Looking after yourself: Clinical understandings of chronic-care self-management strategies in rural and urban contexts of the United Kingdom and Australia.
This article reports on the outcomes of two similar projects undertaken during 2011-2012 in Australia (Rural Northern New South Wales) and the United Kingdom (Urban Northern United Kingdom) that sought to identify the strategies that health professionals employ to actively involve patients with chronic conditions in the planning and delivery of their care. In particular, this study explored understandings and contexts of care that impacted on the participants' practices. This study was informed by the global shift to partnership approaches in health policy and the growing imperative to deliver patient or client-centred care. An ethnomethodological design was used, as ethnomethodology does not dictate a set of research methods or procedures, but rather is congruent with any method that seeks to explore what people do in their routine everyday lives. Focus groups and interviews were employed to explore the strategies used by a range of primary health-care providers, such as general practitioners, nurses, social workers, diabetes educators, dieticians and occupational therapists, to support clients to effectively manage their own chronic conditions. Data from both studies were synthesised and analysed thematically, with the themes reflecting the context, similarities and differences of the two studies that the participants felt had either facilitated or blocked their efforts to support their clients to adopt self-care strategies. Supporting patients/clients to engage in actively self-managing their health-care needs requires changes to clients' and clinicians' traditional perspectives on their roles. The barriers and enablers to supporting clients to manage their own health needs were similar across both locations and included tensions in role identity and functions, the discourse of health-care professionals as 'experts' who deliver care and their level of confidence in being facilitators who 'educate' clients to effectively manage their health-care needs, rather than only the 'providers' of care.


Detergent Desorption of Membrane Proteins Exhibits Two Kinetic Phases.
Gradual dissociation of detergent molecules from water-insoluble membrane proteins culminates in protein aggregation. However, the time-dependent trajectory of this process remains ambiguous because the signal-to-noise ratio of most spectroscopic and calorimetric techniques is drastically declined by the presence of protein aggregates in solution. We show that by using steady-state fluorescence polarization (FP) spectroscopy the dissociation of the protein-detergent complex (PDC) can be inspected in real time at detergent concentrations below the critical micelle concentration. This article provides experimental evidence of the coexistence of two distinct phases of the dissociations of detergent monomers from membrane proteins. We first noted a slow detergent predesolvation process, which was accompanied by a relatively modest change in the FP anisotropy, suggesting a small number of dissociated detergent monomers from the proteomicelles. This predesolvation phase was followed by a fast detergent desolvation process, which was highlighted by a major alteration in the FP anisotropy. The durations and rates of these phases were dependent on both the detergent concentration and the interfacial PDC interactions. Further development of this approach might lead to the creation of a new semiquantitative method for the assessment of the kinetics of association and dissociation of proteomicelles.


Inflammatory markers in schizophrenia: comparing antipsychotic effects in phase 1 of the clinical antipsychotic trials of intervention effectiveness study.
C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment. The IM outcomes were compared between antipsychotic treatment groups in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial phase 1 with subjects with laboratory assessments at baseline and 3 months (n = 789). There were significant treatment differences in CRP, E-selectin, and ICAM-1 at 3 months, with a differential impact of baseline values on the CRP and ICAM-1 results. In overall comparisons, quetiapine and olanzapine had the highest median levels for CRP, and olanzapine for E-selectin and ICAM-1. Olanzapine was significantly different after baseline adjustment than perphenazine (p = .001) for E-selectin, and in those with low baseline CRP (<1 mg/L), olanzapine was significantly different than perphenazine (p < .001), risperidone (p < .001), and ziprasidone (p = .002) for CRP. Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median, but the differences were not statistically significant versus olanzapine (p = .010), quetiapine (p = .010), and risperidone (p = .006) after controlling for multiple comparisons. The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP. This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation. C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients.


SU-E-T-233: Evaluation of Superficial Doses for Postmastectomy Radiotherapy.
To measure and to evaluate the surface and superficial doses for patients requiring postmastectomy radiotherapy (PMRT) with different treatment techniques. An elliptic cylinder cork and super-flab boluses were used to simulate the lung and the chest wall, respectively. Sets of CT images with chest wall thicknesses of 5, 8, 10, 13, and 15 mm were acquired. Hypothetical clinical target volumes were outlined and modified to fit a margin of 1 -3 mm away from the surface. The planning target volume was initially created by expanding an isotropic 3 mm margin from CTV and then a margin of 1-3 mm was shrunk from the phantom surface. Treatment techniques using a pair of tangential wedged fields (TWF) and 4-field IMRT were designed with a prescribed fraction dose (Dp) of 180 cGy. Superficial dose profiles around the phantom circumference at depths of 0, 1, 2, 3, and 5 mm were obtained for each treatment technique using radiochromic external beam therapy (EBT) films. The TWF plans show a dose buildup about 3 mm at the median and lateral tangential incident regions with a surface dose of about 52% of Dp. Dose profiles were more uniform in the PTV region for the 4-F IMRT plans. Most of the PTV region had doses higher than 94% of Dp at depths larger than 1 mm. The mean surface dose was about 65% of Dp for the 4-F IMRT plans. The maximum dose for the 4-F IMRT plans was less than 118.4% of Dp. The dose variations caused by the oblique incidence and a thin chest wall are modulated and reduced in the IMRT plans. More uniform dose distributions within the PTV are obtained with the 4-F IMRT plans.


Comparison of soft tissue balancing, femoral component rotation, and joint line change between the gap balancing and measured resection techniques in primary total knee arthroplasty: A meta-analysis.
This meta-analysis was designed to compare the accuracy of soft tissue balancing and femoral component rotation as well as change in joint line positions, between the measured resection and gap balancing techniques in primary total knee arthroplasty. Studies were included in the meta-analysis if they compared soft tissue balancing and/or radiologic outcomes in patients who underwent total knee arthroplasty with the gap balancing and measured resection techniques. Comparisons included differences in flexion/extension, medial/lateral flexion, and medial/lateral extension gaps (LEGs), femoral component rotation, and change in joint line positions. Finally, 8 studies identified via electronic (MEDLINE, EMBASE, and the Cochrane Library) and manual searches were included. All 8 studies showed a low risk of selection bias and provided detailed demographic data. There was some inherent heterogeneity due to uncontrolled bias, because all included studies were observational comparison studies. The pooled mean difference in gap differences between the gap balancing and measured resection techniques did not differ significantly (-0.09 mm, 95% confidence interval [CI]: -0.40 to +0.21 mm; P = 0.55), except that the medial/LEG difference was 0.58 mm greater for measured resection than gap balancing (95% CI: -1.01 to -0.15 mm; P = 0.008). Conversely, the pooled mean difference in femoral component external rotation (0.77°, 95% CI: 0.18° to 1.35°; P = 0.01) and joint line change (1.17 mm, 95% CI: 0.82 to 1.52 mm; P < 0.001) were significantly greater for the gap balancing than the measured resection technique. The gap balancing and measured resection techniques showed similar soft tissue balancing, except for medial/LEG difference. However, the femoral component was more externally rotated and the joint line was more elevated with gap balancing than measured resection. These differences were minimal (around 1 mm or 1°) and therefore may have little effect on the biomechanics of the knee joint. This suggests that the gap balancing and measured resection techniques are not mutually exclusive.


Cultures in chimpanzees.
As an increasing number of field studies of chimpanzees (Pan troglodytes) have achieved long-term status across Africa, differences in the behavioural repertoires described have become apparent that suggest there is significant cultural variation. Here we present a systematic synthesis of this information from the seven most long-term studies, which together have accumulated 151 years of chimpanzee observation. This comprehensive analysis reveals patterns of variation that are far more extensive than have previously been documented for any animal species except humans. We find that 39 different behaviour patterns, including tool usage, grooming and courtship behaviours, are customary or habitual in some communities but are absent in others where ecological explanations have been discounted. Among mammalian and avian species, cultural variation has previously been identified only for single behaviour patterns, such as the local dialects of song-birds. The extensive, multiple variations now documented for chimpanzees are thus without parallel. Moreover, the combined repertoire of these behaviour patterns in each chimpanzee community is itself highly distinctive, a phenomenon characteristic of human cultures but previously unrecognised in non-human species.


Fronts and patterns in a spatially forced CDIMA reaction.
We use the CDIMA chemical reaction and the Lengyel-Epstein model of this reaction to study resonant responses of a pattern-forming system to time-independent spatial periodic forcing. We focus on the 2 : 1 resonance, where the wavenumber of a one-dimensional periodic forcing is about twice the wavenumber of the natural stripe pattern that the unforced system tends to form. Within this resonance, we study transverse fronts that shift the phase of resonant stripe patterns by π. We identify phase fronts that shift the phase discontinuously, and pairs of phase fronts that shift the phase continuously, clockwise and anti-clockwise. We further identify a front bifurcation that destabilizes the discontinuous front and leads to a pair of continuous fronts. This bifurcation is the spatial counterpart of the nonequilibrium Ising-Bloch (NIB) bifurcation in temporally forced oscillatory systems. The spatial NIB bifurcation that we find occurs as the forcing strength is increased, unlike earlier studies of the NIB bifurcation. Furthermore, the bifurcation is subcritical, implying a range of forcing strength where both discontinuous Ising fronts and continuous Bloch fronts are stable. Finally, we find that both Ising fronts and Bloch fronts can form discrete families of bound pairs, and we relate arrays of these front pairs to extended rectangular and oblique patterns.


