Elastic turbulence in shear banding wormlike micelles.
We study the dynamics of the Taylor-Couette flow of shear banding wormlike micelles. We focus on the high shear rate branch of the flow curve and show that for sufficiently high Weissenberg numbers, this branch becomes unstable. This instability is strongly subcritical and is associated with a shear stress jump. We find that this increase of the flow resistance is related to the nucleation of turbulence. The flow pattern shows similarities with the elastic turbulence, so far only observed for polymer solutions. The unstable character of this branch led us to propose a scenario that could account for the recent observations of Taylor-like vortices during the shear banding flow of wormlike micelles.


Studies on the rate of selective uptake of amino acids by Trichinella larvae in vivo.
Groups of C57BL/6J mice, orally infected with 300 larvae each of Trichinella spiralis or T. pseudospiralis were injected with [3H]-alanine, tyrosine, tryptophan or glycine. The incorporation of isotope labelled amino acids into larval proteins was measured at 2, 6, and 12 months post-infection. It was shown that there is a significant increase in the in vivo uptake of isotope labelled amino acids with time by the larvae of T. spiralis and T. pseudospiralis. The level of uptake was highest for tyrosine followed by tryptophan, alanine and then glycine, for both species. The in vivo uptake of amino acids by T. pseudospiralis larvae was always higher than T. spiralis or the host at 6 and 12 months post-infection. At 2 months post-infection, T. spiralis uptake of these amino acids was higher, except for tyrosine. This may be related to the special needs of these larvae during the process of encystation. The higher metabolic requirements of T. pseudospiralis may be related to the higher energy needs of these non encapsulated, highly motile and mobile muscle larvae.


Condition-specific Streaming versus an Acuity-based Model of Cardiovascular Care: A Historically-controlled Quality Improvement Study Evaluating the Association with Early Clinical Events.
Ensuring optimal evidence translation is challenging when health-service design has not kept pace with developments in care. Differences in patient outcomes were evident when specific cardiac conditions were discordant with the subspecialty of the cardiologists managing their care. We prospectively explored the clinical and health service implications of a "condition-based" redesign in cardiac care delivery, rather than acuity-based, within a tertiary hospital. Prospective evaluation of a disease-specific streaming model of care compared to propensity-matched historical controls, among cardiac patients admitted to a tertiary hospital cardiology unit was undertaken. The outcome measures of 30-day death, and readmission for myocardial infarction, cardiac arrhythmia, and heart failure were explored. In total, 2018 patients admitted subsequent to the implementation of the streaming model were compared with 1830 patients admitted prior. The median age was 68.9 years, and 39.5% were female. There was no significant difference in the overall proportion of patients admitted with an acute coronary syndrome, arrthythmia or heart failure, nor their Charlson index before and after streaming. Subsequent to the implementation, there was a reduction in the use of angiography (pre: 35.4% vs. post: 31.2%, p=0.007) and echocardiography (pre: 59.4% vs. post: 55.6%, p=0.007). A reduction in length of length-of-stay was observed in the entire cohort (pre: 2.7 (range: 1.2-5.0) days vs. post: 2.3 (range 1.0-4.5) days, p=0.0003). By 30 days, the propensity-adjusted hazard ratio for major adverse cardiac events and death or any cardiovascular admission was 0.76 (95% C.I. 0.59-0.97, p=0.026). Cardiac service redesign that streams cardiac patients by presenting diagnosis into teams designed to treat that condition may provide capacity and productivity gains for health services striving to improve outcome and efficiency.


Bayesian sparsity-path-analysis of genetic association signal using generalized t priors.
We explore the use of generalized t priors on regression coefficients to help understand the nature of association signal within "hit regions" of genome-wide association studies. The particular generalized t distribution we adopt is a Student distribution on the absolute value of its argument. For low degrees of freedom, we show that the generalized t exhibits "sparsity-prior" properties with some attractive features over other common forms of sparse priors and includes the well known double-exponential distribution as the degrees of freedom tends to infinity. We pay particular attention to graphical representations of posterior statistics obtained from sparsity-path-analysis (SPA) where we sweep over the setting of the scale (shrinkage/precision) parameter in the prior to explore the space of posterior models obtained over a range of complexities, from very sparse models with all coefficient distributions heavily concentrated around zero, to models with diffuse priors and coefficients distributed around their maximum likelihood estimates. The SPA plots are akin to LASSO plots of maximum a posteriori (MAP) estimates but they characterise the complete marginal posterior distributions of the coefficients plotted as a function of the precision of the prior. Generating posterior distributions over a range of prior precisions is computationally challenging but naturally amenable to sequential Monte Carlo (SMC) algorithms indexed on the scale parameter. We show how SMC simulation on graphic-processing-units (GPUs) provides very efficient inference for SPA. We also present a scale-mixture representation of the generalized t prior that leads to an expectation-maximization (EM) algorithm to obtain MAP estimates should only these be required.


Solvent manipulation of the pre-reduction metal-ligand complex and particle-ligand binding for controlled synthesis of Pd nanoparticles.
Understanding how to control the nucleation and growth rates is crucial for designing nanoparticles with specific sizes and shapes. In this study, we show that the nucleation and growth rates are correlated with the thermodynamics of metal-ligand/solvent binding for the pre-reduction complex and the surface of the nanoparticle, respectively. To obtain these correlations, we measured the nucleation and growth rates by in situ small angle X-ray scattering during the synthesis of colloidal Pd nanoparticles in the presence of trioctylphosphine in solvents of varying coordinating ability. The results show that the nucleation rate decreased, while the growth rate increased in the following order, toluene, piperidine, 3,4-lutidine and pyridine, leading to a large increase in the final nanoparticle size (from 1.4 nm in toluene to 5.0 nm in pyridine). Using density functional theory (DFT), complemented by 31P nuclear magnetic resonance and X-ray absorption spectroscopy, we calculated the reduction Gibbs free energies of the solvent-dependent dominant pre-reduction complex and the solvent-nanoparticle binding energy. The results indicate that lower nucleation rates originate from solvent coordination which stabilizes the pre-reduction complex and increases its reduction free energy. At the same time, DFT calculations suggest that the solvent coordination affects the effective capping of the surface where stronger binding solvents slow the nanoparticle growth by lowering the number of active sites (not already bound by trioctylphosphine). The findings represent a promising advancement towards understanding the microscopic connection between the metal-ligand thermodynamic interactions and the kinetics of nucleation and growth to control the size of colloidal metal nanoparticles.


Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight into metastatic potential.
Metastatic melanoma is associated with a poor prognosis, but no method reliably predicts which melanomas of a given stage will ultimately metastasize and which will not. While sentinel lymph node biopsy (SLNB) has emerged as the most powerful predictor of metastatic disease, the majority of people dying from metastatic melanoma still have a negative SLNB. Here we analyze pump-probe microscopy images of thin biopsy slides of primary melanomas to assess their metastatic potential. Pump-probe microscopy reveals detailed chemical information of melanin with subcellular spatial resolution. Quantification of the molecular signatures without reference standards is achieved using a geometrical representation of principal component analysis. Melanin structure is analyzed in unison with the chemical information by applying principles of mathematical morphology. Results show that melanin in metastatic primary lesions has lower chemical diversity than non-metastatic primary lesions, and contains two distinct phenotypes that are indicative of aggressive disease. Further, the mathematical morphology analysis reveals melanin in metastatic primary lesions has a distinct "dusty" quality. Finally, a statistical analysis shows that the combination of the chemical information with spatial structures predicts metastatic potential with much better sensitivity than SLNB and high specificity, suggesting pump-probe microscopy can be an important tool to help predict the metastatic potential of melanomas.


Bifunctionalized hollow nanospheres for the one-pot synthesis of methyl isobutyl ketone from acetone.
Pd-doped propyl sulfonic acid-functionalized hollow nanospheres proved to be efficient bifunctionalized catalysts for the one-pot synthesis of methyl isobutyl ketone (MIBK) from acetone and hydrogen in liquid phase. These hollow nanospheres exhibited a higher activity than their bulk mesoporous counterparts (SBA-15 or FDU-12), mainly due to the short diffusion resistance of hollow nanospheres. Hollow nanospheres with silica frameworks showed higher activity and selectivity for MIBK than those with ethane-bridged frameworks, suggesting that hollow nanospheres with hydrophilic surface properties favor the formation of MIBK. This is probably due to the increased affinity of the hydrophilic surface towards acetone and its decreased affinity towards MIBK, which precludes deep condensation of MIBK with acetone. Under optimal conditions, up to 90 % selectivity for MIBK can be obtained with conversions of acetone as high as 43 %. This result is among the best reported so far for mesoporous silica-based catalysts. The control/fine-tuning of morphology and surface properties provides an efficient strategy for improving the catalytic performance of solid catalysts.


A neuromorphic systems approach to in-memory computing with non-ideal memristive devices: from mitigation to exploitation.
Memristive devices represent a promising technology for building neuromorphic electronic systems. In addition to their compactness and non-volatility, they are characterized by their computationally relevant physical properties, such as their state-dependence, non-linear conductance changes, and intrinsic variability in both their switching threshold and conductance values, that make them ideal devices for emulating the bio-physics of real synapses. In this paper we present a spiking neural network architecture that supports the use of memristive devices as synaptic elements and propose mixed-signal analog-digital interfacing circuits that mitigate the effect of variability in their conductance values and exploit their variability in the switching threshold for implementing stochastic learning. The effect of device variability is mitigated using pairs of memristive devices configured in a complementary push-pull mechanism and interfaced to a current-mode normalizer circuit. The stochastic learning mechanism is obtained by mapping the desired change in synaptic weight into a corresponding switching probability that is derived from the intrinsic stochastic behavior of memristive devices. We demonstrate the features of the CMOS circuits and apply the architecture proposed to a standard neural network hand-written digit classification benchmark based on the MNIST data-set. We evaluate the performance of the approach proposed in this benchmark using behavioral-level spiking neural network simulation, showing both the effect of the reduction in conductance variability produced by the current-mode normalizer circuit and the increase in performance as a function of the number of memristive devices used in each synapse.


Stress, health and quality of life of female migrant domestic workers in Singapore: a cross-sectional study.
There is a global increase in migrant workers. In Singapore, there are over 230,000 migrant domestic workers (MDWs). Female MDWs may experience high levels of stress and social isolation, which may negatively impact on their health and quality of life. There have also been documented cases of abuse and exploitation. However, there is a lack of empirical research with this population. This study aimed to investigate factors impacting on the health and quality of life of female MDWs in Singapore, including socio-demographic and job related characteristics, stress, social isolation, and working management style. A cross-sectional survey was carried out with 182 female MDWs in Singapore. The survey examined health and quality of life (WHOQoL-Bréf), social connectedness (the Friendship Scale), and preferred and experienced working management style (the Theory X and Theory Y Questionnaire). Descriptive analyses were carried out in addition to ANOVA, t-tests, and chi-square tests, followed by a multivariate analysis using linear regression. Participants were found to have good overall quality of life and satisfaction with health. Age and working experience were found to be significantly (p < 0.05) associated with overall quality of life and three domains (psychological, social, and environmental health). Agreement between experienced and preferred working management style was also found to be associated with higher quality of life scores (with the exception of the social relationships domain). Though women reported relatively good overall quality of life, more than half of participants reported feeling stressed. In addition, nearly 20% of participants reported being isolated or very isolated. Stress was identified to be associated with isolation. In the multivariate analysis, stress was found to contribute to worse quality of life in all domains except social relationships, after adjusting for confounders. Social connectedness was positively associated with all domains of quality of life, and agreement of working management style was positively associated with physical health, psychological health and environmental quality of life. The findings serve as an evidence-base pointing to the need for policies aimed at decreasing stress and social isolation among female MDWs in order to improve their health and quality of life.


Structural and functional characterization of Schistosoma mansoni Thioredoxin.
Schistosomiasis, the human parasitosis caused by various species of the blood-fluke Schistosoma, is a debilitating disease affecting 200 million people in tropical areas. The massive administration of the only effective drug, praziquantel, leads to the appearance of less sensitive parasite strains, thus, making urgent the search for new therapeutic approaches and new suitable targets. The thiol-mediated detoxification pathway has been identified as a promising target, being essential during all the parasite developmental stages and sufficiently different from the host counterpart. As a part of a project aimed at the structural characterization of all the proteins involved in this pathway, we describe hereby the high-resolution crystal structure of Schistosoma mansoni Thioredoxin (SmTrx) in three states, namely: the wild-type oxidized adult enzyme and the oxidized and reduced forms of a juvenile isoform, carrying an N-terminal extension. SmTrx shows a typical thioredoxin fold, highly similar to the other components of the superfamily. Although probably unlikely to be a reasonable drug target given its high similarity with the human counterpart, SmTrx completes the characterization of the whole set of thiol-mediated detoxification pathway components. Moreover, it can reduce oxidized glutathione and is one of the few defence proteins expressed in mature eggs and in the hatch fluid, thus confirming an important role in the parasite. We believe its crystal structure may provide clues for the formation of granulomas and the pathogenesis of the chronic disease.


Medical privacy and the public's right to vote: what presidential candidates should disclose.
We argue that while presidential candidates have the right to medical privacy, the public nature and importance of the presidency generates a moral requirement that candidates waive those rights in certain circumstances. Specifically, candidates are required to disclose information about medical conditions that are likely to seriously undermine their ability to fulfill what we call the "core functions" of the office of the presidency. This requirement exists because (1) people have the right to be governed only with their consent, (2) people's consent is meaningful only when they have access to information necessary for making informed voting decisions, (3) such information is necessary for making informed voting decisions, and (4) there are no countervailing reasons sufficiently strong to override this right. We also investigate alternative mechanisms for legally encouraging or requiring disclosure. Protecting the public's right to this information is of particular importance because of the documented history of deception and secrecy regarding the health of presidents and presidential candidates.


Expression of CYP4A1 in U251 human glioma cell induces hyperproliferative phenotype in vitro and rapidly growing tumors in vivo.
Exogenous 20-hydroxyeicosatetraenoic acid (20-HETE) increases the growth of human glioma cells in vitro. However, glioma cells in culture show negligible 20-HETE synthesis. We examined whether inducing the expression of a 20-HETE synthase in a human glioma U251 cell line would increase proliferation. U251 cells transfected with CYP4A1 cDNA (termed U251 O) increased the formation of 20-HETE from less than 1 to over 60 pmol/min/mg proteins and increased their proliferation rate by 2-fold (p < 0.01). Compared with control U251, U251 O cells were rounded, smaller, showed a disorganized cytoskeleton, exhibited reduced vinculin staining, and were easily detached from the growing surface. They showed a marked increase in dihydroethidium staining, suggesting increased oxidative stress. The expression of phosphorylated extracellular signal-regulated kinase 1/2, cyclin D1/2, and vascular endothelial growth factor was markedly elevated in U251 O. The hyperproliferative and signaling effects seen in U251 O cells are abolished by selective CYP4A inhibition of 20-HETE formation with HET0016 [N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine], by small interfering RNA against the enzyme, and by the putative 20-HETE antagonist, 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid. In vivo, implantation of U251O cells in the brain of nude rats resulted in a approximately 10-fold larger tumor volume (10 days postimplantation) compared with animals receiving mock-transfected U251 cells. These data show that elevations in 20-HETE synthesis in U251 cells lead to an increased growth both in vitro and in vivo. This suggests that 20-HETE may have proto-oncogenic properties in U251 human gliomas. Further studies are needed to determine whether 20-HETE plays a role promoting growth of some human gliomas.


Breast cancer presentation delays among Arab and national women in the UAE: a qualitative study.
Breast cancer (BC) is a disease that has improved prospects for survival if detected and treated early. Delayed help-seeking behavior, with poor survival as a consequence, is an important public health issue in the Middle East. More than 75% of breast cancer patients in the United Arab Emirates (UAE) seek medical advice after experiencing a sign or symptom of the disease and many seek such advice late. Our aim was to explore factors influencing delayed presentation for treatment after self-discovery of symptoms consistent with breast cancer in Arab women in the United Arab Emirates (UAE), and to explore facilitators and barriers of women's health seeking behavior in the complex religiously dominated society of the UAE. A qualitative descriptive approach using semi-structured interviews was used. We interviewed nineteen BC survivors aged 35-70 who have experienced delayed presentation to treatment after symptomatic recognition of BC. The time interval between initial experience of symptoms consistent with BC, and taking action to seek medical help was between three months to three years. The key themes that emerged from the interviews were varying responses to symptom recognition, fear of societal stigmatization, and concerns regarding abandonment by spouse because of BC. Culture has a strong influence on the decisions of women in the UAE society. The lack of awareness about signs and symptoms of BC and routine screening has an important effect on symptom appraisal and subsequently decision making regarding options for treatment.


Visual Morbidities among Patients at a Geriatric Center in Southwest Nigeria and the Merits of Designated Geriatric Health Care Centers Incorporating Eye Care Services.
: Visual morbidities increase the burden of care and negatively impact the quality of life of older people. Few empirical reports exist on the visual status of older Nigerians. This study describes the visual morbidities and determinants of visual impairment among persons aged 60 years and above who presented at a geriatric center in southwestern Nigeria and discusses the merits of focused geriatric care at a single location. Data were obtained from electronic health records and case files of 628 older patients (≥60 years) who attended the facility between January 1, 2014 and December 31, 2018. Data extracted included, age, sex, married status, occupational status, visual acuity, eye diagnoses, eye medications, previous surgeries, and anthropometric measurements. Mean age of patients was 70.1 ± 7.4 years and 378 (60.2%) were females. Two out of every three patients had more than one visual diagnosis. Significantly, glaucoma (P < 0.001) and cataract (P = 0.01) were common among men, whereas dry eye syndrome (P < 0.001) and allergic conjunctivitis (P = 0.01) were common in women. Antiglaucoma medications (55.8%) were the commonest medications used and 21.0% had previous eye surgery. Assessment of presenting visual acuity demonstrated that 28.7% of patients had moderate-severe visual impairment (MSVI) in both eyes at presentation while 10.3% were bilaterally blind. Increasing age (P < 0.001) and male sex (P = 0.01) were the factors significantly associated with blindness. MSVI and blindness were common in our setting with glaucoma and cataract being the most prevalent associated diagnosis. Information obtained should stimulate advocacy for the prompt management of preventable causes of poor vision in older Nigerians.


