Cost-effectiveness of interventions to prevent HIV and STDs among women: a randomized controlled trial.
Injection drug use is a leading transmission route of HIV and STDs, and disease prevention among drug users is an important public health concern. This study assesses cost-effectiveness of behavioral interventions for reducing HIV and STDs infections among injection drug-using women. Cost-effectiveness analysis was conducted from societal and provider perspectives for randomized trial data and Bernoullian model estimates of infections averted for three increasingly intensive interventions: (1) NIDA's standard intervention (SI); (2) SI plus a well woman exam (WWE); and (3) SI, WWE, plus four educational sessions (4ES). Trial results indicate that 4ES was cost-effective relative to WWE, which was dominated by SI, for most diseases. Model estimates, however, suggest that WWE was cost-effective relative to SI and dominated 4ES for all diseases. Trial and model results agree that WWE is cost-effective relative to SI per hepatitis C infection averted ($109 308 for in trial, $6 016 in model) and per gonorrhea infection averted ($9 461 in trial, $14 044 in model). In sensitivity analysis, trial results are sensitive to 5 % change in WWE effectiveness relative to SI for hepatitis C and HIV. In the model, WWE remained cost-effective or cost-saving relative to SI for HIV prevention across a range of assumptions. WWE is cost-effective relative to SI for preventing hepatitis C and gonorrhea. WWE may have similar effects as the costlier 4ES.


High-power figure-of-eight fiber laser with passive sub-ring loops for repetition rate control.
The operation of an erbium figure-of-eight all-fiber laser with a fundamental repetition rate of 5.68 MHz, peak power of 0.7 kW and pulse width of 420 fs is reported. Four times the fundamental repetition rate is achieved with two passive sub-ring loops at a repetition rate of 22.8 MHz. The sub-ring loop consists of only a single-mode fiber coupler with an input port and output port connected so as to make the time delay an odd multiple half-period of the input pulse period. This method is simple and inexpensive when compared with conventional methods employing sub-ring cavity or special fiber Bragg grating to control repetition rate.


Identification of adenoviruses in fecal specimens from wild chimpanzees (Pan trogylodytes schweinfurthii) in western Tanzania.
DNA of two distinctive adenoviruses was detected in wild chimpanzees in western Tanzania that showed clinical signs of acute, upper respiratory disease, notably coughing. The amplified sequences from part of the capsid hexon gene suggests that one virus is a novel adenovirus serotype candidate and the other virus is a species C adenovirus most closely related to recent isolates from captive chimpanzees in the United States, Simian AdV 37 with 86% nucleic acid identity and Simian AdV 40 with 95% nucleic acid identity, respectively. The species C adenovirus sequences suggest possible recombination with a human adenovirus. The source of these viruses and disease association is not known.


Facile and novel synthesis of palladium nanoparticles supported on a carbon aerogel for ultrasensitive electrochemical sensing of biomolecules.
Highly stable palladium nanoparticles (Pd NPs) supported on a porous carbon aerogel (Pd/CA) prepared by a facile microwave reduction route is reported. The as-prepared Pd/CA composites were characterized by various techniques, viz. XRD, Raman, SEM-EDX, FE-TEM, BET, and TGA. The Pd NPs were found to disperse uniformly in the porous carbon matrix, which possesses a large surface area (851.8 m2 g-1) and pore volume (3.021 cm3 g-1). The Pd/CA composite was found to possess extraordinary electrocatalytic activity and excellent selectivity for simultaneous detection of dopamine (DA) and melatonin (ML). The Pd/CA-modified electrode exhibited a wide linear response range for electrochemical sensing of DA (0.01-100 μM) and ML (0.02-500 μM) with a detection limit of 0.0026 and 0.0071 μM, respectively. In addition, the electrochemical sensor reported herein was successfully applied for the detection of DA and ML in human serum and urine samples, revealing perspective practical applications.


Dynamic imaging of protease activity with fluorescently quenched activity-based probes.
Protease activity is tightly regulated in both normal and disease conditions. However, it is often difficult to monitor the dynamic nature of this regulation in the context of a live cell or whole organism. To address this limitation, we developed a series of quenched activity-based probes (qABPs) that become fluorescent upon activity-dependent covalent modification of a protease target. These reagents freely penetrate cells and allow direct imaging of protease activity in living cells. Targeted proteases are directly identified and monitored biochemically by virtue of the resulting covalent tag, thereby allowing unambiguous assignment of protease activities observed in imaging studies. We report here the design and synthesis of a selective, cell-permeable qABP for the study of papain-family cysteine proteases. This probe is used to monitor real-time protease activity in live human cells with fluorescence microscopy techniques as well as standard biochemical methods.


Alcohol consumption among partners of pregnant women in Sweden: a cross sectional study.
Antenatal care in Sweden involves a visit in pregnancy week 6-7 for counseling about lifestyle issues, including alcohol. The aim of this study was to investigate alcohol consumption among partners of pregnant women, their motives for changing drinking patterns when becoming a parent and their perceptions of the midwife's counseling about alcohol. The study was conducted at 30 antenatal care centers across Sweden in 2009-2010. All partners who accompanied a pregnant women in pregnancy week >17 were asked to participate. The questionnaire included questions on alcohol consumption. Questionnaires from 444 partners were analyzed. Most, 95 %, of the partners reported alcohol consumption before pregnancy; 18 % were binge drinking (6 standard drinks or more per occasion, each drink containing 12 grams of pure alcohol) at least once every month during the last year. More than half, 58 %, of all partners had decreased their alcohol consumption following pregnancy recognition and a higher proportion of binge drinkers decreased their consumption compared to non-frequent binge drinkers (p = 0.025). Their motives varied; the pregnancy itself, fewer social gatherings (potentially involving alcohol consumption) and a sense of responsibility for the pregnant partner were reported. Of the partners, 37 % reported support for decreased drinking from others (pregnant partner, parents, friend or workmates). Further, most partners appreciated the midwife's counseling on alcohol. A majority of partners decreased their alcohol consumption in transition to parenthood, which also appears to be a crucial time for changing alcohol-drinking patterns. The partners with higher AUDIT-C scores reported more support for decreased drinking. Most partners appreciated the midwife's talk about alcohol and pregnancy and those who filled out AUDIT in early pregnancy reported that the counseling was more engaging. During pregnancy it is possible to detect partners with high alcohol consumption, and promote interventions for decreased drinking, also for the partners. Written information addressing alcohol use and directed to partners is needed.


Femoral adipose tissue may accumulate the fat that has been recycled as VLDL and nonesterified fatty acids.
Gluteo-femoral, in contrast to abdominal, fat accumulation appears protective against diabetes and cardiovascular disease. Our objective was to test the hypothesis that this reflects differences in the ability of the two depots to sequester fatty acids, with gluteo-femoral fat acting as a longer-term "sink." A total of 12 healthy volunteers were studied after an overnight fast and after ingestion of a mixed meal. Blood samples were taken from veins draining subcutaneous femoral and abdominal fat and compared with arterialized blood samples. Stable isotope-labeled fatty acids were used to trace specific lipid fractions. In 36 subjects, adipose tissue blood flow in the two depots was monitored with (133)Xe. Blood flow increased in response to the meal in both depots, and these responses were correlated (r(s) = 0.44, P < 0.01). Nonesterified fatty acid (NEFA) release was suppressed after the meal in both depots; it was lower in femoral fat than in abdominal fat (P < 0.01). Plasma triacylglycerol (TG) extraction by femoral fat was also lower than that by abdominal fat (P = 0.05). Isotopic tracers showed that the difference was in chylomicron-TG extraction. VLDL-TG extraction and direct NEFA uptake were similar in the two depots. Femoral fat shows lower metabolic fluxes than subcutaneous abdominal fat, but differs in its relative preference for extracting fatty acids directly from the plasma NEFA and VLDL-TG pools compared with chylomicron-TG.


'Impact hunters' catalyse cooperative hunting in two wild chimpanzee communities.
Even when hunting in groups is mutually beneficial, it is unclear how communal hunts are initiated. If it is costly to be the only hunter, individuals should be reluctant to hunt unless others already are. We used 70 years of data from three communities to examine how male chimpanzees 'solve' this apparent collective action problem. The 'impact hunter' hypothesis proposes that group hunts are sometimes catalysed by certain individuals that hunt more readily than others. In two communities (Kasekela and Kanyawara), we identified a total of five males that exhibited high hunt participation rates for their age, and whose presence at an encounter with red colobus monkeys increased group hunting probability. Critically, these impact hunters were observed to hunt first more often than expected by chance. We argue that by hunting first, these males dilute prey defences and create opportunities for previously reluctant participants. This by-product mutualism can explain variation in group hunting rates within and between social groups. Hunting rates declined after the death of impact hunter FG in Kasekela and after impact hunter MS stopped hunting frequently in Kanyawara. There were no impact hunters in the third, smaller community (Mitumba), where, unlike the others, hunting probability increased with the number of females present at an encounter with prey.


Effects of low level exposure to lead on neurophysiological functions among lead battery workers.
Assessment of neurophysiological functions in workers with low level exposure to lead and evaluation of the efficacy of bone lead measurements in the prediction of effects of lead. Exposure to lead of 60 workers from a lead battery battery factory was estimated from historical blood lead measurements and analysis of lead in the tibial and calcaneal bones with x ray fluorescence. Peripheral and central nervous system functions were assessed by measuring conduction velocities, sensory distal latencies, sensory amplitudes, and vibration thresholds as well as by quantitative measurement of the absolute and relative powers and mean frequencies of different electroencephalograph (EEG) channels. Sensory amplitudes, and to a smaller degree sensory or motor conduction velocities, showed a negative correlation with long term exposure to lead, most clearly with integrated blood lead concentration and exposure time. Vibration thresholds measured in the arm were related to recent exposure to lead, those measured in the leg to long term exposure. The alpha and beta activities of the EEG were more abundant in subjects with higher long term exposure to lead. Calcaneal lead content reflected short term exposure, tibial lead content reflected long term exposure. Blood lead history showed a closer relation with effects of lead than the tibial or calcaneal lead concentrations. Vibratory thresholds, quantitative EEG, and to a smaller extent the sensory amplitude, provide sensitive measures of effects of lead in occupationally exposed adults. Most accurate estimates of health risks induced by lead can be obtained from a good history of blood lead measurements. If such a history of blood lead concentrations is not available, analysis of bone lead may be used for the assessment of health risks.


