Water quality assessment of Malad Creek, Mumbai, India: an impact of sewage and tidal water.
The aim of the study was to carry out water quality assessment and to identify sources responsible for deterioration of quality in the Malad creek, Mumbai, India. Creek receives sewage and wastewater from various drains and partially treated effluent from Malad and Versova treatment facilities. To assess the water quality, sampling locations were identified in the creek based on discharges of wastewater and sewage. Identified locations were traced in physical space by a global positioning system. Samples were collected during low and high tides and analyzed for physical, chemical and bacteriological parameters such as pH, Turbidity, DO, BOD, NH(3)-N, PO(4) and FC and compared with SW-II Standards. Parameters were also analyzed statistically and correlated to determine the relationship amongst the parameters using SPSS software. The idea was to determine the probable causes contributing to the pollution in the creek. Various options were suggested for improvement in the creek quality based on water quality assessment.


Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis.
Hydroxylation of debrisoquine, catalyzed by the cytochrome P450 CYP2D6 exhibits genetic polymorphism, with large inter-individual differences in metabolic capacity. About 7% of Caucasians carry deficient CYP2D6 alleles and lack the CYP2D6 enzyme (poor metabolizers). We have shown in two Swedish families, individuals carrying duplicated or amplified functional CYP2D6L-genes (CYP2D6L2), causing the opposite phenomenon, ultrarapid metabolism of debrisoquine. In the present study, the occurrence of extra copies of CYP2D6L-alleles was studied in relation to debrisoquine metabolic ratio (MR) in 270 Swedish Caucasians including 64 selected subjects with very rapid metabolism (MR < or = 0.2). Thirteen of the 64 subjects carried a duplicated CYP2D6-gene as identified by EcoRI and XbaI restriction fragment length polymorphism and allele-specific polymerase chain reaction-amplification of genomic DNA. A new allele with three active CYP2D6L-genes was identified, characterized by an XbaI 54 kilobase fragment. This indicates a preference of the CYP2D6L-gene to be amplified compared to other CYP2D6 genes. Only one subject with an MR higher than 0.2 carried the duplicated CYP2D6L-allele, also being heterozygous for the defect CYP2D6B-allele. The overall frequency of the duplicated/amplified CYP2D6-allele was about 1%, and was present in 40% of subjects with MRs < or = 0.1. Thus, other variant CYP2D6-genes may exist that cause increased CYP2D6 activity. In conclusion, a haplotype with duplicated or amplified functional CYP2D6 genes predicts, with high accuracy, ultrarapid metabolism of debrisoquine. Genotyping for this CYP2D locus variant might be of value in patients not responding to generally recommended doses of CYP2D6 substrates, to distinguish between high metabolic capacity and noncompliance.


Dangerous Abusive Relationships and Sources of Resilience for South Asian Immigrant Women Survivors of Intimate Partner Violence.
This study explored South Asian immigrant women survivors' perspectives on intimate partner relationships that could lead to severe violence or a homicide and sources of resilience for South Asian immigrant survivors in the United States. The study recruited 16 South Asian immigrant survivors for in-depth interviews and focus groups. Data were analyzed using thematic analysis. Survivors shared some characteristics of dangerous partner such as controlling behavior, anger issues, infidelity, alcohol and drug problems, and history of childhood abuse. Incidents of severe physical abuse, threats to kill, possession of a weapon, and suspicious behavior led survivors to feel fearful for their lives. Sources of resilience in the community (e.g., support from formal sources of help) and at the individual level (e.g., education) were discussed. The needs for culturally informed services and to generate awareness of services among South Asian immigrants were highlighted.


Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study.
Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.


Subunit interactions and protein stability in the cyanobacterial light-harvesting proteins.
Strain 4R is a phycocyanin-minus mutant of the unicellular cyanobacterium Synechocystis sp. strain 6803. Although it lacks the light-harvesting protein phycocyanin, 4R has normal levels of phycocyanin (cpc) transcripts. Sequence analysis of the cpcB gene encoding the phycocyanin beta subunit shows an insertion mutation in 4R that causes early termination of translation. Other work has shown that the phycocyanin alpha subunit and the linker proteins encoded on the cpc transcripts are all functional in 4R, yet the defective phycocyanin beta subunit results in the complete absence of the alpha subunit and the linkers. Phycocyanin-minus mutants were constructed in a wild-type background by interruption of cpcB and cpcA with an antibiotic resistance gene and were compared with the 4R strain. Immunoblot analysis of the mutants demonstrated that interruption of one subunit was accompanied by a complete absence of the unassembled partner subunit. Phycocyanin assembly begins with the formation of the alpha beta heterodimer (the monomer) and continues through higher-order trimeric and hexameric aggregates that associate with linker proteins to form the phycobilisome rods. The results in this paper indicate that monomer formation is a critical stage in the biliprotein assembly pathway and that unassembled subunits are subject to stringent controls that prevent their appearance in vivo.


Carbohydrate and nitrogen stores in Festuca paniculata under mowing explain dominance in subalpine grasslands.
Cessation of traditional management threatens semi-natural grassland diversity through the colonisation or increase of competitive species adapted to nutrient-poor conditions. Regular mowing is one practice that controls their abundance. This study evaluated the ecophysiological mechanisms limiting short- and long-term recovery after mowing for Festuca paniculata, a competitive grass that takes over subalpine grasslands in the Alps following cessation of mowing. We quantified temporal variations in carbon (C) and nitrogen (N) content, starch, fructan and total soluble sugars in leaves, stem bases and roots of F. paniculata during one growth cycle in mown and unmown fields and related them to the dynamics of soil mineral N concentration and soil moisture. Short-term results suggest that the regrowth of F. paniculata following mowing might be N-limited, first because of N dilution by C increments in the plant tissue, and second, due to low soil mineral N and soil moisture at this time of year. However, despite short-term effects of mowing on plant growth, C and N content and concentration at the beginning of the following growing season were not affected. Nevertheless, total biomass accumulation at peak standing biomass was largely reduced compared to unmown fields. Moreover, lower C storage capacity at the end of the growing season impacted C allocation to vegetative reproduction during winter, thereby dramatically limiting the horizontal growth of F. paniculata tussocks in the long term. We conclude that mowing reduces the growth of F. paniculata tussocks through both C and N limitation. Such results will help understanding how plant responses to defoliation regulate competitive interactions within plant communities.


New insights into sympathetic regulation of glucose and fat metabolism.
The autonomic nervous system modulates glucose and fat metabolism through both direct neural effects and hormonal effects. This review presents recent concepts on the sympathetic regulation of glucose and fat metabolism. Focally released norepinephrine from sympathetic nerves is likely to increase glucose uptake in skeletal muscle and adipose tissues independent of insulin but norepinephrine does not contribute so much as epinephrine to hepatic glucose production. Epinephrine increases hepatic glucose production and inhibits insulin secretion and the glucose uptake by tissues that is induced by insulin. Additionally, catecholamines can increase thermogenesis and lipolysis, leading to increased energy expenditure and decreased fat stores. It is likely that beta-(beta3)-adrenergic receptors mediate these responses. Alterations of central neurotransmission and environmental factors can change the relative contribution of sympathetic outflow to the pancreas, liver, adrenal medulla and adipose tissues, leading to the modulation of glucose and fat metabolism. Recent studies have proposed that leptin, an adipocyte hormone, affects the central nervous system to increase sympathetic outflow independent of feeding. The effects of leptin on glucose and fat metabolism could be in part mediated by the sympathetic nervous system. Studies using mice with a genetic disruption of serotonin 5-HT2c receptor indicate that central neural mechanisms in the regulation of sympathetic outflow and satiety could be dissociated. Abnormalities of sympathetic effects, including disturbances of leptin and beta3-adrenergic receptor signalling, are likely to cause obesity and impaired glucose tolerance in rodents and humans. These findings indicate that dysfunction of the sympathetic nervous system could predispose to obesity and Type II (non-insulin-dependent) diabetes mellitus.


Three-stage extraction of gelatines from tendons of abattoir cattle: 2--properties of gelatines.
The subject of our previous paper (part 1) was three-stage extraction of gelatines from short cattle tendons. In this paper, we studied influence of extraction conditions on quality of produced gelatines-protein content, ash content, rigidity of gelatine gels, viscosity, and distribution of molecular weights. Ash content of gelatines ranged in limits 3.5-10.5 %. Rigidity of the gels was influenced by extraction conditions and by elastin content in gelatines; highest-quality gels display rigidity of 213 Bloom. Viscosity of gelatines ranged from 2.47 to 12.11 mPa s. Molecular weights of gelatines display a proportion of fractions from 20 to 36 kDa, a quite high proportion of fractions from approximately 50 to 100 kDa, in some cases even fractions above 200 kDa appear. It was found that transition temperature and melting temperature of gelatines extracted from tendons are in accord with data on gelatines obtained by traditional extraction techniques from skins and bones. With respect to efficiency of the whole extraction process and to quality of extracted gelatine, we may recommend extraction conditions as follows: in the 1st processing stage, shaking degreased starting material with water in ratio 1:10 at 25 °C for 5 h; in the 2nd stage, treating the swelled material with 5 % (w/w) added proteolytic enzyme at 40 °C for 25 h; in 3rd stage, extracting gelatine while boiling for 16 min.


Safe physiotherapy interventions in large cervical disc herniations.
A 34-year-old woman was seen in a physiotherapy department with signs and symptoms of cervical radiculopathy. Loss of cervical lordosis and a large paracentral to intraforaminal disc prolapse (8 mm) at C5-C6 level was reported on MRI. She was taking diclofenac sodium, tramadol HCl, diazepam and pregabalin for the preceding 2 months and no significant improvement, except temporary relief, was reported. She was referred to physiotherapy while awaiting a surgical opinion from a neurosurgeon. In physiotherapy she was treated with mobilisation of the upper thoracic spine from C7 to T6 level. A cervical extension exercise was performed with prior voluntary extension of the thoracic spine and elevated shoulders. She was advised to continue the same at home. General posture advice was given. Signs and symptoms resolved within the following four sessions of treatment over 3 weeks. Surgical intervention was subsequently deemed unnecessary.


