The effects of changing chemistry on the shock response of basic polymers

The shock response of four common semicrystalline thermoplastic polymers—polyethylene (PE), polyvinylchloride (PVC), polytetrafluoroethylene (PTFE) and polychlorotrifluoroethylene (PCTFE)—have been studied in terms of their Hugoniots, release velocities and shear strengths. Through the variations in behaviour caused by changes to the attached atoms to the carbon backbone, it has been possible to suggest that there are two main factors in play. The first is an electrostatic repulsion between adjacent polymer chains. Where this force is large, for example in PTFE with highly electronegative fluorine atoms, this results in this force dominating the shock response, with low shock velocities, high release velocities and little if no hardening behind the shock front. In contrast, in materials such as PE, this force is now weaker, due to the lower electronegativity of hydrogen, and hence this force is easier to overcome by the applied shock stress. Now the main factor affecting shock behaviour is controlled by the shape of the polymer chain allowing inter chain tangling (tacticity). This results in higher shock velocities, lower release speeds and significant hardening behind the shock front as the chains are forced together. This is prevalent in materials with a relatively open structure such as PE and is enhanced with the presence of large side groups or atoms off the main polymer chain

Changes in toxin content, biomass and pigments of the dinoflagellate Alexandrium minutum during nitrogen refeeding and growth into nitrogen or phosphorus stress

Two strains oi the paralytic shellfish toxin (PST) producing dinoflagellate Alexandrium minutum Halim (highly toxic ALl V and weakly toxic AL2V) were grown in batch culture with either nitrate or phosphate as the limiting nutrient. In comparison with cells of the strain AL1V, cells of AL2V grew at a similar C-specific Tale, had a higher C/N ratio, and lower ratios of chl a/chl C2and chl a/peridinin. Neither chlorophylls flor carotenoids could be used to estimate C-biomass, N-biomass or toxin content for this organismo The toxin profile for both strains was dominated (up to 95 %) by the gonyautoxin GTX4, with smaller proportions of GTX1, GTX2 and GTX3. The Tale of toxin synthesis for both strains was greatest 1 to 2 d after the N-refeeding of N-deprived cells, with the net Tale of toxin syn- .thesis exceeding that of C-biomass and cell division by a factor of up to 4. Toxin synthesis was not enhanced by short-term P-stress. N-stress alone led to a decrease in toxin cell-I, but P-stress followed by N-stress did not result in such a decline, implicating phosphorus in the regulation of toxin metabolism. Although arginine is a majar precursor for PST synthesis, taurine, glycine, glutamine, and cell N showed similar relations to that observed for arginine with respect to toxin contento Furthermore, the mole ratio of arginine/toxin could vary by a factor of up to 5 between AL1V and AL2V at peak values of toxin cell-1, and by more than 5 within a strain when growing under different conditions. These observations suggest that the relationship between free arginine content and toxin content is complex. No explanation for the higher toxin content of AL1V is apparent, except that AL1V has a higher N-content per cell and this may be conducive to a higher Tale of synthesis of the N-rich toxins.Publicado

Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss of survival motor neuron (SMN) protein. While SMN restoration therapies are beneficial, they are not a cure. We aimed to identify potentially novel treatments to alleviate muscle pathology combining transcriptomics, proteomics, and perturbational data sets. This revealed potential drug candidates for repurposing in SMA. One of the candidates, harmine, was further investigated in cell and animal models, improving multiple disease phenotypes, including lifespan, weight, and key molecular networks in skeletal muscle. Our work highlights the potential of multiple and parallel data-driven approaches for the development of potentially novel treatments for use in combination with SMN restoration therapies

Characterization of ten highly polymorphic microsatellite loci for the intertidal mussel Perna perna, and cross species amplification within the genus

The brown mussel Perna perna (Linnaeus, 1758) is a dominant constituent of intertidal communities and a strong invader with multiple non-native populations distributed around the world. In a previous study, two polymorphic microsatellite loci were developed and used to determine population-level genetic diversity in invasive and native P. perna populations. However, higher number of microsatellite markers are required for reliable population genetic studies. In this context, in order to understand P. perna origins and history of invasion and to compare population genetic structure in native versus invaded areas, we developed 10 polymorphic microsatellite markers. Findings Described microsatellite markers were developed from an enriched genomic library. Analyses and characterization of loci using 20 individuals from a population in Western Sahara revealed on average 11 alleles per locus (range: 5–27) and mean gene diversity of 0.75 (range: 0.31 - 0.95). One primer pair revealed possible linkage disequilibrium while heterozygote deficiency was significant at four loci. Six of these markers cross-amplified in P. canaliculus (origin: New Zealand). Conclusions Developed markers will be useful in addressing a variety of questions concerning P. perna, including dispersal scales, genetic variation and population structure, in both native and invaded areas.Peer Reviewe

Outcome of primary resurfacing hip replacement: evaluation of risk factors for early revision: 12,093 replacements from the Australian Joint Registry

BACKGROUND AND PURPOSE: The outcome of modern resurfacing remains to be determined. The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) started collection of data on hip resurfacing at a time when modern resurfacing was started in Australia. The rate of resurfacing has been higher in Australia than in many other countries. As a result, the AOANJRR has one of the largest series of resurfacing procedures. This study was undertaken to determine the results of this series and the risk factors associated with revision. PATIENTS AND METHODS: Data from the AOANJRR were used to analyze the survivorship of 12,093 primary resurfacing hip replacements reported to the Joint Replacement Registry between September 1999 and December 2008. This was compared to the results of primary conventional total hip replacement reported during the same period. The Kaplan-Meier method and proportional hazards models were used to determine risk factors such as age, sex, femoral component size, primary diagnosis, and implant design. RESULTS: Female patients had a higher revision rate than males; however, after adjusting for head size, the revision rates were similar. Prostheses with head sizes of less than 50 mm had a higher revision rate than those with head sizes of 50 mm or more. At 8 years, the cumulative per cent revision of hip resurfacing was 5.3 (4.6-6.2), as compared to 4.0 (3.8-4.2) for total hip replacement. However, in osteoarthritis patients aged less than 55 years with head sizes of 50 mm or more, the 7-year cumulative per cent revision for hip resurfacing was 3.0 (2.2-4.2). Also, hips with dysplasia and some implant designs had an increased risk of revision. INTERPRETATION: Risk factors for revision of resurfacing were older patients, smaller femoral head size, patients with developmental dysplasia, and certain implant designs. These results highlight the importance of patient and prosthesis selection in optimizing the outcome of hip resurfacing

Self-care and adherence to medication: a survey in the hypertension outpatient clinic

<p>Abstract</p> <p>Background</p> <p>Self-care practices for patients with hypertension include adherence to medication, use of blood pressure self-monitoring and use of complementary and alternative therapies (CAM) The prevalence of CAM use and blood pressure self-monitoring have not been described in a UK secondary care population of patients with hypertension and their impact on adherence to medication has not been described. Adherence to medication is important for blood pressure control, but poor adherence is common. The study aimed to determine the prevalence of self-care behaviours in patients attending a secondary care hypertension clinic.</p> <p>Methods</p> <p>Cross-sectional questionnaire survey. 196 patients attending a secondary care hypertension clinic in a teaching hospital serving a multiethnic population, Birmingham, UK. Main outcome measures: Prevalence of use of CAM, home monitors, adherence to anti-hypertensive medication.</p> <p>Results</p> <p>CAM use in previous 12 months was reported by 66 (43.1%) respondents. CAM users did not differ statistically from non-CAM users by age, gender, marital status or education. Vitamins, prayer a dietary supplements were the most commonly used CAM. Nine (12.7%) women reported using herbal CAM compared to one man (1.2%), (p = 0.006). Ten (6.7%) respondents reported ever being asked by a doctor about CAM use. Perfect adherence to anti-hypertensive medication was reported by 26 (44.8%) CAM-users and 46 (60.5%) non-CAM users (p = 0.07). Being female and a CAM user was significantly associated with imperfect adherence to anti-hypertensive medication. Older and white British respondents were significantly more likely to report perfect adherence. Blood pressure monitors were used by 67 (43.8%) respondents, which was not associated with gender, CAM use or adherence to medication.</p> <p>Conclusion</p> <p>Hypertensive patients use a variety of self-care methods, including CAM, home blood pressure monitors, and adherence to prescribed medication. This study found the prevalence of CAM use in hypertensive patients was higher than in the UK population. It is important to acknowledge the self-care behaviour of hypertensive patients, in order to assess potential harm, and encourage effective methods of self-care.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility.

Spontaneous dizygotic (DZ) twinning occurs in 1%-4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1.54 × 10(-9), and rs17293443 in SMAD3, p = 1.57 × 10(-8)) and replicated (p = 3 × 10(-3) and p = 1.44 × 10(-4), respectively). Based on ∼90,000 births in Iceland, the risk of a mother delivering twins increased by 18% for each copy of allele rs11031006-G and 9% for rs17293443-C. A higher polygenic risk score (PRS) for DZ twinning, calculated based on the results of the DZ twinning GWAS, was significantly associated with DZ twinning in Iceland (p = 0.001). A higher PRS was also associated with having children (p = 0.01), greater lifetime parity (p = 0.03), and earlier age at first child (p = 0.02). Allele rs11031006-G was associated with higher serum FSH levels, earlier age at menarche, earlier age at first child, higher lifetime parity, lower PCOS risk, and earlier age at menopause. Conversely, rs17293443-C was associated with later age at last child. We identified robust genetic risk variants for DZ twinning: one near FSHB and a second within SMAD3, the product of which plays an important role in gonadal responsiveness to FSH. These loci contribute to crucial aspects of reproductive capacity and health.Support for the Netherlands Twin Register was obtained from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW) grants, 904-61-193,480-04-004, 400-05-717, Addiction-31160008, 911-09-032, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB; European Research Council (ERC-230374 and ERC-284167); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1). Part of the genotyping was funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health and Grand Opportunity grants 1RC2 MH089951). We acknowledge support from VU Amsterdam and the Institute for Health and Care Research (EMGO+). The Berghofer Medical Research Institute (QIMR) study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1050208, 1075175). Dale R. Nyholt was supported by the Australian Research Council (ARC) Future Fellowship (FT0991022), NHMRC Research Fellowship (APP0613674) Schemes and by the Visiting Professors Programme (VPP) of the Royal Netherlands Academy of Arts and Sciences (KNAW). Allan F. McRae was supported by an NRMRC Career Development Fellowship (APP1083656). Grant W. Montgomery was supported by NIH grant (HD042157, a collaborative study of the genetics of DZ twinning) and NHMRC Fellowship (GNT1078399). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886), and the National Institute on Drug Abuse (DA05147, DA13240, and DA024417). We would like to thank also 23andMe's consented research participants for contributing data on age at menarche for the FSHB gene locus and the Twinning Gwas Consortium (TGC). Co-authors from: Finland (Anu Loukola, Juho Wedenoja, Emmi Tikkanen, Beenish Qaiser), Sweden (Nancy Pedersen, Andrea Ganna), United kingdom King's College London (Department of Twin Research & Genetic Epidemiology: Pirro Hysi, Massimo Mangino), Institute of Psychiatry, Psychology & Neuroscience, Medical Research Council Social, Genetic and Developmental Psychiatry Centre (Eva Krapohl, Andrew McMillan).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ajhg.2016.03.00