Approaches and advances in the genetic causes of autoimmune disease and their implications.
Genome-wide association studies are transformative in revealing the polygenetic basis of common diseases, with autoimmune diseases leading the charge. Although the field is just over 10 years old, advances in understanding the underlying mechanistic pathways of these conditions, which result from a dense multifactorial blend of genetic, developmental and environmental factors, have already been informative, including insights into therapeutic possibilities. Nevertheless, the challenge of identifying the actual causal genes and pathways and their biological effects on altering disease risk remains for many identified susceptibility regions. It is this fundamental knowledge that will underpin the revolution in patient stratification, the discovery of therapeutic targets and clinical trial design in the next 20 years. Here we outline recent advances in analytical and phenotyping approaches and the emergence of large cohorts with standardized gene-expression data and other phenotypic data that are fueling a bounty of discovery and improved understanding of human physiology.


Mater semper certa est: motherhood is always certain.
The development of oocyte donation has led to a reexamination of the facets of motherhood: the genetic, gestational, and psychosocial contributions. In addition, the practice of oocyte donation has prompted a consideration of the unique psychosocial and legal aspects of this form of family building. In this section of Views and Reviews a summary and discussion of the long-term psychosocial adjustment of oocyte donor-conceived children and their parents is presented. Next, the current permeability around donor anonymity is investigated and questions regarding whether donor anonymity can still exist is discussed. Third, the evolution of oocyte cryopreservation and banking is reviewed and the future of oocyte banking is explored. Finally, as oocyte donation continues to grow and evolve, so too does the legal landscape in which it is practiced. Seminal legal cases are presented to describe the legal landscape that has shaped the practice of oocyte donation.


Clinical features, pathogenesis and treatment of juvenile and adult dermatomyositis.
Juvenile and adult dermatomyositis (DM) have multiple commonalities, yet display differing prevalence of features, outcomes and comorbidities. In general, compared with the disease in adults, children with DM have more vasculopathy and a greater likelihood of calcinosis, periungual and gingival telangiectasias, and ulceration, but have a better long-term prognosis with improved survival. Adults with DM are more likely to have myositis-specific antibodies, develop interstitial lung disease, have amyopathic disease, and have a marked association with malignancy and other comorbidities. Both diseases have similar features on muscle biopsy and interferon gene signature, although subtle differences can exist in pathogenesis and pathology, such as more capillary loss and a greater degree of C5b-9 complement deposition in affected muscle of juvenile patients. Initiatives are underway to improve classification, markers of disease activity and ability to predict outcome of juvenile and adult DM. The purpose of this Review is to compare and contrast the unique features between juvenile and adult disease and to outline new initiatives in the field.


RANDGAN: Randomized generative adversarial network for detection of COVID-19 in chest X-ray.
COVID-19 spread across the globe at an immense rate and has left healthcare systems incapacitated to diagnose and test patients at the needed rate. Studies have shown promising results for detection of COVID-19 from viral bacterial pneumonia in chest X-rays. Automation of COVID-19 testing using medical images can speed up the testing process of patients where health care systems lack sufficient numbers of the reverse-transcription polymerase chain reaction tests. Supervised deep learning models such as convolutional neural networks need enough labeled data for all classes to correctly learn the task of detection. Gathering labeled data is a cumbersome task and requires time and resources which could further strain health care systems and radiologists at the early stages of a pandemic such as COVID-19. In this study, we propose a randomized generative adversarial network (RANDGAN) that detects images of an unknown class (COVID-19) from known and labelled classes (Normal and Viral Pneumonia) without the need for labels and training data from the unknown class of images (COVID-19). We used the largest publicly available COVID-19 chest X-ray dataset, COVIDx, which is comprised of Normal, Pneumonia, and COVID-19 images from multiple public databases. In this work, we use transfer learning to segment the lungs in the COVIDx dataset. Next, we show why segmentation of the region of interest (lungs) is vital to correctly learn the task of classification, specifically in datasets that contain images from different resources as it is the case for the COVIDx dataset. Finally, we show improved results in detection of COVID-19 cases using our generative model (RANDGAN) compared to conventional generative adversarial networks for anomaly detection in medical images, improving the area under the ROC curve from 0.71 to 0.77.


Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.
The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.


Endoscopic transpapillary stenting for the management of acute cholecystitis.
Cholecystectomy is the gold standard treatment of acute cholecystitis. Patients who are considered not to be candidates for cholecystectomy are commonly recommended to undergo percutaneous transhepatic gallbladder drainage (PTGBD) tube placement; however, external drainage is undesirable for many patients. Endoscopic transpapillary stent placement (ETSP) has been described as an alternative method for decompression of the gallbladder. Data in support of this technique is limited to a handful of observational studies with variable indications. Our study sought to expand on the available data for the use of ETSP exclusively in the context of acute cholecystitis. We performed a retrospective chart review of patients with cholecystitis who underwent ETSP at our institution between January 2012 and July 2018. We collected data on indication, comorbidities, length of stay, laboratory values, outcomes, additional procedures, and whether cholecystectomy was eventually performed. During the study period, 12 patients underwent ETSP. The mean age was 68.2 years (± SD 12.4) with an average Anesthesia Society Assessment (ASA) class of 3.2. The Charlson Comorbidity Index was greater than seven in 75% of patients, indicating a 0% estimated 10-year survival. The National Surgical Quality Improvement Program (NSQIP) surgical risk calculator was used to estimate an average mortality risk for laparoscopic cholecystectomy of 4.8% (± 3.3, 95% CI) in our study population; the estimated risk in the general population is 0.1%. Immediate resolution of symptoms with endoscopic drainage was achieved in 11 of 12 patients (91.7%); one patient experienced no symptom resolution with endoscopic drainage nor subsequent PTGBD tube placement. Six of 12 (50%) patients experienced recurrence of symptoms requiring hospitalization, and two of 12 patients (16.7%) died secondary to biliary sepsis. Endoscopic transpapillary stent placement is an alternative method for the management of acute cholecystitis patients who are not candidates for surgery. ETSP has a high technical success rate; however, it may result in a high rate of symptom recurrence and should only be utilized in select patients. Randomized studies would be beneficial to further investigate the utility and safety of ETSP in the management of acute cholecystitis.


Post-traumatic Stress Disorder Symptoms and Mental Health over Time among Low-Income Women at Increased Risk of HIV in the U.S.
Women living in poverty suffer more post-traumatic stress disorder (PTSD) symptoms than do members of the general population; however we know little about factors associated with changes in their PTSD symptoms over time. Using data from HPTN 064, a cohort of women from low-income, high-HIV-prevalence communities across six eastern states (n=1,860), we assessed the prevalence of and changes in PTSD symptoms over 12 months and the effect of potential predictors on symptom acquisition and remission (via the Primary Care-PTSD symptoms scale). Forty-three percent screened positive for PTSD symptoms. Those reporting food insecurity, ongoing abuse, depressive symptoms, or binge drinking were more likely to acquire PTSD symptoms. Those with ongoing abuse or depressive symptoms were less likely to experience PTSD symptom remission. Findings suggest a need to integrate programs to reduce abuse, depression, and economic hardship with those that address sexual health risks among women living in low-income, high-HIV-prevalence neighborhoods.


Internal Carotid Artery Strains During High-Speed, Low-Amplitude Spinal Manipulations of the Neck.
The primary objective of this study was to quantify the strains applied to the internal carotid artery (ICA) during neck spinal manipulative treatments and range of motion (ROM)/diagnostic testing of the head and neck. Strains of the ICA (n = 12) were measured in 6 fresh, unembalmed cadaveric specimens using sonomicrometry. Peak and average strains of the ICA obtained during cervical spinal manipulations given by experienced doctors of chiropractic were compared with the corresponding strains obtained during ROM and diagnostic testing of the head and neck. Peak and average strains of the ICA for cervical spinal manipulative treatments were significantly smaller (P < .001) than the corresponding strains obtained for the ROM and diagnostic testing. All strains during ROM and treatment testing were dramatically smaller than the initial failure strains of the ICA. This study showed that maximal ICA strains imparted by cervical spinal manipulative treatments were well within the normal ROM. Chiropractic manipulation of the neck did not cause strains to the ICA in excess of those experienced during normal everyday movements. Therefore, cervical spinal manipulative therapy as performed by the trained clinicians in this study, did not appear to place undue strain on the ICA and thus does not seem to be a factor in ICA injuries.


Lack of Sexual Minorities' Rights as a Barrier to HIV Prevention Among Men Who Have Sex with Men and Transgender Women in Asia: A Systematic Review.
This study set out to assess the relationship between variation in human rights for sexual minorities in Asian countries and indicators of HIV prevention among men who have sex with men (MSM) and transgender women. To quantitatively measure the relationship between variation in HIV prevention and variation in human rights for sexual minorities, this study developed the Sexual Orientation and Gender Identity (SOGI) Human Rights Index (an original index with scores ranging from 0.0 to 1.0). Subsequently, this study collected 237 epidemiological and behavioral studies from 22 Asian countries and performed a series of meta-analyses in order to calculate national averages for five indicators of HIV prevention: HIV prevalence, inconsistent condom use, recent HIV testing, adequate HIV knowledge, and exposure to HIV prevention services. A change of human rights for sexual minorities from a score of 0.0 to 1.0 as measured by the SOGI Human Rights Index was correlated with a decrease in unprotected anal intercourse by 25.5% (p=0.075), and increases in recent HIV testing by 42.9% (p=0.011), HIV knowledge by 29.5% (p=0.032), and exposure to HIV prevention services by 37.9% (p=0.119). The relationship between HIV prevalence and variation in human rights for sexual minorities was not statistically significant. Our study found correlations between human rights and indicators of HIV prevention, further supporting the need for increased rights among marginalized populations. The paucity of studies from many Asian countries as well as the disparity in how indicators of HIV prevention are measured reveals a need for increased coverage and standardization of MSM serological and behavioral data in order to better inform evidence-based policymaking.