Social support and self-rated health revisited: is there a gender difference in later life?
This study examines the physical, behavioral, emotional and social determinants of self-rated health among Chinese older persons, and investigates if the effect of social support varies by gender. A representative sample of 1589 elderly community dwellers in Hong Kong were interviewed using a structured questionnaire. Gender difference in the effect of social support was tested by an interaction term, 'gender x social support', in a hierarchical regression analysis. The frequency of falling ill, the number of chronic illnesses, sleep quality, mobility and positive emotions were most important determinants of self-rated health. The effect of social support was completely redundant when these factors were taken into account. The interaction term 'gender x social support' was significant and indicated a stronger effect for women, but the effect size was negligible (adding only 0.3% to the explained variance). This suggests that the effect of social support by and large is gender free. These findings suggest a high degree of similarity in the determinants of self-rated health between Western and Chinese older populations.


Coping support factors among Australians affected by terrorism: 2002 Bali bombing survivors speak.
To examine terrorism survivors' perceptions of factors likely to promote coping and recovery, and to determine whether coping supports vary according to demographic, physical and mental health, incident-exposure and bereavement variables. Individuals directly exposed to and/or bereaved by the 2002 Bali bombings and who had participated in a New South Wales Health therapeutic support program completed cross-sectional telephone interviews during July-November 2010. Spoken passages were categorised into coping support themes. Advocated supports were then examined by demographic, physical and mental health, incident-exposure and bereavement variables. Based on their experiences, respondents identified personal, social and service-related factors that they believed would optimally support future survivors of terrorism. Of the 81 people contacted, 55 (68%) participated, providing a total of 114 comments. Thirty-two respondents were women, and 54 had lost relatives or friends in the bombing. Mean age was 50 years (range, 20-73 years). Four meaningful coping support themes emerged, with excellent inter-rater reliability: professional help and counselling; social support; proactive government response and policy; and personal coping strategies. Women were significantly more likely to advocate the need for proactive government response (P = 0.03). Men were more likely to endorse the use of personal coping strategies (P < 0.01). Respondents diagnosed with a mental health condition since the bombings were significantly less likely to advocate social support processes (P = 0.04). Our findings highlight the perceived value of counselling-related services for terrorism-affected groups. Male survivors may benefit more from mental health interventions that initially build on problem-focused forms of coping, including brief education about reactions and periodic check-ups. Proactive government health and support services that allow simplified and longer-term access were consistently identified as priority areas.


Glacier surge after ice shelf collapse.
The possibility that the West Antarctic Ice Sheet will collapse as a consequence of ice shelf disintegration has been debated for many years. This matter is of concern because such an event would imply a sudden increase in sea level. Evidence is presented here showing drastic dynamic perturbations on former tributary glaciers that fed sections of the Larsen Ice Shelf on the Antarctic Peninsula before its collapse in 1995. Satellite images and airborne surveys allowed unambiguous identification of active surging phases of Boydell, Sjögren, Edgeworth, Bombardier, and Drygalski glaciers. This discovery calls for a reconsideration of former hypotheses about the stabilizing role of ice shelves.


Sample size calculations for cluster randomised controlled trials with a fixed number of clusters.
Cluster randomised controlled trials (CRCTs) are frequently used in health service evaluation. Assuming an average cluster size, required sample sizes are readily computed for both binary and continuous outcomes, by estimating a design effect or inflation factor. However, where the number of clusters are fixed in advance, but where it is possible to increase the number of individuals within each cluster, as is frequently the case in health service evaluation, sample size formulae have been less well studied. We systematically outline sample size formulae (including required number of randomisation units, detectable difference and power) for CRCTs with a fixed number of clusters, to provide a concise summary for both binary and continuous outcomes. Extensions to the case of unequal cluster sizes are provided. For trials with a fixed number of equal sized clusters (k), the trial will be feasible provided the number of clusters is greater than the product of the number of individuals required under individual randomisation (nI) and the estimated intra-cluster correlation (ρ). So, a simple rule is that the number of clusters (k) will be sufficient provided: [formula in text]. Where this is not the case, investigators can determine the maximum available power to detect the pre-specified difference, or the minimum detectable difference under the pre-specified value for power. Designing a CRCT with a fixed number of clusters might mean that the study will not be feasible, leading to the notion of a minimum detectable difference (or a maximum achievable power), irrespective of how many individuals are included within each cluster.


Micro-epidemiology of mixed-species malaria infections in a rural population living in the Colombian Amazon region.
Malaria outbreaks have been reported in recent years in the Colombian Amazon region, malaria has been re-emerging in areas where it was previously controlled. Information from malaria transmission networks and knowledge about the population characteristics influencing the dispersal of parasite species is limited. This study aimed to determine the distribution patterns of Plasmodium vivax, P. malariae and P. falciparum single and mixed infections, as well as the significant socio-spatial groupings relating to the appearance of such infections. An active search in 57 localities resulted in 2,106 symptomatic patients being enrolled. Parasitaemia levels were assessed by optical microscopy, and parasites were detected by PCR. The association between mixed infections (in 43.2% of the population) and socio-spatial factors was modelled using logistic regression and multiple correspondence analyses. P. vivax occurred most frequently (71.0%), followed by P. malariae (43.2%), in all localities. The results suggest that a parasite density-dependent regulation model (with fever playing a central role) was appropriate for modelling the frequency of mixed species infections in this population. This study highlights the under-reporting of Plasmodium spp. mixed infections in the malaria-endemic area of the Colombian Amazon region and the association between causative and environmental factors in such areas.


Prenatal maternal psychopathology and stress and offspring HPA axis function at 6 years.
Intrauterine exposures such as maternal psychopathology and stress are known to influence the physical and mental health of the offspring. One of the proposed pathways underlying these associations is dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity in the offspring. This study examined the relation of perinatal maternal symptoms of psychopathology and stress with offspring HPA axis activity at 6 years as measured by hair cortisol and cortisone concentrations. The study was part of the population-based Generation R Study, a prospective population-based cohort from fetal life onwards. 2546 children and their mothers formed the study population. Perinatal maternal psychopathology and stress were assessed by questionnaires in the second and third trimester. Principal components for both psychopathology and stress were created to reduce the number of explanatory variables. Child hair samples for cortisol and cortisone measurements were collected at the age of 6. Linear regression analysis, adjusted for covariates, was used to examine associations between maternal psychopathology and stress and child hair cortisol and cortisone levels. The maternal psychopathology principal component was associated with higher child hair cortisone (adjusted B = 0.24, 95%CI 0.08;0.40, p-value < 0.01). Effect estimates of the individual dimensions ranged from 0.97 (95%CI 0.21;1.73, p-value = 0.01) for interpersonal sensitivity to 1.67 (95%CI 0.86;2.47, p-value < 0.01) for paranoid ideation. In addition, children exposed to intrauterine stress, as measured by the principal component, had higher hair cortisone levels (adjusted B = 0.54, 95%CI 0.21;0.88, p-value < 0.01). Exposure to maternal psychopathology and stress was not associated with offspring hair cortisol. Stratification by child sex resulted in associations between maternal symptoms of psychopathology during pregnancy and child hair cortisone levels in boys and associations between maternal symptoms of stress during pregnancy and child hair cortisone levels in girls. Our results suggest that maternal psychopathology and stress during pregnancy are associated with long-term HPA axis activity of the offspring. The association of maternal psychopathology and stress during pregnancy with offspring hair cortisone levels is a novel finding. Future studies should examine whether these psychophysiological differences between exposed and non-exposed children underlie offspring morbidity associated with maternal psychopathology and stress during pregnancy.


Renin-angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis.
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension. In this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296. Among 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84-1·14) or combination use exposure (1·01, 0·90-1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68-1·21; with heterogeneity of >40%) or combination use (0·95, 0·83-1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79-0·99) and non-significant for monotherapy (0·85, 0·69-1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons. No clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19. Wellcome Trust, UK National Institute for Health Research, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, South Korean Ministry of Health and Welfare Republic, Australian National Health and Medical Research Council, and European Health Data and Evidence Network.