Neural control: novel evaluation of stretch reflex sensitivity.
We evaluated the stretch reflex activities of the elbow flexor and extensor muscles considering the relationship between the reflex electromyographic (EMG) responses and their corresponding standardized muscle stretch velocities. Specifically, muscular stretch velocity was estimated by using ultrasonograms. Stretch reflex EMG responses were elicited in the biceps brachii, brachioradialis and triceps brachii with a ramp-and-hold rotation at the elbow joint, which consisted of various angular velocities for the extension- or flexion-direction. The whole muscle stretch velocity induced by each ramp-and-hold rotation was calculated on the basis of fibre length changes associated with the elbow joint angle. A linear regression equation was fitted to the relation between the whole muscle stretch velocity and the reflex EMG responses, and the variables from the equation were used to quantify sensitivity of each reflex EMG component. The reflex EMG responses were increased as the ramp-and-hold rotational velocity increased. There were no significant differences in the recorded magnitudes of reflex EMG responses with equivalent joint rotational velocity between the brachioradialis and the triceps brachii medial head. These muscles showed the highest reflex responses in the flexor and extensor muscles, respectively. To the contrary, the reflex EMG response elicited by the standardized muscle stretches was significantly greater in the extensor muscles, indicating a higher reflex sensitivity. This was because of the lower muscle stretch velocity of the triceps brachii with an equivalent elbow joint rotation. The stretch reflex sensitivity in both the elbow flexor and extensor muscles might be regulated so as to make the reflex responses the same when the equivalent joint rotational velocity is applied to these muscles.


Evolutionary silencing of the human elastase I gene (ELA1).
The human pancreatic elastase I gene is transcriptionally silent, despite the apparent integrity of the structural gene. The transcriptional regulatory sequences necessary and sufficient for transcription of the active rat homologue are localized within 205 base pairs (bp) of the transcriptional start and comprise a pancreas-specific transcriptional enhancer of 134 bp immediately upstream of a 71 bp non-specific promoter. The human gene has 58 nucleotide differences within this region, 13 of which are in the three functional elements (A, B and C) that constitute the enhancer. Through cell transfection analyses with a pancreatic acinar tumor cell line, we show that the nucleotide differences in the human 5' flanking gene sequences have inactivated both the enhancer and the promoter. The changes in the three elements of the human enhancer alone are sufficient to inactivate the enhancer; conversely, restoring these to the rat configuration partially restores the activity of the human enhancer. The two mutations in the A element and the four mutations in the B element abolish the binding of the transcription factors previously shown to mediate the activity of these elements. Replacing the active 71 bp rat promoter with the human promoter also prevents expression. Therefore, the evolutionary silencing of the human elastase I gene appears due to mutations that inactivate crucial enhancer and promoter elements.


The Kaposi's sarcoma-associated herpesvirus ORF34 protein binds to HIF-1α and causes its degradation via the proteasome pathway.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for Kaposi's sarcoma (KS) and two other lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). Kaposi's sarcoma is a highly vascular tumor, and recently both hypoxia-inducible factor 1α (HIF-1α) and HIF-2α were detected in KS samples, indicating a role of HIFs in the KSHV life cycle. Previously, we showed that ORF34, a lytic gene of unassigned function, was activated by hypoxia and that ORF34 transcription was upregulated by both HIFs (M. Haque, D. A. Davis, V. Wang, I. Widmer, and R. Yarchoan, J Virol. 77:6761-6768, 2003). In the present study, we show that coexpression of ORF34 with HIF-1αm (degradation-resistant HIF-1α) caused substantial reduction in HIF-1α-dependent transcription, as evidenced by reporter assays. Two-way immunoprecipitation experiments revealed that ORF34 physically interacted with HIF-1αm in transient expression experiments. Deletion analysis revealed that three different ORF34 domains interacted with the amino-terminal domain of HIF-1α. Also, purified HIF-1α and ORF34 proteins interacted with each other. The observed transcriptional inhibition of HIF-1α-dependent promoters was attributed to degradation of HIF-1α after binding with ORF34, since the overall amount of wild-type HIF-1α but not the degradation-resistant one (HIF-1αm) was reduced in the presence of ORF34. Moreover, ORF34 caused degradation of HIF-1α in a dose-dependent manner. Inhibition of the ubiquitin-dependent pathway by the chemical proteasome inhibitor MG132 prevented HIF-1α degradation in the presence of ORF34. These results show that ORF34 binds to HIF-1α, leading to its degradation via the proteasome-dependent pathway.


Attentional biases for food cues in overweight and individuals with obesity: a systematic review of the literature.
Obesity rates have increased dramatically in recent decades, and it has proven difficult to treat. An attentional bias towards food cues may be implicated in the aetiology of obesity and influence cravings and food consumption. This review systematically investigated whether attentional biases to food cues exist in overweight/obese compared with healthy weight individuals. Electronic database were searched for relevant papers from inception to October 2014. Only studies reporting food-related attentional bias between either overweight (body mass index [BMI] 25.0-29.9 kg m(-2)) or obese (BMI ≥ 30) participants and healthy weight participants (BMI 18.5-24.9) were included. The findings of 19 studies were reported in this review. Results of the literature are suggestive of differences in attentional bias, with all but four studies supporting the notion of enhanced reactivity to food stimuli in overweight individuals and individuals with obesity. This support for attentional bias was observed primarily in studies that employed psychophysiological techniques (i.e. electroencephalogram, eye-tracking and functional magnetic resonance imaging). Despite the heterogeneous methodology within the featured studies, all measures of attentional bias demonstrated altered cue-reactivity in individuals with obesity. Considering the theorized implications of attentional biases on obesity pathology, researchers are encouraged to replicate flagship studies to strengthen these inferences.


Effects of a physical activity intervention for women.
Physical activity is associated with health and reduced mortality risk, yet only 15% of U.S. adults achieve adequate activity. This study is an experimental repeated measures nested design randomizing two similar rural communities to investigate the effectiveness of the Heart and Soul Physical Activity Program (HSPAP) (Peterson, 2002) in promoting physical activity in midlife women (n=42) aged 35 to 65 years. The HSPAP, an innovative church-based health promotion intervention, is conceptualized in social support and designed to increase physical activity, energy expenditure (EE), and cardiorespiratory fitness (VO2 max), measured over time. A significant interaction (p<.001) was found for EE in one HSPAP group increasing their EE by 1,010 kcals/week. HSPAP participants increased their VO2 max level by 75% (p<.001) and 10%; comparison groups stayed the same or declined 16%. Study results provide preliminary support for the HSPAP intervention as an effective treatment to improve physical activity levels in sedentary, rural, midlife women.


The accessory optic system of rabbit. I. Basic visual response properties.
1. The response properties of accessory optic system (AOS) neurons were assessed using single-unit extracellular recording from each of the three AOS terminal nuclei [medial, lateral, and dorsal terminal nuclei (MTN, LTN, and DTN)] in the anesthetized rabbit. 2. AOS neurons had large, monocular (contralateral) receptive fields (tens of degrees on a side) and exhibited a pronounced selectivity to the speed and direction of movement of large, textured patterns. The greatest responses occurred at slow speeds on the order of 0.5 degrees/s. 3. MTN and LTN neurons responded best to movement in near vertical directions. However, the stimulus directions corresponding to the greatest excitation and the greatest inhibition both had a posterior component and, thus, the preferred excitatory and inhibitory directions were not opposite each other. DTN neurons responded most strongly to horizontal movement and were excited by temporal to nasal movement. 4. AOS neurons were unresponsive to natural vestibular stimulation presented as sinusoidal oscillations of the rabbit about the yaw, pitch, and roll axes. 5. The response properties of AOS neurons are remarkably similar to those of the ON, direction-selective ganglion cells of the rabbit retina, and therefore this class of ganglion cell is most likely the predominant, if not the only, direct retinal input to the AOS. The local direction-selective properties of AOS neurons can be accounted for by combining the tuning curves of ON, direction-selective ganglion cells in a simple manner. 6. The low speed preference of AOS neurons, along with their large receptive fields suggests that they are suited to complement the vestibular system in detecting self-motion.


Endophytic bacteria as a source of novel antibiotics: An overview.
World human population is increasing with an alarming rate; and a variety of new types of health issues are popping up. For instance, increase in number of drug-resistant bacteria is a cause of concern. Research on antibiotics and other microbial natural products is pivotal in the global fight against the growing problem of antibiotic resistance. It is necessary to find new antibiotics to tackle this problem. The use of therapeutic plant species in traditional medicine is as old as mankind; and currently, it is strongly believed that all types of plant species across the plant kingdom do harbour endophytic bacteria (EB). The natural therapeutic compounds produced by EB do have several potential applications in pharmaceutical industry. The EB derived natural products such as Ecomycins, Pseudomycins, Munumbicins and Xiamycins are antibacterial, antimycotic and antiplasmodial. Some of these natural products have been reported to possess even antiviral (including Human Immunodeficiency Virus (HIV)) properties. Therefore, to deal with increasing number of drug-resistant pathogens EB could serve as a potential source of novel antibiotics.