Comparison of black-white disparities in preterm birth between Canada and the United States.
A higher risk of preterm birth among black women than among white women is well established in the United States. We compared differences in preterm birth between non-Hispanic black and white women in Canada and the US, hypothesizing that disparities would be less extreme in Canada given the different historical experiences of black populations and Canada's universal health care system. Using data on singleton live births in Canada and the US for 2004-2006, we estimated crude and adjusted risk ratios and risk differences in preterm birth (< 37 wk) and very preterm birth (< 32 wk) among non-Hispanic black versus non-Hispanic white women in each country. Adjusted models for the US were standardized to the covariate distribution of the Canadian cohort. In Canada, 8.9% and 5.9% of infants born to black and white mothers, respectively, were preterm; the corresponding figures in the US were 12.7% and 8.0%. Crude risk ratios for preterm birth among black women relative to white women were 1.49 (95% confidence interval [CI] 1.32 to 1.66) in Canada and 1.57 (95% CI 1.56 to 1.58) in the US (p value for heterogeneity [pH] = 0.3). The crude risk differences for preterm birth were 2.94 (95% CI 1.91 to 3.96) in Canada and 4.63 (95% CI 4.56 to 4.70) in the US (pH = 0.003). Adjusted risk ratios for preterm birth (pH = 0.1) were slightly higher in Canada than in the US, whereas adjusted risk differences were similar in both countries. Similar patterns were observed for racial disparities in very preterm birth. Relative disparities in preterm birth and very preterm birth between non-Hispanic black and white women were similar in magnitude in Canada and the US. Absolute disparities were smaller in Canada, which reflects a lower overall risk of preterm birth in Canada than in the US in both black and white populations.


Induction of gynogenesis in muskellunge with irradiated sperm of yellow perch proves diploid muskellunge male homogamety.
Diploid gynogenesis was induced in muskellunge Esox masquinongy using UV-irradiated muskellunge sperm as the first step in producing monosex females. In this approach, we have to rely on negative controls as an indirect reference for sperm genetic material destruction. In the first experiment, equal proportions of gynogenetic females and males were produced. Negative controls, UV-irradiated sperm without heat shock, yielded some normal hatching larvae, described as spontaneous diploids. In the second experiment, muskellunge eggs were activated using sperm from yellow perch. Because hybrids between these species are not viable, we produced unambiguous gynogens. When UV-irradiated yellow perch sperm was used to inseminate muskellunge eggs, haploids resulted (22.5% +/- 2.8% survival to the eyed stage). To produce diploid gynogens, a heat shock of 31 degrees C was applied to inseminated eggs 20 min after activation for a duration of 6 min. This process yielded several hundreds of gynogens for rearing. Several treatments of masculinizing hormone, 17alpha-methyltestosterone (MT), were carried out. Fish were dissected and gonads examined histologically for sex determination. Gynogens produced using yellow-perch sperm confirmed the presence of males in the control group, whereas the MT bath treatment (400 microg/liter) resulted in the production of fish with ovotestis. These results provide evidence for male homogamety in muskellunge and imply that a change of strategy is needed to produce monosex populations.


TROY (TNFRSF19) promotes glioblastoma survival signaling and therapeutic resistance.
Of the features that characterize glioblastoma, arguably none is more clinically relevant than the propensity of malignant glioma cells to aggressively invade into the surrounding normal brain tissue. These invasive cells render complete resection impossible, confer significant resistance to chemo- and radiation-therapy, and virtually assure tumor recurrence. Expression of TROY (TNFRSF19), a member of the TNF receptor superfamily, inversely correlates with patient survival and stimulates glioblastoma cell migration and invasion in vitro. In this study, we report that TROY is overexpressed in glioblastoma tumor specimens and TROY mRNA expression is increased in the invasive cell population in vivo. In addition, inappropriate expression of TROY in mouse astrocytes in vivo using glial-specific gene transfer in transgenic mice induces astrocyte migration within the brain, validating the importance of the TROY signaling cascade in glioblastoma cell migration and invasion. Knockdown of TROY expression in primary glioblastoma xenografts significantly prolonged survival in vivo. Moreover, TROY expression significantly increased resistance of glioblastoma cells to both IR- and TMZ-induced apoptosis via activation of Akt and NF-κB. Inhibition of either Akt or NF-κB activity suppressed the survival benefits of TROY signaling in response to TMZ treatment. These findings position aberrant expression and/or signaling by TROY as a contributor to the dispersion of glioblastoma cells and therapeutic resistance. Targeting of TROY may increase tumor vulnerability and improve therapeutic response in glioblastoma. Mol Cancer Res; 11(8); 865-74. ©2013 AACR.


Who applies and who gets admitted to UK graduate entry medicine? - An analysis of UK admission statistics.
Graduate-entry medicine is a recent development in the UK, intended to expand and broaden access to medical training. After eight years, it is time to evaluate its success in recruitment. This study aimed to compare the applications and admissions profiles of graduate-entry programmes in the UK to traditional 5 and 6-year courses. Aggregate data on applications and admissions were obtained from the Universities and Colleges Admission Service covering 2003 to 2009. Data were extracted, grouped as appropriate and analysed with the Statistical Package for the Social Sciences. Graduate-entry attracts 10,000 applications a year. Women form the majority of applicants and admissions to graduate-entry and traditional medicine programmes. Graduate-entry age profile is older, typically 20's or 30's compared to 18 or 19 years in traditional programmes. Graduate-entry applications and admissions were higher from white and black UK ethnic communities than traditional programmes, and lower from southern and Chinese Asian groups. Graduate-entry has few applications or admissions from Scotland or Northern Ireland. Secondary educational achievement is poorer amongst graduate-entry applicants and admissions than traditional programmes. Graduate-entry has succeeded in recruiting substantial additional numbers of older applicants to medicine, in which white and black groups are better represented and Asian groups more poorly represented than in traditional undergraduate programmes.


Factor XI-deficient mice display reduced inflammation, coagulopathy, and bacterial growth during listeriosis.
In mice infected sublethally with Listeria monocytogenes, fibrin is deposited at low levels within hepatic tissue, where it functions protectively by limiting bacterial growth and suppressing hemorrhagic pathology. Here we demonstrate that mice infected with lethal doses of L. monocytogenes produce higher levels of fibrin and display evidence of systemic coagulopathy (i.e., thrombocytopenia, fibrinogen depletion, and elevated levels of thrombin-antithrombin complexes). When the hepatic bacterial burden exceeds 1×10(6) CFU, levels of hepatic fibrin correlate with the bacterial burden, which also correlates with levels of hepatic mRNA encoding the hemostatic enzyme factor XI (FXI). Gene-targeted FXI-deficient mice show significantly improved survival upon challenge with high doses of L. monocytogenes and also display reduced levels of hepatic fibrin, decreased evidence of coagulopathy, and diminished cytokine production (interleukin-6 [IL-6] and IL-10). While fibrin limits the bacterial burden during sublethal listeriosis in wild-type mice, FXI-deficient mice display a significantly improved capacity to restrain the bacterial burden during lethal listeriosis despite their reduced fibrin levels. They also show less evidence of hepatic necrosis. In conjunction with suboptimal antibiotic therapy, FXI-specific monoclonal antibody 14E11 improves survival when administered therapeutically to wild-type mice challenged with high doses of L. monocytogenes. Together, these findings demonstrate the utility of murine listeriosis as a model for dissecting qualitative differences between protective and pathological host responses and reveal novel roles for FXI in exacerbating inflammation and pathogen burden during a lethal bacterial infection.


Pruritus Is Common and Undertreated in Patients With Primary Biliary Cholangitis in the United Kingdom.
Little is known about the prevalence or treatment of pruritus associated with primary biliary cholangitis (PBC). We analyzed data from patients with PBC recruited from all clinical centers in the United Kingdom (UK) to characterize the prevalence, severity, progression, and treatment of pruritus. We performed cross-sectional and longitudinal studies of patients in the UK-PBC cohort to assess trajectories of pruritus. Data on pruritus frequency, severity, and therapy were collected via paper questionnaires completed by 2194 patients at their initial assessment in 2011 and then again in 2014 and 2017. Self-reported treatment data were validated against the prescription record of PBC cohort in the Clinical Practice Research Datalink, a primary care database. We defined persistent pruritus as itch that occurs frequently or all the time and severe pruritus as PBC-40 pruritus domain scores of 12 or more, throughout their disease course. Latent class mixed models were used to study pruritus trajectories and identify factors associated with high pruritus. At initial assessment, 1613 (73.5%) patients had experienced pruritus at some point since their development of PBC-persistent pruritus was reported by 34.5% of the patients and severe pruritus by 11.7%. Only 37.4% of patients with persistent pruritus and 50% with severe pruritus reported ever receiving cholestyramine. Frequencies of rifampicin use were 11% in patients with persistent pruritus and 23% in patients with severe pruritus. Comparison of 2011 and 2014 surveys (comprising 1423 patients) showed consistent self-reported data on pruritus. Proportions of patients in the UK-PBC cohort treated with cholestyramine or naltrexone (37.4% and 4.4%) did not differ significantly from proportions treated in the Clinical Practice Research Datalink cohort (30.4% and 4.4%) (P = .07 for cholestyramine and P = .32 for naltrexone). Latent class mixed models (n = 1753) identified 3 different groups of pruritus. Multivariable analysis identified younger age at diagnosis and higher level of alkaline phosphatase at 12 months after diagnosis as factors significantly associated with persistent high pruritus. In a large national cohort study of patients with PBC, we found a high prevalence of pruritus and inadequate guideline-recommended therapy. Patient-reported data used to determine pruritus prevalence and treatment are reliable. Younger age and levels of higher alkaline phosphatase were associated with persistent pruritus. We need to increase awareness and management of pruritus in PBC in the UK.


