Low coordinate magnesium sulfide and selenide complexes

Funding: Authors thank the University of St Andrews and the EPSRC doctoral training grant (EP/N509759/1) for support. We gratefully acknowledge computational support via the EaStCHEM Research Computing Facility.The reactions of [{(iPrDipNacNac)Mg}2] 1 (iPrDipnacnac = HC(iPrCNDip)2) with Ph3P═O at 100 °C afforded the phosphinate complex [(iPrDipNacNac)Mg(OPPh3)(OPPh2)] 3 . Reactions of 1 with Ph3P═E (E = S, Se) proceeded rapidly at room temperature to low-coordinate chalcogenide complexes [{(iPrDipNacNac)Mg}2(μ-S)] 4 and [{(iPrDipNacNac)Mg}2(μ-Se)] 5 , respectively. Similarly, reactions of RNHC═S ((MeCNR)2C═S with R = Me, Et, or iPr) with 1 afforded NHC adducts of magnesium sulfide complexes, [{(iPrDipNacNac)Mg(RNHC)}(μ-S){Mg(iPrDipNacNac)}] 6 , that could alternatively be obtained by adding the appropriate RNHC to sulfide complex 4 . Complex 4 reacted with 1-adamantylazide (AdN3) to give [{(iPrDipNacNac)Mg}2(μ-SN3Ad)] 7 and can form various simple donor adducts in solution, of which [(iPrDipNacNac)Mg(OAd)}2(μ-S)] 8a (OAd = 2-adamantanone) was structurally characterized. The nature of the ionic Mg–E–Mg unit is described by solution and solid-state studies of the complexes and by DFT computational investigations.Publisher PDFPeer reviewe

Aligning assessment with the needs of work-integrated learning: the challenges of authentic assessment in a complex context

Work-integrated learning (WIL) is a feature of university courses, both in professional areas, where it is commonplace, but also across many different disciplines. Assessment of WIL can be complex as it involves parties and settings external to the university, and it can be problematic because of difficulties in aligning learning activities during placements with what is or can be assessed by the university. This paper explores the relationship between students’ placement experiences and accompanying assessments in contexts where activities are tightly coupled with the curriculum, and in those where it is not. It draws on a qualitative analysis of student interviews and drawings by the interviewees of their WIL experiences, supplemented with analysis of unit guides. Our findings highlight that students’ perceptions of authenticity of assessment were undermined by misalignments between the student, university and industry. Assessment authenticity was perceived by students as based on alignment between their current and future selves in the assessment process, involvement of industry supervisors and relevance of placement activities to assessment activities. The paper discusses the complexity of coordination of educational activities with external partners, especially when one party drives assessment. It then suggests a reframing of WIL assessment to promote alignment and authenticity

A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism

We present 109 near full-length HIV genomes amplified from blood serum samples obtained during early 1986 from across Uganda, which to our knowledge is the earliest and largest population sample from the initial phase of the HIV epidemic in Africa. Consensus sequences were made from paired-end Illumina reads with a target-capture approach to amplify HIV material following poor success with standard approaches. In comparisons with a smaller 'intermediate' genome dataset from 1998 to 1999 and a 'modern' genome dataset from 2007 to 2016, the proportion of subtype D was significantly higher initially, dropping from 67% (73/109), to 57% (26/46) to 17% (82/465) respectively (p < 0.0001). Subtype D has previously been shown to have a faster rate of disease progression than other subtypes in East African population studies, and to have a higher propensity to use the CXCR4 co-receptor ("X4 tropism"); associated with a decrease in time to AIDS. Here we find significant differences in predicted tropism between A1 and D subtypes in all three sample periods considered, which is particularly striking the 1986 sample: 66% (53/80) of subtype D env sequences were predicted to be X4 tropic compared with none of the 24 subtype A1. We also analysed the frequency of subtype in the envelope region of inter-subtype recombinants, and found that subtype A1 is over-represented in env, suggesting recombination and selection have acted to remove subtype D env from circulation. The reduction of subtype D frequency over three decades therefore appears to be a result of selective pressure against X4 tropism and its higher virulence. Lastly, we find a subtype D specific codon deletion at position 24 of the V3 loop, which may explain the higher propensity for subtype D to utilise X4 tropism

Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance

Dolutegravir (DTG), a second-generation integrase strand-transfer inhibitor (INSTI), is equivalent or superior to current non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and first-generation INSTI-based antiretroviral regimens (ARVs). It has the potential to make big improvements in HIV control globally and within patients. This is perhaps the most “precious” HIV drug available. The integrase mutation R263K has been observed in tissue culture experiments and in patients treated with dolutegravir monotherapy in clinical trials. Globally, adherence and monitoring may be less than optimal and therefore DTG resistance more common. This is particularly important in low–middle-income countries, where patients may remain on failing regimens for longer periods of time and accumulate drug resistance. Data on this mutation in non–subtype B infections do not exist. We describe the first report of the R263K integrase mutation in a dolutegravir-exposed subtype D–infected individual with vertically acquired HIV. We have used deep sequencing of longitudinal samples to highlight the change in resistance over time while on a failing regimen. The case highlights that poorly adherent patients should not be offered dolutegravir even as part of a combination regimen and that protease inhibitors should be used preferentially

Low oxygen tension primes aortic endothelial cells to the reparative effect of tissue-protective cytokines