In vivo characterization of 123/125I-2-iodo-L-phenylalanine in an R1M rhabdomyosarcoma athymic mouse model as a potential tumor tracer for SPECT.
The application of 123I-3-iodo-alpha-methyltyrosine is limited to diagnosis of brain tumors due to its marked long-term uptake in kidneys. In vitro evaluation of 125I-2-iodo-L-phenylalanine showed high uptake in R1M cells by L-type amino acid transport system 1 (LAT1). This study evaluates 123I-2-iodo-L-phenylalanine as a new specific tumor tracer for SPECT. 123/125I-2-Iodo-L-phenylalanine is prepared as a one-pot kit using the Cu1+-assisted isotopic exchange method. The characteristics of 125I-2-iodo-L-phenylalanine were examined in vivo in R1M tumor-bearing athymic mice and in acute inflammation-bearing NMRI mice. The uptake of 123/125I-2-iodo-L-phenylalanine in tumor and other organs of interest was measured by dynamic planar imaging (DPI) and gamma-counting after dissection. Displacement of 123I-2-iodo-L-phenylalanine radioactivity by L-phenylalanine, L-methionine, and L-cysteine was measured. 123I-Iodo-human serum albumin planar imaging was performed to correct for blood-pool activity and MRI was performed to delineate the tumor in DPI. 18F-FDG uptake was measured with an animal PET scanner. 125I-2-Iodo-L-phenylalanine and 18F-FDG uptake in inflamed muscle were compared. 123/125I-2-Iodo-L-phenylalanine showed a high and fast tumor uptake and followed a reversible first-order pattern allowing calculation of the half-life and the time to reach equilibrium (t(R)). Net tumor-to-background ratios up to 6.7 at 60 min were obtained. This radioactivity was significantly displaced by L-phenylalanine, L-methionine, and L-cysteine, pointing to reversible LAT transport. When plotting t(R) of the tumor uptake as a function of tumor volume, a rectangular hyperbolic curve was obtained. The almost constant t(R) values at higher tumor volumes (>4 mL) could be linked to increased necrotic tissue. Fast blood clearance of the tracer through the kidneys to the bladder and low tracer activity in the abdomen and brain were observed. The inflamed muscle showed only a slight increase of 125I-2-iodo-L-phenylalanine uptake (inflammation-to-background ratio, RIB = 1.30 +/- 0.02), in contrast to the high 18F-FDG uptake (RIB = 11.1 +/- 1.7). The in vivo stability of 123/125I-2-iodo-L-phenylalanine was good: Only 7% of free radioiodide and no other labeled metabolites were observed after 90 min. 123/125I-2-Iodo-L-phenylalanine is quickly taken up by the overexpressed LAT1 system in R1M tumors with high tumor specificity. The availability of a kit and the specificity of the tracer make 123I-2-iodo-L-phenylalanine a promising tool for oncologic SPECT.


The effects of extreme heat on human mortality and morbidity in Australia: implications for public health.
Most regions of Australia are exposed to hot summers and regular extreme heat events; and numerous studies have associated high ambient temperatures with adverse health outcomes in Australian cities. Extreme environmental heat can trigger the onset of acute conditions, including heat stroke and dehydration, as well as exacerbate a range of underlying illnesses. Consequently, in the absence of adaptation, the associated mortality and morbidity are expected to increase in a warming climate, particularly within the vulnerable populations of the elderly, children, those with chronic diseases, and people engaged in physical labour in noncooled environments. There is a need for further research to address the evidence needs of public health agencies in Australia. Building resilience to extreme heat events, especially for the most vulnerable groups, is a priority. Public health professionals and executives need to be aware of the very real and urgent need to act now.


Early face processing specificity: it's in the eyes!
Unlike most other objects that are processed analytically, faces are processed configurally. This configural processing is reflected early in visual processing following face inversion and contrast reversal, as an increase in the N170 amplitude, a scalp-recorded event-related potential. Here, we show that these face-specific effects are mediated by the eye region. That is, they occurred only when the eyes were present, but not when eyes were removed from the face. The N170 recorded to inverted and negative faces likely reflects the processing of the eyes. We propose a neural model of face processing in which face- and eye-selective neurons situated in the superior temporal sulcus region of the human brain respond differently to the face configuration and to the eyes depending on the face context. This dynamic response modulation accounts for the N170 variations reported in the literature. The eyes may be central to what makes faces so special.


Consciousness of perception after brain damage.
Disturbances of visual perception after brain damage provide clues to understanding consciousness and the brain. In this article we review six visual disorders in which perception and consciousness are dissociated as a result of brain damage: blindsight, implicit shape perception in apperceptive visual agnosia, covert recognition of faces in prosopagnosia, unconscious perception in neglect and extinction, implicit reading in pure alexia, and implicit object recognition in associative visual agnosia. We consider these six disorders from the standpoint of three main schools of thought concerning consciousness and the brain, namely a localized system for consciousness, consciousness as a state of integration, and consciousness as a property of graded representation. The findings suggest that these syndromes do not share a single mechanism and that it is conceivable that more than one explanation will be necessary both within and across syndromes. We conclude on the basis of the current evidence that it is unlikely that any single brain system is necessary for conscious awareness of perception that does not play a role in perception as well.


Closing the Performance Gap between Siamese Networks for Dissimilarity Image Classification and Convolutional Neural Networks.
In this paper, we examine two strategies for boosting the performance of ensembles of Siamese networks (SNNs) for image classification using two loss functions (Triplet and Binary Cross Entropy) and two methods for building the dissimilarity spaces (FULLY and DEEPER). With FULLY, the distance between a pattern and a prototype is calculated by comparing two images using the fully connected layer of the Siamese network. With DEEPER, each pattern is described using a deeper layer combined with dimensionality reduction. The basic design of the SNNs takes advantage of supervised k-means clustering for building the dissimilarity spaces that train a set of support vector machines, which are then combined by sum rule for a final decision. The robustness and versatility of this approach are demonstrated on several cross-domain image data sets, including a portrait data set, two bioimage and two animal vocalization data sets. Results show that the strategies employed in this work to increase the performance of dissimilarity image classification using SNN are closing the gap with standalone CNNs. Moreover, when our best system is combined with an ensemble of CNNs, the resulting performance is superior to an ensemble of CNNs, demonstrating that our new strategy is extracting additional information.


Association of terminal deoxynucleotidyl transferase with Ku.
Terminal deoxynucleotidyl transferase (TdT) catalyzes the addition of nucleotides at the junctions of rearranging Ig and T cell receptor gene segments, thereby generating antigen receptor diversity. Ku is a heterodimeric protein composed of 70- and 86-kDa subunits that binds DNA ends and is required for V(D)J recombination and DNA double-strand break (DSB) repair. We provide evidence for a direct interaction between TdT and Ku proteins. Studies with a baculovirus expression system show that TdT can interact specifically with each of the Ku subunits and with the heterodimer. The interaction between Ku and TdT is also observed in pre-T cells with endogenously expressed proteins. The protein-protein interaction is DNA independent and occurs at physiological salt concentrations. Deletion mutagenesis experiments reveal that the N-terminal region of TdT (131 amino acids) is essential for interaction with the Ku heterodimer. This region, although not important for TdT polymerization activity, contains a BRCA1 C-terminal domain that has been shown to mediate interactions of proteins involved in DNA repair. The induction of DSBs in Cos-7 cells transfected with a human TdT expression construct resulted in the appearance of discrete nuclear foci in which TdT and Ku colocalize. The physical association of TdT with Ku suggests a possible mechanism by which TdT is recruited to the sites of DSBs such as V(D)J recombination intermediates.


Enterococci, Clostridium difficile and ESBL-producing bacteria: epidemiology, clinical impact and prevention in ICU patients.
Most hospital-acquired infections arise from colonising bacteria. Intensive care patients and immunocompromised individuals are at highest risk for microbial invasion and subsequent infection due to multiple invasive procedures in addition to frequent application of chemotherapeutics and presence of poor microperfusion leading to mucosal disruption. In this narrative review, we summarise the literature on bacterial colonisation in intensive care patients, in particular the epidemiology, the clinical impact and respective infection control strategies of three pathogens, i.e., Enterococcus spp., extended-spectrum ß-lactamase producing gram-negative bacteria and Clostridium difficile, which have evolved from commensals to a public health concern today.


Spectral and structural analysis of a red fluorescent protein from Acropora digitifera.
Fluorescent proteins (FPs) possess a wide variety of spectral properties that make them of widespread interest as optical markers. These proteins can be applied as pH indicators or metal biosensors. The discovery and characterization of new fluorescent proteins is expected to further extend their application. Here, we report the spectral and structural analysis of a red fluorescent protein from Acropora digitifera (designated AdRed). This protein shows a tetrameric state and is red emitting, with excitation and emission maxima at 567 and 612 nm, respectively. Its crystal structure shows the tetrameric interface stabilized by hydrogen bonding and salt bridges. The electron density map of the chromophore, consisting of Asp66-Tyr67-Gly68, shows the decarboxylated side chain of Asp66. Ser223, located near the chromophore, has the role of bridging His202 and Glu221, and is part of the hydrogen bond network. Mutated AdRed with Cys148Ser reveals a blue shift in fluorescence excitation and emission. Our results provide insights into understanding the molecular function of AdRed and other FPs.


Inferred vs realized patterns of gene flow: an analysis of population structure in the Andros Island Rock Iguana.
Ecological data, the primary source of information on patterns and rates of migration, can be integrated with genetic data to more accurately describe the realized connectivity between geographically isolated demes. In this paper we implement this approach and discuss its implications for managing populations of the endangered Andros Island Rock Iguana, Cyclura cychlura cychlura. This iguana is endemic to Andros, a highly fragmented landmass of large islands and smaller cays. Field observations suggest that geographically isolated demes were panmictic due to high, inferred rates of gene flow. We expand on these observations using 16 polymorphic microsatellites to investigate the genetic structure and rates of gene flow from 188 Andros Iguanas collected across 23 island sites. Bayesian clustering of specimens assigned individuals to three distinct genotypic clusters. An analysis of molecular variance (AMOVA) indicates that allele frequency differences are responsible for a significant portion of the genetic variance across the three defined clusters (Fst = 0.117, p<<0.01). These clusters are associated with larger islands and satellite cays isolated by broad water channels with strong currents. These findings imply that broad water channels present greater obstacles to gene flow than was inferred from field observation alone. Additionally, rates of gene flow were indirectly estimated using BAYESASS 3.0. The proportion of individuals originating from within each identified cluster varied from 94.5 to 98.7%, providing further support for local isolation. Our assessment reveals a major disparity between inferred and realized gene flow. We discuss our results in a conservation perspective for species inhabiting highly fragmented landscapes.