Postmortem perianal findings in children.
The postmortem finding of anal dilation or an exposed pectinate line in children who have died under suspicious circumstances continues to raise the concern of possible sexual abuse. The following multicenter, collaborative study was designed to help address that question. Sixty-five subjects, ranging in age from birth to 17 years, were autopsied at three different sites. A standard protocol along with 35-mm cameras were used to record the results. Thirty-eight (58%) subjects were boys, and 27 (42%) were girls. Forty-two (65%) were white, 10 (15%) African-American, five (8%) Asian, three (5%) white Hispanic and five (8%) other. Fifty-seven (88%) were in Tanner stage I of secondary sexual development. Thirty-four (52%) died of natural causes, 26 (40%) from accidental injuries, three (5%) from other causes, and four (6%) as a result of a homicide. Forty-eight subjects (74%) had some dilation of the anal sphincters. In 21 children (32%), the entire anal canal, including the rectal ampulla, could be visualized. In another 21 (32%) subjects, the pectinate line was exposed. Only the outer portion of the anal canal opened in six children (10%), whereas 17 (26%) had no dilatation of the anus. Anal laxity led to flattened skin folds in 50 (77%), a shallow anal canal in 40 (62%), the exposure of both the pectinate line in 38 (59%), and the anal mucosa in 24 (37%). Venous congestion was present in 14 (22%), venous pooling in three (5%), erythema in six (9%), and increased pigmentation in eight (12%). Funneling was found in two (3%). Blood was present in three (5%), and an abrasion was discovered in one (2%). No fissures, lacerations, hemorrhoids, or scars were found in any of the children. Anal orifice size varied with the age of the child, the amount of traction applied to the buttocks, and a history of a CNS injury at the time of death. It is suggested, finally, that anal dilatation alone cannot be used a marker for prior sexual abuse and the exposure of the pectinate line should not be confused with tears or fissures of the anal verge. Further studies of children known to have been sodomized prior to death are required.


Anticoagulant rodenticide screening in dogs: 123 cases (1996-2003).
To identify dogs with anticoagulant rodenticide (AR) screens submitted, determine whether detected concentrations of the anticoagulants correlated with severity of clinical signs for dogs with positive results on AR screens, and identify the most common disease processes present and the prognosis for those with negative AR screens. Retrospective case series. 123 dogs. History, signalment, clinical signs, physical examination findings, PCV, total solids concentration, prothrombin time, activated partial thromboplastin time, platelet count, AR concentrations, duration of hospitalization, blood products administered, final diagnosis, and outcome were recorded from medical records of dogs that underwent AR toxicology screenings. 75 of 123 (60.9%) dogs tested positive for AR. Dogs tested positive for brodifacoum, diphacinone (also called diphenadione), and chlorophacinone. Dogs with positive AR screenings weighed significantly less, received significantly more fresh frozen plasma, had significantly longer initial prothrombin time, and were significantly more likely to survive, compared with those with negative screens. Anticoagulant rodenticide concentrations ranged from trace amounts to 1,120 parts per billion and were not correlated with any recorded parameter. The most common conditions diagnosed in the 48 dogs with negative screens included neoplasia in 15 (31.3%), immune-mediated disease in 7 (14.6%), and gastrointestinal bleeding in 5 (10.4%) dogs. AR concentrations were not correlated with severity of clinical signs or the degree of prolongation of coagulation times in this series of patients. Patients with severe coagulopathies but negative results of AR screening had a poor prognosis, with neoplasia as the most common diagnosis. Anticoagulant rodenticide intoxication had the best prognosis, with a survival rate of 98.7% in this study.


A systematic methodology to estimate added sugar content of foods.
The effect of added sugar on health is a topical area of research. However, there is currently no analytical or other method to easily distinguish between added sugars and naturally occurring sugars in foods. This study aimed to develop a systematic methodology to estimate added sugar values on the basis of analytical data and ingredients of foods. A 10-step, stepwise protocol was developed, starting with objective measures (six steps) and followed by more subjective estimation (four steps) if insufficient objective data are available. The method developed was applied to an Australian food composition database (AUSNUT2007) as an example. Out of the 3874 foods available in AUSNUT2007, 2977 foods (77%) were assigned an estimated value on the basis of objective measures (steps 1-6), and 897 (23%) were assigned a subjectively estimated value (steps 7-10). Repeatability analysis showed good repeatability for estimated values in this method. We propose that this method can be considered as a standardised approach for the estimation of added sugar content of foods to improve cross-study comparison.


Central pathology laboratory review of HER2 and ER in early breast cancer: an ALTTO trial [BIG 2-06/NCCTG N063D (Alliance)] ring study.
Choice of therapy for breast cancer relies on human epidermal growth factor receptor-2 (HER2) and estrogen receptor α (ER) status. Before randomization in the phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial for HER2-positive disease, HER2 and ER were centrally reviewed by Mayo Clinic (Rochester, MN, and Scottsdale, AZ) for North America and by the European Institute of Oncology (IEO; Milan, Italy) for the rest of world (except China). Discordance rates (local vs. central review) differed between Mayo and IEO. Among locally HER2-positive cases, 5.8 % (Mayo) and 14.5 % (IEO) were centrally HER2 negative. Among locally ER-positive cases, 16.2 % (Mayo) and 4.2 % (IEO) were centrally ER-negative. Among locally ER-negative cases, 3.4 % (Mayo) and 21.4 % (IEO) were centrally ER-positive. We, therefore, performed a ring study to identify features contributing to these differing discordance rates. Mayo and IEO exchanged slides for 25 HER2 and 35 ER locally/centrally discordant cases. Both laboratories performed IHC and FISH for HER2 using the HercepTest(®) and PathVysion HER2 DNA probe kit/HER2/centromere 17 probe mixture. IHC for ER was tested centrally using the monoclonal ER 1D5 antibody (Mayo) or the DAKO cocktail of ER 1D5 and 2.123 antibodies (IEO). Mayo and IEO confirmed the central HER2-negative result in 100 % of 25 cases. Mayo and IEO confirmed the central ER result in 29 (85 %) of 34 evaluable cases. The five Mayo-negative/IEO-positive cases were ER-positive when retested at Mayo using the DAKO ER cocktail. In this ring study, ALTTO ineligibility did not change when HER2 testing was performed by either IEO or Mayo central laboratories. However, a dual antibody ER assay had fewer false-negative test results than an assay with a single antibody, and there was more discordance between the two ER reagents than has been previously reported. Using even slightly different assay methods yielded different results, even between experienced central laboratories.


Implementing antibiotic stewardship in high-prescribing English general practices: a mixed-methods study.
Trials have identified antimicrobial stewardship (AMS) strategies that effectively reduce antibiotic use in primary care. However, many are not commonly used in England. The authors co-developed an implementation intervention to improve use of three AMS strategies: enhanced communication strategies, delayed prescriptions, and point-of-care C-reactive protein tests (POC-CRPTs). To investigate the use of the intervention in high-prescribing practices and its effect on antibiotic prescribing. Nine high-prescribing practices had access to the intervention for 12 months from November 2019. This was primarily delivered remotely via a website with practices required to identify an 'antibiotic champion'. Routinely collected prescribing data were compared between the intervention and the control practices. Intervention use was assessed through monitoring. Surveys and interviews were conducted with professionals to capture experiences of using the intervention. There was no evidence that the intervention affected prescribing. Engagement with intervention materials differed substantially between practices and depended on individual champions' preconceptions of strategies and the opportunity to conduct implementation tasks. Champions in five practices initiated changes to encourage use of at least one AMS strategy, mostly POC-CRPTs; one practice chose all three. POC-CRPTs was used more when allocated to one person. Clinicians need detailed information on exactly how to adopt AMS strategies. Remote, one-sided provision of AMS strategies is unlikely to change prescribing; initial clinician engagement and understanding needs to be monitored to avoid misunderstanding and suboptimal use.


Clonal dispersion and evidence for asymmetric cell division in ferret cortex.
Cell lineage analysis with retroviral libraries suggests that clonal progeny disperse widely in rodent cortex. To determine whether widespread dispersion is a general mammalian plan and to investigate phylogenetic differences in cortical development, we analyzed cell lineage in the ferret, a carnivore and near relative of the cat. The ferret possesses a highly developed, folded cerebral cortex, characteristic of higher mammalian species. Progenitor cells of the ferret cerebral cortex were tagged with an amphotropic retroviral library encoding alkaline phosphatase, and sibling relationships were determined using the polymerase chain reaction. Neuronal clones were single neurons (52%) or large clones (48%; average, 7 neurons) containing neurons and glia in widespread cortical locations. Neuronal clones in the ferret labeled at middle to late neurogenesis (embryonic day 33-35) contained large numbers of neurons and showed little tendency to cluster. The large proportion of single neuron clones, contrasted with the large size of multicell clones, suggests that some progenitors divide asymmetrically, producing a postmitotic neuron and regenerating a multipotential cell.


Methanol-related deaths in Ontario.
Methanol poisoning accounts for several deaths annually in the province of Ontario. Our study was aimed at identifying the associated epidemiological factors for fatal outcomes following methanol poisoning in order to develop preventative strategies. The records of the Ontario Provincial Coroner's Office were reviewed retrospectively for all poison-related, alcohol-related, and chronic alcohol use-related deaths for the period of January 1, 1986 to December 31, 1991. Age, gender, reason for ingestion (accidental or intentional), and source of methanol for each victim were recorded. There were 43 fatalities during this period, 39 males and 4 females with a mean age of 45 years (range 18-80). Suicide attempts accounted for 21 (49%) cases while the remaining 22 (51%) deaths were classified as accidental. Fourteen (64%) of these 22 patients consumed products labeled as methyl alcohol or wood alcohol as a substitute for ethanol. In 3 cases, the accidental ingestion was the direct result of methanol being improperly stored in containers normally associated with ethanol. The remaining 5 patients were poisoned through the consumption of liquor from illicit sources. Over half of the methanol-related deaths in Ontario are accidental and potentially preventable. Possible preventative strategies include mandatory product relabeling to eliminate the word alcohol, enhanced public education, and the addition of aversive agents to methanol-containing commercial products.


