Dealing with anxiety:Relationships among interpersonal attachment style, psychological wellbeing and trait anxiety

Anxiety is a major contributor to poor quality mental health for many people in our community, and is a leading cause of presentations at medical and health clinics. Patterns of trait anxiety, or dysfunctional responding, have become ingrained in individuals’ approaches to problems they face. Research has shown that psychological wellbeing and interpersonal attachment style are both predictors of trait anxiety. However, the relationships among these variables have not been clarified. The current study sought to determine whether psychological wellbeing mediates the relationship between interpersonal attachment style and trait anxiety, and which of the six psychological wellbeing subscales would contribute most to any mediation effects. A convenience sample of 149 adult participants from South East Queensland, Australia completed a series of online questionnaires including a demographic questionnaire, the Trait Anxiety subscale of the State-Trait Anxiety Inventory (STAI-Form Y2), the Inventory of Parent and Peer Attachment (IPPA), Ryff’s Psychological Wellbeing Scale (PWB), and a Social Desirability Scale (SDS-17). Psychological Wellbeing was found to partially mediate the relationship between interpersonal attachment style and trait anxiety. The Positive Relations with Others subscale of the PWB was the only significant sub-scale of the PWB that significantly predicted trait anxiety. Overcoming anxiety appears to be most related in our sample to those who deal better with interpersonal relations. Targeting this aspect in treatment approaches appears most likely to lead to improved outcomes for clients.</jats:p

A measurement of σ(Z → μμ) using the LHCb detector at CERN

LHCb is one of four main experiments at the LHC in CERN. This thesis analyses 1.03 fb−1 of √s = 7 TeV data collected in 2011. Measurements of the Z → μμ cross-section and a differential measurement with respect to Z boson rapidity are presented. The primary motivations for making these measurements are to probe the accuracy of the Standard Model and constrain theoretical parton distribution functions. Final state radiation causes a downward shift in the reconstructed dimuon invariant mass and broadening in the peak. Reconstructing the radiated photon means the invariant mass distribution shift can be corrected for. Here final state radiation is implemented in LHCb simulation for the first time. It is used to study the effect on the reconstructed Z mass distribution. Selections are placed on the distance between the photon and muon, and the photon PT . The distribution is fitted to be 12% narrower than the non-reconstructed sample. The measured mass of the Z boson is increased from 91.047 GeV to 91.054 GeV. The kinematic requirements placed on the muons are: both muons must have transverse momentum, PT > 20 GeV; the dimuon invariant mass, 6

Sublethal effects of natural parasitism act through maternal, but not paternal; reproductive success in a wild population

Parasites are a major component of all animal populations. Males and females often differ in their levels of parasite prevalence, potentially leading to sex differences in the impact of parasitism on fitness, with important implications for the evolution of parasite and host traits including resistance, tolerance, and virulence. However, quantitative measures of the impact of parasitism under free‐living conditions are extremely rare, as they require detailed host demographic data with measures of parasite burden over time. Here, we use endoscopy for direct quantification of natural‐parasite burdens and relate these to reproductive success over 7 yr in a wild population of seabirds. Contrary to predictions, only female burdens were associated with negative impacts of parasitism on breeding success, despite males having significantly higher burdens. Female reproductive success declined by 30% across the range of natural parasite burdens. These effects persisted when accounting for interannual population differences in breeding success. Our results provide quantitative estimates of profound sub‐lethal effects of parasitism on the population. Importantly, they highlight how parasites act unpredictably to shape ecological and evolutionary processes in different components of the same population, with implications for demography and selection on host and parasite traits

Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus

In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya

Community pharmacist views on the early stages of implementation of a pathfinder sore throat test and treat service in Wales: an exploratory study

Objectives: To explore the views and opinions of community pharmacists regarding their initial experience of and levels of preparedness for the pathfinder sore throat test and treat (STTT) service in Wales. Methods: A phenomenological qualitative approach with constructivist paradigm was adopted as the first cycle of ongoing action research. Semi-structured interviews with community pharmacists who had completed at least three consultations within the first 3 weeks of the service were conducted, with informed consent and audio recorded. Interviews were transcribed ad verbatim and data were thematically analysed both inductively and deductively. Results: A total of seven interviews with pharmacists who had conducted more than three consultations identified three main themes: 1) perceived impact of the service on patient care, including the value of the structure and technology infrastructure, the role of STTT towards antimicrobial stewardship, and its potential role in rebalancing primary care resources so that workload is distributed appropriately among healthcare professionals; 2) factors that empower pharmacists to deliver the service, in particular quality and consistency of training, appropriate staffing resource and internally motivated willingness to engage; 3) interface with GP surgeries such as nature of existing relationships before implementing the service, role of GP staff and GP perceived value of STTT. Conclusion: The pathfinder STTT service has been well received by pharmacists who recognised the service’s role in providing patient education and contributing to principles of antimicrobial stewardship and described factors that would empower them to deliver the service confidently. Results have been fed back to the service implementation team to inform future developments

