proteinuria as a single endpoint, most ACEIs/ARBs consistently showed favorable antiproteinuric effect, with little difference in the possibility of being the superior treatment for improving albuminuria/proteinuria. Primary outcomes did not change substantially in meta-regressions and sensitivity analyses. Findings were limited by lack of dose equivalence and paucity of data for some outcomes. Based on the available evidence, individual ACEIs and ARBs at goal doses appeared to have no or little differences in their effect on major renal outcomes.


Clock and cycle limit starvation-induced sleep loss in Drosophila.
Neural systems controlling the vital functions of sleep and feeding in mammals are tightly interconnected: sleep deprivation promotes feeding, whereas starvation suppresses sleep. Here we show that starvation in Drosophila potently suppresses sleep, suggesting that these two homeostatically regulated behaviors are also integrated in flies. The sleep-suppressing effect of starvation is independent of the mushroom bodies, a previously identified sleep locus in the fly brain, and therefore is regulated by distinct neural circuitry. The circadian clock genes Clock (Clk) and cycle (cyc) are critical for proper sleep suppression during starvation. However, the sleep suppression is independent of light cues and of circadian rhythms as shown by the fact that starved period mutants sleep like wild-type flies. By selectively targeting subpopulations of Clk-expressing neurons, we localize the observed sleep phenotype to the dorsally located circadian neurons. These findings show that Clk and cyc act during starvation to modulate the conflict of whether flies sleep or search for food.


Oil film thickness measurement using airborne laser-induced water Raman backscatter.
The use of laser-induced water Raman backscatter for remote thin oil film detection and thickness measurement is reported here for the first time. A 337.1-nm nitrogen laser was used to excite the 3400-cm(-1) OH stretch band of natural ocean water beneath the oil slick from an altitude of 150 m. The signal strength of the 381-nm water Raman backscatter was always observed to depress when the oil was encountered and then return to its original undepressed value after complete aircraft traversal of the floating slick. After removal of background and oil fluorescence contributions, the ratio of the depressed-to-undepressed airborne water Raman signal intensities, together with laboratory measured oil extinction coefficients, is used to calculate the oil film thickness.


Activation of stress signaling pathways by the end product of lipid peroxidation. 4-hydroxy-2-nonenal is a potential inducer of intracellular peroxide production.
In the present study, we studied the signal transduction mechanism that is involved in the expression of c-Jun protein evident after exposure of rat liver epithelial RL34 cells to the major end product of oxidized fatty acid metabolism, 4-hydroxy-2-nonenal (HNE). HNE treatment of the cells resulted in depletion of intracellular glutathione (GSH) and in the formation of protein-bound HNE in plasma membrane. In addition, HNE strongly induced intracellular peroxide production, suggesting that HNE exerted oxidative stress on the cells. Potent expression of c-Jun occurred within 30 min of HNE treatment, which was accompanied by a time-dependent increase in activator protein-1 (AP-1) DNA binding activity. We found that HNE caused an immediate increase in tyrosine phosphorylation in RL34 cells. In addition, HNE strongly induced phosphorylation of c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases and also moderately induced phosphorylation of extracellular signal-regulated kinases. The phosphorylation of JNK was accompanied by a rapid and transient increase in JNK and p38 activities, whereas changes in the activity of extracellular signal-regulated kinase were scarcely observed. GSH depletion by L-buthionine-S, R-sulfoximine, a specific inhibitor of GSH biosynthesis, only slightly enhanced peroxide production and JNK activation, suggesting that HNE exerted these effects independent of GSH depletion. This and the findings that (i) HNE strongly induced intracellular peroxide production, (ii) HNE-induced JNK activation was inhibited by pretreatment of the cells with a thiol antioxidant, N-acetylcysteine, and (iii) H2O2 significantly activated JNK support the hypothesis that pro-oxidants play a crucial role in the HNE-induced activation of stress signaling pathways. In addition, we found that, among the inhibitors of tyrosine kinases, cyclooxygenase, and Ca2+ influx, only quercetin exerted a significant inhibitory effect on HNE-induced JNK activation. In light of the JNK-dependent induction of c-jun transcription and the AP-1-induced transcription of xenobiotic-metabolizing enzymes, these data may show a potential critical role for JNK in the induction of a cellular defense program against toxic products generated from lipid peroxidation.


Safety and immunogenicity of a varicella vaccine without human serum albumin (HSA) versus a HSA-containing formulation administered in the second year of life: a phase III, double-blind, randomized study.
A new formulation of the live-attenuated varicella vaccine Varilrix (GSK) produced without human serum albumin (HSA) was developed to minimize a theoretical risk of transmission of infectious diseases. A previous study showed that the vaccine was immunologically non-inferior to the HSA-containing vaccine and well-tolerated in toddlers; low-grade fever was numerically higher in children receiving the vaccine without HSA, but the study lacked power to conclude on this difference. In this phase III, double-blind, multi-center study, healthy 12-23-month-olds were randomized (1:1) to receive two doses of the varicella vaccine without (Var-HSA group) or with HSA (Var + HSA group) at days 0 and 42. The primary objective compared safety of the vaccines in terms of incidence of fever > 39.0 °C in the 15-day period post-first vaccination. The objective was considered met if the upper limit of the 95% confidence interval for the between-group difference in the incidence of fever > 39.0 °C was ≤5% (Var-HSA group minus Var + HSA group). Safety, reactogenicity and immune responses were evaluated. Six hundred fifteen children in the Var-HSA group and 616 in the Var + HSA group received ≥1 vaccination. Fever > 39.0 °C was reported in 3.9 and 5.2% of participants in the Var-HSA and Var + HSA groups, with a between-group difference of - 1.29 (95% confidence interval: - 3.72-1.08); therefore, the primary objective was achieved. Fever rates post-each dose and the incidence of solicited local and general adverse events (AEs) were comparable between groups. Unsolicited AEs were reported for 43.9 and 36.5% of children in the Var-HSA group and 45.8 and 36.0% of children in the Var + HSA group, during 43 days post-dose 1 and 2, respectively. Serious AEs occurred in 2.1% (group Var-HSA) and 2.4% (group Var + HSA) of children, throughout the study. In a sub-cohort of 364 children, all had anti-varicella-zoster virus antibody concentrations ≥50 mIU/mL post-dose 2; comparable geometric mean concentrations were observed between the groups. The varicella vaccine formulated without HSA did not induce higher rates of fever during the 15 day-post-vaccination period, as compared with the original HSA-containing vaccine. The two vaccines displayed similar safety and immunogenicity profiles in toddlers. NCT02570126 , registered on 5 October 2015 (www.clinicaltrials.gov).