NETGEM: Network Embedded Temporal GEnerative Model for gene expression data.
Temporal analysis of gene expression data has been limited to identifying genes whose expression varies with time and/or correlation between genes that have similar temporal profiles. Often, the methods do not consider the underlying network constraints that connect the genes. It is becoming increasingly evident that interactions change substantially with time. Thus far, there is no systematic method to relate the temporal changes in gene expression to the dynamics of interactions between them. Information on interaction dynamics would open up possibilities for discovering new mechanisms of regulation by providing valuable insight into identifying time-sensitive interactions as well as permit studies on the effect of a genetic perturbation. We present NETGEM, a tractable model rooted in Markov dynamics, for analyzing the dynamics of the interactions between proteins based on the dynamics of the expression changes of the genes that encode them. The model treats the interaction strengths as random variables which are modulated by suitable priors. This approach is necessitated by the extremely small sample size of the datasets, relative to the number of interactions. The model is amenable to a linear time algorithm for efficient inference. Using temporal gene expression data, NETGEM was successful in identifying (i) temporal interactions and determining their strength, (ii) functional categories of the actively interacting partners and (iii) dynamics of interactions in perturbed networks. NETGEM represents an optimal trade-off between model complexity and data requirement. It was able to deduce actively interacting genes and functional categories from temporal gene expression data. It permits inference by incorporating the information available in perturbed networks. Given that the inputs to NETGEM are only the network and the temporal variation of the nodes, this algorithm promises to have widespread applications, beyond biological systems.The source code for NETGEM is available from https://github.com/vjethava/NETGEM.


A Novel, Real-Time, In Vivo Mouse Retinal Imaging System.
To develop an efficient, low-cost instrument for robust real-time imaging of the mouse retina in vivo, and assess system capabilities by evaluating various animal models. Following multiple disappointing attempts to visualize the mouse retina during a subretinal injection using commercially available systems, we identified the key limitation to be inadequate illumination due to off axis illumination and poor optical train optimization. Therefore, we designed a paraxial illumination system for Greenough-type stereo dissecting microscope incorporating an optimized optical launch and an efficiently coupled fiber optic delivery system. Excitation and emission filters control spectral bandwidth. A color coupled-charged device (CCD) camera is coupled to the microscope for image capture. Although, field of view (FOV) is constrained by the small pupil aperture, the high optical power of the mouse eye, and the long working distance (needed for surgical manipulations), these limitations can be compensated by eye positioning in order to observe the entire retina. The retinal imaging system delivers an adjustable narrow beam to the dilated pupil with minimal vignetting. The optic nerve, vasculature, and posterior pole are crisply visualized and the entire retina can be observed through eye positioning. Normal and degenerative retinal phenotypes can be followed over time. Subretinal or intraocular injection procedures are followed in real time. Real-time, intravenous fluorescein angiography for the live mouse has been achieved. A novel device is established for real-time viewing and image capture of the small animal retina during subretinal injections for preclinical gene therapy studies.


Quantum-classical crossover and apparent metal-insulator transition in a weakly interacting 2D Fermi liquid.
We report the observation of an apparent parallel magnetic-field-induced metal-insulator transition in a high-mobility two-dimensional electron gas for which spin and localization physics most likely play no major role. The high-mobility metallic phase at low field is consistent with the established Fermi liquid transport theory including phonon scattering, whereas the phase at higher field shows a large insulatinglike negative temperature dependence at resistances much smaller than the quantum of resistance h/e(2). We argue that this observation is a direct manifestation of a quantum-classical crossover arising predominantly from the magneto-orbital coupling between the finite width of the two-dimensional electron gas and the in-plane magnetic field.


A DFT+U study of A-site and B-site substitution in BaFeO3-δ.
BaFeO3-δ (BFO)-based perovskites have emerged as cheap and effective oxygen electrocatalysts for oxygen reduction reaction at high temperatures. The BFO cubic phase facilitates a high oxygen deficiency and is commonly stabilised by partial substitution. Understanding the electronic mechanisms of substitution and oxygen deficiency is key to rational material design, and can be realised through DFT analysis. In this work an in-depth first principle DFT+U study is undertaken to determine site distinctive characteristics for 12.5%, Y, La and Ce substitutions in BFO. In particular, it is shown that B-site doped structures exhibit a lower energy cost for oxygen vacancy formation relative to A site doping and pristine BFO. This is attributed to the stabilisation of holes in the oxygen sub-lattice and increased covalency of the Fe-O bonds of the FeO6 octahedra in B-site-substituted BFO. Charge analysis shows that A-site substitution amounts to donor doping and consequently impedes the accommodation of other donors (i.e. oxygen vacancies). However, A-site substitution may also exhibit a higher electronic conductivity due to less lattice distortion for oxygen deficiency compared to B-site doped structures. Furthermore, analysis of the local structural effects provides physical insight into stoichiometric expansions observed for this material.


Relationship Between the of Type of Accessory Navicular Bone and Radiological Parameters of the Foot.
In this study, we evaluated to the relationship between the type of accessory navicular bone (ANB) and radiological parameters of foot in patients with bilateral ANB of different types. Patients with bilateral ANB of different types participated in this study, from May 2019 to April 2020. Patient data, including age, sex, body mass index (BMI), and presence of symptoms were obtained. We aimed to compare the radiological parameters of both the feet for evaluate the differences from one another in patients with bilateral ANB of different types (one side type 1 and contralateral side type 2) because the foot angles may differ in each person. Seven radiographic parameters were measured, including calcaneal pitch angle, talocalcaneal angle, tibiocalcaneal angle, naviculocuboid overlap, talonavicular coverage angle, anteroposterior talo-first metatarsal angle, and the lateral talo-first metatarsal angle, which evaluated hindfoot, midfoot, and forefoot alignment. Twenty patients (13 women and 7 men) with a mean age (and standard deviation) of 38.5 {plus minus} 12.3 years were included in the study. The patients had a mean height of 168.1 {plus minus} 7.1 cm, a mean weight of 77.2 {plus minus} 10.5 kg, and a mean BMI of 27.4 {plus minus} 4.3 kg/m2. There was no significant difference between type 1 and type 2 in all radiological parameters. There was no significant correlation between radiological parameters and age, BMI, or the presence of symptoms. We found that the type of ANB had no effect on the radiological measurements of the foot in which we evaluate the parameters patients with bilateral ANB of different types. Additionally, age, BMI, and the presence of symptoms, also demonstrated no correlation with the radiological parameters of the foot.


The trade-off between meticulousness and methodological variance in normalization of low back EMG.
Normalization of surface electromyography (EMG) is a common and recommended practice, however this methodological step itself introduces variability to a data set. Quantification of this variance is necessary to correctly interpret overall EMG variability. This information is also paramount to identifying experimentally and clinically relevant normalization task(s) which minimize induced variance yet are time-efficient. The goal of this study was to quantify the within-day variance of two commonly reported, sub-maximal tasks utilised for low back EMG normalization: one collected with a high degree of meticulousness, and the other collected in a more rapid manner. Only minimal differences were seen between tasks in the magnitude of within-day variance for EMG amplitude at all recording sites, save the right-side L5 location, which showed a significant difference (p=0.020). For trunk posture, within-day variance for the highly meticulous tasks was significantly higher than for the less-meticulous task (p=0.011). A less meticulous sub-maximal normalization task performed in a standing position was equal or superior to a more meticulously collected task in terms of kinematic task repeatability and within-day EMG variance. These findings are encouraging for field study applications where meticulous methods are not feasible, and provide a time saving strategy for lab studies.


Upregulation of integrins alpha v beta 3 and alpha v beta 5 on human monocytes and T lymphocytes facilitates adenovirus-mediated gene delivery.
Entry of human adenovirus into host cells involves interaction of virus particles with two distinct receptors. The initial binding event is mediated by the fiber protein, while subsequent interaction of the penton base protein with alpha v integrins promotes virus internalization and/or penetration. Although these interactions in epithelial and endothelial cells have been well characterized, relatively little is known as to whether these events occur during virus infection of human peripheral blood mononuclear cells. We demonstrate that freshly isolated peripheral blood monocytes and T lymphocytes express very small amounts of alpha v integrins and also are resistant to adenovirus infection. Exposure of monocytes to hematopoietic growth factors granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor induced expression of cell surface alpha v integrins, promoted the binding of penton base protein, and also rendered these cells susceptible to adenovirus-mediated gene delivery. Stimulation of T cells with a mitogen, phytohemagglutinin, or a cell-activating agent, phorbol myristate acetate, induced expression of alpha v integrins and also enhanced adenovirus-mediated gene delivery. These studies further indicate that alpha v integrins play a crucial role in adenovirus infection and also provide a useful strategy for enhancing adenovirus-mediated gene delivery into human peripheral blood mononuclear cells.


Helminth parasites in pigs: new challenges in pig production and current research highlights.
Helminths in pigs have generally received little attention from veterinary parasitologists, despite Ascaris suum, Trichuris suis, and Oesophagostomum sp. being common worldwide. The present paper presents challenges and current research highlights connected with these parasites. In Danish swine herds, new indoor production systems may favour helminth transmission and growing knowledge on pasture survival and infectivity of A. suum and T. suis eggs indicates that they may constitute a serious threat to outdoor pig production. Furthermore, it is now evident that A. suum is zoonotic and the same may be true for T. suis. With these 'new' challenges and the economic impact of the infections, further research is warranted. Better understanding of host-parasite relationships and A. suum and T. suis egg ecology may also improve the understanding and control of human A. lumbricoides and T. trichiura infections. The population dynamics of the three parasites are well documented and may be used to study phenomena, such as predisposition and worm aggregation. Furthermore, better methods to recover larvae have provided tools for quantifying parasite transmission. Thus, an on-going study using helminth naïve tracer pigs has surprisingly demonstrated that soil infectivity with A. suum and T. suis increases during the first 2-3 years after pasture contamination. Though all three helminth species stimulate the Th2 arm of the immune system, Oesophagostomum seems weakly immunogenic, perhaps via specific modulation of the host immune system. A. suum and T. suis potently modulate the host immune response, up-regulating Th2 and down-regulating Th1. As a consequence, A. suum may compromise the efficacy of certain bacterial vaccines, whereas T. suis, which establish only short-term in humans, is a favourite candidate for down-regulating autoimmune Th1-related diseases in man. Some basic research findings have offered new possibilities for future sustainable control measures. For example, the heredity of host resistance to A. suum and T. suis is so high that breeding for resistant pigs may be a possibility. Experimental studies have demonstrated that fermentable dietary carbohydrates have an antagonistic effect on Oesophagostomum and to a lesser extent on T. suis and A. suum, whereas egg-destroying microfungi may be used to inactivate the hard-shelled A. suum and T. suis eggs in the environment. Helminth control in Denmark has previously relied solely on anthelmintic treatment in herds with low helminth transmission. When indoor transmission rates increase, or in outdoor herds with high pasture contamination levels, medication may advantageously be combined with sustainable control measures, such as selected pig genomes, bioactive forages, and egg-destroying microfungi.


Augmented compared with nonaugmented surgical repair of a fresh total Achilles tendon rupture. A prospective randomized study.
Augmented and nonaugmented techniques have been used for the operative repair of a fresh complete Achilles tendon rupture. Augmented techniques have been favored for their stronger pullout strengths but have been avoided because of the risk of wound complications. If proven to be equally good, the nonaugmented technique would be the method of choice. In the present study, we hypothesized that augmentation with a down-turned gastrocnemius fascia flap would not provide better results than would end-to-end suture repair with use of the Krackow locking loop surgical technique. Sixty patients with an acute Achilles tendon rupture were randomized preoperatively to receive end-to-end suture repair with use of the Krackow locking loop technique either without augmentation (simple repair group) or with a down-turned gastrocnemius fascia flap as described by Silfverskiöld (augmented repair group). A brace allowed free active plantar flexion of the ankle postoperatively, whereas dorsiflexion was restricted to neutral for the first three weeks. Weight-bearing was limited for six weeks. The follow-up period was one year, and the patients were evaluated in terms of clinical measurements, an outcome score, isokinetic calf muscle performance tests, and tendon elongation measurements. The mean operative time was twenty-five minutes longer and the incision was 7 cm longer in the augmented repair group as compared with the simple repair group (p < 0.001 for both). In the simple repair group, the overall ankle score was excellent for nineteen patients (63%) and good for eight patients (27%) and three patients (10%) had an early failure (all because of rerupture). In the augmented repair group, the ankle score was excellent for fourteen patients (56%) and good for six patients (24%) and five patients (20%) had a failure because of rerupture (three) or deep infection (two). The difference between the groups with regard to the overall result was not significant (p = 0.68). In the simple repair group the isokinetic calf muscle strength score was excellent for eleven patients (37%), good for fourteen patients (47%), and fair for two patients (7%), with three patients (10%) having a failure, whereas in the augmented repair group the score was excellent for nine patients (36%), good for seven patients (28%), fair for three patients (12%), and poor for one patient (4%), with five patients (20%) having an early failure. Achilles tendon elongation occurred in both groups, and elongation correlated significantly with isokinetic peak torque deficits (rho = 0.64, p = 0.001) and isometric strength deficits (rho = 0.48, p = 0.026) in the simple repair group. No significant differences were seen between the two groups at the three-month and twelve-month checkups with regard to pain, stiffness, subjective calf muscle weakness, footwear restrictions, range of ankle motion, overall outcome, isokinetic calf muscle strength, mean peak work-displacement relationships, or tendon elongation. Augmented repair of a fresh total Achilles tendon rupture does not have any advantage over simple end-to-end repair.


Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines.
Matrix metalloproteinases (MMPs) are involved in the degradation of protein components of the extracellular matrix and thus play an important role in tumor invasion and metastasis. Their expression is related to the progression of gynecological cancers (e.g. endometrial, cervical or ovarian carcinoma). In this study we investigated the expression pattern of the 23 MMPs, currently known in humans, in different gynecological cancer cell lines. In total, cell lines from three endometrium carcinomas (Ishikawa, HEC-1-A, AN3 CA), three cervical carcinomas (HeLa, Caski, SiHa), three chorioncarcinomas (JEG, JAR, BeWo), two ovarian cancers (BG-1, OAW-42) and one teratocarcinoma (PA-1) were examined. The expression of MMPs was analyzed by RT-PCR, Western blot and gelatin zymography. We demonstrated that the cell lines examined can constitutively express a wide variety of MMPs on mRNA and protein level. While MMP-2, -11, -14 and -24 were widely expressed, no expression was seen for MMP-12, -16, -20, -25, -26, -27 in any of the cell lines. A broad range of 16 MMPs could be found in the PA1 cells and thus this cell line could be used as a positive control for general MMP experiments. While the three cervical cancer cell lines expressed 10-14 different MMPs, the median expression in endometrial and choriocarcinoma cells was 7 different enzymes. The two investigated ovarian cancer cell lines showed a distinctive difference in the number of expressed MMPs (2 vs. 10). Ishikawa, Caski, OAW-42 and BeWo cell lines could be the best choice for all future experiments on MMP regulation and their role in endometrial, cervical, ovarian or choriocarcinoma development, whereas the teratocarcinoma cell line PA1 could be used as a positive control for general MMP experiments.


Anti-nucleoprotein antibody response in influenza A infection.
The nucleoprotein (NP) antigen isolated from influenza A virus by solubilization with Triton X-100 (TX-100) and further electrophoresis with SDS-cellulose acetate membrane gave a single band on SDS-polyacrylamide gel electrophoresis. Rabbit anti-serum hyperimmunized with the NP reacted only against the NP antigen. Moreover, a well-defined single precipitin line was shown between the NP and human sera. These results suggested that the NP was possible to detect anti-NP antibody in human serum. Immuno double diffusion (IDD) and single radial immunodiffusion (SRD) tests using the NP were established to detect the anti-NP antibody in human sera. During an epidemic caused by antigenic drift strain, anti-NP antibody was detected by the IDD test in the cases which did not show any significant rise in HAI titer. During a mixed epidemic caused by the different strain of HA antigen, the infection ratio in mass population was revealed more convenient and sensitive by SRD than HAI. The anti-NP antibody was detected by IDD for long periods of one year or more after infection. These results suggest that the detection of anti-NP antibody is applicable to serologic studies, particularly serologic diagnosis and serologic surveys of influenza infection in mass population.


Intuitive Honesty Versus Dishonesty: Meta-Analytic Evidence.
Is self-serving lying intuitive? Or does honesty come naturally? Many experiments have manipulated reliance on intuition in behavioral-dishonesty tasks, with mixed results. We present two meta-analyses (with evidential value) testing whether an intuitive mind-set affects the proportion of liars (k = 73; n = 12,711) and the magnitude of lying (k = 50; n = 6,473). The results indicate that when dishonesty harms abstract others, promoting intuition causes more people to lie, log odds ratio = 0.38, p = .0004, and people to lie more, Hedges's g = 0.26, p < .0001. However, when dishonesty inflicts harm on concrete others, promoting intuition has no significant effect on dishonesty (p > .63). We propose one potential explanation: The intuitive appeal of prosociality may cancel out the intuitive selfish appeal of dishonesty, suggesting that the social consequences of lying could be a promising key to the riddle of intuition's role in honesty. We discuss limitations such as the relatively unbalanced distribution of studies using concrete versus abstract victims and the overall large interstudy heterogeneity.


Unresolved question of the 10He ground state resonance.
The ground state of (10)He was populated using a 2p2n-removal reaction from a 59 MeV/u (14)Be beam. The decay energy of the three-body system, (8)He+n+n, was measured and a resonance was observed at E=1.60(25) MeV with a 1.8(4) MeV width. This result is in agreement with previous invariant mass spectroscopy measurements, using the (11)Li(-p) reaction, but is inconsistent with recent transfer reaction results. The proposed explanation that the difference, about 500 keV, is due to the effect of the extended halo nature of (11)Li in the one-proton knockout reaction is no longer valid as the present work demonstrates that the discrepancy between the transfer reaction results persists despite using a very different reaction mechanism, (14)Be(-2p2n).


Absence of the p53 tumor suppressor gene promotes osteogenesis in mesenchymal stem cells.
Osteosarcoma arises predominantly in the metaphyseal growth plate of children during the growth spurt years. These tumors develop during physiological growth from an expanding cell population, suggesting that the transformed cell is a bone-forming progenitor. An absence of the p53 oncogene has been implicated in the origin and progression of osteosarcoma, and because mesenchymal stem cells (MSCs) are the physiological osteogenic progenitor cell population, we hypothesized that a p53-/- mutation would enhance bone differentiation of MSC in a mouse model of in vitro osteogenesis. Clonal MSC populations were derived from p53-/- mice. P53-/- and wild-type cells were placed in osteogenic culture and assessed via Alizarin Red quantification and alkaline phosphatase staining. The osteogenic marker genes Cbfa1, osteopontin, and osteocalcin were assessed by quantitative real time polymerase chain reaction during differentiation. Bone nodule formation and alkaline phosphatase staining was accelerated and enhanced in the p53-/- cells. The early and intermediate osteogenic markers, Cbfa1 and osteopontin, were upregulated in p53-/- MSCs compared with wild-type cells during osteogenesis. The terminal osteogenic marker gene osteocalcin was paradoxically lower in p53-/- MSCs indicating impaired terminal differentiation. The p53-/- mutation enhances and accelerates early osteogenesis in MSCs, but prevents terminal differentiation toward a mature osteocyte phenotype. These findings may have important implications for the regulation of the MSC compartment during the derivation of osteosarcoma in children.


A feasibility study for a randomised controlled trial of the Positive Reappraisal Coping Intervention, a novel supportive technique for recurrent miscarriage.
Recurrent miscarriage (RM) is diagnosed when a woman has had three or more miscarriages. Increased levels of distress and anxiety are common during the waiting period of any subsequent pregnancies, posing a significant threat to psychological well-being. However, only limited support and therapy are available for these women, and many are left to cope alone. The Positive Reappraisal Coping Intervention (PRCI) is a novel self-administered supportive technique which has been shown to be effective in patients awaiting the outcome of in vitro fertilisation treatment. The primary objective of this study is to assess the feasibility and effectiveness of the PRCI in improving quality of life in the difficult waiting period which women with previous RM endure before an ongoing pregnancy can be confirmed. A randomised controlled trial (RCT) feasibility study will establish the viability of conducting a multicentre RCT to definitively test the effects of the PRCI on the psychological well-being of women who have experienced RM during the initial waiting period of a subsequent pregnancy. A second component consists of a qualitative process evaluation exploring the initial experience of pregnancy following repeated miscarriages. Participants (n=50) will be randomised into one of two groups. The PRCI intervention group will receive the PRCI card and weekly questionnaires to assess their psychological well-being during the waiting period of their new pregnancy. The non-intervention group will be asked to complete the same weekly questionnaires. The qualitative process analysis will employ semistructured interviews (n=20) to address relevant aspects of the study objectives. Ethics approval has been obtained from the National Research Ethics Service Committee South Central-Hampshire A. Participating centres have given National Health Service R&D approval. Study findings will be disseminated through peer reviewed journals, national and international conferences and lay user groups. ISRCTN43571276. This study was registered with the ISRCTN 18/02/2014 following adoption onto the United Kingdom Clinical Research Network (UKCRN) portfolio. Recruitment of the first participant occurred 04/02/2014.


Heterodimerization of glycosylated insulin-like growth factor-1 receptors and insulin receptors in cancer cells sensitive to anti-IGF1R antibody.
Identification of predictive biomarkers is essential for the successful development of targeted therapy. Insulin-like growth factor 1 receptor (IGF1R) has been examined as a potential therapeutic target for various cancers. However, recent clinical trials showed that anti-IGF1R antibody and chemotherapy are not effective for treating lung cancer. In order to define biomarkers for predicting successful IGF1R targeted therapy, we evaluated the anti-proliferation effect of figitumumab (CP-751,871), a humanized anti-IGF1R antibody, against nine gastric and eight hepatocellular cancer cell lines. Out of 17 cancer cell lines, figitumumab effectively inhibited the growth of three cell lines (SNU719, HepG2, and SNU368), decreased p-AKT and p-STAT3 levels, and induced G 1 arrest in a dose-dependent manner. Interestingly, these cells showed co-overexpression and altered mobility of the IGF1R and insulin receptor (IR). Immunoprecipitaion (IP) assays and ELISA confirmed the presence of IGF1R/IR heterodimeric receptors in figitumumab-sensitive cells. Treatment with figitumumab led to the dissociation of IGF1-dependent heterodimeric receptors and inhibited tumor growth with decreased levels of heterodimeric receptors in a mouse xenograft model. We next found that both IGF1R and IR were N-linked glyosylated in figitumumab-sensitive cells. In particular, mass spectrometry showed that IGF1R had N-linked glycans at N913 in three figitumumab-sensitive cell lines. We observed that an absence of N-linked glycosylation at N913 led to a lack of membranous localization of IGF1R and figitumumab insensitivity. The data suggest that the level of N-linked glycosylated IGF1R/IR heterodimeric receptor is highly associated with sensitivity to anti-IGF1R antibody in cancer cells.


Preliminary psychometric properties of the Chinese version of the Chronic Pain Coping Inventory (ChCPCI) in a Hong Kong Chinese population.
The Chronic Pain Coping Inventory (CPCI) is a frequently used measure that assesses 8 categories of coping strategies that patients might use to cope with chronic pain. Despite its good psychometric properties and widespread use, the instrument has not been tested for its applicability and validity in non-Western populations, such as among Chinese. This study evaluated the reliability and validity of a Chinese translation of the 42-item CPCI (ChCPCI-42) in a sample of Chinese patients with chronic pain (n = 208). In addition to the ChCPCI-42, the patients were administered the Chronic Pain Grade (CPG) questionnaire, the Pain Catastrophizing Scale (PCS), the Centre for Epidemiological Studies-Depression Scale (CES-D), and questions assessing sociodemographic characteristics. Results of confirmatory factor analyses revealed that of the ChCPCI-42 8 scales, 6 demonstrated acceptable-to-good data-model fit (CFI >or= 0.90) and 2 demonstrated medium fit (CFI >or= 0.85). The 8 scales demonstrated adequate to good internal consistency (Cronbach alpha, 0.69 to 0.79) and correlated with CES-D, PCS, pain intensity, and disability in expected directions. Results of hierarchical multiple regression analyses showed that the ChCPCI-42 scales predicted concurrent depression (F (8,177) = 3.07, P < .01) and pain disability (F (1, 179) = 4.35, P < .001) scores, the Task Persistence scale being the strongest unique predictor among the 8 scales. The findings support the factorial validity and reliability of a 42-item CPCI that can be used among Chinese patients with chronic pain. The report outlines the first validation of the CPCI for use in Hong Kong Chinese. This makes available a suitable instrument for chronic pain research in the Southern Chinese population and will help to elucidate similarities and differences in pain coping between Chinese and other ethnic groups.


The Association Between Eating-Compensatory Behaviors and Affective Temperament in a Brazilian Population.
Eating-compensatory behaviors are associated with biological and psychological complications, with high rates of morbidity and mortality. Different elements may contribute to the development of eating-compensatory behaviors, such as genetic, physiological, environmental, and temperamental factors. Therefore, the aim of this study was to examine the association between affective temperaments and eating-compensatory behaviors. A sample of 27,501 volunteers, between 18 and 55 years old, mean age 28.9 ± 8.7 years (69.6% women), were assessed by the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). The results showed that eating-compensatory behaviors were associated with distinctive affective temperaments. Cyclothymic types were more associated with eating-compensatory behaviors. The avoidant and irritable types presented lower percentages of eating-compensatory behaviors in women and men, respectively. In conclusion, this study highlighted that participants who adopted frequent eating-compensatory behaviors are more likely to have dysfunctional affective traits. Consequently, the affective temperaments should be considered as a strategy to build capacity for prevention, treatment, and care of eating-compensatory behaviors.


Characteristics of qualitative studies in influential journals of general medicine: a critical review.
Although qualitative studies have increased since the 1990s, some reports note that relatively few influential journals published them up until 2000. This study critically reviewed the characteristics of qualitative studies published in top tier medical journals since 2000. We assessed full texts of qualitative studies published between 2000 and 2004 in the Annals of Internal Medicine, BMJ, JAMA, Lancet, and New England Journal of Medicine. We found 80 qualitative studies, of which 73 (91%) were published in BMJ. Only 10 studies (13%) combined qualitative and quantitative methods. Sixty-two studies (78%) used only one method of data collection. Interviews dominated the choice of data collection. The median sample size was 36 (range: 9-383). Thirty-three studies (41%) did not specify the type of analysis used but rather described the analytic process in detail. The rest indicated the mode of data analysis, in which the most prevalent methods were the constant comparative method (23%) and the grounded theory approach (22%). Qualitative data analysis software was used by 33 studies (41%). Among influential journals of general medicine, only BMJ consistently published an average of 15 qualitative study reports between 2000 and 2004. These findings lend insight into what qualities and characteristics make a qualitative study worthy of consideration to be published in an influential journal, primarily BMJ.


WHO cardiovascular disease risk prediction model performance in 10 regions, China.
To validate the World Health Organization (WHO) non-laboratory-based cardiovascular disease risk prediction model in regions of China. We performed an external validation of the WHO model for East Asia using the data set of China Kadoorie Biobank, an ongoing cohort study with 512 725 participants recruited from 10 regions of China from 2004-2008. We also recalculated the recalibration parameters for the WHO model in each region and evaluated the predictive performance of the model before and after recalibration. We assessed discrimination performance by Harrell's C index. We included 412 225 participants aged 40-79 years. During a median follow-up of 11 years, 58 035 and 41 262 incident cardiovascular disease cases were recorded in women and men, respectively. Harrell's C of the WHO model was 0.682 in women and 0.700 in men but varied among regions. The WHO model underestimated the 10-year cardiovascular disease risk in most regions. After recalibration in each region, discrimination and calibration were both improved in the overall population. Harrell's C increased from 0.674 to 0.749 in women and from 0.698 to 0.753 in men. The ratios of predicted to observed cases before and after recalibration were 0.189 and 1.027 in women and 0.543 and 1.089 in men. The WHO model for East Asia yielded moderate discrimination for cardiovascular disease in the Chinese population and had limited prediction for cardiovascular disease risk in different regions in China. Recalibration for diverse regions greatly improved discrimination and calibration in the overall population.


Collagen induced MMP-2 activation in human breast cancer.
Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP-2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasiveness in vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasive in vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (Vitrogen; Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP-2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP-2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2 in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production, and MMP-2-activation. Such cooperativity may exist in vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer.