Intimate partner violence and cardiovascular risk: is there a link?
This paper is a report of a study of the relationship between stress associated with intimate partner violence and smoking and cardiovascular risk. Stress related to intimate partner violence persists after a woman leaves an abusive relationship. Persistent stress is associated with cardiovascular disease, the leading single cause of death among women. Smoking, an established risk factor for cardiovascular disease, is a coping mechanism commonly used to decrease the anxiety and stress of intimate partner violence. However, cardiovascular health is poorly understood in abused women. Secondary analysis of data collected between 2004 and 2005 with a community sample of 309 women who had separated from an abusive partner 3 months to 3 years previously was conducted to create a descriptive profile of cardiovascular risk. Bivariate tests of association and logistic regression analysis were used to test relationships among variables. Of the women, 44.1% were smokers; 53.2% had body mass indices classified as overweight or obese; 54.7% had blood pressures above normal range; and 50.8% reported cardiovascular symptoms. Neither severity of intimate partner violence nor smoking behaviours were statistically significant in explaining the presence of cardiovascular symptoms. The prevalence of hypertension, obesity and smoking suggests that survivors of intimate partner violence may be at heightened risk for cardiovascular disease and warrant clinical attention. Because cardiac symptoms develop as women get older, the mean age of 39 years in this sample may explain why intimate partner violence severity and smoking did not sufficiently explain the presence of cardiac symptoms.


Systematic capsule gene disruption reveals the central role of galactose metabolism on Cryptococcus neoformans virulence.
The polysaccharidic capsule is the main virulence factor of Cryptococcus neoformans. It primarily comprised of two polysaccharides: glucuronoxylomannan (GXM, 88% of the capsule mass) and galactoxylomannan (GalXM, 7% of the capsule mass). We constructed a large collection of mutant strains in which genes potentially involved in capsule biosynthesis were deleted. We used a new post-genomic approach to study the virulence of the strains. Primers specific for unique tags associated with the disruption cassette were used in a real-time PCR virulence assay to measure the fungal burden of each strain in different organs of mice in multi-infection experiments. With this very sensitive assay, we identified a putative UDP-glucose epimerase (Uge1p) and a putative UDP-galactose transporter (Ugt1p) essential for C. neoformans virulence. The uge1Delta and ugt1Delta strains are temperature sensitive and do not produce GalXM but synthesize a larger capsule. These mutant strains (GalXM negative, GXM positive) are not able to colonize the brain even at the first day of infection whereas GXM-negative strains (GalXM positive) can still colonize the brain, although less efficiently than the wild-type strain.


Intermediate filament-deficient cells are mechanically softer at large deformation: a multi-scale simulation study.
The cell's cytoskeleton, providing cells with structure and shape, consists of different structural proteins, including microtubules, actin microfilaments and intermediate filaments. It has been suggested that intermediate filaments play a crucial role in providing mechanical stability to cells. By utilizing a simple coarse-grained computational model of the intermediate filament network in eukaryotic cells, we show here that intermediate filaments play a significant role in the cell mechanical behavior at large deformation, and reveal mechanistic insight into cell deformation under varying intermediate filament densities. We find that intermediate filament-deficient cells display an altered mechanical behavior, featuring a softer mechanical response at large deformation while the mechanical properties remain largely unchanged under small deformation. We compare the results with experimental studies in vimentin-deficient cells, showing good qualitative agreement. Our results suggest that intermediate filaments contribute to cell stiffness and deformation at large deformation, and thus play a significant role in maintaining cell structural integrity in response to applied stress and strain, in agreement with earlier hypotheses. The simulation results also suggest that changes in the filament density result in profound alterations of the deformation state of the cell nucleus, leading to greater stretch in the direction of loading and greater contraction in the orthogonal direction as the intermediate filament density is increased. Our model opens the door to future studies to investigate disease states, the effects of amino acid mutations and how structural changes at different levels in the cell's structural makeup influence biomechanical properties.


Promoting informed choice: evaluating a decision-making tool for family planning clients and providers in Mexico.
The World Health Organization (WHO) has developed a decision-making tool to be used by providers and clients during family planning visits to improve the quality of services. It is important to examine the tool's usability and its impact on counseling and decision-making processes during family planning consultations. Thirteen providers in Mexico City were videotaped with family planning clients three months before and one month after attending a training session on the WHO decision-making tool. The videotapes were coded for client-provider communication and eye contact, and decision-making behaviors were rated. In-depth interviews and focus group discussions explored clients' and providers' opinions of the tool. After providers began using the decision-making tool, they gave clients more information on family planning, tailored that information more closely to clients' situations and more often discussed HIV/AIDS prevention, dual protection and condom use. Client involvement in the decision-making process and client active communication increased, contributing to a shift from provider-dominated to shared decision making. Clients reported that the tool helped them understand the provider's explanations and made them feel more comfortable talking and asking questions during consultations. After one month of practice with the decision-making tool, most providers felt comfortable with it and found it useful; however, they recommended some changes to the tool to help engage clients in the decision-making process. The decision-making tool was useful both as a job aid for providers and as a decision aid for clients.


Increased urinary interleukin 22 binding protein levels correlate with lupus nephritis activity.
Interleukin 22 (IL-22) plays an important role in the promotion of antimicrobial immunity. However, dysregulated IL-22 action leads to inflammation and is involved in autoimmune diseases, including systemic lupus erythematosus (SLE). IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We investigated the expression and potential significance of serum and urinary IL-22BP levels in patients with SLE. A total of 112 patients with SLE and healthy control subjects participated in our study. Patients were classified according to kidney involvement and disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, complement factor 3 (C3), C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The concentrations of IL-22BP and IL-22 were measured by ELISA. The expression of IL-22BP in the renal tissue was detected by immunohistochemistry. Patients with active renal disease had urinary levels of IL-22BP higher than (1) patients with active SLE but no renal involvement, (2) patients with a history of lupus nephritis in remission with no systemic disease activity and no history of renal involvement, and (3) control subjects. There was no difference in serum levels of IL-22BP among the groups. Urinary levels of IL-22BP in patients with active renal disease were positively correlated with SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics renal activity score, and histological activity index. IL-22BP was highly expressed in renal tissue of patients with active renal disease. After 6 months of treatment, urinary IL-22BP levels decreased significantly in patients with complete response, but remained unchanged in those with partial or no response. Urinary but not serum IL-22BP levels were associated with active renal disease. Urinary levels of IL-22BP might be a potential marker for the presence of renal involvement in patients with SLE.


Occurrence and biological effect of exogenous steroids in the Elkhorn River, Nebraska, USA.
Recent studies of surface waters in North America, Japan and Europe have reported the presence of steroidogenic agents as contaminants. The current study has three objectives: 1) to determine if steroidogenic compounds are present in the Elkhorn River, 2) to determine if sediments collected from the Elkhorn River can act as a source of steroidogenic compounds to aquatic organisms, and 3) to determine if site-specific biological effects are apparent in the hepatic gene expression of fathead minnows. Evidence was obtained using three approaches: 1) deployment of polar organic chemical integrative samplers (POCIS), 2) deployment of caged fathead minnows, and 3) a laboratory experiment in which POCIS and fish were exposed to sediments from the deployment sites. Deployment sites included: the Elkhorn River immediately downstream from a Nebraska wastewater treatment plant, two waterways (Fisher Creek and Sand Creek) likely to be impacted by runoff from cattle feeding operations, and a reference site unlikely to be impacted by waste water inputs. The POCIS extracts were analyzed for a number of natural steroids and metabolites, as well as four different synthetic steroids: ethinylestradiol, zearalonol, 17beta-trenbolone and melengestrol acetate. Estrogenic and androgenic metabolites, as well as progesterone and trace levels of melengestrol acetate were detected in POCIS deployed at each site. POCIS deployed in tanks containing field sediments from the four sites did not accumulate the synthetic steroids except for ethinylestradiol, which was detected in the aquarium containing sediments collected near the wastewater treatment plant. Fish deployed in Sand Creek and at the wastewater treatment plant experienced significantly elevated levels of gene expression for two genes (StAR and P450scc) relative to those deployed in Fisher Creek. Fish exposed to the sediments collected from Sand Creek had significantly higher levels of hepatic StAR and P450scc gene expression than did fish exposed to sediments from the two other field sites, as well as the no-sediment control tank. 1) detectable levels of steroidogenic compounds were detected in passive samplers deployed in the Elkhorn River, 2) sediments do not appear to be a significant source for steroidogenic compounds, and 3) site-specific differences were found in mRNA expression among the different treatment groups of fish; however, a functional explanation for these differences is not readily forthcoming.


Directed evolution of adeno-associated virus for enhanced gene delivery and gene targeting in human pluripotent stem cells.
Efficient approaches for the precise genetic engineering of human pluripotent stem cells (hPSCs) can enhance both basic and applied stem cell research. Adeno- associated virus (AAV) vectors are of particular interest for their capacity to mediate efficient gene delivery to and gene targeting in various cells. However, natural AAV serotypes offer only modest transduction of human embryonic and induced pluripotent stem cells (hESCs and hiPSCs), which limits their utility for efficiently manipulating the hPSC genome. Directed evolution is a powerful means to generate viral vectors with novel capabilities, and we have applied this approach to create a novel AAV variant with high gene delivery efficiencies (~50%) to hPSCs, which are importantly accompanied by a considerable increase in gene-targeting frequencies, up to 0.12%. While this level is likely sufficient for numerous applications, we also show that the gene-targeting efficiency mediated by an evolved AAV variant can be further enhanced (>1%) in the presence of targeted double- stranded breaks (DSBs) generated by the co-delivery of artificial zinc finger nucleases (ZFNs). Thus, this study demonstrates that under appropriate selective pressures, AAV vectors can be created to mediate efficient gene targeting in hPSCs, alone or in the presence of ZFN- mediated double-stranded DNA breaks.