A unified approach to diffusion direction sensitive slice registration and 3-D DTI reconstruction from moving fetal brain anatomy.
This paper presents an approach to 3-D diffusion tensor image (DTI) reconstruction from multi-slice diffusion weighted (DW) magnetic resonance imaging acquisitions of the moving fetal brain. Motion scatters the slice measurements in the spatial and spherical diffusion domain with respect to the underlying anatomy. Previous image registration techniques have been described to estimate the between slice fetal head motion, allowing the reconstruction of 3D a diffusion estimate on a regular grid using interpolation. We propose Approach to Unified Diffusion Sensitive Slice Alignment and Reconstruction (AUDiSSAR) that explicitly formulates a process for diffusion direction sensitive DW-slice-to-DTI-volume alignment. This also incorporates image resolution modeling to iteratively deconvolve the effects of the imaging point spread function using the multiple views provided by thick slices acquired in different anatomical planes. The algorithm is implemented using a multi-resolution iterative scheme and multiple real and synthetic data are used to evaluate the performance of the technique. An accuracy experiment using synthetically created motion data of an adult head and an experiment using synthetic motion added to sedated fetal monkey dataset show a significant improvement in motion-trajectory estimation compared to current state-of-the-art approaches. The performance of the method is then evaluated on challenging but clinically typical in utero fetal scans of four different human cases, showing improved rendition of cortical anatomy and extraction of white matter tracts. While the experimental work focuses on DTI reconstruction (second-order tensor model), the proposed reconstruction framework can employ any 5-D diffusion volume model that can be represented by the spatial parameterizations of an orientation distribution function.


[Central nervous system relapse with multiple brain masses in an acute promyelocytic leukemia patient treated with all-trans retinoic acid].
A 22-year-old woman with fever and bleeding tendency was given a diagnosis of acute promyelocytic leukemia (APL) on the basis of laboratory findings including a WBC count of 106 x 10(3)/microliter (90% blasts) and a platelet count of 1.6 x 10(4)/microliter. Induction therapy was started with all-trans retinoic acid (ATRA) and cytotoxic chemotherapy. After the patient achieved complete remission, ATRA was discontinued and consolidation chemotherapy was started. However, 4 months after onset, leukemic blasts were detected in cerebrospinal fluid. Temporal central nervous system remission was induced by intrathecal chemotherapy only. However, 2 months later, multiple focal mass lesions had developed in the brain. ATRA (45 mg/m2) was restarted together with multiple intrathecal injections of anticancer drugs, and a third remission was achieved. It is conceivable that the incorporation of ATRA in induction chemotherapy is related to the development of this rather rare complication of APL. The outcome in this case suggested orally administered ATRA may be effective in treating brain metastasis of APL.


Is caring associated with an increased risk of mortality? A longitudinal study.
Informal care is a fundamental component of care in the community which, given current demographic trends and increasing prevalence of debilitating chronic disease, is likely to assume even greater significance in future. Research indicates that caregivers are more likely than non-carers to report poor health, though this has usually been measured in terms of psychological or emotional health such as depression or 'caregiver strain'. Relatively little is known about the effects of caring on physical health. This study examines the health of caregivers recorded in the 2001 Northern Ireland Census and their subsequent mortality over the following four years. Caregivers were a heterogeneous group, with those providing fewer hours of care being relatively more affluent than those providing care at greater intensities. Overall, caregivers had lower mortality risks than non-carers and effects were more pronounced for women, older people, and for those reporting poorer health at the start of the study period. While this study does not exclude the possibility of significant detrimental health effects of caring for some sub-groups of caregivers, it does add support to the growing body of literature which suggests that the positive aspects of caring have been underreported.


Zoledronic acid results in better health-related quality of life following hip fracture: the HORIZON-Recurrent Fracture Trial.
This study evaluated the benefits of ZOL versus placebo on health-related quality of life (HRQoL) among patients from HORIZON-RFT. At month 24 and end of the study visit, ZOL significantly improved patients' overall health state compared to placebo as assessed by the EQ-5D VAS. To evaluate the benefits of zoledronic acid (ZOL) versus placebo on health-related quality of life (HRQoL) among patients from The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Recurrent Fracture Trial (HORIZON-RFT). In this randomized, double-blind, placebo-controlled trial, 2,127 patients were randomized to receive annual infusion of ZOL 5 mg (n = 1,065) or placebo (n = 1,062) within 90 days after surgical repair of low-trauma hip fracture. HRQoL was measured using EQ-5D Visual Analogue Scale (VAS) and utility scores (EuroQol instrument) at months 6, 12, 24, 36, and end of the study visit. Analysis of covariance model included baseline EQ-5D value, region, and treatment as explanatory variables. At baseline, patients (mean age 75 years; 24% men and 76% women) were well matched between treatment groups with mean EQ-5D VAS of 65.82 in ZOL and 65.70 in placebo group. At the end of the study, mean change from baseline in EQ-5D VAS was greater for ZOL vs. placebo in all patients (7.67 ± 0.56 vs. 5.42 ± 0.56), and in subgroups of patients experiencing clinical vertebral fractures (8.86 ± 4.91 vs. -1.69 ± 3.42), non-vertebral fractures (5.03 ± 2.48 vs. -1.07 ± 2.16), and clinical fractures (5.19 ± 2.25 vs. -0.72 ± 1.82) with treatment difference significantly in favor of ZOL. EQ-5D utility scores were comparable for ZOL and placebo groups, but more patients on placebo consistently had extreme difficulty in mobility (1.74% for ZOL vs. 2.13% for placebo; p = 0.6238), self-care (4.92% vs. 6.69%; p = 0.1013), and usual activities (10.28% vs. 12.91%; p = 0.0775). ZOL significantly improves HRQoL in patients with low-trauma hip fracture.


Monitoring, sources, receptors, and control measures for three European Union watch list substances of emerging concern in receiving waters - A 20year systematic review.
Pollution of European receiving waters with contaminants of emerging concern (CECs), such as with 17-beta-estradiol (a natural estrogenic hormone, E2), along with pharmaceutically-active compounds diclofenac (an anti-inflammatory drug, DCL) and 17-alpha-ethynylestradiol (a synthetic estrogenic hormone, EE2)) is a ubiquitous phenomenon. These three CECs were added to the EU watch list of emerging substances to be monitoring in 2013, which was updated in 2015 to comprise 10 substances/groups of substances in the field of water policy. A systematic literature review was conducted of 3952 potentially relevant articles over period 1995 to 2015 that produced a new EU-wide database consisting of 1268 publications on DCL, E2 and EE2. European surface water concentrations of DCL are typically reported below the proposed annual average environmental quality standard (AA EQS) of 100ng/l, but that exceedances frequently occur. E2 and EE2 surface water concentrations are typically below 50ng/l and 10ng/l respectively, but these values greatly exceed the proposed AA EQS values for these compounds (0.04 and 0.035ng/l respectively). However, levels of these CECs are frequently reported to be disproportionately high in EU receiving waters, particularly in effluents at control points that require urgent attention. Overall it was found that DCL and EE2 enter European aquatic environment mainly following human consumption and excretion of therapeutic drugs, and by incomplete removal from influent at urban wastewater treatment plants (WWTPs). E2 is a natural hormone excreted by humans which also experiences incomplete removal during WWTPs treatment. Current conventional analytical chemistry methods are sufficiently sensitive for the detection and quantification of DCL but not for E2 and EE2, thus alternative, ultra-trace, time-integrated monitoring techniques such as passive sampling are needed to inform water quality for these estrogens. DCL appears resistant to conventional wastewater treatment while E2 and EE2 have high removal efficiencies that occur through biodegradation or sorption to organic matter. There is a pressing need to determine fate and behaviour of these CECs in European receiving waters such as using GIS-modelling of river basins as this will identify pressure points for informing priority decision making and alleviation strategies for upgrade of WWTPs and for hospital effluents with advanced treatment technologies. More monitoring data for these CECs in receiving waters is urgently needed for EU legislation and effective risk management.


The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action.
The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves' disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves' disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AIDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future.


Retrospective monitoring of synthetic musk compounds in aquatic biota from German rivers and coastal areas.
The polycyclic musk compounds HHCB (Galaxolide) and AHTN (Tonalide) are commonly used as synthetic fragrances in personal care products and household cleaners. These and other synthetic musk fragrances were quantified in different aquatic samples from the German Environmental Specimen Bank (ESB). While HHCB and AHTN were found in almost all samples, most of the other musk fragrances were detected only in a few samples and mostly at lower concentration levels. Blue mussels from the North Sea showed varying levels of 0.5-1.7 ng g(-1) ww for HHCB and 0.4-2.5 ng g(-1) ww for AHTN (ww, wet weight) in the period from 1986 to 2000, while blue mussels from the Baltic Sea were only slightly contaminated with synthetic musk fragrances. Lipid weight-related concentrations of synthetic musk compounds in blue mussels were higher than in eelpout muscles, bladder wrack and herring gull eggs. In comparison to the marine specimens, muscles of bream from German rivers had higher concentrations of HHCB and AHTN. The ranges of HHCB and AHTN concentrations in bream from the Elbe River were 545-6400 ng g(-1) lw and 48-2130 ng g(-1) lw, respectively (lw, lipid weight; five sampling sites, period 1993-2003). In the Rhine River, HHCB and AHTN levels of bream muscles were highest at the Iffezheim site (up to 9750 ng g(-1) lw HHCB, 1998). Even higher synthetic musk levels were detected in bream from the rivers Saale and Saar. In recent years, levels of both compounds determined in bream from most sampling sites have decreased from maximum values in the 1990s. As the concentrations of AHTN have decreased faster, the ratio of HHCB to AHTN increased from 2-4 in the 1990s to 10-20 in recent years.


Estimating the risk of incident SARS-CoV-2 infection among healthcare workers in quarantine hospitals: the Egyptian example.
In response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1- to 2-week working shifts. Using a mathematical model accounting for the false-negative rates of RT-PCR tests, we computed the incidence rate of SARS-CoV-2 infection among HCWs, while unveiling the proportion of infections remaining undiagnosed despite routine testing. We relied on longitudinal data, including results of routine RT-PCR tests, collected within three Egyptian quarantine hospitals. We estimated an incidence rate (per 100 person-day, PD) of 1.05 (95% CrI 0.58-1.65) at Hospital 1, 1.92 (95% CrI 0.93-3.28) at Hospital 2 and 7.62 (95% CrI 3.47-13.70) at Hospital 3. We found that the risk for an HCW to be infected during a working shift lay within the range of risk levels previously documented in standard healthcare settings for Hospitals 1-2, whereas it was > threefold higher for Hospital 3. This large variation suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.