A mixed-methods evaluation of the effectiveness of tailored smoking cessation training for healthcare practitioners who work with older people.
Older people who smoke derive significant health benefits from stopping smoking in later life. Healthcare practitioners have an important role to play in raising the issue of smoking cessation with this client group; however, they often fail to do so. To assess the effectiveness of smoking cessation training for healthcare practitioners who have regular contact with older adults. Mixed-methods were used to explore satisfaction with the training, the participants' learning and any resultant changes in behaviour. The effectiveness of the training was assessed using a two-group parallel design randomised controlled trial, followed by semistructured qualitative interviews. Participants (n = 57) were recruited from a cohort of community nurses and allied health professionals (e.g., occupational therapists) working in Scotland. The intervention was 1-day brief intervention smoking cessation training. Validated measures of knowledge, attitudes and practice, were used to assess learning and behaviour at baseline, 1 week and 3 months post training. Data were analysed using two-factor repeated measure analysis of variance, where the factors were "group" and "time." Qualitative data were gathered from members of the intervention group during semistructured interviews (n = 8) and were analysed thematically. Levels of satisfaction with the training were high. There was a statistically significant improvement in the knowledge and attitudes of the intervention group following the training, with a noticeable, but nonsignificant, improvement in practice. The qualitative findings demonstrate how the training impacted positively on practice. Smoking cessation interventions in later life are important, as older smokers generally have long-term conditions caused or complicated by smoking. The delivery of brief smoking cessation interventions is known to be highly cost-effective; however, research demonstrates that practitioners often fail to raise the issue of smoking cessation with older adults. This study has demonstrated the effectiveness of a 1-day training course for practitioners. Further research is recommended.


[Prevalence and risk factors associated with syphilis in women].
Although the incidence of syphilis is generally low, it remains an important global public health problem, given its interaction with other sexually transmitted diseases (STDs). It has been shown that syphilis, due to the genital ulcers it produces, is a co-factor for acquiring other STDs, principally those of viral origin such as herpes simples type 2, hepatitis B and HIV. Many female commercial sex workers (FCSW) in Mexico have been found to have acquired good levels of knowledge about STD prevention. Nevertheless, they constitute a heterogeneous group in terms of socio-economic level, health status and type of work site; these factors in turn appear to determine their attitudes, knowledge and behavior related to acquiring and transmitting STDs, including syphilis. This study, therefore, focused on the factors associated with Treponema pallidum infection in this group of women. Based on a sample frame of sites where female commercial sex work takes place within Mexico City, a sample of 807 FCSWs was selected; after providing informed consent, they completed a structured questionnaire. A blood sample for identifying serologic markers for STDs was collected and analyzed according to a procedure manual for STD diagnosis. Treponema pallidum was diagnosed using the RPR (Bigaux Diagnostica) screening test, and FTA-ABS (Pasteur Diagnostics) for confirmation. The prevalence of syphilis in this sample of FCSWs was 6.4% (52/807), and was higher among women who worked at street sites than among those who worked in massage parlors. The age of the women interviewed ranged from 17 to 58 years, with a mean of 29.2 years (SD 7.3 years); syphilis was more prevalent among women over 30 years of age. Age at first sexual intercourse ranged from 11 to 30 years, with a mean of 16 years (SD 3.1 years), which is similar to that of the general female population in Mexico. Predictive factors for T. pallidum infection, determined adjusted logistic regression, included: tupe of by work site (bar and street sites); socio-economic level (middle and low); age (over 30 years); duration of involvement in sex work (> 5 years) and number of clients per week (> 10). In spite of some limitations regarding statistical precision, this study shows that FCSWs are heterogeneous in terms of risk of acquiring STDs, including syphilis; the principal differentiating factor was shown to be the type of work site. Given that it is not belonging to a risk group but rather participating in risky practices that leads to acquiring STDs, situations that facilitate riskier or safer practices (such as type of sex work site, for sex workers) should be taken into account when studying people's risk level. STD prevention campaigns must also consider these factors, in addition to focusing on FCSWs and their clients and personal partners, so that all involved assume their responsibility for safer sex.