Mechanisms of host manipulation by Neisseria gonorrhoeae

Neisseria gonorrhoeae (also known as gonococcus) has been causing gonorrhoea in humans since ancient Egyptian times. Today, global gonorrhoea infections are rising at an alarming rate, in concert with an increasing number of antimicrobial-resistant strains. The gonococcus has concurrently evolved several intricate mechanisms that promote pathogenesis by evading both host immunity and defeating common therapeutic interventions. Central to these adaptations is the ability of the gonococcus to manipulate various host microenvironments upon infection. For example, the gonococcus can survive within neutrophils through direct regulation of both the oxidative burst response and maturation of the phagosome; a concerning trait given the important role neutrophils have in defending against invading pathogens. Hence, a detailed understanding of how N. gonorrhoeae exploits the human host to establish and maintain infection is crucial for combating this pathogen. This review summarizes the mechanisms behind host manipulation, with a central focus on the exploitation of host epithelial cell signaling to promote colonization and invasion of the epithelial lining, the modulation of the host immune response to evade both innate and adaptive defenses, and the manipulation of host cell death pathways to both assist colonization and combat antimicrobial activities of innate immune cells. Collectively, these pathways act in concert to enable N. gonorrhoeae to colonize and invade a wide array of host tissues, both establishing and disseminating gonococcal infection

Specialist Respiratory Outreach : a case-finding initiative for identifying undiagnosed COPD in primary care

Acknowledgments This report is independent research funded by the National Institute for Health Research Wessex ARC. The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. We are very grateful to Optimum Patient care and their team for their help and support with the data extraction and application of the case-finding risk score. We would also like to thank: The participants, Mark Stafford-Watson (PPI) in memorial, Colin Newell, Dr Fiona McKenna, Dr Andy Powell, Dr Helen Myers, Dr Stuart McKinnes, Dr Mark Williams, Dr Louisa Egbe, Dr Richard Baxter, Dr Sarah A’Court, Dr Elisabeth Willows, Dr Gareth Morris, Dr Ford, Dr Kate Lippiett, Wessex Clinical Research Network, West Hampshire CCG and Southampton City CCGPeer reviewedPublisher PD

In Vitro and In Silico Analysis of New n-Butyl and Isobutyl Quinoxaline-7-carboxylate 1,4-di-N-oxide Derivatives against Trypanosoma cruzi as Trypanothione Reductase Inhibitors

American trypanosomiasis is a worldwide health problem that requires attention due to ineffective treatment options. We evaluated n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives against trypomastigotes of the Trypanosoma cruzi strains NINOA and INC-5. An in silico analysis of the interactions of 1,4-di-N-oxide on the active site of trypanothione reductase (TR) and an enzyme inhibition study was carried out. The n-butyl series compound identified as T-150 had the best trypanocidal activity against T. cruzi trypomastigotes, with a 13% TR inhibition at 44 μM. The derivative T-147 behaved as a mixed inhibitor with Ki and Ki' inhibition constants of 11.4 and 60.8 µM, respectively. This finding is comparable to the TR inhibitor mepacrine (Ki = 19 µM)

Bayesian approach to determining penetrance of pathogenic SDH variants.

BACKGROUND: Until recently, determining penetrance required large observational cohort studies. Data from the Exome Aggregate Consortium (ExAC) allows a Bayesian approach to calculate penetrance, in that population frequencies of pathogenic germline variants should be inversely proportional to their penetrance for disease. We tested this hypothesis using data from two cohorts for succinate dehydrogenase subunits A, B and C (SDHA-C) genetic variants associated with hereditary pheochromocytoma/paraganglioma (PC/PGL). METHODS: Two cohorts were 575 unrelated Australian subjects and 1240 unrelated UK subjects, respectively, with PC/PGL in whom genetic testing had been performed. Penetrance of pathogenic SDHA-C variants was calculated by comparing allelic frequencies in cases versus controls from ExAC (removing those variants contributed by The Cancer Genome Atlas). RESULTS: Pathogenic SDHA-C variants were identified in 106 subjects (18.4%) in cohort 1 and 317 subjects (25.6%) in cohort 2. Of 94 different pathogenic variants from both cohorts (seven in SDHA, 75 in SDHB and 12 in SDHC), 13 are reported in ExAC (two in SDHA, nine in SDHB and two in SDHC) accounting for 21% of subjects with SDHA-C variants. Combining data from both cohorts, estimated lifetime disease penetrance was 22.0% (95% CI 15.2% to 30.9%) for SDHB variants, 8.3% (95% CI 3.5% to 18.5%) for SDHC variants and 1.7% (95% CI 0.8% to 3.8%) for SDHA variants. CONCLUSION: Pathogenic variants in SDHB are more penetrant than those in SDHC and SDHA. Our findings have important implications for counselling and surveillance of subjects carrying these pathogenic variants

UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation

Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses ≥ 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjustments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments