205 research outputs found

    PGI29 SELECTING CHRONIC CONSTIPATION (CC) CLINICAL TRIAL ENDPOINTS: INCORPORATING THE PATIENT'S VOICE

    Get PDF

    Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

    Get PDF
    Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

    Urban women's socioeconomic status, health service needs and utilization in the four weeks after postpartum hospital discharge: findings of a Canadian cross-sectional survey

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Postpartum women who experience socioeconomic disadvantage are at higher risk for poor health outcomes than more advantaged postpartum women, and may benefit from access to community based postpartum health services. This study examined socioeconomically disadvantaged (SED) postpartum women's health, and health service needs and utilization patterns in the first four weeks post hospital discharge, and compared them to more socioeconomically advantaged (SEA) postpartum women's health, health service needs and utilization patterns.</p> <p>Methods</p> <p>Data collected as part of a large Ontario cross-sectional mother-infant survey were analyzed. Women (N = 1000) who had uncomplicated vaginal births of single 'at-term' infants at four hospitals in two large southern Ontario, Canada cities were stratified into SED and SEA groups based on income, social support and a universally administered hospital postpartum risk screen. Participants completed a self-administered questionnaire before hospital discharge and a telephone interview four weeks after discharge. Main outcome measures were self-reported health status, symptoms of postpartum depression, postpartum service needs and health service use.</p> <p>Results</p> <p>When compared to the SEA women, the SED women were more likely to be discharged from hospital within the first 24 hours after giving birth [OR 1.49, 95% CI (1.01–2.18)], less likely to report very good or excellent health [OR 0.48, 95% CI (0.35–0.67)], and had higher rates of symptoms of postpartum depression [OR 2.7, 95% CI(1.64–4.4)]. No differences were found between groups in relation to self reported need for and ability to access services for physical and mental health needs, or in use of physicians, walk-in clinics and emergency departments. The SED group were more likely to accept public health nurse home visits [OR 2.24, 95% CI(1.47–3.40)].</p> <p>Conclusion</p> <p>Although SED women experienced poorer mental and overall health they reported similar health service needs and utilization patterns to more SEA women. The results can assist policy makers, health service planners and providers to develop and implement necessary and accessible services. Further research is needed to evaluate SED postpartum women's health service needs and barriers to service use.</p

    Testing Multiple Coordination Constraints with a Novel Bimanual Visuomotor Task

    Get PDF
    The acquisition of a new bimanual skill depends on several motor coordination constraints. To date, coordination constraints have often been tested relatively independently of one another, particularly with respect to isofrequency and multifrequency rhythms. Here, we used a new paradigm to test the interaction of multiple coordination constraints. Coordination constraints that were tested included temporal complexity, directionality, muscle grouping, and hand dominance. Twenty-two healthy young adults performed a bimanual dial rotation task that required left and right hand coordination to track a moving target on a computer monitor. Two groups were compared, either with or without four days of practice with augmented visual feedback. Four directional patterns were tested such that both hands moved either rightward (clockwise), leftward (counterclockwise), inward or outward relative to each other. Seven frequency ratios (3∶1, 2∶1, 3∶2, 1∶1, 2∶3. 1∶2, 1∶3) between the left and right hand were introduced. As expected, isofrequency patterns (1∶1) were performed more successfully than multifrequency patterns (non 1∶1). In addition, performance was more accurate when participants were required to move faster with the dominant right hand (1∶3, 1∶2 and 2∶3) than with the non-dominant left hand (3∶1, 2∶1, 3∶2). Interestingly, performance deteriorated as the relative angular velocity between the two hands increased, regardless of whether the required frequency ratio was an integer or non-integer. This contrasted with previous finger tapping research where the integer ratios generally led to less error than the non-integer ratios. We suggest that this is due to the different movement topologies that are required of each paradigm. Overall, we found that this visuomotor task was useful for testing the interaction of multiple coordination constraints as well as the release from these constraints with practice in the presence of augmented visual feedback

    Fast Statistical Alignment

    Get PDF
    We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment—previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches—yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/

    Physicians' attitudes about obesity and their associations with competency and specialty: A cross-sectional study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Physicians frequently report negative attitudes about obesity which is thought to affect patient care. However, little is known about how attitudes toward treating obese patients are formed. We conducted a cross-sectional survey of physicians in order to better characterize their attitudes and explore the relationships among attitudes, perceived competency in obesity care, including report of weight loss in patients, and other key physician, training, and practice characteristics.</p> <p>Methods</p> <p>We surveyed all 399 physicians from internal medicine, pediatrics, and psychiatry specialties at one institution regarding obesity care attitudes, competency, including physician report of percent of their patients who lose weight. We performed a factor analysis on the attitude items and used hierarchical regression analysis to explore the degree to which competency, reported weight loss, physician, training and practice characteristics explained the variance in each attitude factor.</p> <p>Results</p> <p>The overall response rate was 63%. More than 40% of physicians had a negative reaction towards obese patients, 56% felt qualified to treat obesity, and 46% felt successful in this realm. The factor analysis revealed 4 factors–<it>Physician Discomfort/Bias, Physician Success/Self Efficacy, Positive Outcome Expectancy</it>, and <it>Negative Outcome Expectancy</it>. Competency and reported percent of patients who lose weight were most strongly associated with the <it>Physician Success/Self Efficacy </it>attitude factor. Greater skill in patient assessment was associated with less <it>Physician Discomfort/Bias</it>. Training characteristics were associated with outcome expectancies with newer physicians reporting more positive treatment expectancies. Pediatric faculty was more positive and psychiatry faculty less negative in their treatment expectancies than internal medicine faculty.</p> <p>Conclusion</p> <p>Physician attitudes towards obesity are associated with competency, specialty, and years since postgraduate training. Further study is necessary to determine the direction of influence and to explore the impact of these attitudes on patient care.</p