Periodic Catatonia Marked by Hypercortisolemia and Exacerbated by the Menses: A Case Report and Literature Review.
Kahlbaum first described catatonia; later Kraepelin, Gjessing, and Leonhard each defined periodic catatonia differently. A 48-year-old female with catatonia, whose grandmother probably died from it, was prospectively followed for >4 years in a US psychiatric state hospital. Through 4 catatonic episodes (one lasting 17 months) there were menstrual exacerbations of catatonia and increases in 4 biological variables: (1) creatine kinase (CK) up to 4,920 U/L, (2) lactate dehydrogenase (LDH) up to 424 U/L, (3) late afternoon cortisol levels up to 28.0 mcg/dL, and (4) white blood cell (WBC) counts up to 24,200/mm3 with neutrophilia without infections. Records from 17 prior admissions documented elevations of WBC and LDH and included an abnormal dexamethasone suppression test (DST) which normalized with electroconvulsive therapy. Two later admissions showed CK and WBC elevations. We propose that these abnormalities reflect different aspects of catatonic biology: (1) the serum CK, the severity of muscle damage probably exacerbated by the menses; (2) the hypercortisolemia, the associated fear; (3) the leukocytosis with neutrophilia, the hypercortisolemia; and (4) the LDH elevations, which appear to be influenced by other biological abnormalities. Twentieth-century literature was reviewed for (1) menstrual exacerbations of catatonia, (2) biological abnormalities related to periodic catatonia, and (3) familial periodic catatonia.


Localizing Carbohydrate Binding Sites in Proteins Using Hydrogen/Deuterium Exchange Mass Spectrometry.
The application of hydrogen/deuterium exchange mass spectrometry (HDX-MS) to localize ligand binding sites in carbohydrate-binding proteins is described. Proteins from three bacterial toxins, the B subunit homopentamers of Cholera toxin and Shiga toxin type 1 and a fragment of Clostridium difficile toxin A, and their interactions with native carbohydrate receptors, GM1 pentasaccharides (β-Gal-(1→3)-β-GalNAc-(1→4)[α-Neu5Ac-(2→3)]-β-Gal-(1→4)-Glc), Pk trisaccharide (α-Gal-(1→4)-β-Gal-(1→4)-Glc) and CD-grease (α-Gal-(1→3)-β-Gal-(1→4)-β-GlcNAcO(CH2)8CO2CH3), respectively, served as model systems for this study. Comparison of the differences in deuterium uptake for peptic peptides produced in the absence and presence of ligand revealed regions of the proteins that are protected against deuterium exchange upon ligand binding. Notably, protected regions generally coincide with the carbohydrate binding sites identified by X-ray crystallography. However, ligand binding can also result in increased deuterium exchange in other parts of the protein, presumably through allosteric effects. Overall, the results of this study suggest that HDX-MS can serve as a useful tool for localizing the ligand binding sites in carbohydrate-binding proteins. However, a detailed interpretation of the changes in deuterium exchange upon ligand binding can be challenging because of the presence of ligand-induced changes in protein structure and dynamics.


Löfgren's syndrome: an acute variant of sarcoidosis diagnosed by mediastinoscopy.
Löfgren's syndrome is an acute clinical form of sarcoidosis that is first described by Sven Löfgren as bilateral hilar lymphadenopathy together with Erythema Nodosum (EN) and accompanying arthritis/arthralgia. This syndrome has some differences in terms of treatment, prognosis and recurrence compared to sarcoidosis. In this report, we describe a 70 years old lady who admitted with multiple erythematous lesions and arthralgia of both lower extremities and she was diagnosed as Löfgren's syndrome via mediastinoscopy.


Australian and New Zealand Veterinary Students' Opinions on Animal Welfare and Ethical Issues Concerning Animal Use within Sport, Recreation, and Display.
Animals used for sport, recreation and display are highly visible and can divide community attitudes. The study of animal welfare and ethics (AWE) as part of veterinary education is important because it is the responsibility of veterinarians to use their scientific knowledge and skills to promote animal welfare in the context of community expectations. To explore the attitudes of veterinary students in Australia and New Zealand to AWE, a survey of the current cohort was undertaken. The survey aimed to reveal how veterinary students in Australia and New Zealand rate the importance of five selected AWE topics for Day One Competences in animals used in sport, recreation and display and to establish how veterinary students' priorities were associated with gender and stage of study. The response rate (n = 851) across the seven schools was just over 25%. Results indicated little variation on ratings for topics. The topics were ranked in the following order (most to least important): Pushing of animals to their physiologic/behavioral limits; ownership/responsibility; euthanasia; educating the public; and behavior, selection, and training for sport and recreation displays. In contrast to related studies, ratings were not associated with stage of study and there were few differences associated with gender. More females rated the pushing of animals to physiologic/behavioral limits as extremely important than did males ( p < .001). The role of veterinarians in advocating for and educating the public about the welfare of animals used in sport, recreation and display merits further discussion.


Mutagenic activity of phthalate esters in bacterial liquid suspension assays.
The mutagenic activities of several phthalate esters have been evaluated in an 8-azaguanine resistance assay in Salmonella typhimurium. Three phthalate esters were found to be mutagenic: dimethyl phthalate, diethyl phthalate and di-n-butyl phthalate. A number of other phthalate esters were not found to be mutagenic, including di(2-ethylhexyl) phthalate, di-n-octyl phthalate, diallyl phthalate, diisobutyl phthalate and diisodecyl phthalate. A metabolite of di(2-ethylhexyl) phthalate, 2-ethylhexanol, was also noted to be mutagenic. The mutagenic activity of this agent and others in this series was dose dependent but weak. No dose-response curve exceeded more than 3.5 times background at maximally testable concentrations. A liquid suspension histidine reversion assay of dimethyl phthalate showed levels of mutagenic activity similar to that observed in the azaguanine resistance assay. The data suggest a need for further investigation of the mutagenic potential of these agents in other assay systems.