Electromagnetic scattering by an aggregate of spheres.
We present a comprehensive solution to the classical problem of electromagnetic scattering by aggregates of an arbitrary number of arbitrarily configured spheres that are isotropic and homogeneous but may be of different size and composition. The profile of incident electromagnetic waves is arbitrary. The analysis is based on the framework of the Mie theory for a single sphere and the existing addition theorems for spherical vector wave functions. The classic Mie theory is generalized. Applying the extended Mie theory to all the spherical constituents in an aggregate simultaneously leads to a set of coupled linear equations in the unknown interactive coefficients. We propose an asymptotic iteration technique to solve for these coefficients. The total scattered field of the entire ensemble is constructed with the interactive scattering coefficients by the use of the translational addition theorem a second time. Rigorous analytical expressions are derived for the cross sections in a general case and for all the elements of the amplitude-scattering matrix in a special case of a plane-incident wave propagating along the z axis. As an illustration, we present some of our preliminary numerical results and compare them with previously published laboratory scattering measurements.


Increased Growth of a Newly Established Mouse Epithelial Cell Line Transformed with HPV-16 E7 in Diabetic Mice.
Epidemiological evidence supports that infection with high-risk types of human papillomavirus (HPV) can interact with host and environmental risk factors to contribute to the development of cervical, oropharyngeal, and other anogenital cancers. In this study, we established a mouse epithelial cancer cell line, designated as Chinese University Papillomavirus-1 (CUP-1), from C57BL/KsJ mice through persistent expression of HPV-16 E7 oncogene. After continuous culturing of up to 200 days with over 60 passages, we showed that CUP-1 became an immortalized and transformed epithelial cell line with continuous E7 expression and persistent reduction of retinoblastoma protein (a known target of E7). This model allowed in-vivo study of interaction between HPV and co-factors of tumorigenesis in syngeneic mice. Diabetes has been shown to increase HPV pathogenicity in different pathological context. Herein, with this newly-established cell line, we uncovered that diabetes promoted CUP-1 xenograft growth in syngeneic db/db mice. In sum, we successfully established a HPV-16 E7 transformed mouse epithelial cell line, which allowed subsequent studies of co-factors in multistep HPV carcinogenesis in an immunocompetent host. More importantly, this study is the very first to demonstrate the promoting effect of diabetes on HPV-associated carcinogenesis in vivo, implicating the importance of cancer surveillance in diabetic environment.


Classifying the torture experiences of refugees living in the United States.
Few research studies have systematically categorized the types of torture experienced around the world. The purpose of this study is to categorize the diverse traumatic events that are defined as torture, and determine how these torture types relate to demographics and symptom presentation. Data for 325 individuals were obtained through a retrospective review of records from the Bellevue/NYU for Survivors of Torture. A factor analysis generated a model with five factors corresponding to witnessing torture of others, torture of family members, physical beating, rape/sexual assault, and deprivation/passive torture. These factors were significantly correlated with a number of demographic variables (sex, education, and region of origin). Post Traumatic Stress Disorder, anxiety, and depression symptoms were significantly correlated with the rape factor but no other factors were uniquely associated with psychological distress. The results offer insight into the nature of torture and differences in responses.


Oncological and functional efficacy of nephron-sparing surgery versus radical nephrectomy in renal cell carcinoma stages ≥cT1b: a single institution, matched analysis.
The purpose of this paper is to compare oncological outcomes of partial nephrectomy (PN) versus radical nephrectomy (RN) in renal cell carcinoma (RCC) clinical stages ≥T1b, in a retrospective propensity-score matched cohort of a high-volume, tertiary referral center. This paper also aims to compare renal function and complication rates between groups. Our single-institution RCC database was queried to select patients with clinical stages defined by tumor size (T), lymph nodes(N), and metastasis (M) scores of T1b-4 N0 M0, that underwent PN or RN between 2000 and 2014. All images of patients that underwent RN were reviewed, and only patients deemed eligible for PN were included. Medical records were reviewed to obtain data on tumor characteristics, comorbidities, renal function, and complications. After propensity score matching, 152 patients (76 per group) were included in the final analysis. Primary outcomes were cancer specific survival (CSS), overall survival (OS), and clinical progression-free survival (CPFS). Secondary outcomes were renal function preservation and post-operative complication rates. Groups were propensity-score matched. The only parameters that were significantly different between groups were the median follow-up time (RN: 79 months, range 24.1-100.5 vs. PN: 38.5 months, range 20.5-72.1) and a better performance status in the RN group (p = 0.002). The five-year CPFS, CSS, and OS rates were 77.2%, 90.5%, and 86.4%, respectively, in the RN group, and 83.6%, 91.1%, and 82.0%, respectively, in the PN group (p = 0.33, p = 0.55, and p = 0.33, respectively). In the multivariate Cox model, the surgical method was not an independent predictor of CPFS, CSS, or OS. The RN group showed a significantly greater reduction in estimated glomerular filtration rate (RN: 14.1 vs. PN: 5.4 ml/min per 1.73 m²; p <0.03). There was no significant difference in complication rates between the two groups (p = 0.3). The main limitations of this study were its retrospective design and the medium-term follow-up. Our results demonstrated the efficacy and safety of PN in patients with RCC in clinical stages ≥T1b. We observed no significant difference in oncological outcomes between the PN and RN groups at medium-term follow ups. The surgical method did not influence these outcomes. Renal function was preserved significantly more frequently in the PN than in the RN group, but the groups had similar complication rates.These findings suggested that PN could be considered an oncologically safe procedure for treating large RCC tumors; thus, PN should always be considered, when technically feasible, regardless of tumor stage.


Long-term survival with diaphanospondylodysostosis (DSD): survival to 5 years and further phenotypic characteristics.
We report on the natural history of diaphanospondylodysostosis (DSD) in the longest known survivor. DSD is a rare form of autosomal recessive vertebral dysotosis recently identified to be caused by a mutation in the BMPER gene. This condition is characterized by absent or severely delayed ossification of vertebral bodies, short broad thorax, short neck, protuberant abdomen, marked respiratory insufficiency, and normal appendicular skeleton. It is one of a number of spinal dysostoses, which are a heterogeneous group of axial skeletal malformations occurring during blastogenesis with continued evolution after birth. Significant medical intervention and at-home support contributed to the long-term survival of our patient. The patient had tracheomalacia, which resulted in respiratory insufficiency with thoracic insufficiency syndrome (TIS). Tracheostomy and vertical expandable prosthetic titanium rib (VEPTR) insertion operations ameliorated his symptoms. In addition, comprehensive physical and occupational therapy was performed due to chronic hypotonia. A consistent feature of all described DSD cases thus far are renal findings of dysplasia, nephrogenic rests or nephroblastomatosis, and/or cysts. The patient's renal cysts were monitored with serial ultrasounds at approximately 6-month intervals. The patient was diagnosed with bilateral renal cysts by ultrasound as a neonate, with eventual diagnosis at approximately 20 months of age with nephroblastoma suggesting this maybe an intrinsic part of DSD. The lack of other cases with nephroblastoma is likely related to the previously reported short period of survival.


Optical trapping microrheology in cultured human cells.
We present the microrheological study of the two close human epithelial cell lines: non-cancerous HCV29 and cancerous T24. The optical tweezers tracking was applied to extract the several seconds long trajectories of endogenous lipid granules at time step of 1μs. They were analyzed using a recently proposed equation for mean square displacement (MSD) in the case of subdiffusion influenced by an optical trap. This equation leads to an explicit form for viscoelastic moduli. The moduli of the two cell lines were found to be the same within the experimental accuracy for frequencies 10(2) - 10(5) Hz. For both cell lines subdiffusion was observed with the exponent close to 3/4, the value predicted by the theory of semiflexible polymers. For times longer than 0.1s the MSD of cancerous cells exceeds the MSD of non-cancerous cells for all values of the trapping force. Such behavior can be interpreted as a signature of the active processes and prevents the extraction of the low-frequency viscoelastic moduli for the living cells by passive microrheology.


The neonatal intensive care unit at the University Hospital of the West Indies: The first few years' experience.
A retrospective analysis of neonates admitted for ventilatory support to the neonatal intensive care unit at the University Hospital of the West Indies between August 2001 and December 2004 was conducted. One hundred and thirty-eight neonates fulfilled criteria for admission into the study. Ninety-eight (71%) were inborn, 88 (64%) survived and 50 (36%) died. The median age at death was 72 hours and 72% of non-survivors died within one week of life. The main reasons for admission into the unit were respiratory distress syndrome 87(63%), followed by hypoxic ischaemic encephalopathy 15 (11%), surgical indications 13 (9%) and meconium aspiration syndrome 11 (8%). Babies with meconium aspiration syndrome and surgical problems had the best survival 82% and 85% respectively. Survival rates increased with increasing birthweight and gestational age. The most common complication seen was air leaks. The judicious use of neonatal intensive care measures in a developing country can result in a reduction of morbidity and mortality. However to maximize on benefits versus cost in an atmosphere of budgetary constraint evidence based management policies and protocols must be developed and implemented


Doppler ultrasonography of the anterior knee tendons in elite badminton players: colour fraction before and after match.
Anterior knee tendon problems are seldom reported in badminton players although the game is obviously stressful to the lower extremities. Painful anterior knee tendons are common among elite badminton players. The anterior knee tendons exhibit colour Doppler activity. This activity increases after a match. Painful tendons have more Doppler activity than tendons without pain. Cohort study. 72 elite badminton players were interviewed about training, pain and injuries. The participants were scanned with high-end ultrasound equipment. Colour Doppler was used to examine the tendons of 64 players before a match and 46 players after a match. Intratendinous colour Doppler flow was measured as colour fraction (CF). The tendon complex was divided into three loci: the quadriceps tendon, the proximal patellar tendon and the insertion on the tibial tuberosity. Interview: Of the 72 players, 62 players had problems with 86 tendons in the lower extremity. Of these 86 tendons, 48 were the anterior knee tendons. Ultrasound: At baseline, the majority of players (87%) had colour Doppler flow in at least one scanning position. After a match, the percentage of the knee complexes involved did not change. CF increased significantly in the dominant leg at the tibial tuberosity; single players had a significantly higher CF after a match at the tibial tuberosity and in the patellar tendon both before and after a match. Painful tendons had the highest colour Doppler activity. Most elite badminton players had pain in the anterior knee tendons and intratendinous Doppler activity both before and after match. High levels of Doppler activity were associated with self-reported ongoing pain.


Preinjury Emotional-Behavioral Functioning of Children With Lingering Problems After Mild Traumatic Brain Injury.
This study aimed to characterize preinjury emotional-behavioral functioning in pediatric patients with lingering problems after mild traumatic brain injury (TBI). The clinical case series design included 278 patients 8-17 years old. Parents retrospectively rated children's preinjury emotional-behavioral functioning on a broadband questionnaire. The rate of clinically significant preinjury anxiety was elevated compared with national norms. The number of previous TBIs was associated with clinically significant preinjury externalizing problems, suggesting a link between externalizing disorders and mild TBI exposure. Premorbid emotional-behavioral difficulties may play an important role in the establishment or maintenance of lingering symptoms after pediatric mild TBI.


Validating five questions of antiretroviral nonadherence in a public-sector treatment program in rural South Africa.
Simple questions are the most commonly used measures of antiretroviral treatment (ART) adherence in sub-Saharan Africa (SSA), but rarely validated. We administered five adherence questions in a public-sector primary care clinic in rural South Africa: 7-day recall of missed doses, 7-day recall of late doses, a six-level Likert item, a 30-day visual analogue scale of the proportion of doses missed, and recall of the time when an ART dose was last missed. We estimated question sensitivity and specificity in detecting immunologic (or virologic) failure assessed within 45 days of the adherence question date. Of 165 individuals, 7% had immunologic failure; 137 individuals had viral loads with 9% failure detected. The Likert item performed best for immunologic failure with sensitivity/specificity of 100%/5% (when defining nonadherence as self-reported adherence less than "excellent"), 42%/55% (less than "very good"), and 25%/95% (less than "good"). The remaining questions had sensitivities ≤17%, even when the least strict cutoffs defined nonadherence. When we stratified the analysis by gender, age, or education, question performance was not substantially better in any of the subsamples in comparison to the total sample. Five commonly used adherence questions performed poorly in identifying patients with treatment failure in a public-sector ART program in SSA. Valid adherence measurement instruments are urgently required to identify patients needing treatment support and those most at risk of treatment failure. Available estimates of ART adherence in SSA are mostly based on studies using adherence questions. It is thus unlikely that our understanding of ART adherence in the region is correct.


Protective effect of the standardized green tea seed extract on UVB-induced skin photoaging in hairless mice.
Ultraviolet B (UVB) irradiation on skin can induce production of reactive oxygen species (ROS), which cause expression of matrix metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of skin to UVB irradiation leads to histological changes consistent with aging, such as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the protective effect of the standardized green tea seed extract (GSE) on UVB-induced skin photoaging in hairless mice. Skin photoaging was induced by UVB irradiation on the back of Skh-1 hairless mice three times per week and UVB irradiation was performed for 10 weeks. Mice were divided into six groups; normal control, UVB irradiated control group, positive control (UVB + dietary supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE 10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200 mg/kg (UVB + dietary supplement of GSE 200 mg/kg). The dietary supplement GSE attenuated UVB irradiation-induced wrinkle formation and the decrease in density of dermal collagen fiber. In addition, results of the antioxidant analysis showed that GSE induced a significant increase in antioxidant enzyme activity compared with the UVB irradiation control group. Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and type-1 collagen. Findings of this study suggest that dietary supplement GSE could be useful in attenuation of UVB irradiation-induced skin photoaging and wrinkle formation due to regulation of antioxidant defense systems and MMPs expression.


High phenotypic plasticity of Suaeda maritima observed under hypoxic conditions in relation to its physiological basis.
Phenotypic plasticity, the potential of specific traits of a genotype to respond to different environmental conditions, is an important adaptive mechanism for minimizing potentially adverse effects of environmental fluctuations in space and time. Suaeda maritima shows morphologically different forms on high and low areas of the same salt marsh. Our aims were to examine whether these phenotypic differences occurred as a result of plastic responses to the environment. Soil redox state, indicative of oxygen supply, was examined as a factor causing the observed morphological and physiological differences. Reciprocal transplantation of seedlings was carried out between high and low marsh sites on a salt marsh and in simulated tidal-flow tanks in a glasshouse. Plants from the same seed source were grown in aerated or hypoxic solution, and roots were assayed for lactate dehydrogenase (LDH) and alcohol dehydrogenase, and changes in their proteome. Transplanted (away) seedlings and those that remained in their home position developed the morphology characteristic of the home or away site. Shoot Na(+), Cl(-) and K(+) concentrations were significantly different in plants in the high and low marsh sites, but with no significant difference between home and away plants at each site. High LDH activity in roots of plants grown in aeration and in hypoxia indicated pre-adaptation to fluctuating root aeration and could be a factor in the phenotypic plasticity and growth of S. maritima over the full tidal range of the salt marsh environment. Twenty-six proteins were upregulated under hypoxic conditions. Plasticity of morphological traits for growth form at extremes of the soil oxygenation spectrum of the tidal salt marsh did not correlate with the lack of physiological plasticity in the constitutively high LDH found in the roots.


Structural characterization of the regulatory proteins TenA and TenI from Bacillus subtilis and identification of TenA as a thiaminase II.
Bacillus subtilis gene products TenA and TenI have been implicated in regulating the production of extracellular proteases, but their role in the regulation process remains unclear. The structural characterization of these proteins was undertaken to help provide insight into their function. We have determined the structure of TenA alone and in complex with 4-amino-2-methyl-5-hydroxymethylpyrimidine, and we demonstrate that TenA is a thiaminase II. The TenA structure suggests that the degradation of thiamin by TenA likely proceeds via the same addition-elimination mechanism described for thiaminase I. Three active-site residues, Asp44, Cys135, and Glu205, are likely involved in substrate binding and catalysis based on the enzyme/product complex structure and the conservation of these residues within TenA sequences. We have also determined the structure of TenI. Although TenI shows significant structural homology to thiamin phosphate synthase, it has no known enzymatic function. The structure suggests that TenI is unable to bind thiamin phosphate, largely resulting from the presence of leucine at position 119, while the corresponding residue in thiamin phosphate synthase is glycine.


Global proteome analysis of the NCI-60 cell line panel.
The NCI-60 cell line collection is a very widely used panel for the study of cellular mechanisms of cancer in general and in vitro drug action in particular. It is a model system for the tissue types and genetic diversity of human cancers and has been extensively molecularly characterized. Here, we present a quantitative proteome and kinome profile of the NCI-60 panel covering, in total, 10,350 proteins (including 375 protein kinases) and including a core cancer proteome of 5,578 proteins that were consistently quantified across all tissue types. Bioinformatic analysis revealed strong cell line clusters according to tissue type and disclosed hundreds of differentially regulated proteins representing potential biomarkers for numerous tumor properties. Integration with public transcriptome data showed considerable similarity between mRNA and protein expression. Modeling of proteome and drug-response profiles for 108 FDA-approved drugs identified known and potential protein markers for drug sensitivity and resistance. To enable community access to this unique resource, we incorporated it into a public database for comparative and integrative analysis (http://wzw.tum.de/proteomics/nci60).


Gross anatomy and ultrasonographic images of the reproductive system of the Malayan tapir (Tapirus indicus).
The Malayan tapir (Tapirus indicus) is the largest among the four tapir species and is listed as an endangered species. Ultrasound examination and description of the external anatomy of the female reproductive system of three adult females were performed, whereas the internal anatomy was investigated in necropsied samples of four adult females and one subadult female. Descriptions of the male external genitalia were conducted on one adult male. Gross examination revealed the presence of a bicornuate uterus. The uterine cervix is firm and muscular with projections towards its lumen, which is also evident on ultrasonography. The elongated and relatively small ovaries, which have a smooth surface, could not be imaged on ultrasonography, due to their anatomical position. The testes are located inside a slightly pendulous scrotum that is sparsely covered with soft, short hairs. The penis has one dorsal and two lateral penile projections just proximal to the glans penis.


Pyruvate cellular uptake and enzymatic conversion probed by dissolution DNP-NMR: the impact of overexpressed membrane transporters.
Pyruvate membrane crossing and its lactate dehydrogenase-mediated conversion to lactate in cells featuring different levels of expression of membrane monocarboxylate transporters (MCT4) were probed by dissolution dynamic nuclear polarization-enhanced NMR. Hyperpolarized 13 C-1-labeled pyruvate was transferred to suspensions of rodent tumor cell carcinoma, cell line 39. The pyruvate-to-lactate conversion rate monitored by dissolution dynamic nuclear polarization-NMR in carcinoma cells featuring native MCT4 expression level was lower than the rate observed for cells in which the human MCT4 gene was overexpressed. The enzymatic activity of lactate dehydrogenase was also assessed in buffer solutions, following the real-time pyruvate-to-lactate conversion speeds at different enzyme concentrations. Copyright © 2016 John Wiley & Sons, Ltd.


