Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Systematic population screening, using biomarkers and genetic testing, identifies 2.5% of the U.K. pediatric diabetes population with monogenic diabetes

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.OBJECTIVE: Monogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing. RESEARCH DESIGN AND METHODS: We studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ≥0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes. RESULTS: A total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients). CONCLUSIONS: This large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.This work presents independent research commissioned by the Health Innovation Challenge Fund, a parallel funding partnership between the Wellcome Trust and the Department of Health (grant HICF-1009-041); and was supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility and the South West Peninsula Diabetes Research Network. M.S. is supported by the NIHR Exeter Clinical Research Facility. T.J.M. is funded by an NIHR CSO Fellowship. S.E. and A.T.H. are both Wellcome Trust Senior Investigators. E.R.P. is a Wellcome Trust New Investigator. A.T.H. is an NIHR Senior Investigator

Callous-unemotional traits, low cortisol reactivity and physical aggression in children: findings from the Wirral Child Health and Development Study

Callous-unemotional (CU) traits are thought to confer risk for aggression via reduced amygdala responsivity to distress cues in others. Low cortisol reactivity is thought to confer risk for aggression via reduced arousal and this effect may be confined to boys. We tested the hypothesis that the association between childhood CU traits and aggression would be greatest in the absence of the inhibitory effects of cortisol reactivity, and that this effect would be sex dependent. Participants were 283 members of a stratified subsample within an epidemiological longitudinal cohort (WCHADS). Cortisol reactivity to a social stressor was assessed at 5 years. CU traits were reported by mothers at 5 years, and physical aggression by mothers and teachers at age 7. Results showed that CU traits were associated with elevated aggression at 7 years controlling for earlier aggression. There was no main effect of cortisol reactivity on regression. The association between CU traits and aggression was moderated by cortisol reactivity (p = .011) with a strong association between CU traits and aggression in the presence of low reactivity, and a small and non-significant association in the presence of high reactivity. This association was further moderated by child sex (p = .041) with the joint effect of high CU traits and low cortisol reactivity seen only in boys (p = .016). We report first evidence that a combined deficit in inhibitory processes associated with CU traits and low cortisol reactivity increases risk for childhood aggression, in a sex-dependent manner

Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II

Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin/lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. A Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wildtype. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin2 inserts into the membrane and we propose this is the first step in pore formation, mediated by the nisin N-terminus–lipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation

Cancer and heart attack survivors’ expectations of employment status: results from the English Longitudinal Study of Ageing

Background: Sociodemographic, health- and work-related factors have been found to influence return to work in cancer survivors. It is feasible though that behavioural factors, such as expectation of being at work, could also affect work-related outcomes. Therefore, the effect of earlier identified factors and expectation of being at work on future employment status in cancer survivors was explored. To assess the degree to which these factors specifically concern cancer survivors, a comparison with heart attack survivors was made. Methods: Data from the English Longitudinal Study of Ageing were used. Cancer and heart attack survivors of working age in the UK were included and followed up for 2 years. Baseline characteristics of both cancer and heart attack survivors were compared regarding employment status. Univariate and multivariate regression analyses were performed in survivors at work, and the interaction between independent variables and diagnose group was assessed. Results: In cancer survivors at work (N = 159), alcohol consumption, participating in moderate or vigorous sport activities, general health and participation were univariate associated with employment status at two-year followup. Only fair general health (compared to very good general health) remained statistically significant in the multivariate model (OR 0.31; 95% CI 0.13–0.76; p = 0.010). In heart attack survivors at work (N = 78), gender, general health and expectation of being at work were univariate associated with employment status at follow-up. Female gender (OR 0.03; 95% CI 0.00–0.57; p = 0.018) and high expectation of being at work (OR 10.68; 95% CI 1.23–93.92; p = 0.033) remained significant in the multivariate model. The influence of gender (p = 0.066) and general health (p = 0.020) regarding employment status was found to differ significantly between cancer and heart attack survivors. Conclusions: When predicting future employment status in cancer survivors in the UK, general health is the most relevant factor to consider. While expectation of being at work did not show any significant influence in cancer survivors, in heart attack survivors, it should not be disregarded though, when developing interventions to affect their employment status. Future research should focus on more specific measures for expectation, and additional behavioural factors, such as self-efficacy, and their effect on employment status

Identification of pyrimethamine- and chloroquine-resistant Plasmodium falciparum in Africa between 1984 and 1998: genotyping of archive blood samples

<p>Abstract</p> <p>Background</p> <p>Understanding the geographical distribution of drug resistance of <it>Plasmodium falciparum </it>is important for the effective treatment of malaria. Drug resistance has previously been inferred mainly from records of clinical resistance. However, clinical resistance is not always consistent with the parasite's genetic resistance. Thus, molecular identification of the parasite's drug resistance is required. In Africa, clinical resistance to pyrimethamine (Pyr) and chloroquine (CQ) was evident before 1980 but few studies investigating the genetic resistance to these drugs were conducted before the late 1990s. In this study, genotyping of genes involved in resistance to Pyr and CQ was performed using archive blood samples from Africa between 1984 and 1998.</p> <p>Methods</p> <p>Parasite DNA was extracted from <it>P. falciparum</it>-infected blood smears collected from travellers returning to Japan from Africa between 1984 and 1998. Genotypes of the dihydrofolate reductase gene (<it>dhfr</it>) and CQ-resistance transporter gene (<it>pfcrt) </it>were determined by polymerase chain reaction amplification and sequencing.</p> <p>Results</p> <p>Genotyping of <it>dhfr </it>and <it>pfcrt </it>was successful in 59 and 80 samples, respectively. One wild-type and seven mutant <it>dhfr </it>genotypes were identified. Three <it>dhfr </it>genotypes lacking the S108N mutation (NRSI, ICSI, IRSI; amino acids at positions 51, 59, 108, and 164 with mutations underlined) were highly prevalent before 1994 but reduced after 1995, accompanied by an increase in genotypes with the S108N mutation. The <it>dhfr </it>IRNI genotype was first identified in Nigeria in 1991 in the present samples, and its frequency gradually increased. However, two double mutants (ICNI and NRNI), the latter of which was exclusively found in West Africa, were more frequent than the IRNI genotype. Only two <it>pfcrt </it>genotypes were found, the wild-type and a Southeast Asian type (CVIET; amino acids at positions 72-76 with mutations underlined). The CVIET genotype was already present as early as 1984 in Tanzania and Nigeria, and appeared throughout Africa between 1984 and 1998.</p> <p>Conclusions</p> <p>This study is the first to report the molecular identification of Pyr- and CQ-resistant genotypes of <it>P. falciparum </it>in Africa before 1990. Genotyping of <it>dhfr </it>and <it>pfcrt </it>using archive samples has revealed new aspects of the evolutionary history of Pyr- and CQ-resistant parasites in Africa.</p

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Barriers to effective discharge planning: a qualitative study investigating the perspectives of frontline healthcare professionals

<p>Abstract</p> <p>Background</p> <p>Studies have shown that effective discharge planning is one of the key factors related to the quality of inpatient care and unnecessary hospital readmission. The perception and understanding of hospital discharge by health professionals is important in developing effective discharge planning. The aims of this present study were to explore the perceived quality of current hospital discharge from the perspective of health service providers and to identify barriers to effective discharge planning in Hong Kong.</p> <p>Methods</p> <p>Focus groups interviews were conducted with different healthcare professionals who were currently responsible for coordinating the discharge planning process in the public hospitals. The discussion covered three main areas: current practice on hospital discharge, barriers to effective hospital discharge, and suggested structures and process for an effective discharge planning system.</p> <p>Results</p> <p>Participants highlighted that there was no standardized hospital-wide discharge planning and policy-driven approach in public health sector in Hong Kong. Potential barriers included lack of standardized policy-driven discharge planning program, and lack of communication and coordination among different health service providers and patients in both acute and sub-acute care provisions which were identified as mainly systemic issues. Improving the quality of hospital discharge was suggested, including a multidisciplinary approach with clearly identified roles among healthcare professionals. Enhancement of health professionals' communication skills and knowledge of patient psychosocial needs were also suggested.</p> <p>Conclusions</p> <p>A systematic approach to develop the structure and key processes of the discharge planning system is critical in ensuring the quality of care and maximizing organization effectiveness. In this study, important views on barriers experienced in hospital discharge were provided. Suggestions for building a comprehensive, system-wide, and policy-driven discharge planning process with clearly identified staff roles were raised. Communication and coordination across various healthcare parties and provisions were also suggested to be a key focus.</p