Ultrasonographic assessment of altered anatomical relationship between internal jugular vein and common carotid artery with supraglottic airway in children: LMA vs i-gel™.
Use of ultrasound (US) during internal jugular vein (IJV) cannulation reduces the risk of associated complications in children under general anaesthesia. We studied the effect of two varieties of supraglottic airway device (SGAD), the Ambu AuraOnce™ LMA (Ambu LMA), and i-gel™ on the anatomical relationship between IJV and common carotid artery (CCA). Both these SGAD are known to have similar safety profile in paediatric age group. A total of 62 children were randomly allocated into 2 groups. In group L: Ambu AuraOnce™ LMA (Ambu LMA) and in group I: i-gel™ was inserted. After induction of GA, US images were taken with head in neutral and 30 degrees rotated to the opposite side both before and after insertion of SGAD. The relationship between IJV and CCA was noted as lateral, anterolateral, and anterior. Degree of overlap between the two vessels was also noted. Lateral rotation of the head significantly alters the relationship between the IJV and CCA and also increases the degree of overlap between them. Though these changes were noted to be similar with both varieties of SGAD, but between the two varieties of SGAD, these changes were significantly higher in group I. Higher oesophageal sealing pressure exerted by i-gel™ as compared to other SGAD might cause increased distortion of the surrounding soft tissue leading to altered anatomical relationship between IJV and CCA, which makes the CCA vulnerable to puncture during IJV cannulation using landmark technique.


DP and E2F proteins: coordinating transcription with cell cycle progression.
Transcriptional control during the G1/S transition is important in regulating cell cycle progression. The transcription factor DRTF1/E2F is believed to play a crucial role in this process by integrating the activity of the machinery that drives the cell cycle with the transcription apparatus. Being the point of convergence for growth-promoting and growth-inhibitory signals, it is a pivotal cellular target for molecules which subvert normal cell cycle control, such as oncoviral proteins. Recent studies have indicated that members of two distinct families of proteins, DP and E2F, interact combinatorially as DP/E2F heterodimers in DRTF1/E2F. The activities of both DP and E2F proteins are under cell cycle control, being influenced by the level of phosphorylation imparted through the cell cycle regulated activity of cyclin-dependent kinases. Both DP and E2F proteins are endowed with proto-oncogenic activity and, conversely, have been implicated in regulating apoptosis. Current evidence suggests therefore that the activity of DRTF1/E2F is instrumental in regulating progression through the cell cycle.


Three-dimensional structure determination protocol for noncrystalline biomolecules using x-ray free-electron laser diffraction imaging.
Coherent and intense x-ray pulses generated by x-ray free-electron laser (XFEL) sources are paving the way for structural determination of noncrystalline biomolecules. However, due to the small scattering cross section of electrons for x rays, the available incident x-ray intensity of XFEL sources, which is currently in the range of 10(12)-10(13) photons/μm(2)/pulse, is lower than that necessary to perform single-molecule diffraction experiments for noncrystalline biomolecules even with the molecular masses of megadalton and submicrometer dimensions. Here, we propose an experimental protocol and analysis method for visualizing the structure of those biomolecules by the combined application of coherent x-ray diffraction imaging and three-dimensional reconstruction methods. To compensate the small scattering cross section of biomolecules, in our protocol, a thin vitreous ice plate containing several hundred biomolecules/μm(2) is used as sample, a setup similar to that utilized by single-molecule cryoelectron microscopy. The scattering cross section of such an ice plate is far larger than that of a single particle. The images of biomolecules contained within irradiated areas are then retrieved from each diffraction pattern, and finally provide the three-dimensional electron density model. A realistic atomic simulation using large-scale computations proposed that the three-dimensional structure determination of the 50S ribosomal subunit embedded in a vitreous ice plate is possible at a resolution of 0.8 nm when an x-ray beam of 10(16) photons/500×500 nm(2)/pulse is available.


Novel antiplatelet and antithrombotic activities of essential oil from Lavandula hybrida Reverchon "grosso".
Lavender extracts are known to produce several mild effects at central and peripheral level. However, no studies are so far available about the potential effects of lavender essential oil on the hemostatic system. In this work, we demonstrated antiplatelet properties of lavender oil towards platelet aggregation induced by arachidonic acid, U46619, collagen and ADP (IC50 = 51, 84, 191 and 640 microg/ml, respectively) on guinea-pig platelet rich plasma (PRP) and its ability to destabilize clot retraction (IC50 = 149 microg/ml) induced by thrombin on rat PRP. Furthermore, antithrombotic properties were studied in an in vivo model of pulmonary thromboembolism induced by intravenous injection of a collagen-epinephrine mixture in mice subacutely treated with lavender oil. In this model, lavender oil (100 mg/kg/day os for 5 days) significantly reduced thrombotic events without inducing prohemorrhagic complications at variance with acetylsalicylic acid used as reference drug. Finally, main components of the oil were studied in vitro in order to assess their antiplatelet effects, but none of them possessed an activity comparable to the oil itself. These results provide the first experimental evidence of lavender oil's antiplatelet/antithrombotic properties which could be due to a synergistic effect of its components.