The Intriguing Interaction of Escherichia coli with the Host Environment and Innovative Strategies To Interfere with Colonization: a Summary of the 2019 E. coli and the Mucosal Immune System Meeting.
The third E. coli and the Mucosal Immune System (ECMIS) meeting was held at Ghent University in Belgium from 2 to 5 June 2019. It brought together an international group of scientists interested in mechanisms of colonization, host response, and vaccine development. ECMIS distinguishes itself from related meetings on these enteropathogens by providing a greater emphasis on animal health and disease and covering a broad range of pathotypes, including enterohemorrhagic, enteropathogenic, enterotoxigenic, enteroaggregative, and extraintestinal pathogenic Escherichia coli As it is well established that the genus Shigella represents a subspecies of E. coli, these organisms along with related enteroinvasive E. coli are also included. In addition, Tannerella forsythia, a periodontal pathogen, was presented as an example of a pathogen which uses its surface glycans for mucosal interaction. This review summarizes several highlights from the 2019 meeting and major advances to our understanding of the biology of these pathogens and their impact on the host.


Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population.
Many of the foods abundant in the traditional Mediterranean diet, such as vegetables and fish, have been associated with slower cognitive decline. We investigated whether adherence to a Mediterranean dietary pattern or to the Healthy Eating Index-2005 (HEI-2005) is associated with cognitive change in older adults. This article is based on analyses of data from an ongoing longitudinal study in adults aged ≥65 y known as the Chicago Health and Aging Project (CHAP). CHAP participants (2280 blacks and 1510 whites) with ≥2 cognitive assessments were evaluated for adherence to 1) the Mediterranean dietary pattern (MedDiet; maximum score: 55) and 2) the HEI-2005 (maximum score: 100). For both scoring systems, higher scores connote greater adherence. Cognitive function was assessed at 3-y intervals on the basis of a composite measure of global cognition. Linear mixed models were used to examine the association of dietary scores to change in cognitive function. Mean follow-up time was 7.6 y. Mean (±SD) scores for participants were 28.2 ± 0.1 for the MedDiet and 61.2 ± 9.6 for the HEI-2005. White participants had higher energy-adjusted MedDiet scores but lower HEI-2005 scores than did black participants. Higher MedDiet scores were associated with slower rates of cognitive decline (β = +0.0014 per 1-point increase, SEE = 0.0004, P = 0.0004) after adjustment for age, sex, race, education, participation in cognitive activities, and energy. No such associations were observed for HEI-2005 scores. The Mediterranean dietary pattern as captured by the MedDiet scoring system may reduce the rate of cognitive decline with older age.


Perceived Mental Workload Classification Using Intermediate Fusion Multimodal Deep Learning.
A lot of research has been done on the detection of mental workload (MWL) using various bio-signals. Recently, deep learning has allowed for novel methods and results. A plethora of measurement modalities have proven to be valuable in this task, yet studies currently often only use a single modality to classify MWL. The goal of this research was to classify perceived mental workload (PMWL) using a deep neural network (DNN) that flexibly makes use of multiple modalities, in order to allow for feature sharing between modalities. To achieve this goal, an experiment was conducted in which MWL was simulated with the help of verbal logic puzzles. The puzzles came in five levels of difficulty and were presented in a random order. Participants had 1 h to solve as many puzzles as they could. Between puzzles, they gave a difficulty rating between 1 and 7, seven being the highest difficulty. Galvanic skin response, photoplethysmograms, functional near-infrared spectrograms and eye movements were collected simultaneously using LabStreamingLayer (LSL). Marker information from the puzzles was also streamed on LSL. We designed and evaluated a novel intermediate fusion multimodal DNN for the classification of PMWL using the aforementioned four modalities. Two main criteria that guided the design and implementation of our DNN are modularity and generalisability. We were able to classify PMWL within-level accurate (0.985 levels) on a seven-level workload scale using the aforementioned modalities. The model architecture allows for easy addition and removal of modalities without major structural implications because of the modular nature of the design. Furthermore, we showed that our neural network performed better when using multiple modalities, as opposed to a single modality. The dataset and code used in this paper are openly available.


Antagonistically pleiotropic allele increases lifespan and late-life reproduction at the cost of early-life reproduction and individual fitness.
Evolutionary theory of ageing maintains that increased allocation to early-life reproduction results in reduced somatic maintenance, which is predicted to compromise longevity and late-life reproduction. This prediction has been challenged by the discovery of long-lived mutants with no loss of fecundity. The first such long-lived mutant was found in the nematode worm Caenorhabditis elegans Specifically, partial loss-of-function mutation in the age-1 gene, involved in the nutrient-sensing insulin/insulin-like growth factor signalling pathway, confers longevity, as well as increased resistance to pathogens and to temperature stress without appreciable fitness detriment. Here, we show that the long-lived age-1(hx546) mutant has reduced fecundity and offspring production in early-life, but increased fecundity, hatching success, and offspring production in late-life compared with wild-type worms under standard conditions. However, reduced early-life performance of long-lived mutant animals was not fully compensated by improved performance in late-life and resulted in reduced individual fitness. These results suggest that the age-1(hx546) allele has opposing effects on early-life versus late-life fitness in accordance with antagonistic pleiotropy (AP) and disposable soma theories of ageing. These findings support the theoretical conjecture that experimental studies based on standing genetic variation underestimate the importance of AP in the evolution of ageing.


Optical temperature measurements in shock tubes from relative emission intensities.
A method is presented for obtaining spectroscopic temperatures in shock tubes using relative emission from two wavelength regions of a molecular band system. Experimental results are given for the OH violet system obtained in the reflected wave region near 3500 degrees K. These results show that equilibrium conditions prevail and that the spectroscopic temperatures agree with those calculated from shock wave velocities. A resume of the appropriate theoretical considerations is given along with a detailed discussion of the experimental techniques required. A brief discussion is also given of some other techniques used to measure temperatures in shock tubes, and comments are made regarding these methods as well as on some of the general problems associated with spectroscopic temperature measurements in shock tubes.


Mandibular symphysis morphology and lower incisor angulation in different anteroposterior jaw relationships and skeletal growth patterns - a cephalometric study.
The purpose of the present study was to assess the symphyseal morphology and lower incisor angulation in different anteroposterior relationship and in different growth patterns and to investigate whether the symphyseal morphology had any correlation with dentofacial parameters. Random Sampling method and lateral cephalograms of 90 subjects, age group 16-30 years, were divided into 30 in each group, i.e. Class I, Class II & Class III after calculating the following parameters (ANB angle, wits appraisal). After that, groups were again divided into 10 in each subgroup i.e. Average, Horizontal and Vertical growers. Results showed the increase in actual symphysis width, inclination of the alveolar part, total height of symphysis and reduction in overall width along with retroclination of lower incisors in class III subjects as compared to class I and class II. Similarly actual and overall width of the symphysis were decreased and inclination of the alveolar part, symphyseal height and symphyseal ratio were increased in vertical growers. The dimensions and configuration of Mandibular Symphysis in class III was found to be different than those in Class I and Class II relationships; the alveolar part of Mandibular Symphyseal compensated for the skeletal relationship in the Class III pattern. Mandibualr Symphysis dimensions were strongly correlated to anterior facial dimensions. Similarly the dimensions and configuration of Mandibular Symphysis was also different in vertical growers as compared to horizontal and average growers, moreover symphyseal morphology and lower incisor angulation had a correlation with dentofacial parameters.


Reduction of Na+, K+-ATPase activity and expression in cerebral cortex of glutaryl-CoA dehydrogenase deficient mice: a possible mechanism for brain injury in glutaric aciduria type I.
Mitochondrial dysfunction has been proposed to play an important role in the neuropathology of glutaric acidemia type I (GA I). However, the relevance of bioenergetics disruption and the exact mechanisms responsible for the cortical leukodystrophy and the striatum degeneration presented by GA I patients are not yet fully understood. Therefore, in the present work we measured the respiratory chain complexes activities I-IV, mitochondrial respiratory parameters state 3, state 4, the respiratory control ratio and dinitrophenol (DNP)-stimulated respiration (uncoupled state), as well as the activities of α-ketoglutarate dehydrogenase (α-KGDH), creatine kinase (CK) and Na+, K+-ATPase in cerebral cortex, striatum and hippocampus from 30-day-old Gcdh-/- and wild type (WT) mice fed with a normal or a high Lys (4.7%) diet. When a baseline (0.9% Lys) diet was given, we verified mild alterations of the activities of some respiratory chain complexes in cerebral cortex and hippocampus, but not in striatum from Gcdh-/- mice as compared to WT animals. Furthermore, the mitochondrial respiratory parameters and the activities of α-KGDH and CK were not modified in all brain structures from Gcdh-/- mice. In contrast, we found a significant reduction of Na(+), K(+)-ATPase activity associated with a lower degree of its expression in cerebral cortex from Gcdh-/- mice. Furthermore, a high Lys (4.7%) diet did not accentuate the biochemical alterations observed in Gcdh-/- mice fed with a normal diet. Since Na(+), K(+)-ATPase activity is required for cell volume regulation and to maintain the membrane potential necessary for a normal neurotransmission, it is presumed that reduction of this enzyme activity may represent a potential underlying mechanism involved in the brain swelling and cortical abnormalities (cortical atrophy with leukodystrophy) observed in patients affected by GA I.


Caregivers' effect on weight management in adults with intellectual and developmental disabilities.
Caregivers of adults with IDD often play a large role in the ability of adults with IDD to lose weight. The purpose of this study was to determine to examine the effects of the caregivers' perceived burdens and self-efficacy and their relationship to an individual (family member or paid staff) on weight changes across a weight management intervention for adults with IDD. Overweight/obese adults with mild to moderate IDD, along with assigned caregivers who served as their study partner, were randomized to an 18-month weight management intervention. The living environment and caregiver relationship were assessed at baseline. Caregivers completed questionnaires regarding perceived hassles, uplifts, and self-efficacy in helping the participant follow a weight management intervention. 147 adults with IDD (∼57% women and ∼16% minorities) were included in data analysis. After 18 months, there were no differences in weight loss between participants who had a family member as their study partner and those who had a paid assistant as their study partner (-5.5 ± 5.2% vs. -5.6± 5.3% p = 0.16). However, paid assistants reported more hassles with following the diet intervention at 6 months (p < 0.05). Participants who had a paid assistant as their study partner were more likely to have multiple study partners during the study, which was correlated with smaller weight loss. While caregivers are important for weight management of adults with IDD, the caregiver's relationship to the participant does not affect weight change in an intervention.