Continuous separation of cells by balanced dielectrophoretic forces at multiple frequencies.
We present a particle-sorting device based on the opposition of dielectrophoretic forces. The forces are generated by an array of electrode chambers located in both sidewalls of a main flow channel. Particles with different dielectric response perceive different force magnitudes and are therefore continuously focused to different streamlines in the flow channel. We relate the particles' dielectric response to their output position in the downstream channel. We demonstrate the performance of the device by separating a mixed yeast cell population into pure fractions of viable and nonviable cells. Finally, we use the device to enrich red blood cells infected with Babesia bovis, a major pathogen in cattle and simultaneously confirm the hypothesis that infection with B. bovis causes significant changes in the dielectric response of red blood cells.


The effects of priming on a public health campaign targeting cardiovascular risks.
Public health interventions are cost-effective methods to reduce heart disease. The present study investigated the impact of a low-cost priming technique on a public health campaign targeting cardiovascular risk. Participants were 415 individuals (66% female) ages 18 and older recruited through clinics and churches. The study consisted of three phases. In Phase I, participants completed a brief survey to assess knowledge of the cardiovascular health indicators. The survey served as the prime (intervention) for the study. At Phase II, participants were provided with access to a public health campaign consisting of an education brochure on cardiovascular health. Following the educational campaign, all participants completed a post-campaign survey in Phase III of the study. Participants who completed the surveys in both Phase I and III were placed in the intervention condition (26%) and those who only completed the Phase III survey were placed in the control condition (74%). Participants who were primed reported greater awareness of the public health campaign. Additionally, more intervention participants reported they had knowledge of their own and the normal ranges for cholesterol, glucose, and body mass index. For participants who were aware of the health promotion campaign, more participants in the primed group indicated they had knowledge of their own cholesterol and glucose levels and had made positive lifestyle changes as a result of the campaign. Results suggest the presence of a priming effect. Public health campaigns may benefit from the inclusion of a low-cost prime prior to intervention.


2016 BioImages Gallery.
BioImages is an annual visual media competition that showcases the finest still, graphics and motion media work in the life sciences and medicine. Entries are evaluated by a distinguished panel of judges based on their impact, clarity, scientific content, technique, lighting, image quality, presentation, creativity, originality and effective use of the medium to fulfill its purpose. Winners are announced at the BioImages Opening Reception and Awards Presentation, held each year in conjunction with the association's annual meeting.


Survival of Casualties Undergoing Prehospital Supraglottic Airway Placement Versus Cricothyrotomy.
Airway compromise is the second leading cause of preventable death on the battlefield. Unlike a cricothyrotomy, supraglottic airway (SGA) placement does not require an incision and is less technically challenging. We compare the survival of causalities undergoing cricothyrotomy versus SGA placement. We used a series of emergency department (ED) procedure codes to search within the Department of Defense Trauma Registry (DODTR) from January 2007 to August 2016. This is a subanalysis of that data set. During the study period, 194 casualties had a documented cricothyrotomy and 22 had a documented SGA as the sole airway intervention. The two groups had similar proportions of explosive injuries (57.7% versus 63.6%, p = .328), similar composite injury severity scores (25 versus 27.5, p = .168), and similar AIS for the head, face, extremities, and external body regions. The cricothyrotomy group had lower AIS for the thorax (0 versus 3, p = .019), a trend toward lower AIS for the abdomen (0 versus 0, p = .077), more serious injuries to the head (67.5% versus 45.5%, p = .039), and similar rates of serious injuries to the face (4.6% versus 4.6%, p = .984). Glasgow Coma Scale (GCS) scores were similar on arrival to the ED (3 versus 3, p = .467) as were the proportion of patients surviving to discharge (45.4% versus 40.9%, p = .691). On repeated multivariable analyses, the odds ratios for survival were not significantly different between the two groups. We found no difference in short-term outcomes between combat casualties who received an SGA vs those who received a cricothyrotomy. Military prehospital personnel rarely used either advanced airway intervention during the recent conflicts in Afghanistan and Iraq.


Contactless actuation of perfluorinated ionomer membranes in salt solution: an experimental investigation.
A variety of modeling frameworks have been proposed for ionic polymer metal composites (IPMCs), but the physical underpinnings of their actuation remain elusive. A critical step toward the validation of existing theories and transition to engineering practice entails the design of new experimental paradigms that could support hypothesis-driven research. While several factors exacerbate the complexity of experimenting with IPMCs, the presence of the electrodes plays a major role by hindering the repeatability of the results and bringing a number of difficult-to-measure parameters into the picture. Here, we seek to address these experimental confounds by investigating contactless actuation of perfluorinated ionomer membranes in salt solution. In contrast to IPMCs that bend toward the anode in response to an applied voltage, ionomer membranes display a consistent deflection toward the cathode. Through hypothesis-driven experiments where the membrane width, solution concentration, and voltage applied across the electrodes are systematically varied, we elucidate electrochemistry and mechanics of contactless actuation. The applied voltage and solution concentration have a dominant role on the electrochemistry, while mechanics is mainly affected by the applied voltage and membrane width. Our results depict a complex scenario, which is expected to inform future theoretical inquiries about IPMC actuation.


Integration of relational and hierarchical network information for protein function prediction.
In the current climate of high-throughput computational biology, the inference of a protein's function from related measurements, such as protein-protein interaction relations, has become a canonical task. Most existing technologies pursue this task as a classification problem, on a term-by-term basis, for each term in a database, such as the Gene Ontology (GO) database, a popular rigorous vocabulary for biological functions. However, ontology structures are essentially hierarchies, with certain top to bottom annotation rules which protein function predictions should in principle follow. Currently, the most common approach to imposing these hierarchical constraints on network-based classifiers is through the use of transitive closure to predictions. We propose a probabilistic framework to integrate information in relational data, in the form of a protein-protein interaction network, and a hierarchically structured database of terms, in the form of the GO database, for the purpose of protein function prediction. At the heart of our framework is a factorization of local neighborhood information in the protein-protein interaction network across successive ancestral terms in the GO hierarchy. We introduce a classifier within this framework, with computationally efficient implementation, that produces GO-term predictions that naturally obey a hierarchical 'true-path' consistency from root to leaves, without the need for further post-processing. A cross-validation study, using data from the yeast Saccharomyces cerevisiae, shows our method offers substantial improvements over both standard 'guilt-by-association' (i.e., Nearest-Neighbor) and more refined Markov random field methods, whether in their original form or when post-processed to artificially impose 'true-path' consistency. Further analysis of the results indicates that these improvements are associated with increased predictive capabilities (i.e., increased positive predictive value), and that this increase is consistent uniformly with GO-term depth. Additional in silico validation on a collection of new annotations recently added to GO confirms the advantages suggested by the cross-validation study. Taken as a whole, our results show that a hierarchical approach to network-based protein function prediction, that exploits the ontological structure of protein annotation databases in a principled manner, can offer substantial advantages over the successive application of 'flat' network-based methods.


Implantable cardioverter defibrillator events in patients with asymptomatic nonsustained ventricular tachycardia: is device implantation justified?
Primary prevention trials have demonstrated that patients with coronary disease, reduced left ventricular function, and nonsustained ventricular tachycardia (NSVT) have improved survival with implantable cardioverter defibrillator (ICD) therapy, presumably secondary to effective termination of life-threatening arrhythmias. However, stored intracardiac electrograms were not always available and specific arrhythmias leading to ICD therapy were not always known. We examined the occurrence of ICD events in 51 consecutive patients who match the described patient profile to determine the frequency of appropriate and inappropriate ICD therapy. ICD detections were noted in 18 (35%) patients during a median follow-up period of 13.1 months. Appropriate therapy for sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) occurred in 11 (22%) patients, with appropriate shocks in 8 (16%) patients and appropriate antitachycardia pacing (ATP) in 4 (8%) patients. The time to first appropriate therapy occurred at a mean of 17 +/- 12 months (median 18 months, range 3-36 months). Inappropriate therapy occurred in 5 (10%) patients with inappropriate shocks in 4 patients and inappropriate ATP in 2 patients. Inappropriate therapy was delivered for supraventricular arrhythmias (SVAs) in 4 patients and for T wave oversensing in 1 patient. The reason for shock therapy was unknown in 1 patient (2%) due to ICD malfunction. The mean arrhythmia rate leading to appropriate therapy for VT/VF was 232 +/- 72 beats/min (range 181-400 beats/min), and the mean rate leading to inappropriate therapy for SVT was 168 +/- 10 beats/min (range 160-180 beats/min). Patients with coronary disease and asymptomatic NSVT commonly receive appropriate defibrillator therapy. These results support the need for ICD implantation for primary prevention, with attention to careful programming of the detection rate to prevent inappropriate therapy.


Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases).
Superficial bacterial folliculitis (SBF) is usually caused by Staphylococcus pseudintermedius and routinely treated with systemic antimicrobial agents. Infection is a consequence of reduced immunity associated with alterations of the skin barrier and underlying diseases that may be difficult to diagnose and resolve; thus, SBF is frequently recurrent and repeated treatment is necessary. The emergence of multiresistant bacteria, particularly meticillin-resistant S. pseudintermedius (MRSP), has focused attention on the need for optimal management of SBF. Provision of an internationally available resource guiding practitioners in the diagnosis, treatment and prevention of SBF. The guidelines were developed by the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases, with consultation and advice from diplomates of the American and European Colleges of Veterinary Dermatology. They describe optimal methods for the diagnosis and management of SBF, including isolation of the causative organism, antimicrobial susceptibility testing, selection of antimicrobial drugs, therapeutic protocols and advice on infection control. Guidance is given for topical and systemic modalities, including approaches suitable for MRSP. Systemic drugs are classified in three tiers. Tier one drugs are used when diagnosis is clear cut and risk factors for antimicrobial drug resistance are not present. Otherwise, tier two drugs are used and antimicrobial susceptibility tests are mandatory. Tier three includes drugs reserved for highly resistant infections; their use is strongly discouraged and, when necessary, they should be used in consultation with specialists. Optimal management of SBF will improve antimicrobial use and reduce selection of MRSP and other multidrug-resistant bacteria affecting animal and human health.


The Role of Genetic Resources in Breeding for Climate Change: The Case of Public Breeding Programmes in Eighteen Developing Countries.
The role of plant breeding in adapting crops to climate changes that affect food production in developing countries is recognized as extremely important and urgent, alongside other agronomic, socio-economic and policy adaptation pathways. To enhance plant breeders' capacity to respond to climate challenges, it is acknowledged that they need to be able to access and use as much genetic diversity as they can get. Through an analysis of data from a global survey, we explore if and how public breeders in selected developing countries are responding to climate challenges through a renewed or innovative use of plant genetic resources, particularly in terms of types of material incorporated into their breeding work as well as sources of such germplasm. It also looks at the possible limitations breeders encounter in their efforts towards exploring diversity for adaptation. Breeders are clearly considering climate challenges. In general, their efforts are aimed at intensifying their breeding work on traits that they were already working on before climate change was so widely discussed. Similarly, the kinds of germplasm they use, and the sources from which they obtain it, do not appear to have changed significantly over the course of recent years. The main challenges breeders faced in accessing germplasm were linked to administrative/legal factors, particularly related to obtaining genetic resources across national borders. They also underscore technical challenges such as a lack of appropriate technologies to exploit germplasm sets such as crop wild relatives and landraces. Addressing these limitations will be crucial to fully enhance the role of public sector breeders in helping to adapt vulnerable agricultural systems to the challenges of climate change.


Patient and parental assessment of factors influencing the choice of treatment in pediatric hydrocephalus.
Choosing between competing options (shunt or endoscopic third ventriculostomy) for the management of hydrocephalus requires patients and caregivers to make a subjective judgment about the relative importance of risks and benefits associated with each treatment. In the context of this particular decision, little is known about what treatment-related factors are important and how they are prioritized in order to arrive at a treatment preference. The Hydrocephalus Association electronically distributed a survey to surgically treated hydrocephalus patients or their families. Respondents rated the importance of various surgical attributes in their decision-making about treatment choice, and also indicated their preference in hypothetical scenarios involving a trade-off between potential risks and benefits of treatment. Rank-order correlations were used to determine whether certain predictor variables affected the rating of factors or hypothetical treatment choice. Eighty percent of 414 respondents rated procedural risks, minimizing repeat surgery, and improving long-term brain function as being very or extremely important factors when deciding on a treatment; 69% rated the need to implant a permanent device similarly. Parent-respondents rated procedural risks higher than patient-respondents. A majority of respondents (n = 209, 54%) chose a procedure with higher surgical risk if it meant that implantation of a permanent device was not required, and respondents were more likely to choose this option if they discussed both treatment options with their surgeon prior to their initial intervention (Spearman rho 0.198, p = 0.001).Although only 144 of 384 total respondents (38%) chose a less established operation if it meant less repeat surgery, patient-respondents were more likely to choose this option compared to parent-respondents (Spearman rho 0.145, p = 0.005). Likewise, patient-respondents were more likely than parent-respondents to choose an operation that involved less repeat surgery and led to worse long-term brain function (Spearman rho 0.160, p = 0.002), an option that was chosen by only 23 (6%) of respondents overall. This study is the first exploration of patient/parental factors that influence treatment preference in pediatric hydrocephalus. Procedural risks, minimizing repeat operations, and the desire to maximize long-term cognitive function appeared to be the most important attributes that influenced treatment decisions that the survey respondents had made in the past. Patients and/or their caregivers appear to see some inherent benefit in being shunt free. It appears that fear of multiple revision operations may drive treatment choice in some circumstances.


[The validity of acute assessments of psychiatric conditions made by psychiatric emergency staff].
Earlier research carried out by the outreach psychiatric emergency team in the region of Uden / Veghel in the Netherlands indicated that the preliminary diagnosis of patients in crisis was associated with aggressive behaviour during the later contact between the patient and the staff of the psychiatric emergency team. An accurate diagnosis by the staff of the psychiatric emergency team is important because it should guide the patient towards the right type of treatment by the most appropriate team. The staff of the psychiatric emergency service who make the initial diagnosis are pressed for time and have only limited information.
 AIM: To find out what differences there are between the crisis team's initial diagnosis of the psychiatric condition of the patient in crisis and the later diagnosis made after more extensive psychiatric tests are carried out following the regular intake procedure.
 METHOD: Our study was based om 129 patients who, in the period of 2009 and 2010, were not known to mental health service and had not had any previous contact with the psychiatric emergency service. The first assessment of a patient's psychiatric condition made by a member of the psychiatric emergency service was compared with the later diagnosis made by a professional psychiatrist after the regular intake procedure. We then investigated the degree of agreement between the two diagnoses using Cohen's kappa so that we could test the validity of the initial screening of the patient's condition.
 RESULTS: We found that the staff of the psychiatric emergency team was able to achieve a result that was better than could be expected on the basis of chance. The Cohen's kappas varied between 0.81 for psychotic disorders to 0.31 for borderline personality disorders. Borderline personality disorders, however, tended to be overestimated by the psychiatric emergency staff.
 CONCLUSION: Although there was only limited agreement regarding various conditions, it is encouraging that the psychiatric emergency staff were able to assess psychotic disorders accurately on the basis of the initial information they had received. This result is important because in other studies psychotic symptoms were found to be associated with a higher likelihood of aggression during the later outreach consultation.


Flower isoforms promote competitive growth in cancer.
In humans, the adaptive immune system uses the exchange of information between cells to detect and eliminate foreign or damaged cells; however, the removal of unwanted cells does not always require an adaptive immune system1,2. For example, cell selection in Drosophila uses a cell selection mechanism based on 'fitness fingerprints', which allow it to delay ageing3, prevent developmental malformations3,4 and replace old tissues during regeneration5. At the molecular level, these fitness fingerprints consist of combinations of Flower membrane proteins3,4,6. Proteins that indicate reduced fitness are called Flower-Lose, because they are expressed in cells marked to be eliminated6. However, the presence of Flower-Lose isoforms at a cell's membrane does not always lead to elimination, because if neighbouring cells have similar levels of Lose proteins, the cell will not be killed4,6,7. Humans could benefit from the capability to recognize unfit cells, because accumulation of damaged but viable cells during development and ageing causes organ dysfunction and disease8-17. However, in Drosophila this mechanism is hijacked by premalignant cells to gain a competitive growth advantage18. This would be undesirable for humans because it might make tumours more aggressive19-21. It is unknown whether a similar mechanism of cell-fitness comparison is present in humans. Here we show that two human Flower isoforms (hFWE1 and hFWE3) behave as Flower-Lose proteins, whereas the other two isoforms (hFWE2 and hFWE4) behave as Flower-Win proteins. The latter give cells a competitive advantage over cells expressing Lose isoforms, but Lose-expressing cells are not eliminated if their neighbours express similar levels of Lose isoforms; these proteins therefore act as fitness fingerprints. Moreover, human cancer cells show increased Win isoform expression and proliferate in the presence of Lose-expressing stroma, which confers a competitive growth advantage on the cancer cells. Inhibition of the expression of Flower proteins reduces tumour growth and metastasis, and induces sensitivity to chemotherapy. Our results show that ancient mechanisms of cell recognition and selection are active in humans and affect oncogenic growth.


Objectively measured physical activity and fat mass in children: a bias-adjusted meta-analysis of prospective studies.
Studies investigating the prevention of weight gain differ considerably in design and quality, which impedes pooling them in conventional meta-analyses, the basis for evidence-based policy making. This study is aimed at quantifying the prospective association between measured physical activity and fat mass in children, using a meta-analysis method that allows inclusion of heterogeneous studies by adjusting for differences through eliciting and incorporating expert opinion. Studies on prevention of weight gain using objectively measured exposure and outcome were eligible; they were adopted from a recently published systematic review. Differences in study quality and design were considered as internal and external biases and captured in checklists. Study results were converted to correlation coefficients and biases were considered either additive or proportional on this scale. The extent and uncertainty of biases in each study were elicited in a formal process by six quantitatively-trained assessors and five subject-matter specialists. Biases for each study were combined across assessors using median pooling. Results were combined across studies by random-effects meta-analysis. The combined correlation of the unadjusted results from the six studies was -0.04 (95%CI: -0.22, 0.14) with considerable heterogeneity (I² = 78%), which makes it difficult to interpret the result. After bias-adjustment the pooled correlation was -0.01 (95%CI: -0.18, 0.16) with apparent study compatibility (I² = 0%). By using this method the prospective association between physical activity and fat mass could be quantitatively synthesized; the result suggests no association. Objectively measured physical activity may not be the key determinant of unhealthy weight gain in children.