Contributions of Hepatic and Intestinal Metabolism to the Disposition of Niclosamide, a Repurposed Drug with Poor Bioavailability.
Niclosamide, an antiparasitic, has been repositioned as a potential therapeutic drug for systemic diseases based on its antiviral, anticancer, and anti-infection properties. However, low bioavailability limits its in vivo efficacy. Our aim was to determine whether metabolic disposition by microsomal P450 enzymes in liver and intestine influences niclosamide's bioavailability in vivo, by comparing niclosamide metabolism in wild-type, liver-Cpr-null (LCN), and intestinal epithelium-Cpr-null (IECN) mice. In vitro stability of niclosamide in microsomal incubations was greater in the intestine than in liver in the presence of NADPH, but it was much greater in liver than in intestine in the presence of UDPGA. NADPH-dependent niclosamide metabolism and hydroxy-niclosamide formation were inhibited in hepatic microsomes of LCN mice, but not IECN mice, compared with wild-type mice. In intestinal microsomal reactions, hydroxy-niclosamide formation was not detected, but rates of niclosamide-glucuronide formation were ∼10-fold greater than in liver, in wild-type, LCN, and IECN mice. Apparent Km and V max values for microsomal niclosamide-glucuronide formation showed large differences between the two tissues, with the intestine having higher Km (0.47 μM) and higher V max (15.8) than the liver (0.09 μM and 0.75, respectively). In vivo studies in LCN mice confirmed the essential role of hepatic P450 in hydroxy-niclosamide formation; however, pharmacokinetic profiles of oral niclosamide were only minimally changed in LCN mice, compared with wild-type mice, and the changes seem to reflect the compensatory increase in hepatic UDP-glucuronosyltransferase activity. SIGNIFICANCE STATEMENT: These results suggest that efforts to increase the bioavailability of niclosamide by blocking its metabolism by P450 enzymes will unlikely be fruitful. In contrast, inhibition of niclosamide glucuronidation in both liver and intestine may prove effective for increasing niclosamide's bioavailability, thereby making it practical to repurpose this drug for treating systemic diseases.


Monitoring adherence to medication by measuring change in blood pressure.
After starting antihypertensives, blood pressure is monitored for several reasons, including assessment of adherence. We aimed to estimate the accuracy of blood pressure monitoring for detecting early nonadherence. We conducted a secondary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a large randomized trial of blood pressure lowering to reduce the risk of recurrent stroke. We compared change in blood pressure 3 months after randomization in people who had discontinued treatment (nonadherent) with those who stayed on treatment (adherent). We also used an indirect method, assessing whether change in blood pressure discriminated between active (adherent) and placebo (nonadherent) groups. Both methods gave similar results. For the 3433 subjects, the mean (SD) of the change in systolic blood pressure was -15.8 mm Hg (SD 18.7 mm Hg) in the adherent group and -4.2 mm Hg (SD 18.1 mm Hg) in the nonadherent group. After recalibration of the mean change in the nonadherent group to 0 mm Hg and in the adherent group to -11.6 mm Hg, the absence of a fall in systolic blood pressure at 3 months had a sensitivity of 50% and a specificity of 80% for detecting nonadherence (50% of nonadherent patients and 20% of adherent patients had a rise in blood pressure). Discriminatory power was modest over the range of cutoffs (area under the receiver-operator curve 0.67). Monitoring blood pressure is poor at detecting nonadherence to blood pressure-lowering treatment. Further research should look at other methods of assessing adherence.


Outcomes and trends of prostate biopsy for prostate cancer in Chinese men from 2003 to 2011.
Prostate-specific antigen (PSA) screening is growing in popularity in China, but its impact on biopsy characteristics and outcomes are poorly understood. Our objective was to characterize prostate biopsy outcomes and trends in Chinese men over a 10-year period, since the increasing use of PSA tests. All men (n = 1,650) who underwent prostate biopsy for PCa at Huashan Hospital, Shanghai, China from 2003-2011 were evaluated. Demographic and clinical information was collected for each patient, including age, digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total prostate-specific antigen (tPSA) levels and free PSA ratio (fPSA/tPSA) prior to biopsy. Prostate biopsy was performed using six cores before October 2007 or ten cores thereafter. Logistic regression and multivariate analysis were used to evaluate our data. The overall positive rate of prostate biopsy for PCa was 47% and the rate decreased significantly over the years from 74% in 2003 to 33% in 2011 (P-trend = 0.004). Age at diagnosis was slightly increased (P-trend = 0.04) while fPSA/tPSA was significantly decreased (P-trend = 1.11×10-5). A statistically significant trend was not observed for tPSA levels, prostate volume, or proportion of positive nodule. The model including multiple demographic and clinical variables (i.e., age, DRE, tPSA, fPSA/tPSA and transrectal ultrasound results) (AUC = 0.93) statistically outperformed models that included only PSA (AUC = 0.85) or fPSA/tPSA (AUC = 0.66) to predict PCa risks (P<0.05). Similar results were observed in a subgroup of men whose tPSA levels were lower than 20 ng/mL (AUC = 0.87, vs. AUC of tPSA = 0.62, P<0.05). Detection rates of PCa and high-grade PCa among men that underwent prostate biopsy at the institution has decreased significantly in the past 10 years, likely due to increasing use of PSA tests. Predictive performance of demographic and clinical variables of PCa was excellent. These variables should be used in clinics to determine the need for prostate biopsy.


Natural history of Mycobacterium fortuitum pulmonary infection presenting with migratory infiltrates: a case report with microbiological analysis.
Presence of Mycobacterium fortuitum in respiratory tracts usually indicates mere colonization or transient infection, whereas true pulmonary infection occurs in patients with gastroesophageal disease. However, little is known about the diagnostic indications for true M. fortuitum pulmonary infection and the natural history of the disease. A 59-year-old man was referred to our hospital for treatment against M. fortuitum pulmonary infection. Fifteen years before the referral, he underwent total gastrectomy, after which he experienced esophageal reflux symptoms. After the referral, the patient was closely monitored without antimicrobial therapy because of mild symptoms and no pathological evidence of M. fortuitum pulmonary infection. During the observation, chest imaging showed migratory infiltrates. Two years after the referral, his lung biopsy specimen revealed foamy macrophages and multinucleated giant cells, indicating lipoid pneumonia. However, he was continually monitored without any treatment because there was no evidence of nontuberculous mycobacterial infection. Four years after the referral, he developed refractory pneumonia despite receiving adequate antibiotic therapy. After confirmation of granulomatous lesions, multiple antimicrobial therapy for M. fortuitum resulted in a remarkable improvement with no exacerbation for over 5 years. Random amplified polymorphic DNA polymerase chain reaction analysis revealed identical M. fortuitum strains in seven isolates from six sputum and one intestinal fluid specimens obtained during the course of the disease. We have described a patient with M. fortuitum pulmonary infection who presented with migratory infiltrates. The pathological evidence and microbiological analysis suggested that M. fortuitum pulmonary infection was associated with lipoid pneumonia and chronic exposure to gastrointestinal fluid. Therefore, physicians should carefully monitor patients with M. fortuitum detected from lower respiratory tract specimens and consider antimicrobial therapy for M. fortuitum infection when the patient does not respond to adequate antibiotic therapy against common pneumonia pathogens.


Knowledge-based IMRT treatment planning for prostate cancer.
To demonstrate the feasibility of using a knowledge base of prior treatment plans to generate new prostate intensity modulated radiation therapy (IMRT) plans. Each new case would be matched against others in the knowledge base. Once the best match is identified, that clinically approved plan is used to generate the new plan. A database of 100 prostate IMRT treatment plans was assembled into an information-theoretic system. An algorithm based on mutual information was implemented to identify similar patient cases by matching 2D beam's eye view projections of contours. Ten randomly selected query cases were each matched with the most similar case from the database of prior clinically approved plans. Treatment parameters from the matched case were used to develop new treatment plans. A comparison of the differences in the dose-volume histograms between the new and the original treatment plans were analyzed. On average, the new knowledge-based plan is capable of achieving very comparable planning target volume coverage as the original plan, to within 2% as evaluated for D98, D95, and D1. Similarly, the dose to the rectum and dose to the bladder are also comparable to the original plan. For the rectum, the mean and standard deviation of the dose percentage differences for D20, D30, and D50 are 1.8% +/- 8.5%, -2.5% +/- 13.9%, and -13.9% +/- 23.6%, respectively. For the bladder, the mean and standard deviation of the dose percentage differences for D20, D30, and D50 are -5.9% +/- 10.8%, -12.2% +/- 14.6%, and -24.9% +/- 21.2%, respectively. A negative percentage difference indicates that the new plan has greater dose sparing as compared to the original plan. The authors demonstrate a knowledge-based approach of using prior clinically approved treatment plans to generate clinically acceptable treatment plans of high quality. This semiautomated approach has the potential to improve the efficiency of the treatment planning process while ensuring that high quality plans are developed.


Regulation of gene expression by a metabolic enzyme.
Gene expression in eukaryotes is normally believed to be controlled by transcriptional regulators that activate genes encoding structural proteins and enzymes. To identify previously unrecognized DNA binding activities, a yeast proteome microarray was screened with DNA probes; Arg5,6, a well-characterized mitochondrial enzyme involved in arginine biosynthesis, was identified. Chromatin immunoprecipitation experiments revealed that Arg5,6 is associated with specific nuclear and mitochondrial loci in vivo, and Arg5,6 binds to specific fragments in vitro. Deletion of Arg5,6 causes altered transcript levels of both nuclear and mitochondrial target genes. These results indicate that metabolic enzymes can directly regulate eukaryotic gene expression.


Adaptation of the RAQoL for use in Australia.
Quality of life is an important patient-reported outcome of rheumatoid arthritis (RA) in addition to structural and functional outcomes. The RAQoL (Rheumatoid Arthritis Quality of Life questionnaire) was developed in the UK and the Netherlands as a disease-specific tool. It was adapted for use in the Australian social context and the reliability and validity was tested. A lay panel assessed the UK version and adapted the wording for use within Australia. Reliability and validity were assessed by a postal survey of the RAQoL and comparator questionnaires to 100 patients with RA. The RAQoL was easily adapted into Australian-English. Test-retest reliability was high with a Spearman rank correlation coefficient of 0.93. RAQoL scores correlated well with patient-perceived disease activity and severity--indicating good validity. The Australian version of the RAQoL is a valid and reliable tool for the assessment of quality of life. It is practical, easy to administer and has good potential for use in clinical settings and trials in Australia.


Engineering synthetic signaling proteins with ultrasensitive input/output control.
Many signaling proteins are built from simple, modular components, yet display highly complex signal-processing behavior. Here we explore how modular domains can be used to build an ultrasensitive switch--a nonlinear input/output function that is central to many complex biological behaviors. By systematically altering the number and affinity of modular autoinhibitory interactions, we show that we can predictably convert a simple linear signaling protein into an ultrasensitive switch.