The Opioid Epidemic: Moving Toward an Integrated, Holistic Analytical Response.
In many jurisdictions, public safety and public health entities are working together to enhance the timeliness and accuracy of the analytical characterization and toxicology testing of novel synthetic opioids. The improved sharing and early detection of these analytical data are intended to inform surveillance, interdiction efforts, patient intervention and treatment, all of which are critical to curbing the opioid epidemic. Forensic practitioners working to identify novel synthetic opioids struggle to provide timely results when encountering new or unknown substances, such as the fentanyl analogs. These compounds, which mimic heroin in pharmacologic effect but can be far more potent, are inconsistently present in chemical identification libraries, and are currently largely unavailable as reference materials for analytical comparison. Additionally, federal, state and local governments as well as nongovernmental organizations require potency, toxicity and potential-for-abuse data to evaluate the potential health risks of emerging drug threats. Subsequent scheduling efforts and criminal prosecutions also require these thorough drug characterization studies. Pilot programs have demonstrated that early communication of real-time drug toxicity and analytical data significantly impacts the successful response to emerging opioids. High-quality, real-time, national-level data on chemical composition, toxicological test data, drug toxicity and overdoses, and analysis of seized materials by law enforcement are needed to track drug trends. However, the USA still lacks a national system to coordinate and communicate toxicology, medical and medical examiner and coroner data with the broader medical and law enforcement communities. Opportunities to address these gaps as well as recent advancements collected through interagency efforts and technical workshops in the toxicology and analytical chemistry communities are presented here. Opportunities for partnership, increased communication and expanding best practices to move toward an integrated, holistic analytical response are also explored.


Most important papers in health costs, cost-effectiveness, and resource utilization.
The following are highlights from the new series, Circulation: Cardiovascular Quality and Outcomes Topic Review. This series will summarize the most important manuscripts (as selected by the Editor) that have published in the Circulation portfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes, and general cardiology audience. The studies included in this article represent the most significant research in the area of health costs, cost-effectiveness, and resource utilization.


Assessing genome assembly quality using the LTR Assembly Index (LAI).
Assembling a plant genome is challenging due to the abundance of repetitive sequences, yet no standard is available to evaluate the assembly of repeat space. LTR retrotransposons (LTR-RTs) are the predominant interspersed repeat that is poorly assembled in draft genomes. Here, we propose a reference-free genome metric called LTR Assembly Index (LAI) that evaluates assembly continuity using LTR-RTs. After correcting for LTR-RT amplification dynamics, we show that LAI is independent of genome size, genomic LTR-RT content, and gene space evaluation metrics (i.e., BUSCO and CEGMA). By comparing genomic sequences produced by various sequencing techniques, we reveal the significant gain of assembly continuity by using long-read-based techniques over short-read-based methods. Moreover, LAI can facilitate iterative assembly improvement with assembler selection and identify low-quality genomic regions. To apply LAI, intact LTR-RTs and total LTR-RTs should contribute at least 0.1% and 5% to the genome size, respectively. The LAI program is freely available on GitHub: https://github.com/oushujun/LTR_retriever.


Spinach latent virus Infecting Tomato in Virginia, United States.
Plants in a single field of commercial tomato (Solanum lycopersicum) of unidentified cultivars in Virginia in July, 2012, were observed showing stunting, leaf distortion, twisting and thickening, discoloration, and color streaking and ringspots on fruits. Serological tests were negative for Cucumber mosaic virus, Groundnut ringspot virus, Tomato spotted wilt virus, Tomato chlorotic spot virus, Impatiens necrotic spot virus, Tobacco mosaic virus, and Tomato bushy stunt virus (Agdia, Inc., Elkhart, IN). Using a membrane-based macroarray (3), hybridization was observed to 8 of 9 70-mer oligonucleotide probes of Spinach latent virus (SpLV; genus Ilarvirus, family Bromoviridae). To confirm the hybridization results, complementary DNA (cDNA) was synthesized using random hexamers and MMLV reverse transcriptase (Promega, Madison, WI), followed by PCR amplification using ilarvirus degenerate primers (4). Fragments of approximately 380 bp were amplified and directly sequenced (GenBank Accession KC_466090); a BLAST search showed a 99% identity to the SpLV RNA 2 reference genome (NC_003809). Primers for SpLV RNA1 (SpLVRNA1f-GGTGTCACCATGCAAACTGG, SpLVRNA1r-AGCTCTTCGTAATAGGCCTGC) and SpLV RNA3 (SpLVCPf-GAAGTCTTTCCCAGGTGAGCA, SpLVCPr-AGGTGGGCATATGGACTTGG) were designed and cDNA was amplified using the IQ supermix (Biorad, Hercules, CA) with thermocycling of 94°C for 4 min, 35× (94°C 45 s, 55°C 45 s, 72°C 45 s), and 72°C for 10 min. The resulting fragments of 538 bp for RNA1 (KC_466088) and 661 bp for RNA3 (KC_466089) showed 100% identity to reference genome sequences for SpLV (NC_003808 and NC_003810, respectively). To demonstrate virus transmissibility, Chenopodium quinoa plants were mechanically inoculated using tomato leaf material (same source described above) ground in 30 mM Na2HPO4 buffer, pH 7.0. Necrotic spots developed on the inoculated leaves 10 dpi. Younger, non-inoculated leaves showed yellow mottling and tested positive for SpLV by RT-PCR (two of two plants tested). The detection of SpLV is rarely reported, with only one record from the United States (2). Although SpLV is described as a latent virus, it has been found associated with tomato fruit symptoms in New Zealand (1). It is not known if the fruit ringspot and other symptoms on the Virginia samples were due to virus infection. Since SpLV is seed-transmissible and seed production takes place in different parts of the world, it has the potential to spread with germplasm and become more widespread in North America. References: (1) B. S. M. Lebas et al. Plant Dis. 91:228, 2007. (2) H. Y. Liu and J. E. Duffus. Phytopathology 76:1087, 1986. (3) K. L. Perry and X. Lu. Phytopathology 100:S100, 2010. (4) M. Untiveros, et al. J. Virol. Methods 165:97, 2010.


Peer Influence, Genetic Propensity, and Binge Drinking: A Natural Experiment and a Replication.
The authors draw data from the College Roommate Study (ROOM) and the National Longitudinal Study of Adolescent Health to investigate gene-environment interaction effects on youth binge drinking. In ROOM, the environmental influence was measured by the precollege drinking behavior of randomly assigned roommates. Random assignment safeguards against friend selection and removes the threat of gene-environment correlation that makes gene-environment interaction effects difficult to interpret. On average, being randomly assigned a drinking peer as opposed to a nondrinking peer increased college binge drinking by 0.5-1.0 episodes per month, or 20%-40% the average amount of binge drinking. However, this peer influence was found only among youths with a medium level of genetic propensity for alcohol use; those with either a low or high genetic propensity were not influenced by peer drinking. A replication of the findings is provided in data drawn from Add Health. The study shows that gene-environment interaction analysis can uncover social-contextual effects likely to be missed by traditional sociological approaches.


Two BRM promoter insertion polymorphisms increase the risk of early-stage upper aerodigestive tract cancers.
Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion-deletion polymorphisms, BRM-741 and BRM-1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case-control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.e., lung, esophageal, head and neck), a group of early-stage malignancies in which molecular and genetic etiologic factors are poorly understood. The effects of various clinical factors on this association were also studied. We analyzed 562 cases of early-stage UADT cancers and 993 matched healthy controls. The double homozygous BRM promoter variants were associated with a significantly increased risk of early stage UADT cancers (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.7-3.8). This association was observed in lung (aOR, 2.61; 95% CI, 1.5-4.9) and head and neck (aOR, 2.75; 95% CI, 1.4-5.6) cancers, but not significantly in esophageal cancer (aOR, 1.66; 95% CI, 0.7-5.8). There was a nonsignificant trend for increased risk in the heterozygotes or single homozygotes. The relationship between the BRM polymorphisms and early-stage UADT cancers was independent of age, sex, smoking status, histology, and clinical stage. These findings suggest that the BRM promoter double insertion homozygotes may be associated with an increased risk of early-stage UADT cancers independent of smoking status and histology, which must be further validated in other populations.


Interactive effects of increased temperature, elevated pCO2 and different nitrogen sources on the coccolithophore Gephyrocapsaoceanica.
As a widespread phytoplankton species, the coccolithophore Gephyrocapsaoceanica has a significant impact on the global biogeochemical cycle through calcium carbonate precipitation and photosynthesis. As global change continues, marine phytoplankton will experience alterations in multiple parameters, including temperature, pH, CO2, and nitrogen sources, and the interactive effects of these variables should be examined to understand how marine organisms will respond to global change. Here, we show that the specific growth rate of G. oceanica is reduced by elevated CO2 (1000 μatm) in [Formula: see text]-grown cells, while it is increased by high CO2 in [Formula: see text]-grown ones. This difference was related to intracellular metabolic regulation, with decreased cellular particulate organic carbon and particulate organic nitrogen (PON) content in the [Formula: see text] and high CO2 condition compared to the low CO2 condition. In contrast, no significant difference was found between the high and low CO2 levels in [Formula: see text] cultures (p > 0.05). The temperature increase from 20°C to 25°C increased the PON production rate, and the enhancement was more prominent in [Formula: see text] cultures. Enhanced or inhibited particulate inorganic carbon production rate in cells supplied with [Formula: see text] relative to [Formula: see text] was observed, depending on the temperature and CO2 condition. These results suggest that a greater disruption of the organic carbon pump can be expected in response to the combined effects of increased [Formula: see text]/[Formula: see text] ratio, temperature, and CO2 level in the oceans of the future. Additional experiments conducted under nutrient limitation conditions are needed before we can extrapolate our findings to the global oceans.


[A comparative study of gallbladder function using echography and HIDA-CCK].
This paper compares two methods of evaluating gall-bladder function after stimulation with cholecystokinin (CCK); One, the echographic method, permits the gall-bladder contraction study by determining variations in face area of the organ. The other, the scintigraphic method (HIDA-CCK test), studies of the gall-bladder emptying registering the decreases of activity by external counts. Out of 20 studies performed: 8 cases presented a contractile response and normal emptying; 7 had an abnormality late initial response (Ti) and contraction and emptying (defined by T1/2) slower than normal. In the 5 patients the gall-bladder traced with HIDA did not respond to CCK. Within this group, one patient had an incomplete painful contraction, evaluation by echography. The onset of pain or sub-costal discomfort was a variable finding within the different study groups. The linear coefficient correlation for the normal group and for the patients with late response was 0.8255 (x = 2.216 gamma-4.59). Based on these data and taking into account cheaper cost, patient comfort, and greater availability of equipment, the echographic method for studying gall-bladder contraction after administration of CCK, can be used instead of the HIDA-CCK procedure.


Characterization of adrenal masses with diffusion-weighted imaging.
The purpose of this article is to assess the role of diffusion-weighted MRI in characterizing adrenal masses. A retrospective review of the MRI database from August 2007 to July 2009 was performed. The MRI examinations of 48 patients, with 49 lesions, were reviewed independently and blindly by two experienced abdominal radiologists who measured the signal intensities on in-phase and opposed-phase T1-weighted imaging and apparent diffusion coefficient (ADC). ADC measurements and quantitative parameters of chemical shift imaging (signal intensity index and adrenal-to-spleen ratio) were assessed separately and in combination. Lesions with indeterminate signal intensity index (< 16.5%) were considered benign if ADC was greater than or equal to 1.0 × 10(-3) mm(2)/s and malignant if ADC was less than 1.0 × 10(-3) mm(2)/s. Stepwise logistic regression analysis and receiver operating characteristic curves analysis were performed. There were 12 malignant and 37 benign lesions. On multivariate analysis, the only significant predictors of lesion status were signal intensity index from reviewer 2 (p = 0.05) and lesion size (p = 0.04); ADC values were not found to be useful. On receiver operating characteristic curve analysis, there was no significant difference in area under the curve for ADC, signal intensity index, adrenal-to-spleen ratio, or the combined signal intensity index and ADC assessment. For lesions that were indeterminate according to signal intensity index, ADC values greater than 1.50 × 10(-3) mm(2)/s were found only in benign lesions, and nine of 11 lesions with ADC less than 1.0 × 10(-3) mm(2)/s were malignant. In general, ADC values are not useful in differentiating adrenal lesions. However, when ADC values are applied to lesions that are indeterminate on signal intensity index, they may help in differentiating a subset of benign and malignant lesions.


Competence, practical rationality and what a patient values.
According to the principle of patient autonomy, patients have the right to be self-determining in decisions about their own medical care, which includes the right to refuse treatment. However, a treatment refusal may legitimately be overridden in cases where the decision is judged to be incompetent. It has recently been proposed that in assessments of competence, attention should be paid to the evaluative judgments that guide patients' treatment decisions. In this paper I examine this claim in light of theories of practical rationality, focusing on the difficult case of an anorexic person who is judged to be competent and refuses treatment, thereby putting themselves at risk of serious harm. I argue that the standard criteria for competence assess whether a treatment decision satisfies the goals of practical decision-making, and that this same criterion can be applied to a patient's decision-guiding commitments. As a consequence I propose that a particular understanding of practical rationality offers a theoretical framework for justifying involuntary treatment in the anorexia case.


Membrane assisted passive sampler for triazine compounds in water bodies--characterization of environmental conditions and field performance.
In this work, a simple, inexpensive and very selective membrane assisted passive sampler (MAPS) that does not use organic solvents, based on a thin walled silicone hollow fibre membrane for extraction of ionizable organic compounds in water bodies is reported. The potential for passive sampling of basic compounds is demonstrated. By changing the acceptor solution from acidic to basic conditions, the MAPS can be successfully used to extract acidic organic compound. The influence of environmental factors such as temperature, sample matrix and hydrodynamics on enrichment factors and sampling rates have been investigated in order to calibrate the passive sampler for measurement of TWA concentration of triazines. The selectivity, extraction efficiency and enrichment factor of the developed sampler has been compared to the Chemcatcher passive sampler. It was found that the chemical uptake of basic triazine compounds into the passive sampler remained linear and integrative throughout the 7 days exposure periods. For atrazine, propazine, prometryne and terbutryne a large 3 days time lag was experienced. A plot of natural logarithms of the amount taken up by the sampler against exposure time gave linear relationship for these compounds. The sampling rates for individual triazine compounds increased with change of hydrodynamic conditions from static to turbulent. The presence of 20 mg L(-1) humic substances in solution was found to have no significant effect on the concentration of compounds trapped in the acceptor solution. Once these compounds are trapped in the acceptor solution they do not diffuse back during the deployment period. A strong dependence of the sampling rates on the type of protective cover used was noted. Stainless steel protective cover was found to be the better than the iron mesh as it did not rust during deployment. The detection limits on HPLC with UV detection ranged from 0.50 to 4.50 μg L(-1) for MAPS, 0.40 to 3.50 μg L(-1) for Chemcatcher passive sampler and 0.35 to 4.50 μg L(-1) for SPE with 7 days exposure of passive samplers. Preliminary field trial of the potential of the MAPS to monitor ionizable triazine compounds in Hartebeespoort dam found west of Johannesburg, South Africa was compared to Chemcatcher and SPE technique with C(18) sorbents for grab samples. No quantifiable amounts of triazine compounds were found in any of the deployed passive samplers in the preliminary field applications. Triazine compounds were also not detected in grab samples after SPE. However, data from laboratory studies support the feasibility of MAPS to measure the freely dissolved fraction of ionizable organic chemicals in water. The MAPS also exhibited slightly better selectivity towards matrix components found in natural water compared to SPE technique or Chemcatcher with C(18) disk as trapping media.


Boosting the efficiency of inverted quantum dot light-emitting diodes by balancing charge densities and suppressing exciton quenching through band alignment.
We report an inverted and multilayer quantum dot light emitting diode (QLED) which boosts high efficiency by tuning the energy band alignment between charge transport and light emitting layers. The electron transport layer (ETL) was ZnO nanoparticles (NPs) with an optimized doping concentration of cesium azide (CsN3) to effectively reduce electron flow and balance charge injection. This is by virtue of a 0.27 eV upshift of the ETL's conduction band edge, which inhibits the quenching of excitons and preserves the superior emissive properties of the quantum dots due to the insulating characteristics of CsN3. The demonstrated QLED exhibits a peak current efficiency, power efficiency and external quantum efficiency of up to 13.5 cd A-1, 10.6 lm W-1 and 13.4% for the red QLED, and correspondingly 43.1 cd A-1, 33.6 lm W-1 and 9.1% for green, and 4.1 cd A-1, 2.0 lm W-1 and 6.6% for the blue counterparts. Compared with QLEDs without optimization, the performance of these modified devices shows drastic improvement by 95.6%, 39.4% and 36.7%, respectively. This novel device architecture with heterogeneous energy levels reported here offers a new design strategy for next-generation high efficiency QLED displays and solid-state lighting technologies.


Global Coagulation Assays in Transgender Women on Oral and Transdermal Estradiol Therapy.
The thrombotic effects of estradiol therapy in transgender women are unclear. Global coagulation assays (GCA) may be better measures of hemostatic function compared with standard coagulation tests. To assess the GCA profiles of transgender women in comparison to cisgender controls and to compare how GCA differ between routes of estradiol therapy in transgender women. Cross-sectional case-control study. General community. Transgender women, cisgender male and cisgender female controls. Citrated blood samples were analyzed for (i) whole blood thromboelastography (TEG®5000), (ii) platelet-poor plasma thrombin generation (calibrated automated thrombogram); and (iii) platelet-poor plasma fibrin generation (overall hemostatic potential assay). Mean difference (95% confidence intervals) between groups are presented. Twenty-six transgender women (16 oral estradiol, 10 transdermal estradiol) were compared with 98 cisgender women and 55 cisgender men. There were no differences in serum estradiol concentration (P = 0.929) and duration of therapy (P = 0.496) between formulations. Transgender women demonstrated hypercoagulable parameters on both thromboelastography (maximum amplitude + 6.94 mm (3.55, 10.33); P < 0.001) and thrombin generation (endogenous thrombin potential + 192.62 nM.min (38.33, 326.91); P = 0.009; peak thrombin + 38.10 nM (2.27, 73.94); P = 0.034) but had increased overall fibrinolytic potential (+4.89% (0.52, 9.25); P = 0.024) compared with cisgender men. No significant changes were observed relative to cisgender women. Route of estradiol delivery or duration of use did not influence the GCA parameters. Transgender women on estradiol therapy demonstrated hypercoagulable GCA parameters compared with cisgender men with a shift towards cisgender female parameters. Route of estradiol delivery did not influence the GCA parameters.


GPU-based real-time soft tissue deformation with cutting and haptic feedback.
This article describes a series of contributions in the field of real-time simulation of soft tissue biomechanics. These contributions address various requirements for interactive simulation of complex surgical procedures. In particular, this article presents results in the areas of soft tissue deformation, contact modelling, simulation of cutting, and haptic rendering, which are all relevant to a variety of medical interventions. The contributions described in this article share a common underlying model of deformation and rely on GPU implementations to significantly improve computation times. This consistency in the modelling technique and computational approach ensures coherent results as well as efficient, robust and flexible solutions.