The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema.
Genome-wide association studies have identified genetic variants in the nicotinic acetylcholine receptor (nAChR) on chromosome 15q24/25 as a risk for nicotine dependence, lung cancer, and chronic obstructive pulmonary disease (COPD). Assessment of bronchial obstruction by spirometry, typically used for diagnosing COPD, fails, however, to detect emphysema. To determine the association of the 15q24/25 locus with emphysema. The rs1051730 variant on 15q24/25 was genotyped in two independent white cohorts of 661 and 456 heavy smokers. Participants underwent pulmonary function tests and computed tomography (CT) of the chest, and took questionnaires assessing smoking behavior and health status. The rs1051730 A-allele correlated with reduced FEV(1) and with increased susceptibility for bronchial obstruction with a pooled odds ratio (OR) of 1.33 (95% confidence interval [CI] = 1.11-1.61; P = 0.0026). In both studies a correlation between the rs1051730 A-allele and lung diffusing capacity (Dl(CO)) and diffusing capacity per unit alveolar volume (Kco) was observed. Consistently, the rs1051730 A-allele conferred increased risk for emphysema as assessed by CT (P = 0.0097 and P = 0.019), with a pooled OR of 1.39 (CI = 1.15-1.68; P = 0.00051). Visual emphysema scores and scores based on densities quantified on CT were more pronounced in A-allele carriers, indicating that rs1051730 correlates with the severity of emphysema. The 15q24/25 locus in nAChR is associated with the presence and severity of emphysema. This association was independent of pack-years smoking, suggesting that nAChR is causally involved in alveolar destruction as a potentially shared pathogenic mechanism in lung cancer and COPD.


Systemic propolis stimulates new bone formation at the expanded suture: a histomorphometric study.
To investigate the effects of systemically given propolis on the expanded premaxillary suture in a rat study model. The 24 rats were randomly divided into three groups-only expansion (OE), expansion plus propolis (PRO), and nonexpansion (control) groups. After the 5-day expansion period was completed, the OE and PRO groups underwent 12 days of mechanical retention. At the end of this period, the animals were euthanatized and their pre-maxillae were dissected and fixed. Histomorphometric examination was performed to determine the number of osteoclasts, osteoblasts, and capillaries as well as the intensity of inflammatory cells and amount of new bone formation. Statistical analysis showed that the intensities of inflammatory cells, number of osteoblasts, and amount of new bone formation were greater in the PRO group than in the other groups. The PRO group also had more osteoclasts and new capillaries. Systemic use of propolis may hasten new bone formation at the expanded suture in rats.


Systematic review including re-analyses of 1148 individual data sets of central venous pressure as a predictor of fluid responsiveness.
Central venous pressure (CVP) has been shown to have poor predictive value for fluid responsiveness in critically ill patients. We aimed to re-evaluate this in a larger sample subgrouped by baseline CVP values. In April 2015, we systematically searched and included all clinical studies evaluating the value of CVP in predicting fluid responsiveness. We contacted investigators for patient data sets. We subgrouped data as lower (<8 mmHg), intermediate (8-12 mmHg) and higher (>12 mmHg) baseline CVP. We included 51 studies; in the majority, mean/median CVP values were in the intermediate range (8-12 mmHg) in both fluid responders and non-responders. In an analysis of patient data sets (n = 1148) from 22 studies, the area under the receiver operating curve was above 0.50 in the <8 mmHg CVP group [0.57 (95% CI 0.52-0.62)] in contrast to the 8-12 mmHg and >12 mmHg CVP groups in which the lower 95% CI crossed 0.50. We identified some positive and negative predictive value for fluid responsiveness for specific low and high values of CVP, respectively, but none of the predictive values were above 66% for any CVPs from 0 to 20 mmHg. There were less data on higher CVPs, in particular >15 mmHg, making the estimates on predictive values less precise for higher CVP. Most studies evaluating fluid responsiveness reported mean/median CVP values in the intermediate range of 8-12 mmHg both in responders and non-responders. In a re-analysis of 1148 patient data sets, specific lower and higher CVP values had some positive and negative predictive value for fluid responsiveness, respectively, but predictive values were low for all specific CVP values assessed.


Structural Modifications to Quaternary Ammonium Polymer Coagulants to Inhibit N-Nitrosamine Formation.
Quaternary ammonium cationic polymers, such as poly(diallyldimethylammonium chloride) (polyDADMAC) and epichlorohydrin-dimethylamine (Epi-DMA), are commonly used by water utilities to enhance removal of particles and dissolved organic matter (DOM) from raw waters. Unfortunately, chloramination of waters treated with quaternary ammonium polymers leads to the formation of carcinogenic N-nitrosodimethylamine (NDMA). In this study, two approaches were developed to modify polyDADMAC and Epi-DMA to inhibit N-nitrosamine formation. The first approach involved treatment of polymers with methyl iodide (MeI), an alkylating agent, to convert polymer-bound tertiary amine groups to less chloramine-reactive quaternary ammonium groups. The second approach involved synthesis of polymers bearing less chloramine-reactive quaternary ammonium groups with dipropylamino (DPA) substituents. Treatment with MeI reduced NDMA formation from polymers by ∼75%, while synthesis of DPA-based polymers eliminated NDMA formation and formed N-nitrosodipropylamine, which is 10-fold less carcinogenic than NDMA, at 20-fold lower yields. Bench-scale jar tests demonstrated that both MeI-treated and DPA-based polymers achieved similar removal of particles and DOM as the original polyDADMAC and Epi-DMA at both low and high doses, but formed significantly less N-nitrosamines. This work demonstrates two approaches for modifying quaternary ammonium cationic polymers, which may enable water utilities to meet potential future regulations on N-nitrosamines while maintaining polymer usage to meet existing regulations.


Factors affecting academic achievement among sexual minority and gender-variant youth.
Experiences of victimization among sexual minority youth (e.g., lesbian, gay, bisexual, transgender; LGBT) and gender-variant youth remain pronounced in many schools. Although much work has shown the connection between homophobic bullying and mental and physical health, there has been limited attention to how victimization impedes learning, academic achievement, and other school-related outcomes for these youth. In this chapter, we propose several pathways through which victimization leads to academic disparities among sexual minority and gender-variant youth, with attention to its effects on individual learning processes (e.g., motivation, concentration, self efficacy, and other cognitive stressors) as well as broader psychological and social processes (e.g., mental health, school avoidance, harmful coping strategies, exclusionary discipline). We also consider protective factors (e.g., social support, Gay-Straight Alliances, extracurricular involvement, nondiscrimination policies, inclusive curriculum) that could promote resilience and suggest potential mechanisms by which they may operate. In doing so, we aim to stimulate ideas for an advancement of research in this area.


High-birefringence linearly chirped grating based optical device for PMD compensation.
We propose a novel delay element for polarization mode dispersion (PMD) compensation by employing a tunable high-birefringence linearly chirped grating. The device can adjust differential group delay in a linearly continuous way and its performance is demonstrated by compensating 10-Gb/s signal with the first-order PMD. The tradeoff between PMD compensation capability of the device and the power penalty caused by the chromatic dispersion of the grating has also been studied.


Improving Precautionary Communication in the EMF Field? Effects of Making Messages Consistent and Explaining the Effectiveness of Precautions.
Many radiation health agencies communicate precautionary measures regarding the use of mobile communication devices, e.g. the use of a headset while talking on the phone. These precautionary messages have, however, been shown to unintentionally increase risk perceptions about radiofrequency electromagnetic fields (RF-EMFs). The current study tested two potential ways of amending precautionary messages in order to minimise this unintentional effect. Firstly, the messages' potential to be perceived as inconsistent and thereby raise suspicions was addressed; secondly, the effectiveness of the precautions was explained. An experimental design was applied in which a quota sample of 1717 Australian residents was randomly assigned to one of six message conditions. Three different risk perception measures served as dependent variables, two of them are conditional measures. The original effect of precautionary messages to amplify risk perceptions could not be replicated. Furthermore, amending precautionary messages in favour of more consistency had no effect, while explaining the effectiveness of the precautions increased conditional risk perception under the condition that no precautions are taken. This was contrary to our assumptions. We infer from these results that changing precautionary messages in terms of consistency and effectiveness in order to reduce risk perception is hardly possible. The use of conditional risk perception measures seems fruitful for studies looking at the effects of precautionary or protective messages, given that previous studies have only investigated effects on unconditional risk perception. However, the present results should not be over-interpreted as the measures' validity in the EMF context still needs further investigation.


Sleep inducing effect of low energy emission therapy.
The sleep inducing effect of a 15 min treatment with either an active or an inactive Low Energy Emission Therapy (LEET) device emitting amplitude-modulated electromagnetic (EM) fields was investigated in a double-blind cross-over study performed on 52 healthy subjects. All subjects were exposed to both active and inactive LEET treatment sessions, with an interval of at least 1 week between the two sessions. LEET consists of 27.12 MHz amplitude-modulated (sine wave) EM fields emitted intrabuccally by means of an electrically conducting mouthpiece in direct contact with the oral mucosa. The estimated local peak SAR is less than 10 W/kg in the oral mucosa and 0.1 to 100 mW/kg in brain tissue. No appreciable sensation is experienced during treatment, and subjects are therefore unable to tell whether they are receiving an active or an inactive treatment. In this study the active treatment consisted of EM fields intermittently amplitude-modulated (sine wave) at 42.7 Hz for 3 s followed by a pause of 1 s during which no EM fields were emitted. During the inactive treatment no EM fields were emitted. Baseline EEGs were obtained and 15 min post-treatment EEGs were recorded and analyzed according to the Loomis classification. A significant decrease (paired t test) in sleep latency to stage B2 (-1.78 +/- 5.57 min, P = 0.013), and an increase in the total duration of stage B2 (1.15 +/- 2.47 min, P = 0.0008) were observed on active treatment as compared with inactive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Visual field asymmetries in visual evoked responses.
Behavioral responses to visual stimuli exhibit visual field asymmetries, but cortical folding and the close proximity of visual cortical areas make electrophysiological comparisons between different stimulus locations problematic. Retinotopy-constrained source estimation (RCSE) uses distributed dipole models simultaneously constrained by multiple stimulus locations to provide separation between individual visual areas that is not possible with conventional source estimation methods. Magnetoencephalography and RCSE were used to estimate time courses of activity in V1, V2, V3, and V3A. Responses to left and right hemifield stimuli were not significantly different. Peak latencies for peripheral stimuli were significantly shorter than those for perifoveal stimuli in V1, V2, and V3A, likely related to the greater proportion of magnocellular input to V1 in the periphery. Consistent with previous results, sensor magnitudes for lower field stimuli were about twice as large as for upper field, which is only partially explained by the proximity to sensors for lower field cortical sources in V1, V2, and V3. V3A exhibited both latency and amplitude differences for upper and lower field responses. There were no differences for V3, consistent with previous suggestions that dorsal and ventral V3 are two halves of a single visual area, rather than distinct areas V3 and VP.


Cellular cardiac electrophysiology modeling with Chaste and CellML.
Chaste is an open-source C++ library for computational biology that has well-developed cardiac electrophysiology tissue simulation support. In this paper, we introduce the features available for performing cardiac electrophysiology action potential simulations using a wide range of models from the Physiome repository. The mathematics of the models are described in CellML, with units for all quantities. The primary idea is that the model is defined in one place (the CellML file), and all model code is auto-generated at compile or run time; it never has to be manually edited. We use ontological annotation to identify model variables describing certain biological quantities (membrane voltage, capacitance, etc.) to allow us to import any relevant CellML models into the Chaste framework in consistent units and to interact with them via consistent interfaces. This approach provides a great deal of flexibility for analysing different models of the same system. Chaste provides a wide choice of numerical methods for solving the ordinary differential equations that describe the models. Fixed-timestep explicit and implicit solvers are provided, as discussed in previous work. Here we introduce the Rush-Larsen and Generalized Rush-Larsen integration techniques, made available via symbolic manipulation of the model equations, which are automatically rearranged into the forms required by these approaches. We have also integrated the CVODE solvers, a 'gold standard' for stiff systems, and we have developed support for symbolic computation of the Jacobian matrix, yielding further increases in the performance and accuracy of CVODE. We discuss some of the technical details of this work and compare the performance of the available numerical methods. Finally, we discuss how this is generalized in our functional curation framework, which uses a domain-specific language for defining complex experiments as a basis for comparison of model behavior.


Fluorinated MOF platform for selective removal and sensing of SO2 from flue gas and air.
Conventional SO2 scrubbing agents, namely calcium oxide and zeolites, are often used to remove SO2 using a strong or irreversible adsorption-based process. However, adsorbents capable of sensing and selectively capturing this toxic molecule in a reversible manner, with in-depth understanding of structure-property relationships, have been rarely explored. Here we report the selective removal and sensing of SO2 using recently unveiled fluorinated metal-organic frameworks (MOFs). Mixed gas adsorption experiments were performed at low concentrations ranging from 250 p.p.m. to 7% of SO2. Direct mixed gas column breakthrough and/or column desorption experiments revealed an unprecedented SO2 affinity for KAUST-7 (NbOFFIVE-1-Ni) and KAUST-8 (AlFFIVE-1-Ni) MOFs. Furthermore, MOF-coated quartz crystal microbalance transducers were used to develop sensors with the ability to detect SO2 at low concentrations ranging from 25 to 500 p.p.m.


Cardiovascular disease in Africa: epidemiological profile and challenges.
From a global perspective, the large and diverse African population is disproportionately affected by cardiovascular disease (CVD). The historical balance between communicable and noncommunicable pathways to CVD in different African regions is dependent on external factors over the life course and at a societal level. The future risk of noncommunicable forms of CVD (predominantly driven by increased rates of hypertension, smoking, and obesity) is a growing public health concern. The incidence of previously rare forms of CVD such as coronary artery disease will increase, in concert with historically prevalent forms of disease, such as rheumatic heart disease, that are yet to be optimally prevented or treated. The success of any strategies designed to reduce the evolving and increasing burden of CVD across the heterogeneous communities living on the African continent will be dependent upon accurate and up-to-date epidemiological data on the cardiovascular profile of every major populace and region. In this Review, we provide a contemporary picture of the epidemiology of CVD in Africa, highlight key regional discrepancies among populations, and emphasize what is currently known and, more importantly, what is still unknown about the CVD burden among the >1 billion people living on the continent.


Advancing Stroke Recovery Through Improved Articulation of Nonpharmacological Intervention Dose.
Dose articulation is a universal issue of intervention development and testing. In stroke recovery, dose of a nonpharmaceutical intervention appears to influence outcome but is often poorly reported. The challenges of articulating dose in nonpharmacological stroke recovery research include: (1) the absence of specific internationally agreed dose reporting guidelines; (2) inadequate conceptualization of dose, which is multidimensional; and (3) unclear and inconsistent terminology that incorporates the multiple dose dimensions. To address these challenges, we need a well-conceptualized and consistent approach to dose articulation that can be applied across stroke recovery domains to stimulate critical thinking about dose during intervention development, as well as promote reporting of planned intervention dose versus actually delivered dose. We followed the Design Research Paradigm to develop a framework that guides how to articulate dose, conceptualizes the multidimensional nature and systemic linkages between dose dimensions, and provides reference terminology for the field. Our framework recognizes that dose is multidimensional and comprised of a duration of days that contain individual sessions and episodes that can be active (time on task) or inactive (time off task), and each individual episode can be made up of information about length, intensity, and difficulty. Clinical utility of this framework was demonstrated via hypothetical application to preclinical and clinical domains of stroke recovery. The suitability of the framework to address dose articulation challenges was confirmed with an international expert advisory group. This novel framework provides a pathway for better articulation of nonpharmacological dose that will enable transparent and accurate description, implementation, monitoring, and reporting, in stroke recovery research.


A Toxoplasma gondii pseudokinase inhibits host IRG resistance proteins.
The ability of mice to resist infection with the protozoan parasite, Toxoplasma gondii, depends in large part on the function of members of a complex family of atypical large GTPases, the interferon-gamma-inducible immunity-related GTPases (IRG proteins). Nevertheless, some strains of T. gondii are highly virulent for mice because, as recently shown, they secrete a polymorphic protein kinase, ROP18, from the rhoptries into the host cell cytosol at the moment of cell invasion. Depending on the allele, ROP18 can act as a virulence factor for T. gondii by phosphorylating and thereby inactivating mouse IRG proteins. In this article we show that IRG proteins interact not only with ROP18, but also strongly with the products of another polymorphic locus, ROP5, already implicated as a major virulence factor from genetic crosses, but whose function has previously been a complete mystery. ROP5 proteins are members of the same protein family as ROP18 kinases but are pseudokinases by sequence, structure, and function. We show by a combination of genetic and biochemical approaches that ROP5 proteins act as essential co-factors for ROP18 and present evidence that they work by enforcing an inactive GDP-dependent conformation on the IRG target protein. By doing so they prevent GTP-dependent activation and simultaneously expose the target threonines on the switch I loop for phosphorylation by ROP18, resulting in permanent inactivation of the protein. This represents a novel mechanism in which a pseudokinase facilitates the phosphorylation of a target by a partner kinase by preparing the substrate for phosphorylation, rather than by upregulation of the activity of the kinase itself.


Combating Racial Health Disparities Through Medical Education: The Need for Anthropological and Genetic Perspectives in Medical Training.
Despite major public health initiatives, significant disparities persist among racially and ethnically defined groups in the prevalence of disease, access to medical care, quality of medical care, and health outcomes for common causes of morbidity and mortality in the United States. It is critical that we develop new and creative strategies to address such inequities; mitigate the social, environmental, institutional, and genetic determinants of poor health; and combat the persistence of racial profiling in clinical contexts that further exacerbates racial/ethnic health disparities. This article argues that medical education is a prime target for intervention and that anthropologists and human population geneticists should play a role in efforts to reform US medical curricula. Medical education would benefit greatly by incorporating anthropological and genetic perspectives on the complexities of race, human genetic variation, epigenetics, and the causes of racial/ethnic disparities. Medical students and practicing physicians should also receive training on how to use this knowledge to improve clinical practice, diagnosis, and treatment for racially diverse populations.


Demographic and Occupational Differences Between Ethnic Minority Workers Who Did and Did Not Complete the Telephone Survey in English.
Limited research indicates that using English language only surveys in prevalence studies conducted in the general population or in specific ethnic populations may result in unrepresentative samples and biased results. In this study, we investigated whether participants from ethnic minorities who chose to answer a study interview in a language other than English (LOTE) differed from those who completed the interview in English. This study was conducted within an Australian population-based telephone survey that assessed the prevalence of occupational exposure to carcinogens among 749 ethnic minority workers. We used modified Poisson regression to determine the factors associated with completing the interview in a LOTE. Participants who elected to complete the interview in a LOTE differed from those who completed it in English on several factors, including sex, country of birth, education, occupation, and occupational exposure to carcinogens (40% compared with 29%, P < 0.01). The participants who chose to complete the study interview in their native language had several demographic differences from those participants who completed it in English, and were more likely to be exposed to carcinogens at work. Prevalence studies that offer only English language study instruments are unlikely to produce representative samples of minority groups, and may therefore produce biased results.


Oscillations or Synchrony? Disruption of Neural Synchrony despite Enhanced Gamma Oscillations in a Model of Disrupted Perceptual Coherence.
It has been hypothesized that neural synchrony underlies perceptual coherence. The hypothesis of loss of central perceptual coherence has been proposed to be at the origin of abnormal cognition in autism spectrum disorders and Williams syndrome, a neurodevelopmental disorder linked with autism, and a clearcut model for impaired central coherence. We took advantage of this model of impaired holistic processing to test the hypothesis that loss of neural synchrony plays a separable role in visual integration using EEG and a set of experimental tasks requiring coherent integration of local elements leading to 3-D face perception. A profound reorganization of brain activity was identified. Neural synchrony was reduced across stimulus conditions, and this was associated with increased amplitude modulation at 25-45 Hz. This combination of a dramatic loss of synchrony despite increased oscillatory activity is strong evidence that synchrony underlies central coherence. This is the first time, to our knowledge, that dissociation between amplitude and synchrony is reported in a human model of impaired perceptual coherence, suggesting that loss of phase coherence is more directly related to disruption of holistic perception.


Thermal conductivity engineering of bulk and one-dimensional Si-Ge nanoarchitectures.
Various theoretical and experimental methods are utilized to investigate the thermal conductivity of nanostructured materials; this is a critical parameter to increase performance of thermoelectric devices. Among these methods, equilibrium molecular dynamics (EMD) is an accurate technique to predict lattice thermal conductivity. In this study, by means of systematic EMD simulations, thermal conductivity of bulk Si-Ge structures (pristine, alloy and superlattice) and their nanostructured one dimensional forms with square and circular cross-section geometries (asymmetric and symmetric) are calculated for different crystallographic directions. A comprehensive temperature analysis is evaluated for selected structures as well. The results show that one-dimensional structures are superior candidates in terms of their low lattice thermal conductivity and thermal conductivity tunability by nanostructuring, such as by diameter modulation, interface roughness, periodicity and number of interfaces. We find that thermal conductivity decreases with smaller diameters or cross section areas. Furthermore, interface roughness decreases thermal conductivity with a profound impact. Moreover, we predicted that there is a specific periodicity that gives minimum thermal conductivity in symmetric superlattice structures. The decreasing thermal conductivity is due to the reducing phonon movement in the system due to the effect of the number of interfaces that determine regimes of ballistic and wave transport phenomena. In some nanostructures, such as nanowire superlattices, thermal conductivity of the Si/Ge system can be reduced to nearly twice that of an amorphous silicon thermal conductivity. Additionally, it is found that one crystal orientation, [Formula: see text]100[Formula: see text], is better than the [Formula: see text]111[Formula: see text] crystal orientation in one-dimensional and bulk SiGe systems. Our results clearly point out the importance of lattice thermal conductivity engineering in bulk and nanostructures to produce high-performance thermoelectric materials.


The relationship between sleep duration and obesity risk among school students: a cross-sectional study in Zhejiang, China.
Obesity has been identified as a major risk factor for a large number of chronic diseases. Understanding factors related to adolescent obesity is critical for prevention of chronic diseases. The associations between sleep duration and obesity among adolescents in the existing literature are controversial. Our study was designed to determine the prevalence of short sleep duration, and assess the association of sleep duration and obesity, among middle and high school students in Zhejiang, China. 18,403 Students in 442 schools were recruited and surveyed using an anonymous, self-administered questionnaires. Weighted multivariable logistic regression models were used for data analyses. The mean (SD) age of the students was 15.9 (1.8) years. 49.7% of students were girls. The mean (SD) height and weight were 166.2 (8.5) cm and 54.6 (11.1) kg, respectively. The overall prevalence of obesity and overweight were 3.4% (95% CI: 3.0-3.8) and 7.8% (95% CI: 7.4-8.3), respectively. The overall prevalence of short sleep duration among students was 66.0% (95% CI: 63.8-68.1), higher among girls than boys (69.8% vs. 62.1%) (P < 0.0001). The figures for middle school, academic high school, and vocational high school were 59.0, 82.4 and 59.7%, respectively (P < 0.0001). As compared with girls who sleep 8 h per day (reference), the odds ratios (95% CI) of obesity for girls who sleep < 7 h, 7 h, 9 h and ≥ 10 h were 1.97 (1.15-3.38), 1.90 (1.18-3.04), 1.38 (0.86-2.20) and 2.12 (1.22-3.67) respectively, after adjustment for socio-demographic status, lifestyle factors, and mental health. The corresponding figures among boys were 1.45 (0.97-2.16), 1.13 (0.81-1.57), 1.25 (0.89-1.74), and 1.12 (0.81-1.54), respectively. Insufficient sleep is prevalent among students in Zhejiang China. A U-shaped relationship was found between sleep duration and obesity risk among girls, with the lowest risk among those who slept for 8 h, but not among boys. Adequate sleep duration may be an important component of obesity prevention initiatives among adolescents.


Analysis of the reactivities of protein C-H bonds to H atom abstraction by OH radical.
Ab initio and density functional theory calculations are used to monitor the process wherein a OH· radical is allowed to approach the various CH groups of a Leu dipeptide, with its CH(2)CH(CH(3))(2) side chain. After forming an encounter complex, the OH· abstracts the pertinent H atom, and the resulting HOH is then dissociated from the complex. The energy barriers for H· abstraction from the β, γ, and δ CH groups are all less than 8 kcal/mol, but a significantly higher barrier is computed for the C(α)H removal. This higher barrier is the result of the strong H-bonds formed in the encounter complex between the OH· and the NH and C═O groups of the peptide units that surround the C(α) atom. This low-energy complex represents a kinetic trap which raises the energy needed to surmount the ensuing H· transfer barrier.


Caffeine Intake and Mental Health in College Students.
Background The effect of caffeine on the human body, both short-term and long-term, has been studied in great depth, particularly its association with psychiatric disorders. This study aims to investigate whether there is a correlation between caffeine intake and anxiety and depression among college students. Methodology A survey was administered to college students at Florida State University. Data regarding participant characteristics and caffeine intake were collected. Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 scores were used to assess symptoms of anxiety and depression, respectively. Results A total of 114 participants were included in the survey, consisting mainly of women (94 [82.5%]) and junior-level students (37 [32.5%]). The main source of caffeine was coffee (64.0%), and the main reasons for caffeine intake were pleasure (43.9%) and to study outside of class (29.8%); however, no association was found between sex or grade point average and number of cups of caffeine consumed. Upper levels of education (super senior or fifth-year students), depressive symptoms (poor appetite, overeating, sleep disorders, depressed mood), and anxiety were statistically associated with greater caffeine intake (P < 0.05). Conclusions As caffeine is commonly consumed and our study showed that its intake was associated with depressive symptoms and higher levels of anxiety in college students, further studies are needed to determine a possible causality, so that measures may be taken to educate these students about alternative methods for increasing energy and alertness.


The pathogenicity determinant of Citrus tristeza virus causing the seedling yellows syndrome maps at the 3'-terminal region of the viral genome.
Citrus tristeza virus (CTV) (genus Closterovirus, family Closteroviridae) causes some of the more important viral diseases of citrus worldwide. The ability to map disease-inducing determinants of CTV is needed to develop better diagnostic and disease control procedures. A distinctive phenotype of some isolates of CTV is the ability to induce seedling yellows (SY) in sour orange, lemon and grapefruit seedlings. In Florida, the decline isolate of CTV, T36, induces SY, whereas a widely distributed mild isolate, T30, does not. To delimit the viral sequences associated with the SY syndrome, we created a number of T36/T30 hybrids by substituting T30 sequences into different regions of the 3' half of the genome of an infectious cDNA of T36. Eleven T36/T30 hybrids replicated in Nicotiana benthamiana protoplasts. Five of these hybrids formed viable virions that were mechanically transmitted to Citrus macrophylla, a permissive host for CTV. All induced systemic infections, similar to that of the parental T36 clone. Tissues from these C. macrophylla source plants were then used to graft inoculate sour orange and grapefruit seedlings. Inoculation with three of the T30/T36 hybrid constructs induced SY symptoms identical to those of T36; however, two hybrids with T30 substitutions in the p23-3' nontranslated region (NTR) (nucleotides 18 394-19 296) failed to induce SY. Sour orange seedlings infected with a recombinant non-SY p23-3' NTR hybrid also remained symptomless when challenged with the parental virus (T36), demonstrating the potential feasibility of using engineered constructs of CTV to mitigate disease.


GlpR Is a Direct Transcriptional Repressor of Fructose Metabolic Genes in Haloferax volcanii.
DeoR-type helix-turn-helix (HTH) domain proteins are transcriptional regulators of sugar and nucleoside metabolism in diverse bacteria and also occur in select archaea. In the model archaeon Haloferax volcanii, previous work implicated GlpR, a DeoR-type transcriptional regulator, in the transcriptional repression of glpR and the gene encoding the fructose-specific phosphofructokinase (pfkB) during growth on glycerol. However, the global regulon governed by GlpR remained unclear. Here, we compared transcriptomes of wild-type and ΔglpR mutant strains grown on glycerol and glucose to detect significant transcript level differences for nearly 50 new genes regulated by GlpR. By coupling computational prediction of GlpR binding sequences with in vivo and in vitro DNA binding experiments, we determined that GlpR directly controls genes encoding enzymes involved in fructose degradation, including fructose bisphosphate aldolase, a central control point in glycolysis. GlpR also directly controls other transcription factors. In contrast, other metabolic pathways appear to be under the indirect influence of GlpR. In vitro experiments demonstrated that GlpR purifies to function as a tetramer that binds the effector molecule fructose-1-phosphate (F1P). These results suggest that H. volcanii GlpR functions as a direct negative regulator of fructose degradation during growth on carbon sources other than fructose, such as glucose and glycerol, and that GlpR bears striking functional similarity to bacterial DeoR-type regulators.IMPORTANCE Many archaea are extremophiles, able to thrive in habitats of extreme salinity, pH and temperature. These biological properties are ideal for applications in biotechnology. However, limited knowledge of archaeal metabolism is a bottleneck that prevents the broad use of archaea as microbial factories for industrial products. Here, we characterize how sugar uptake and use are regulated in a species that lives in high salinity. We demonstrate that a key sugar regulatory protein in this archaeal species functions using molecular mechanisms conserved with distantly related bacterial species.


The effectiveness of chemonucleolysis with condoliase for treatment of painful lumbar disc herniation.
Chemonucleolysis with condoliase, which degrades chondroitin sulfate, could be a new, minimally invasive therapeutic option for patients with lumbar disc herniation (LDH). The purpose of this study was to analyze prognostic factors for clinical outcomes in LDH patients subjected to chemonucleolysis with condoliase. Inclusion criteria for this procedure were 1) 18-70 years of age; 2) unilateral leg pain and positive straight leg raise (SLR) (<70°) or femoral nerve stretching test; 3) subligamentous extrusion verified on magnetic resonance imaging; 4) neurological symptoms consistent with a compressed nerve root on magnetic resonance imaging (MRI) images; and 5) minimum six months of follow-up. In total, 82 patients (55 men, 27 women; mean age, 47.2 ± 15.5 years; mean follow-up, 9.1 ± 3.0 months) who underwent chemonucleolysis with condoliase for painful LDH were included. An improvement of 50% or more in the Visual analogue scale (VAS) of leg pain was classified as effective. Seventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006-26.204) was significantly associated with clinical effectiveness. Chemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc.


Evolving an evidence-based model for homelessness prevention.
While some progress has been made in addressing chronic homelessness through supportive models, a comprehensive solution for housing loss must include prevention. The purpose of this article is twofold: to conduct a review of the literature on the domains of the Framework for Homelessness Prevention; and to use literature on the concept of quaternary prevention, preventing the harms of service provision, to theorise an additional domain. The Framework for Homelessness Prevention draws upon theory from public health exploring primary, secondary and tertiary prevention, and also integrates primordial prevention. This leads to a typology of homelessness prevention that incorporates the following five domains: (a) Structural prevention; (b) Systems prevention; (c) Early intervention; (d) Eviction prevention; and (e) Housing stability. By systematically reviewing the literature we build out the evidence-base supporting these domains. The team used research databases, internet searches and retrospective reference list reviews to identify high-quality journal articles on prevention, which were then sorted by level of prevention. Through this process, we evolved our thinking on the Framework in considering that quaternary prevention was not initially included. Therefore, we explored the literature related to quaternary prevention in the context of homelessness and offer a sixth domain for the Framework: Empowerment. Ultimately, a comprehensive Framework for Homelessness Prevention will support communities and governments to more effectively prevent homelessness through upstream approaches.


P53, bcl-2, ki-67 li (labeling index) status in benign, proliferative, and malignant ovarian surface epithelial neoplasms.
Approximately 50% of human malignancies present with mutations in p53, which is the most common tumor suppressor gene involved with human malignancies. Bcl-2 is a protooncogene, and expression of its protein product is associated with a better prognosis in several malignancies. Ki-67 is a marker of cellular proliferation. The purpose of this study was to determine whether simultaneous detection of p53, bcl-2 and Ki-67 using immunohistochemical staining can be used as a diagnostic factor in the assessment of human ovarian epithelial tumors. The study was performed on formalin-fixed, paraffin-embedded tissue samples from 75 epithelial ovarian tumors, 15 serous cystadenomas, 15 mucinous cystadenomas, 5 borderline serous cystadenomas, 5 borderline mucinous cystadenomas, 15 serous cystadenocarcinomas, 15 mucinous cystadenocarcinomas and 5 endometrioid carcinomas. Immunohistochemical staining was performed using monoclonal antibodies against p53, bcl-2, and Ki-67(MIB1). Anti-p53 reactivity was observed in 14 tumors, all of which were malignant tumors, and no reactivity was observed in borderline or benign tumors. Overexpression of bcl-2 was observed in 12 benign neoplasms (40%), 5 of which were borderline (50%), but was not observed in any of the malignant tumors. There was a statistically significantly higher level of Ki-67 LI positivity in the malignant tumors than in the benign and borderline tumors (p<0.005). These data show significant differences in the expression of these markers in ovarian tumors and suggest a possible role for these tumor-associated genes as supplemental tools in diagnostic pathology. Furthermore, our findings support the redesignation of low malignant potential tumors (current nomenclature) to benign ovarian carcinoma.


Medial Meniscus Posterior Root Tear Treatment: A Matched Cohort Comparison of Nonoperative Management, Partial Meniscectomy, and Repair.
There are limited data comparing the outcomes of similarly matched patients with a medial meniscus posterior root tear (MMPRT) treated with nonoperative management, partial meniscectomy, or repair. The purpose was to compare treatment failure, clinical outcome scores, and radiographic findings for a matched cohort of patients who underwent either nonoperative management, partial meniscectomy, or transtibial pull-through repair for an MMPRT. We hypothesized that patients who underwent meniscus root repair will have lower rates of progression to arthroplasty than patients who were treated with nonoperative management or partial meniscectomy. Cohort study; Level of evidence, 3. Patients who underwent transtibial medial meniscus posterior horn root repair were matched by meniscal laterality, age, sex, and Kellgren-Lawrence (K-L) grades to patients treated nonoperatively or with a partial meniscectomy. Progression to arthroplasty rates, International Knee Documentation Committee and Tegner scores, and radiographic outcomes were analyzed between groups. Forty-five patients were included in this study (15 nonoperative, 15 partial meniscectomy, 15 root repair). Progression to arthroplasty demonstrated significant differences among treatment groups at a mean of 74 months (nonoperative, 4/15; partial meniscectomy, 9/15; meniscal repair, 0/15; P = .0003). The meniscus root repair group had significantly less arthritic progression, as measured by change in K-L grade from pre- to postoperatively (nonoperative, 1.0; partial meniscectomy, 1.1; meniscal repair, 0.1; P = .001). Meniscus root repair leads to significantly less arthritis progression and subsequent knee arthroplasty compared with nonoperative management and partial meniscectomy in a matched cohort based on patient characteristics.


Structure of social networks in a passerine bird: consequences for sexual selection and the evolution of mating strategies.
The social environment is a critical determinant of fitness and, in many taxa, is shaped by an individual's behavioral discrimination among social contexts, suggesting that animals can actively influence the selection they experience. In competition to attract females, males may modify sexual selection by choosing social environments in which they are more attractive relative to rivals. Across the population, such behaviors should influence sexual selection patterns by altering the relationship between male mating success and sexual ornament elaboration. Here we use network analysis to examine patterns of male social behavior in relation to plumage ornamentation and mating success in a free-living population of house finches. During the nonbreeding season, less elaborate males changed associations with distinct social groups more frequently, compared to more elaborate males that showed greater fidelity to a single social group. By the onset of pair formation, socially labile males effectively increased their attractiveness relative to other males in the same flocks. Consequently, males that frequently moved between social groups had greater pairing success than less social individuals with equivalent sexual ornamentation. We discuss these results in relation to conditional mating tactics and the role of social behavior in evolutionary change by sexual selection.


The Influence of Infective Dose on the Virulence of a Generalist Pathogen in Rainbow Trout (Oncorhynchus mykiss) and Zebra Fish (Danio rerio).
Pathogen density and genetic diversity fluctuate in the outside-host environment during and between epidemics, affecting disease emergence and the severity and probability of infections. Although the importance of these factors for pathogen virulence and infection probability has been acknowledged, their interactive effects are not well understood. We studied how an infective dose in an environmentally transmitted opportunistic fish pathogen, Flavobacterium columnare, affects its virulence both in rainbow trout, which are frequently infected at fish farms, and in zebra fish, a host that is not naturally infected by F. columnare. We used previously isolated strains of confirmed high and low virulence in a single infection and in a co-infection. Infection success (measured as host morbidity) correlated positively with dose when the hosts were exposed to the high-virulence strain, but no response for the dose increase was found when the hosts were exposed to the low-virulence strain. Interestingly, the co-infection resulted in poorer infection success than the single infection with the high-virulence strain. The rainbow trout were more susceptible to the infection than the zebra fish but, in both species, the effects of the doses and the strains were qualitatively similar. We suggest that as an increase in dose can lead to increased host morbidity, both the interstrain interactions and differences in infectivity in different hosts may influence the severity and consequently the evolution of disease. Our results also confirm that the zebra fish is a good laboratory model to study F. columnare infection.


Neurocysticercosis in radiographically imaged seizure patients in U.S. emergency departments.
Neurocysticercosis appears to be on the rise in the United States, based on immigration patterns and published cases series, including reports of domestic acquisition. We used a collaborative network of U.S. emergency departments to characterize the epidemiology of neurocysticercosis in seizure patients. Data were collected prospectively at 11 university-affiliated, geographically diverse, urban U.S. emergency departments from July 1996 to September 1998. Patients with a seizure who underwent neuroimaging were included. Of the 1,801 patients enrolled in the study, 38 (2.1%) had seizures attributable to neurocysticercosis. The disease was detected in 9 of the 11 sites and was associated with Hispanic ethnicity, immigrant status, and exposure to areas where neurocysticercosis is endemic. This disease appears to be widely distributed and highly prevalent in certain populations (e.g., Hispanic patients) and areas (e.g., Southwest).


Perceptions of molecular epidemiology studies of HIV among stakeholders.
Background: Advances in viral sequence analysis make it possible to track the spread of infectious pathogens, such as HIV, within a population. When used to study HIV, these analyses (i.e., molecular epidemiology) potentially allow inference of the identity of individual research subjects. Current privacy standards are likely insufficient for this type of public health research. To address this challenge, it will be important to understand how stakeholders feel about the benefits and risks of such research. Design and Methods: To better understand perceived benefits and risks of these research methods, in-depth qualitative interviews were conducted with HIV-infected individuals, individuals at high-risk for contracting HIV, and professionals in HIV care and prevention. To gather additional perspectives, attendees to a public lecture on molecular epidemiology were asked to complete an informal questionnaire. Results: Among those interviewed and polled, there was near unanimous support for using molecular epidemiology to study HIV. Questionnaires showed strong agreement about benefits of molecular epidemiology, but diverse attitudes regarding risks. Interviewees acknowledged several risks, including privacy breaches and provocation of anti-gay sentiment. The interviews also demonstrated a possibility that misunderstandings about molecular epidemiology may affect how risks and benefits are evaluated. Conclusions: While nearly all study participants agree that the benefits of HIV molecular epidemiology outweigh the risks, concerns about privacy must be addressed to ensure continued trust in research institutions and willingness to participate in research.


Immunolocalization of Kisspeptin Associated with Amyloid-β Deposits in the Pons of an Alzheimer's Disease Patient.
The pons region of the Alzheimer's disease (AD) brain is one of the last to show amyloid-β (Aβ) deposits and has been suggested to contain neuroprotective compounds. Kisspeptin (KP) is a hormone that activates the hypothalamic-pituitary-gonadal axis and has been suggested to be neuroprotective against Aβ toxicity. The localization of KP, plus the established endogenous neuroprotective compounds corticotropin releasing hormone (CRH) and catalase, in tissue sections from the pons region of a male AD subject has been determined in relation to Aβ deposits. Results showed Aβ deposits also stained with KP, CRH, and catalase antibodies. At high magnification the staining of deposits was either KP or catalase positive, and there was only a limited area of the deposits with KP-catalase colocalization. The CRH does not bind Aβ, whilst both KP and catalase can bind Aβ, suggesting that colocalization in Aβ deposits is not restricted to compounds that directly bind Aβ. The neuroprotective actions of KP, CRH, and catalase were confirmed in vitro, and fibrillar Aβ preparations were shown to stimulate the release of KP in vitro. In conclusion, neuroprotective KP, CRH, and catalase all colocalize with Aβ plaque-like deposits in the pons region from a male AD subject.


Surface-profile reconstruction using reflection differential phase-contrast microscopy.
The use of optical differential phase-contrast microscopy to obtain the surface profile of samples is outlined. The range of accurate feature height determination was calculated as a function of steepness of the side of the feature. Heights of thin features (height <0.1 microm) were accurately determined experimentally. Sample tilting and oblique stage scanning were required in order to determine the heights of thicker samples. Reconstructed profile heights were measured as a function of defocus.


Parasympathetic effects on in vivo rat heart can be regulated through an alpha 1-adrenergic receptor.
A prejunctional mechanism involving an alpha 1-adrenergic receptor may exert control on the release of acetylcholine from parasympathetic nerve endings in the heart. To test this hypothesis in vivo, rats were prepared for electrical stimulation of the vagus nerves. Blood pressures and heart rates were monitored, and the animals were treated with alpha-agonists and alpha-antagonists. The alpha 1-selective agonist phenylephrine significantly attenuated vagally induced bradycardia in a dose-dependent fashion (ED50 = 19 micrograms/kg). This is consistent with the hypothesis that there is alpha-adrenergic inhibition of ACh release. In contrast, the alpha 2-selective agonist, BHT-920, caused no change in heart rate during vagal stimulation. The effects of phenylephrine to raise heart rate and blood pressure during vagal stimulation were blocked by the alpha 1-selective antagonist prazosin (ID50 approximately 1 microgram/kg) but not by the alpha 2-selective antagonists yohimbine and rauwolscine. This further supports an alpha 1 assignment to the prejunctional adrenergic receptor mechanism, which can regulate the release of acetylcholine from cardiac parasympathetic neurons.


Structural variation among retroviral primer-DNA junctions: solution structure of the HIV-1 (-)-strand Okazaki fragment r(gcca)d(CTGC).d(GCAGTGGC).
The three-dimensional solution structure of the hybrid-chimeric duplex r(gcca)d(CTGC).d(GCAGTGGC) has been determined by two-dimensional NMR, restrained molecular dynamics (rMD), and NOE back-calculation methods. This chimera, consisting of a chimeric RNA-DNA strand and its complementary DNA strand, is formed after priming (-)-strand DNA synthesis by tRNA(Lys3) and subsequent (+)-strand DNA synthesis by reverse transcriptase and is an obligatory intermediate in the formation of double-stranded DNA prior to HIV-1 retrovirus integration. The duplex consists of two different types of double helix: a hybrid form (H-form) and a B-form structure connected by a junction. It is chemically similar to several other Okazaki fragments whose structures have been previously determined in our laboratory. However, some structural parameters are not the same and were found to be sequence dependent. In particular, the sugar conformations at the DNA base pair proximal to the hybrid segment vary from O4'-endo to C2'-endo depending on the base composition. The position of the transition from the relatively wide groove of H-form to the narrow groove of B-form is also sequence dependent, occurring either exactly at the RNA-DNA junction or within the purely DNA segment of the chimera-as is the case in the structure of the present HIV-1 (-)-strand primer. This structural change produces a kink at the DNA-DNA step adjacent to the RNA-DNA junction in the HIV-1 (-)-strand primer. The sequence dependence of structures of RNA-DNA chimeric duplexes may be responsible for the variable cleavage pattern of different Okazaki fragments by reverse transcriptase RNase H.


Dependence of cell-type proportioning and sorting on cell cycle phase in Dictyostelium discoideum.
The relationship between the cell cycle phase of vegetative amoebae and prestalk and prespore differentiation in the slug stage were investigated in the slime mould Dictyostelium discoideum. Cells were synchronized by release from the stationary phase. Samples were taken at various times during the course of a synchronous cell doubling, fluorescently labelled and mixed with cells of random cell cycle phase from exponentially growing cultures. The fate of the fluorescently labelled cells was recorded at the slug stage. Cells early in the cycle exhibit strong prestalk sorting; cells taken later in the cycle exhibit strong prespore sorting. The period of prestalk sorting occurs immediately following mitosis and lasts about 1 h in a cell cycle of about 7 h duration. Accompanying the altered sorting behaviour is a marked changed in the prestalk-prespore proportions in slugs formed from synchronized populations of cells. Cells synchronized early in the cycle form slugs with 55% prespore cells; cells synchronized late in the cycle form slugs with 90% prespore. The results are discussed in terms of models for the formation of the prestalk-prespore pattern in slugs.


DMP1 prevents osteocyte alterations, FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease.
During chronic kidney disease (CKD), alterations in bone and mineral metabolism include increased production of the hormone fibroblast growth factor 23 (FGF23) that may contribute to cardiovascular mortality. The osteocyte protein dentin matrix protein 1 (DMP1) reduces FGF23 and enhances bone mineralization, but its effects in CKD are unknown. We tested the hypothesis that DMP1 supplementation in CKD would improve bone health, prevent FGF23 elevations and minimize consequent adverse cardiovascular outcomes. We investigated DMP1 regulation and effects in wild-type (WT) mice and the Col4a3-/- mouse model of CKD. Col4a3-/- mice demonstrated impaired kidney function, reduced bone DMP1 expression, reduced bone mass, altered osteocyte morphology and connectivity, increased osteocyte apoptosis, increased serum FGF23, hyperphosphatemia, left ventricular hypertrophy (LVH), and reduced survival. Genetic or pharmacological supplementation of DMP1 in Col4a3-/- mice prevented osteocyte apoptosis, preserved osteocyte networks, corrected bone mass, partially lowered FGF23 levels by attenuating NFAT-induced FGF23 transcription, and further increased serum phosphate. Despite impaired kidney function and worsened hyperphosphatemia, DMP1 prevented development of LVH and improved Col4a3-/- survival. Our data suggest that CKD reduces DMP1 expression, whereas its restoration represents a potential therapeutic approach to lower FGF23 and improve bone and cardiac health in CKD.


Cardiometabolic Risks and Severity of Obesity in Children and Young Adults.
The prevalence of severe obesity among children and young adults has increased over the past decade. Although the prevalence of cardiometabolic risk factors is relatively low among children and young adults who are overweight or obese, those with more severe forms of obesity may be at greater risk. We performed a cross-sectional analysis of data from overweight or obese children and young adults 3 to 19 years of age who were included in the National Health and Nutrition Examination Survey from 1999 through 2012 to assess the prevalence of multiple cardiometabolic risk factors according to the severity of obesity. Weight status was classified on the basis of measured height and weight. We used standard definitions of abnormal values for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, glycated hemoglobin, and fasting glucose and report the prevalence of abnormal values in children and young adults according to weight status. Among 8579 children and young adults with a body-mass index at the 85th percentile or higher (according to the Centers for Disease Control and Prevention growth charts), 46.9% were overweight, 36.4% had class I obesity, 11.9% had class II obesity, and 4.8% had class III obesity. Mean values for some, but not all, cardiometabolic variables were higher with greater severity of obesity in both male and female participants, and the values were higher in male participants than in female participants; for HDL cholesterol, the mean values were lower with greater severity of obesity. Multivariable models that controlled for age, race or ethnic group, and sex showed that the greater the severity of obesity, the higher the risks of a low HDL cholesterol level, high systolic and diastolic blood pressures, and high triglyceride and glycated hemoglobin levels. Severe obesity in children and young adults was associated with an increased prevalence of cardiometabolic risk factors, particularly among boys and young men.


Differences in regional diagnostic strategies and in intended versus actual first-line treatment of patients with advanced ovarian cancer in Denmark.
Triage of patients with ovarian cancer to primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT) is challenging. In Denmark, the use of NACT has increased, but substantial differences in the use of NACT or PDS exist among centers. We aimed to characterize the differences between intended and actual first-line treatments in addition to the differences in the triage process among the centers and to evaluate the different diagnostic modalities and the clinical aspects' influence in the triage process. From 4 centers, forms containing data about the diagnostic process and intended treatment were prospectively collected and merged with data from the Danish Gynecological Cancer Database and medical records. Of the 671 completed forms, 540 patients had stage IIIC or IV epithelial ovarian cancer. Of the 238 (44%) referred to PDS, 91% received PDS and 4% never had debulking surgery. Of the 288 patients (53%) referred to NACT, 44% were never debulked. Fourteen patients (3%) were referred to palliative treatment. The use of different imaging modalities, diagnostic laparoscopy, and laparotomy varied significantly among the centers. Diagnostic surgical procedures were considered to be most influential in the triage process. Regardless of the intended first-line treatment or center, the tumor size and dissemination was the most influential clinical aspect. In Denmark, substantial differences exist between intended and actual first-line treatments as well as in the diagnostic process and use of NACT, calling for further discussion on diagnostic strategy and therapeutically approach for patients with advanced ovarian cancer.


Discriminative parameter estimation for random walks segmentation.
The Random Walks (RW) algorithm is one of the most efficient and easy-to-use probabilistic segmentation methods. By combining contrast terms with prior terms, it provides accurate segmentations of medical images in a fully automated manner. However, one of the main drawbacks of using the RW algorithm is that its parameters have to be hand-tuned. we propose a novel discriminative learning framework that estimates the parameters using a training dataset. The main challenge we face is that the training samples are not fully supervised. Specifically, they provide a hard segmentation of the images, instead of a probabilistic segmentation. We overcome this challenge by treating the optimal probabilistic segmentation that is compatible with the given hard segmentation as a latent variable. This allows us to employ the latent support vector machine formulation for parameter estimation. We show that our approach significantly outperforms the baseline methods on a challenging dataset consisting of real clinical 3D MRI volumes of skeletal muscles.


Detection of virulence factors in culturable Escherichia coli isolates from water samples by DNA probes and recovery of toxin-bearing strains in minimal o-nitrophenol-beta-D-galactopyranoside-4-methylumbelliferyl-beta-D-g luc uronide media.
A total of 449 Escherichia coli isolates in treated and raw water sources were submitted to DNA-DNA hybridization using seven different DNA probes to detect homology to sequences that code for Shiga-like toxins I and II; heat-stabile and heat-labile toxins, adherence factors EAF and eae, and the fimbrial antigen of entero-hemorrhagic E. coli. Fifty-nine (13%) of the isolates demonstrated homology with one or more specific DNA probes. More than 50% of the isolates in treated water were not recovered in MMO-4-methylumbelliferyl-beta-D-glucuronide media designed for detection of this indicator.


Directional dependence of the electronic and transport properties of 2D borophene and borophane.
Very recently two dimensional layers of boron atoms, so called borophene, have been successfully synthesized. It presents a metallic band structure, with a strong anisotropic character. Upon further hydrogen adsorption a new material is obtained, borophane; giving rise to a Dirac cone structure like the one in graphene. We have performed a first-principles study of the electronic and transport properties of borophene and borophane through the Landauer-Büttiker formalism. We find that borophene presents an electronic current two orders of magnitude larger than borophane. In addition we verified the direction dependence of the electronic current in two perpendicular directions, namely, Ix and Iy; where for both systems, we found a current ratio, η = Ix/Iy, of around 2. Aiming to control such a current anisotropy, η, we performed a study of its dependence with respect to an external strain. Where, by stretching the borophane sheet, η increases by 11% for a bias voltage of 50 mV.


Modeling human nonalcoholic steatohepatitis-associated changes in drug transporter expression using experimental rodent models.
Nonalcoholic fatty liver disease is a prevalent form of chronic liver disease that can progress to the more advanced stage of nonalcoholic steatohepatitis (NASH). NASH has been shown to alter drug transporter regulation and may have implications in the development of adverse drug reactions. Several experimental rodent models have been proposed for the study of NASH, but no single model fully recapitulates all aspects of the human disease. The purpose of the current study was to determine which experimental NASH model best reflects the known alterations in human drug transporter expression to enable more accurate drug disposition predictions in NASH. Both rat and mouse NASH models were used in this investigation and include the methionine and choline deficient (MCD) diet model, atherogenic diet model, ob/ob and db/db mice, and fa/fa rats. Pathologic scoring evaluations demonstrated that MCD and atherogenic rats, as well as ob/ob and db/db mice, developed NASH. Liver mRNA and protein expression analyses of drug transporters showed that in general, efflux transporters were induced and uptake transporters were repressed in the rat MCD and the mouse ob/ob and db/db models. Lastly, concordance analyses suggest that both the mouse and rat MCD models as well as mouse ob/ob and db/db NASH models show the most similarity to human transporter mRNA and protein expression. These results suggest that the MCD rat and mouse model, as well as the ob/ob and db/db mouse models, may be useful for predicting altered disposition of drugs with similar kinetics across humans and rodents.


TYGS is an automated high-throughput platform for state-of-the-art genome-based taxonomy.
Microbial taxonomy is increasingly influenced by genome-based computational methods. Yet such analyses can be complex and require expert knowledge. Here we introduce TYGS, the Type (Strain) Genome Server, a user-friendly high-throughput web server for genome-based prokaryote taxonomy, connected to a large, continuously growing database of genomic, taxonomic and nomenclatural information. It infers genome-scale phylogenies and state-of-the-art estimates for species and subspecies boundaries from user-defined and automatically determined closest type genome sequences. TYGS also provides comprehensive access to nomenclature, synonymy and associated taxonomic literature. Clinically important examples demonstrate how TYGS can yield new insights into microbial classification, such as evidence for a species-level separation of previously proposed subspecies of Salmonella enterica. TYGS is an integrated approach for the classification of microbes that unlocks novel scientific approaches to microbiologists worldwide and is particularly helpful for the rapidly expanding field of genome-based taxonomic descriptions of new genera, species or subspecies.


Reproductive Factors Predicting Angiographic Obstructive Coronary Artery Disease: The KoRean wOmen'S Chest Pain rEgistry (KoROSE).
Whether reproductive factors are associated with coronary artery disease (CAD) has been debated. The aim of this study was to investigate etiologic associations of a wide range of reproductive factors of women with the presence of angiographic obstructive CAD. Study data were obtained from a nationwide registry that enrolled 687 Korean women (59.9 ± 11.4 years) with chest pain undergoing invasive coronary angiography (ICA). Obstructive CAD was defined as ≥50% luminal stenosis of one or more epicardial coronary arteries in ICA. Information on reproductive history, including ages at menarche and menopause, duration of reproductive capacity, number of pregnancies, hormonal replacement therapy, and history of twin pregnancy, was obtained using a standardized questionnaire. A total of 178 women (25.9%) had obstructive CAD. Multivariable logistic regression analysis identified that later age at menarche (odds ratio [OR] = 1.265, 95% confidence interval [CI] = 1.064-1.504, p = 0.008, per year) and increased number of pregnancies (OR = 1.223, 95% CI = 1.026-1.457, p = 0.025, per pregnancy) were the independent predictors of obstructive CAD even after controlling for potential confounders, including age, diabetes mellitus, hypertension, dyslipidemia, renal function, high-density lipoprotein level, white blood cell count, hemoglobin, and E/e'. Later age at menarche and increased number of pregnancies may be reproductive risk factors for angiographic obstructive CAD, suggesting the important role of hormonal status in the development of CAD.


Sex chromosome evolution in amniotes: applications for bacterial artificial chromosome libraries.
Variability among sex chromosome pairs in amniotes denotes a dynamic history. Since amniotes diverged from a common ancestor, their sex chromosome pairs and, more broadly, sex-determining mechanisms have changed reversibly and frequently. These changes have been studied and characterized through the use of many tools and experimental approaches but perhaps most effectively through applications for bacterial artificial chromosome (BAC) libraries. Individual BAC clones carry 100-200 kb of sequence from one individual of a target species that can be isolated by screening, mapped onto karyotypes, and sequenced. With these techniques, researchers have identified differences and similarities in sex chromosome content and organization across amniotes and have addressed hypotheses regarding the frequency and direction of past changes. Here, we review studies of sex chromosome evolution in amniotes and the ways in which the field of research has been affected by the advent of BAC libraries.


Evolutionary diversity of the mitochondrial calcium uniporter.
Calcium uptake into mitochondria occurs via a recently identified ion channel called the uniporter. Here, we characterize the phylogenomic distribution of the uniporter's membrane-spanning pore subunit (MCU) and regulatory partner (MICU1). Homologs of both components tend to co-occur in all major branches of eukaryotic life, but both have been lost along certain protozoan and fungal lineages. Several bacterial genomes also contain putative MCU homologs that may represent prokaryotic calcium channels. The analyses indicate that the uniporter may have been an early feature of mitochondria.


Comorbidities and impairments explaining the association between diabetes and lower extremity disability: The Women's Health and Aging Study.
To elucidate the role of diabetes-related impairments and comorbidities in the association between diabetes and physical disability, this study examined the association between diabetes and lower extremity function in a sample of disabled older women. Cross-sectional analysis of 1,002 women (aged >or=65 years) enrolled in the Women's Health and Aging Study (one-third most disabled of the total community-dwelling population). Diabetes and other medical conditions were ascertained by standard criteria that used multiple sources of information. Functional status was assessed using self-reported and objective performance measures. Women with diabetes were significantly more likely to have cardiovascular diseases, peripheral nerve dysfunction, visual impairment, obesity, and depression. After adjustment for age, women with diabetes had a greater prevalence of mobility disability (odds ratio [OR] 1.85, 95% CI 1.12-3.06), activities of daily living disability (1.61, 1.06-2.43), and severe walking limitation (2.34, 1.56-3.50), and their summary mobility performance score (0-12 scale based on balance, gait speed, chair stands) was 1.4 points lower than in nondiabetic women (P < 0.001). Peripheral artery disease, peripheral nerve dysfunction, and depression were the main individual contributing factors; however, none of these conditions alone fully explained the association between diabetes and disability. Conversely, only after adjusting for all potential mediators was the relationship between diabetes and disability reduced to a large degree. Even among physically impaired older women, diabetes is associated with a major burden of disability. A wide range of impairments and comorbidities explains the diabetes-disability relationship, suggesting that the mechanism for such an association is multifactorial.


Interferometry using binary holograms without high order diffraction effects.
We describe a technique for a phase-stepping interferometer based on programmable binary phase holograms, particularly useful for optical testing of aspheric or free-form surfaces. It is well-known that binary holograms can be used to generate reference surfaces for interferometry, but a major problem is that cross talk from higher diffraction orders and aliasing can reduce the fidelity of the system. Here, we propose a new encoding technique which improves the accuracy of the technique and demonstrate its implementation using a binary liquid crystal spatial light modulator.