Self-adaptation of mutation operator and probability for permutation representations in genetic algorithms.
The choice of mutation rate is a vital factor in the success of any genetic algorithm (GA), and for permutation representations this is compounded by the availability of several alternative mutation operators. It is now well understood that there is no one "optimal choice"; rather, the situation changes per problem instance and during evolution. This paper examines whether this choice can be left to the processes of evolution via self-adaptation, thus removing this nontrivial task from the GA user and reducing the risk of poor performance arising from (inadvertent) inappropriate decisions. Self-adaptation has been proven successful for mutation step sizes in the continuous domain, and for the probability of applying bitwise mutation to binary encodings; here we examine whether this can translate to the choice and parameterisation of mutation operators for permutation encodings. We examine one method for adapting the choice of operator during runtime, and several different methods for adapting the rate at which the chosen operator is applied. In order to evaluate these algorithms, we have used a range of benchmark TSP problems. Of course this paper is not intended to present a state of the art in TSP solvers; rather, we use this well known problem as typical of many that require a permutation encoding, where our results indicate that self-adaptation can prove beneficial. The results show that GAs using appropriate methods to self-adapt their mutation operator and mutation rate find solutions of comparable or lower cost than algorithms with "static" operators, even when the latter have been extensively pretuned. Although the adaptive GAs tend to need longer to run, we show that is a price well worth paying as the time spent finding the optimal mutation operator and rate for the nonadaptive versions can be considerable. Finally, we evaluate the sensitivity of the self-adaptive methods to changes in the implementation, and to the choice of other genetic operators and population models. The results show that the methods presented are robust, in the sense that the performance benefits can be obtained in a wide range of host algorithms.


Economic games quantify diminished sense of guilt in patients with damage to the prefrontal cortex.
Damage to the ventromedial prefrontal cortex (VMPFC) impairs concern for other people, as reflected in the dysfunctional real-life social behavior of patients with such damage, as well as their abnormal performances on tasks ranging from moral judgment to economic games. Despite these convergent data, we lack a formal model of how, and to what degree, VMPFC lesions affect an individual's social decision-making. Here we provide a quantification of these effects using a formal economic model of choice that incorporates terms for the disutility of unequal payoffs, with parameters that index behaviors normally evoked by guilt and envy. Six patients with focal VMPFC lesions participated in a battery of economic games that measured concern about payoffs to themselves and to others: dictator, ultimatum, and trust games. We analyzed each task individually, but also derived estimates of the guilt and envy parameters from aggregate behavior across all of the tasks. Compared with control subjects, the patients donated significantly less and were less trustworthy, and overall our model found a significant insensitivity to guilt. Despite these abnormalities, the patients had normal expectations about what other people would do, and they also did not simply generate behavior that was more noisy. Instead, the findings argue for a specific insensitivity to guilt, an abnormality that we suggest characterizes a key contribution made by the VMPFC to social behavior.


Dengue dynamics in Binh Thuan province, southern Vietnam: periodicity, synchronicity and climate variability.
Dengue is a major global public health problem with increasing incidence and geographic spread. The epidemiology is complex with long inter-epidemic intervals and endemic with seasonal fluctuations. This study was initiated to investigate dengue transmission dynamics in Binh Thuan province, southern Vietnam. Wavelet analyses were performed on time series of monthly notified dengue cases from January 1994 to June 2009 (i) to detect and quantify dengue periodicity, (ii) to describe synchrony patterns in both time and space, (iii) to investigate the spatio-temporal waves and (iv) to associate the relationship between dengue incidence and El Niño-Southern Oscillation (ENSO) indices in Binh Thuan province, southern Vietnam. We demonstrate a continuous annual mode of oscillation and a multi-annual cycle of around 2-3-years was solely observed from 1996-2001. Synchrony in time and between districts was detected for both the annual and 2-3-year cycle. Phase differences used to describe the spatio-temporal patterns suggested that the seasonal wave of infection was either synchronous among all districts or moving away from Phan Thiet district. The 2-3-year periodic wave was moving towards, rather than away from Phan Thiet district. A strong non-stationary association between ENSO indices and climate variables with dengue incidence in the 2-3-year periodic band was found. A multi-annual mode of oscillation was observed and these 2-3-year waves of infection probably started outside Binh Thuan province. Associations with climatic variables were observed with dengue incidence. Here, we have provided insight in dengue population transmission dynamics over the past 14.5 years. Further studies on an extensive time series dataset are needed to test the hypothesis that epidemics emanate from larger cities in southern Vietnam.


Habitat Predicts Levels of Genetic Admixture in Saccharomyces cerevisiae.
Genetic admixture can provide material for populations to adapt to local environments, and this process has played a crucial role in the domestication of plants and animals. The model yeast, Saccharomyces cerevisiae, has been domesticated multiple times for the production of wine, sake, beer, and bread, but the high rate of admixture between yeast lineages has so far been treated as a complication for population genomic analysis. Here, we make use of the low recombination rate at centromeres to investigate admixture in yeast using a classic Bayesian approach and a locus-by-locus phylogenetic approach. Using both approaches, we find that S. cerevisiae from stable oak woodland habitats are less likely to show recent genetic admixture compared with those isolated from transient habitats such as fruits, wine, or human infections. When woodland yeast strains do show recent genetic admixture, the degree of admixture is lower than in strains from other habitats. Furthermore, S. cerevisiae populations from oak woodlands are genetically isolated from each other, with only occasional migration between woodlands and local fruit habitats. Application of the phylogenetic approach suggests that there is a previously undetected population in North Africa that is the closest outgroup to the European S. cerevisiae, including the domesticated Wine population. Careful testing for admixture in S. cerevisiae leads to a better understanding of the underlying population structure of the species and will be important for understanding the selective processes underlying domestication in this economically important species.