Change in estradiol and follicle-stimulating hormone across the early menopausal transition: effects of ethnicity and age.
Serum reproductive hormone concentrations were measured longitudinally in a community-based, multiethnic population of midlife women to assess whether ethnic differences exist in the patterns of change in estradiol (E2) and FSH and, if so, whether these differences are explained by host characteristics. We studied 3257 participants from seven clinical sites in the Study of Women's Health Across the Nation (SWAN) who were aged 42-52 yr at baseline and self-identified as African American (28.2%), Caucasian (47.1%), Chinese (7.7%), Hispanic (8.4%), or Japanese (8.6%). E2 and FSH were assayed in serum collected primarily in the early follicular phase of a spontaneous menstrual cycle in three consecutive annual visits. The primary explanatory variables included in repeated-measures regression analyses were race/ethnicity, menopausal status, age, body mass index (BMI), day of the cycle, smoking, parity, socioeconomic status, study site, and the self-report of diabetes at baseline. At the baseline visit, 46.2% of the women were classified as being early perimenopausal, with the remaining being premenopausal. By the second follow-up visit, 5.5% of the women in that cohort were postmenopausal, 66.8% were early perimenopausal, 8.3% were late perimenopausal, and 19.4% remained premenopausal. Serum E2 concentrations decreased significantly with age, with a steeper decline at higher ages. FSH concentrations increased significantly with age, with a steeper increase at higher ages. Similar patterns in the decline of E2 and the increase in FSH with age were found across ethnic groups, but the levels of these hormones differed by race/ethnicity. Specifically, over time, Chinese and Japanese women had lower E2 concentrations but similar FSH levels, compared with Caucasian women, and African American women had higher FSH concentrations but comparable E2 levels with those of Caucasian women. These ethnic differences in E2 and FSH were independent of menopausal status. The effect of BMI on serum E2 and FSH levels varied by menopausal status. Increasing BMI was associated with decreasing concentrations of E2 among premenopausal and early perimenopausal women but was associated with increasing concentrations of E2 among late perimenopausal and postmenopausal women. Increasing BMI was associated with decreasing concentrations of FSH, with the effect of BMI becoming larger as women transitioned through menopause. We conclude that serum E2 levels decrease and FSH concentrations increase with increasing age in midlife women, that ethnic differences in E2 over time differ from ethnic differences in FSH and suggest ethnic differences in the pituitary-ovarian relationship, and that the effect of BMI on E2 and FSH concentrations varies by menopausal status.


Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination.
Seasonal influenza vaccine protects 60 to 90% of healthy young adults from influenza infection. The immunological events that lead to the induction of protective antibody responses remain poorly understood in humans. We identified the type of CD4+ T cells associated with protective antibody responses after seasonal influenza vaccinations. The administration of trivalent split-virus influenza vaccines induced a temporary increase of CD4+ T cells expressing ICOS, which peaked at day 7, as did plasmablasts. The induction of ICOS was largely restricted to CD4+ T cells coexpressing the chemokine receptors CXCR3 and CXCR5, a subpopulation of circulating memory T follicular helper cells. Up to 60% of these ICOS+CXCR3+CXCR5+CD4+ T cells were specific for influenza antigens and expressed interleukin-2 (IL-2), IL-10, IL-21, and interferon-γ upon antigen stimulation. The increase of ICOS+CXCR3+CXCR5+CD4+ T cells in blood correlated with the increase of preexisting antibody titers, but not with the induction of primary antibody responses. Consistently, purified ICOS+CXCR3+CXCR5+CD4+ T cells efficiently induced memory B cells, but not naïve B cells, to differentiate into plasma cells that produce influenza-specific antibodies ex vivo. Thus, the emergence of blood ICOS+CXCR3+CXCR5+CD4+ T cells correlates with the development of protective antibody responses generated by memory B cells upon seasonal influenza vaccination.


Dimetallaborane analogues of pentaborane.
The structures of five-vertex dimetallaboranes Cp2M2B3H7 (Cp = η(5)-C5H5) of the second and third row transition metals, including the experimentally known Cp*2Rh2B3H7 (Cp* = η(5)-Me5C5), have been investigated by density functional theory. The predicted low-energy structures for Cp2M2B3H7 (M = Rh, Ir) are tetragonal pyramids similar to Cp*2Rh2B3H7 and pentaborane-9 B5H9 and consistent with their 14 Wadean skeletal electrons. Two Cp*2Rh2B3H7 structures with the same central Rh2B3 tetragonal prism are found with energies within ∼1 kcal mol(-1) of each other, consistent with the experimental observation of two isomers in solution. The electron-richer Cp2M2B3H7 (M = Pd, Pt) systems having 16 Wadean skeletal electrons are predicted to exhibit more open structures analogous to the known structure for the valence isoelectronic pentaborane-11 B5H11. Trigonal bipyramids with the metal atoms at equatorial vertices are typically found to be low-energy structures for the hypoelectronic Cp2M2B3H7 systems (M = Ru, Os, Re, Mo, W, Ta). In addition, the low-energy Cp2Re2B3H7 structures of the rhenium derivatives Cp2Re2B3H7 provide examples of structures based on a central Re2B2 tetrahedron with the Re-Re edge bridged by the third boron atom. Such structures can be derived from a trigonal bipyramid by the rupture of one of the axial-equatorial edges.


Hydrogen-rich saline protects against spinal cord injury in rats.
In the present study, we examined the mechanisms of hydrogen-rich saline, a reported therapeutic antioxidant, in the treatment of acute spinal cord contusion injury. Male Sprague-Dawley rats were used to produce a standardized model of contuses spinal cord injury (125 kdyn force). Hydrogen-rich saline was injected intraperitoneally (5 ml/kg) immediately, and at 24 and 48 h after injury. All rats were sacrificed at 72 h after spinal cord injury (SCI). Apoptotic cell death, oxidative stress, inflammation, level of Brain derived neurotrophic factor (BDNF) were evaluated. In addition, locomotor behavior was assessed using the Basso, Beattice and Bresnahan (BBB) scale. We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of BDNF. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.


Protein-protein interactions in trans-AT polyketide synthases.
Covering: up to 2018 The construction of polyketide natural products by type I modular polyketide synthases (PKSs) requires the coordinated action of several protein subunits to ensure biosynthetic fidelity. This is particularly the case for trans-AT PKSs, which in contrast to most cis-AT PKSs, contain split modules and employ several trans-acting catalytic domains. This article summarises recent advances in understanding the protein-protein interactions underpinning subunit assembly and intra-subunit communication in such systems and highlights potential avenues and approaches for future research.


Semi-supervised learning of probabilistic models for ECG segmentation.
We present a novel semi-supervised learning algorithm, based upon the EM algorithm for maximum likelihood estimation, which can be used to learn probabilistic models from subjectively labelled data. We demonstrate the method on the task of automated ECG segmentation, with a particular emphasis on the accurate measurement of the QT interval. In addition we discuss the use of wavelet methods for the representation of the ECG, and advanced duration modelling techniques for hidden Markov models applied to ECG segmentation.


Characterization of proanthocyanidin metabolism in pea (Pisum sativum) seeds.
Proanthocyanidins (PAs) accumulate in the seeds, fruits and leaves of various plant species including the seed coats of pea (Pisum sativum), an important food crop. PAs have been implicated in human health, but molecular and biochemical characterization of pea PA biosynthesis has not been established to date, and detailed pea PA chemical composition has not been extensively studied. PAs were localized to the ground parenchyma and epidermal cells of pea seed coats. Chemical analyses of PAs from seeds of three pea cultivars demonstrated cultivar variation in PA composition. 'Courier' and 'Solido' PAs were primarily prodelphinidin-types, whereas the PAs from 'LAN3017' were mainly the procyanidin-type. The mean degree of polymerization of 'LAN3017' PAs was also higher than those from 'Courier' and 'Solido'. Next-generation sequencing of 'Courier' seed coat cDNA produced a seed coat-specific transcriptome. Three cDNAs encoding anthocyanidin reductase (PsANR), leucoanthocyanidin reductase (PsLAR), and dihydroflavonol reductase (PsDFR) were isolated. PsANR and PsLAR transcripts were most abundant earlier in seed coat development. This was followed by maximum PA accumulation in the seed coat. Recombinant PsANR enzyme efficiently synthesized all three cis-flavan-3-ols (gallocatechin, catechin, and afzalechin) with satisfactory kinetic properties. The synthesis rate of trans-flavan-3-ol by co-incubation of PsLAR and PsDFR was comparable to cis-flavan-3-ol synthesis rate by PsANR. Despite the competent PsLAR activity in vitro, expression of PsLAR driven by the Arabidopsis ANR promoter in wild-type and anr knock-out Arabidopsis backgrounds did not result in PA synthesis. Significant variation in seed coat PA composition was found within the pea cultivars, making pea an ideal system to explore PA biosynthesis. PsANR and PsLAR transcript profiles, PA localization, and PA accumulation patterns suggest that a pool of PA subunits are produced in specific seed coat cells early in development to be used as substrates for polymerization into PAs. Biochemically competent recombinant PsANR and PsLAR activities were consistent with the pea seed coat PA profile composed of both cis- and trans-flavan-3-ols. Since the expression of PsLAR in Arabidopsis did not alter the PA subunit profile (which is only comprised of cis-flavan-3-ols), it necessitates further investigation of in planta metabolic flux through PsLAR.


The psychoanalytic process in the treatment of Little Hans.
This paper studies the psychoanalytic process in the treatment of Little Hans, using Samuel Abrams's 1988 paper in which he defines the psychoanalytic process as the sequence of steps which appears within the mind of the patient as the treatment proceeds. As with the adult, the child can affectively recall or reenact the past in the transference, but the child also tries to promote whatever developmental phase is being clocked in. In January 1908 Max Graf, Hans's father and a member of the Vienna Psychoanalytic Society who was a musicologist, wrote Freud that his son had developed a fear that a horse would bite him in the street. Freud first suggested that the father give his son some enlightenment in the matter of sexual knowledge, such as his mother and other females have no "widdlers." The enlightenments only increased Hans's anxiety, prompting Freud to meet with Hans and his father and interpret the fear of the horse as fear of the father. While Max Graf was able to help Hans understand some dreams and fantasies, he exhibited a punitive attitude toward Hans's masturbation, which was reinforced by Freud's attitude that it was harmful. The father did not promote his son's development when he withheld knowledge of how babies are born, neither did Freud when he withheld any contrary suggestions from the father.