Erythropoietin (EPO) has both erythropoietic and tissue-protective properties. The EPO analogues carbamylated EPO (CEPO) and pyroglutamate helix B surface peptide (pHBSP) lack the erythropoietic activity of EPO but retain the tissue-protective properties that are mediated by a heterocomplex of EPO receptor (EPOR) and the β common receptor (βCR). We studied the action of EPO and its analogues in a model of wound healing where a bovine aortic endothelial cells (BAECs) monolayer was scratched and the scratch closure was assessed over 24 h under different oxygen concentrations. We related the effects of EPO and its analogues on repair to their effect on BAECs proliferation and migration (evaluated using a micro-Boyden chamber). EPO, CEPO and pHBSP enhanced scratch closure only at lower oxygen (5%), while their effect at atmospheric oxygen (21%) was not significant. The mRNA expression of EPOR was doubled in 5% compared to 21% oxygen, and this was associated with increased EPOR assessed by immunofluorescence and Western blot. By contrast βCR mRNA levels were similar in 5% and 21% oxygen. EPO and its analogues increased both BAECs proliferation and migration, suggesting that both may be involved in the reparative process. The priming effect of low oxygen tension on the action of tissue-protective cytokines may be of relevance to vascular disease, including atherogenesis and restenosis

Long-term MRA follow-up after coiling of intracranial aneurysms: impact on mood and anxiety

Magnetic resonance angiography (MRA) screening for recurrence of a coiled intracranial aneurysm and formation of new aneurysms long-term after coiling may induce anxiety and depression. In coiled patients, we evaluated effects on mood and level of anxiety from long-term follow-up MRA in comparison to general population norms. Of 162 patients participating in a long-term (> 4.5 years) MRA follow-up after coiling, 120 completed the EQ-5D questionnaire, a visual analog health scale and a self-developed screening related questionnaire at the time of MRA. Three months later, the same questionnaires were completed by 100 of these 120 patients. Results were compared to general population norms adjusted for gender and age. Any problem with anxiety or depression was reported in 56 of 120 patients (47%; 95%CI38a dagger"56%) at baseline and 42 of 100 patients (42%; 95%CI32a dagger"52%) at 3 months, equally for screen-positives and -negatives. Compared to the reference population, participants scored 38% (95%CI9a dagger"67%) and 27% (95%CI4a dagger"50%) more often any problem with anxiety or depression. Three months after screening, 21% (20 of 92) of screen-negatives and 13% (one of eight) of screen-positives reported to be less afraid of subarachnoid hemorrhage (SAH) compared to before screening. One of eight screen-positives reported increased fear of SAH. Patients with coiled intracranial aneurysms participating in long-term MRA screening reported significantly more often to be anxious or depressed than a reference group. Screening did not significantly increase anxiety or depression temporarily. However, subjectively, patients did report an increase in anxiety caused by screening, which decreased after 3 months

Hepatitis delta virus testing, epidemiology and management: A multicentre cross-sectional study of patients in London

Department of Health’s NIHR Biomedical Research Centres funding scheme

Inflammatory Disease Processes and Interactions with Nutrition

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain ω-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (ω-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are require

Workplace violence in a large correctional health servce in New South Wales, Australia: a retrospective review of incident management records

BackgroundLittle is known about workplace violence among correctional health professionals. This studyaimed to describe the patterns, severity and outcomes of incidents of workplace violenceamong employees of a large correctional health service, and to explore the help-seekingbehaviours of staff following an incident.MethodsThe study setting was Justice Health, a statutory health corporation established to providehealth care to people who come into contact with the criminal justice system in New SouthWales, Australia. We reviewed incident management records describing workplace violenceamong Justice Health staff. The three-year study period was 1/7/2007-30/6/2010.ResultsDuring the period under review, 208 incidents of workplace violence were recorded. Verbalabuse (71%) was more common than physical abuse (29%). The most (44%) incidents ofworkplace violence (including both verbal and physical abuse) occurred in adult maleprisons, although the most (50%) incidents of physical abuse occurred in a forensic hospital.Most (90%) of the victims were nurses and two-thirds were females. Younger employees andmales were most likely to be a victim of physical abuse. Preparing or dispensing medicationand attempting to calm and/or restrain an aggressive patient were identified as ‘high risk’work duties for verbal abuse and physical abuse, respectively. Most (93%) of the incidents ofworkplace violence were initiated by a prisoner/patient. Almost all of the incidents receivedeither a medium (46%) or low (52%) Severity Assessment Code. Few victims of workplaceviolence incurred a serious physical injury – there were no workplace deaths during the studyperiod. However, mental stress was common, especially among the victims of verbal abuse(85%). Few (6%) victims of verbal abuse sought help from a health professional.ConclusionsAmong employees of a large correctional health service, verbal abuse in the workplace wassubstantially more common than physical abuse. The most incidents of workplace violenceoccurred in adult male prisons. Review of the types of adverse health outcomes experiencedby the victims of workplace violence and the assessments of severity assigned to violentincidents suggests that, compared with health care settings in the community, correctionalsettings are fairly safe places in which to practice

Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study

The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974–2007, initially aged 20–50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13–1.20), 1.20 (1.14–1.27), 1.26 (1.19–1.34) and 1.09 (0.96–1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01–1.04), 1.03 (1.00–1.05), 1.03 (1.00–1.06) and 0.99 (0.92–1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women