    Natural Single-Nucleosome Epi-Polymorphisms in Yeast

    Get PDF
    Epigenomes commonly refer to the sequence of presence/absence of specific epigenetic marks along eukaryotic chromatin. Complete histone-borne epigenomes have now been described at single-nucleosome resolution from various organisms, tissues, developmental stages, or diseases, yet their intra-species natural variation has never been investigated. We describe here that the epigenomic sequence of histone H3 acetylation at Lysine 14 (H3K14ac) differs greatly between two unrelated strains of the yeast Saccharomyces cerevisiae. Using single-nucleosome chromatin immunoprecipitation and mapping, we interrogated 58,694 nucleosomes and found that 5,442 of them differed in their level of H3K14 acetylation, at a false discovery rate (FDR) of 0.0001. These Single Nucleosome Epi-Polymorphisms (SNEPs) were enriched at regulatory sites and conserved non-coding DNA sequences. Surprisingly, higher acetylation in one strain did not imply higher expression of the relevant gene. However, SNEPs were enriched in genes of high transcriptional variability and one SNEP was associated with the strength of gene activation upon stimulation. Our observations suggest a high level of inter-individual epigenomic variation in natural populations, with essential questions on the origin of this diversity and its relevance to gene x environment interactions

    The views of young children in the UK about obesity, body size, shape and weight: a systematic review

    Get PDF
    BACKGROUND: There are high levels of concern about childhood obesity, with obese children being at higher risk of poorer health both in the short and longer terms. Children's attitudes to, and beliefs about, their bodies have also raised concern. Children themselves have a stake in this debate; their perspectives on this issue can inform the ways in which interventions aim to work.This systematic review of qualitative and quantitative research aimed to explore the views of UK children about the meanings of obesity and body size, shape or weight and their own experiences of these issues. METHODS: We conducted sensitive searches of electronic databases and specialist websites, and contacted experts. We included studies published from the start of 1997 which reported the perspectives of UK children aged 4-11 about obesity or body size, shape or weight, and which described key aspects of their methods. Included studies were coded and quality-assessed by two reviewers independently.Findings were synthesised in two analyses: i) an interpretive synthesis of findings from open-ended questions; and ii) an aggregative synthesis of findings from closed questions. We juxtaposed the findings from the two syntheses. The effect of excluding the lowest quality studies was explored. We also consulted young people to explore the credibility of a subset of findings. RESULTS: We included 28 studies. Instead of a focus on health, children emphasised the social impact of body size, describing experiences and awareness of abuse and isolation for children with a greater weight. Body size was seen as under the individual's control and children attributed negative characteristics to overweight people. Children actively assessed their own size; many wished their bodies were different and some were anxious about their shape.Reviewers judged that children's engagement and participation in discussion had only rarely been supported in the included studies, and few study findings had depth or breadth. CONCLUSIONS: Initiatives need to consider the social aspects of obesity, in particular unhelpful beliefs, attitudes and discriminatory behaviours around body size. Researchers and policy-makers should involve children actively and seek their views on appropriate forms of support around this issue

    Engineered Single-Domain Antibodies with High Protease Resistance and Thermal Stability

    Get PDF
    The extreme pH and protease-rich environment of the upper gastrointestinal tract is a major obstacle facing orally-administered protein therapeutics, including antibodies. Through protein engineering, several Clostridium difficile toxin A-specific heavy chain antibody variable domains (VHHs) were expressed with an additional disulfide bond by introducing Ala/Gly54Cys and Ile78Cys mutations. Mutant antibodies were compared to their wild-type counterparts with respect to expression yield, non-aggregation status, affinity for toxin A, circular dichroism (CD) structural signatures, thermal stability, protease resistance, and toxin A-neutralizing capacity. The mutant VHHs were found to be well expressed, although with lower yields compared to wild-type counterparts, were non-aggregating monomers, retained low nM affinity for toxin A, albeit the majority showed somewhat reduced affinity compared to wild-type counterparts, and were capable of in vitro toxin A neutralization in cell-based assays. Far-UV and near-UV CD spectroscopy consistently showed shifts in peak intensity and selective peak minima for wild-type and mutant VHH pairs; however, the overall CD profile remained very similar. A significant increase in the thermal unfolding midpoint temperature was observed for all mutants at both neutral and acidic pH. Digestion of the VHHs with the major gastrointestinal proteases, at biologically relevant concentrations, revealed a significant increase in pepsin resistance for all mutants and an increase in chymotrypsin resistance for the majority of mutants. Mutant VHH trypsin resistance was similar to that of wild-type VHHs, although the trypsin resistance of one VHH mutant was significantly reduced. Therefore, the introduction of a second disulfide bond in the hydrophobic core not only increases VHH thermal stability at neutral pH, as previously shown, but also represents a generic strategy to increase VHH stability at low pH and impart protease resistance, with only minor perturbations in target binding affinities. These are all desirable characteristics for the design of protein-based oral therapeutics
    corecore