Non-ST elevation myocardial infarction (NSTEMI) in three hospital settings in South Africa: does geography influence management and outcome? A retrospective cohort study.
Guidelines advise early angiography in non-ST elevation myocardial infarction (NSTEMI) to ensure an optimal outcome. Resource limitations in secondary hospitals in the Western Cape dictate a local guideline to treat NSTEMIs medically with out-patient assessment for angiography, unless mandatory indications for early angiography occur. A retrospective cohort study assessed NSTEMIs at Tygerberg Hospital (TBH), Karl Bremer Hospital (KBH) and Worcester Hospital (WH) over one year. Two cohorts were analysed, secondary hospitals (KBH and WH; SH) and secondary service within a tertiary hospital (TBH). Where differences were found, sub-analysis compared WH and KBH. TBH and SH were similar at baseline and in clinical presentation. Cases at TBH were more likely to receive in-patient angiography (94 vs 51%, p < 0.0001), and had a lower in-patient mortality rate (6 vs 23%, p = 0.0326). There was no difference between KBH and WH in sub-analysis. This study confirmed that the management and mortality of NSTEMIs in the public health sector in the Western Cape, South Africa is not influenced by geography, but rather by the level of service available in the hospital of first presentation.


Contamination rates of three urine-sampling methods to assess bacteriuria in pregnant women.
To estimate and compare contamination rates of three different urine-sampling methods in pregnant women to assess bacteriuria. In this cross-sectional study, 113 pregnant women collected three different midstream urine samples consecutively: morning (first void); midstream (void without further instructions); and clean-catch sample (void after cleaning). The following end points were considered contaminants: epithelial cells, Gram-positive rods or mixed bacteria in the Gram stain, and mixed growth or skin flora in the urine culture. Intraindividual variability in contaminants was quantified with Fleiss-Cohen's weighted κ statistic. Differences between samples were assessed using generalized estimating equations. Mainly low numbers of Gram-positive rods were more likely to be present in Gram stains of midstream samples compared with clean-catch samples (77.7% compared with 66.7%, P=.022). Morning samples showed more mixed growth compared with midstream samples (6.2% compared with 0.9%, P=.050). No consistency in quantity of contaminants was found in midstream samples compared with morning and clean-catch samples. No differences were found between the other end points in all three urine samples (P>.05). The study could detect an odds ratios of 2.0 for differences in urine-sampling methods with 80% power and 5% significance for most end points. In pregnant women, the contamination rate of midstream samples is comparable with the contamination rates of morning and clean-catch samples. The quantity of contaminants varied among the three samples collected by one woman. These results show that more complex, unpractical, and time-consuming morning and clean-catch samples are not superior. Therefore, we recommend a midstream sample to assess bacteriuria in pregnant women. II.


Computational analysis of bacterial RNA-Seq data.
Recent advances in high-throughput RNA sequencing (RNA-seq) have enabled tremendous leaps forward in our understanding of bacterial transcriptomes. However, computational methods for analysis of bacterial transcriptome data have not kept pace with the large and growing data sets generated by RNA-seq technology. Here, we present new algorithms, specific to bacterial gene structures and transcriptomes, for analysis of RNA-seq data. The algorithms are implemented in an open source software system called Rockhopper that supports various stages of bacterial RNA-seq data analysis, including aligning sequencing reads to a genome, constructing transcriptome maps, quantifying transcript abundance, testing for differential gene expression, determining operon structures and visualizing results. We demonstrate the performance of Rockhopper using 2.1 billion sequenced reads from 75 RNA-seq experiments conducted with Escherichia coli, Neisseria gonorrhoeae, Salmonella enterica, Streptococcus pyogenes and Xenorhabdus nematophila. We find that the transcriptome maps generated by our algorithms are highly accurate when compared with focused experimental data from E. coli and N. gonorrhoeae, and we validate our system's ability to identify novel small RNAs, operons and transcription start sites. Our results suggest that Rockhopper can be used for efficient and accurate analysis of bacterial RNA-seq data, and that it can aid with elucidation of bacterial transcriptomes.


Japanese Encephalitis in Assam, India: Need to Increase Healthcare Workers' Understanding to Improve Health Care.
Japanese encephalitis (JE) is a major cause of high morbidity and mortality in several states across India. However, in 2014, a sharp rise was observed in the number of cases of JE in north-eastern Assam state, and 51% of the total cases of JE in India were reported from the Assam in the same year. In this regard, a study was conducted to evaluate the knowledge and attitudes of healthcare workers in Darrang, a district of Assam highly affected by JE. A cross sectional study was conducted for 2 months among HCWs in the major district hospital of Darrang, Assam. A pre-tested, self-administered questionnaire was used to collect data from the participants. Convenience sampling approach was used to collect data from different departments of the hospitals. Descriptive and logistic regression analyses were used to express the results. The knowledge of HCWs regarding JE was poor with a mean knowledge score of 11.02±2.39 (out of 17), while their attitudes were positive with a mean attitudes score of 43.16± 2.47 (ranging from 13 to 52). Overall, 40.4% and 74.3% of participants demonstrated good knowledge and positive attitudes respectively. Cut-off score for good knowledge and positive attitudes toward JE was set as ≥12 and >40 respectively. Older participants (40-49 years) and experienced workers (>10 years) were significantly associated with good knowledge as compared to their referent group (p<0.05), while knowledge of nurses and other orderlies were significantly lower than physicians (p<0.01). Similar factors were associated with the positive attitudes of the participants with the exception of experience. Television was the major source of information regarding JE reported by HCWs (79%). Although the knowledge was not optimized, HCWs exhibited positive attitudes towards JE. Future research is required to design, implement and evaluate interventions to improve the knowledge of JE among HCWs.