Determination of absorbed dose to water around a clinical HDR (192)Ir source using LiF:Mg,Ti TLDs demonstrates an LET dependence of detector response.
Experimental radiation dosimetry with thermoluminescent dosimeters (TLDs), calibrated in a (60)Co or megavoltage (MV) photon beam, is recommended by AAPM TG-43U1for verification of Monte Carlo calculated absorbed doses around brachytherapy sources. However, it has been shown by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] that for TLDs of LiF:Mg,Ti, detector response was 4% higher in a (137)Cs beam than in a (60)Co one. The aim of this work was to investigate if similar over-response exists when measuring absorbed dose to water around (192)Ir sources, using LiF:Mg,Ti dosimeters calibrated in a 6 MV photon beam. LiF dosimeters were calibrated to measure absorbed dose to water in a 6 MV photon beam and used to measure absorbed dose to water at distances of 3, 5, and 7 cm from a clinical high dose rate (HDR) (192)Ir source in a polymethylmethacrylate (PMMA) phantom. Measured values were compared to values of absorbed dose to water calculated using a treatment planning system (TPS) including corrections for the difference in energy absorption properties between calibration quality and the quality in the users' (192)Ir beam and for the use of a PMMA phantom instead of the water phantom underlying dose calculations in the TPS. Measured absorbed doses to water around the (192)Ir source were overestimated by 5% compared to those calculated by the TPS. Corresponding absorbed doses to water measured in a previous work with lithium formate electron paramagnetic resonance (EPR) dosimeters by Antonovic et al. [Med. Phys. 36, 2236-2247 (2009)], using the same irradiation setup and calibration procedure as in this work, were 2% lower than those calculated by the TPS. The results obtained in the measurements in this work and those obtained using the EPR lithium formate dosimeters were, within the expanded (k = 2) uncertainty, in agreement with the values derived by the TPS. The discrepancy between the results using LiF:Mg,Ti TLDs and the EPR lithium formate dosimeters was, however, statistically significant and in agreement with the difference in relative detector responses found for the two detector systems by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] and by Adolfsson et al. [Med. Phys. 37, 4946-4959 (2010)]. When calibrated in (60)Co or MV photon beams, correction for the linear energy transfer (LET) dependence of LiF:Mg,Ti detector response will be needed as to measure absorbed doses to water in a (192)Ir beam with highest accuracy. Such corrections will depend on the manufacturing process (MTS-N Poland or Harshaw TLD-100) and details of the annealing and read-out schemes used.


On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics.
Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic. The kynurenic acid hypothesis of schizophrenia has attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto prevailing serological research approach to one which focuses on immunological factors. An open clinical pilot study in which, during 2006, eight female and five male patients with psychotic symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. On one year follow-up, six out of the eight female patients showed stable excellent treatment results, whereas two were rated as showing significant treatment results. Four of the five men who entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe acute catatonic schizophrenia. Two of the male patients showed significant treatment results, whereas three of them were rated as having had a slight to moderate improvement. No less than three of the women had suffered their first episode of psychosis after giving birth to their first (and only) child. This finding, as these women all responded excellently to treatment with antibiotics, indicates that post partum psychosis could be regarded as an infectious complication of childbirth of, as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms. As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.


Comparison of heartworm extract-induced shock and endotoxin-induced shock in dogs by determination of serum tumor necrosis factor concentrations.
To compare the mechanisms of heartworm (HW) extract-induced shock and endotoxin-induced shock in dogs by determination of serum tumor necrosis factor (TNF) concentrations. 11 mixed-breed dogs (7 without and 4 with HW infections). Eight dogs were treated with 2 ml of HW extract IV, and 3 dogs were given endotoxin (Escherichia coli lipopolysaccharide [LPS]) at 40 or 400 microg/kg of body weight, IV. Changes in clinical and hematologic findings and serum TNF concentrations were examined from before treatment to 120 minutes after treatment in dogs given HW extract or from before treatment to 180 minutes after treatment in dogs given LPS. Tumor necrosis factor concentration was determined by cytotoxic assay, using WEHI-164 murine sarcoma cells, and plasma endotoxin concentration was determined in 2 dogs treated with HW extract, using the endotoxin-specific chromogenic test. Eight dogs developed shock 3 to 16 minutes after HW extract treatment. Rectal temperature did not change during examination. Serum TNF concentration was detected at a low concentration only 60 and 120 minutes after HW extract treatment, and plasma endotoxin was not detected during examination. In dogs treated with LPS, rectal temperature increased to > 40 C in 2 of 3 dogs, and serum TNF concentration began to increase 30 minutes after LPS treatment, reaching a maximum concentration by 60 minutes. The cause and mechanism of HW extract-induced shock may be different from those of endotoxin-induced shock, because TNF, which was a pivotal mediator in endotoxin-induced shock, increased minimally in serum of dogs treated with HW extract.


The use of acetazolamide-enhanced regional cerebral blood flow measurement to predict risk to arteriovenous malformation patients.
Regional hemodynamic disturbances may complicate the treatment of certain cerebral arteriovenous malformations (AVM) and occasionally produce life-threatening situations. Acetazolamide-enhanced quantitative regional cerebral blood flow studies were performed preoperatively in 35 patients to determine if patterns of vasoreactivity could be identified that might be markers for postoperative morbidity. Ipsilateral and contralateral regions of hypoperfusion were identified on resting studies, and a steal index was calculated by dividing the regional cerebral blood flow in the steal region by the flow in a normal cerebellar region. Flow in these regions of interest was again quantitated after the administration of acetazolamide, a known cerebral vasodilator. A delta value was calculated by subtracting the resting index values from the acetazolamide indices. Abnormally enhanced vasoreactivity (vasodilation) to acetazolamide stimulation was noted in these threatened territories in AVM that had perforating vessel feeding and angiographic steal phenomena, that developed hyperemic disturbances, and that resulted in poor outcomes. These findings call into question traditional theories of AVM-related hemodynamic decompensation and suggest unique smooth muscle derangements in cerebral vasculature in some AVM patients.


Mechanical tuning of the evaporation rate of liquid on crossed fibers.
We investigate experimentally the drying of a small volume of perfectly wetting liquid on two crossed fibers. We characterize the drying dynamics for the three liquid morphologies that are encountered in this geometry: drop, column, and a mixed morphology, in which a drop and a column coexist. For each morphology, we rationalize our findings with theoretical models that capture the drying kinetics. We find that the evaporation rate significantly depends upon the liquid morphology and that the drying of the liquid column is faster than the evaporation of the drop and the mixed morphology for a given liquid volume. Finally, we illustrate that shearing a network of fibers reduces the angle between them, changes the morphology toward the column state, and therefore, enhances the drying rate of a volatile liquid deposited on it.


A review of sustainable septage management strategies on the islands in Croatia.
This paper analyzes the problem of septage management on Croatian islands in accordance with the circular economy framework. The systems approach methodology has been used to analyze management issues. A large number of individual housing facilities on Croatian islands are not connected to the public sewage system. As a solution to the requirements of the competent services, holding tanks are used which are largely permeable. Due to tourism activities the amount of wastewater seasonally varies considerably and in summer is up to 10 times higher than in winter. Such a situation creates major problems for property owners due to mostly uncontrolled disposing of septage, which endangers the environment and human health. Although the situation is improving by application of EU directives, due to poor population density septage management will remain a permanent problem. The EU legal framework requires that organic waste be disposed of in accordance with the principles of a circular economy. This also applies to septage. It has been found that simple and robust options are sustainable and the best choice for a small island environment. After appropriate treatment, septage becomes a resource that strengthens the viability of living on the islands.


Positioning of aquatic animals based on time-of-arrival and random walk models using YAPS (Yet Another Positioning Solver).
Aquatic positional telemetry offers vast opportunities to study in vivo behaviour of wild animals, but there is room for improvement in the data quality provided by current procedures for estimating positions. Here we present a novel positioning method called YAPS (Yet Another Positioning Solver), involving Maximum Likelihood analysis of a state-space model applied directly to time of arrival (TOA) data in combination with a movement model. YAPS avoids the sequential positioning-filtering-approach applied in alternative tools by using all available data in a single model, and offers better accuracy and error control. Feasibility and performance of YAPS was rigorously tested in a simulation study and by applying YAPS to data from an acoustic transmitter towed in a receiver array. Performance was compared to an alternative positioning model and proprietary software. The simulation study and field test revealed that YAPS performance was better and more consistent than alternatives. We conclude that YAPS outperformed the compared alternative methods, and that YAPS constitute a vast improvement to currently available positioning software in acoustic telemetry. Additionally, in contrast to vendor-supplied solutions, YAPS is transparent, flexible and can easily be adapted and extended for further improvements or to meet study specific requirements such as three-dimensional positioning.


Estimating HIV Incidence in Populations Using Tests for Recent Infection: Issues, Challenges and the Way Forward.
INTRODUCTION: HIV incidence is the rate of new infections in a population over time. HIV incidence is a critical indicator needed to assess the status and trends of the HIV epidemic in populations and guide and assess the impact of prevention interventions. METHODS: Several methods exist for estimating population-level HIV incidence: direct observation of HIV incidence through longitudinal follow-up of persons at risk for new HIV infection, indirect measurement of HIV incidence using data on HIV prevalence and mortality in a population, and direct measurement of HIV incidence through use of tests for recent infection (TRIs) that can differentiate "recent" from "non-recent" infections based on biomarkers in cross-sectional specimens. Given the limitations in measuring directly observed incidence and the assumptions needed for indirect measurements of incidence, there is an increasing demand for TRIs for HIV incidence surveillance and program monitoring and evaluation purposes. RESULTS: Over ten years since the introduction of the first TRI, a number of low-, middle-, and high-income countries have integrated this method into their HIV surveillance systems to monitor HIV incidence in the population. However, the accuracy of these assays for measuring HIV incidence has been unsatisfactory to date, mainly due to misclassification of chronic infections as recent infection on the assay. To improve the accuracy of TRIs for measuring incidence, countries are recommended to apply case-based adjustments, formula-based adjustments using local correction factors, or laboratory-based adjustment to minimize error related to assay misclassification. Multiple tests may be used in a recent infection testing algorithm (RITA) to obtain more accurate HIV incidence estimates. CONCLUSION: There continues to be a high demand for improved TRIs and RITAs to monitor HIV incidence, determine prevention priorities, and assess impact of interventions. Current TRIs have noted limitations, but with appropriate adjustments, interpreted in parallel with other epidemiologic data, may still provide useful information on new infections in a population. New TRIs and RITAs with improved accuracy and performance are needed and development of these tools should be supported.


Essential steps in bioprinting: From pre- to post-bioprinting.
An increasing demand for directed assembly of biomaterials has inspired the development of bioprinting, which facilitates the assembling of both cellular and acellular inks into well-arranged three-dimensional (3D) structures for tissue fabrication. Although great advances have been achieved in the recent decade, there still exist issues to be addressed. Herein, a review has been systematically performed to discuss the considerations in the entire procedure of bioprinting. Though bioprinting is advancing at a rapid pace, it is seen that the whole process of obtaining tissue constructs from this technique involves multiple-stages, cutting across various technology domains. These stages can be divided into three broad categories: pre-bioprinting, bioprinting and post-bioprinting. Each stage can influence others and has a bearing on the performance of fabricated constructs. For example, in pre-bioprinting, tissue biopsy and cell expansion techniques are essential to ensure a large number of cells are available for mass organ production. Similarly, medical imaging is needed to provide high resolution designs, which can be faithfully bioprinted. In the bioprinting stage, compatibility of biomaterials is needed to be matched with solidification kinetics to ensure constructs with high cell viability and fidelity are obtained. On the other hand, there is a need to develop bioprinters, which have high degrees of freedom of movement, perform without failure concerns for several hours and are compact, and affordable. Finally, maturation of bioprinted cells are governed by conditions provided during the post-bioprinting process. This review, for the first time, puts all the bioprinting stages in perspective of the whole process of bioprinting, and analyzes their current state-of-the art. It is concluded that bioprinting community will recognize the relative importance and optimize the parameter of each stage to obtain the desired outcomes.


A simplified approach to the pooled analysis of calibration of clinical prediction rules for systematic reviews of validation studies.
Estimating calibration performance of clinical prediction rules (CPRs) in systematic reviews of validation studies is not possible when predicted values are neither published nor accessible or sufficient or no individual participant or patient data are available. Our aims were to describe a simplified approach for outcomes prediction and calibration assessment and evaluate its functionality and validity. Methodological study of systematic reviews of validation studies of CPRs: a) ABCD(2) rule for prediction of 7 day stroke; and b) CRB-65 rule for prediction of 30 day mortality. Predicted outcomes in a sample validation study were computed by CPR distribution patterns ("derivation model"). As confirmation, a logistic regression model (with derivation study coefficients) was applied to CPR-based dummy variables in the validation study. Meta-analysis of validation studies provided pooled estimates of "predicted:observed" risk ratios (RRs), 95% confidence intervals (CIs), and indexes of heterogeneity (I(2) ) on forest plots (fixed and random effects models), with and without adjustment of intercepts. The above approach was also applied to the CRB-65 rule. Our simplified method, applied to ABCD(2) rule in three risk strata (low, 0-3; intermediate, 4-5; high, 6-7 points), indicated that predictions are identical to those computed by univariate, CPR-based logistic regression model. Discrimination was good (c-statistics =0.61-0.82), however, calibration in some studies was low. In such cases with miscalibration, the under-prediction (RRs =0.73-0.91, 95% CIs 0.41-1.48) could be further corrected by intercept adjustment to account for incidence differences. An improvement of both heterogeneities and P-values (Hosmer-Lemeshow goodness-of-fit test) was observed. Better calibration and improved pooled RRs (0.90-1.06), with narrower 95% CIs (0.57-1.41) were achieved. Our results have an immediate clinical implication in situations when predicted outcomes in CPR validation studies are lacking or deficient by describing how such predictions can be obtained by everyone using the derivation study alone, without any need for highly specialized knowledge or sophisticated statistics.


Prognostic significance of baseline ST-T-wave abnormalities in diagnostic stress echocardiography.
The aim of this study was to determine whether resting ST-T wave abnormalities (ST-Ta) provide incremental prognostic information in patients with no history of coronary artery disease undergoing dobutamine stress echocardiography (DSE). We evaluated 1308 consecutive patients without previous myocardial infarction (MI) or revascularization who underwent DSE. Ischemia was defined as new or worsening wall motion abnormalities. End points during follow-up were all-cause death and cardiac death/nonfatal MI. ST-Ta were detected in 162 (12%) patients. The incidence of ischemia was higher in patients with baseline ST-Ta than patients without [74 (46%) vs. 327 (28%), P=0.00001]. During a follow-up of 4.6 ± 3 years, cardiac death/nonfatal MI occurred in 42 (26%) patients with resting ST-Ta and in 157 (14%) patients without resting ST-Ta (P<0.001). Patients with ST-Ta had a higher annual cardiac death/nonfatal MI rate compared with patients without, both in the presence of normal DSE (3.2 vs. 1.4%, P=0.01) as well as abnormal DSE (5.3 vs. 3%, P<0.001). In a Cox proportional modeling, resting ST-Ta added incremental value over clinical and stress echocardiographic data for the prediction of death (global χ 125, 140, 150, respectively; P<0.05) and cardiac death/nonfatal MI (global χ 79, 100, 111, respectively; P<0.05). Baseline ST-Ta are associated with an increased risk of cardiac death/nonfatal MI and all-cause mortality, incremental to clinical data and DSE results. The associated risk is persistent among patients with normal DSE.


A.T. Still's Osteopathic Lesion Theory and Evidence-Based Models Supporting the Emerged Concept of Somatic Dysfunction.
Andrew Taylor Still, MD, DO, coined the original idea of lesion based on the obstruction of flow of body fluids, but primarily referring to bony structures and more precisely to the spine. Throughout the 20th century, this idea was shaped and developed into the concept of somatic dysfunction, a term that is familiar to both US-trained osteopathic physicians and foreign-trained osteopaths and has been an essential cornerstone of osteopathic practice and teaching. The present historical narrative review offers an overview of the evolution of Still's original lesion concept, major evidence-based models of somatic dysfunction that attempt to explain the clinical findings, and a critique of the concept.


Toxic emissions from mobile sources: a total fuel-cycle analysis for conventional and alternative fuel vehicles.
Mobile sources are among the largest contributors of four hazardous air pollutants--benzene, 1,3-butadiene, acetaldehyde, and formaldehyde--in urban areas. At the same time, federal and state governments are promoting the use of alternative fuel vehicles as a means to curb local air pollution. As yet, the impact of this movement toward alternative fuels with respect to toxic emissions has not been well studied. The purpose of this paper is to compare toxic emissions from vehicles operating on a variety of fuels, including reformulated gasoline (RFG), natural gas, ethanol, methanol, liquid petroleum gas (LPG), and electricity. This study uses a version of Argonne National Laboratory's Greenhouse Gas, Regulated Emissions, and Energy Use in Transportation (GREET) model, appropriately modified to estimate toxic emissions. The GREET model conducts a total fuel-cycle analysis that calculates emissions from both downstream (e.g., operation of the vehicle) and upstream (e.g., fuel production and distribution) stages of the fuel cycle. We find that almost all of the fuels studied reduce 1,3-butadiene emissions compared with conventional gasoline (CG). However, the use of ethanol in E85 (fuel made with 85% ethanol) or RFG leads to increased acetaldehyde emissions, and the use of methanol, ethanol, and compressed natural gas (CNG) may result in increased formaldehyde emissions. When the modeling results for the four air toxics are considered together with their cancer risk factors, all the fuels and vehicle technologies show air toxic emission reduction benefits.