The effect of smoking on the severity of mechanisms of acute exacerbations of COPD

COPD (Chronic Obstructive Pulmonary Disease) worldwide has a prevalence of 10% in men and 8.5% in women. Exacerbations of COPD account for approximately 10% of all acute medical admissions. Projected prevalence figures suggest that by 2020 COPD will be the third leading cause of mortality worldwide thus imposing a significant burden on healthcare resources in the future. Acute exacerbations are not only responsible for a decline in the patient’s quality of life, but have a major socioeconomic impact. Following a pilot study that showed current smokers recover lung function much more slowly from their exacerbation than ex smokers, I initiated a properly powered prospective study to investigate the difference between the two groups.A total of 58 patients admitted with acute infectious exacerbations of COPD were recruited to the study to determine the effect of smoking status on their exacerbation. Throughout the admission lung function was measured. Sputum was cultured for bacteria, and PCR used to detect viral infection. Blood and sputum cells were analyzed by flow cytometry. Serum was collected for CRP levels.Ex-smokers recovered significantly more quickly than current smokers in all spirometric parameters (P<0.01), and were discharged sooner (mean 3.08 vs 5.59 days, P<0.001). Sputum culture was positive for more pathogenic bacteria in current smokers, especially H. influenzae, which was associated with a significantly higher CRP rise (p<0.05) than any other organism. CD8+ T cells predominated in the sputum of ex-smokers while CD4+ T cells were the dominant cell type in current smokers (p<0.01).Current smoking is a risk factor for more severe exacerbations, delayed recovery and prolonged hospitalization. This may result from a variety of factors including bacterial, immune mediated responses and systemic inflammation

The International Law Commission’s Draft Articles on the Law of International Watercourses: Principles and Planned Measures

52 pages. Contains 6 pages of footnotes

The International Law Commission’s Draft Articles on the Law of International Watercourses: Principles and Planned Measures

52 pages. Contains 6 pages of footnotes

Contrasted morphologies of the Western and Eastern Piedmonts of the Mt Lofty Ranges, South Australia

The Mt Lofty Ranges is a horst that evolved in two stages. The western margin developed as part of the South Australian Shatter Belt during the separation of Australia and Antarctica. Gulf St Vincent formed at this time. Though recurrently active the upland dates essentially from the Early Eocene with major uplift in the later Cenozoic. By contrast, the eastern faulted margin postdates the Middle Miocene. Also, whereas the western piedmont and upland were affected by Late Cenozoic sea level changes and all that those imply for river behaviour, the eastern sector was buttressed against such fluctuations by the massive Miocene limestone deposited in the Murray Basin immediately to the east. Consequently, the western piedmont is dominated by alluvial fans, but the eastern is complex, with well-developed scarp-foot depressions, exhumed landforms, and dunefields in some sectors.La cadena montañosa del Monte Lofty es un horst que se originó en dos etapas. Su margen oeste se desarrolló como parte del “Shatter Belt” de Australiadel Sur durante la separación de Australia y la Antártida. El golfo de San Vicente se originó en esa época. Aunque recurrentes en el tiempo, los levantamientos tectónicos se inician esencialmente al inicio del Eoceno y con el mayor ascenso al final del Cenozoico. Por el contrario, el margen fallado del este es al final el Mioceno Medio. Por otra parte, mientras el piedemonte y las zonas levantadas del oeste se vieron afectadas por los cambios del nivel del mar durante el Cenozoico tardío, y lo que ello implicó en el comportamiento de los ríos, el sector este fue protegido de esos cambios por la gran masa de calizas del Mioceno que rellenan la cuenca Murray, inmediatamente al este. Por tanto, el piedemonte oeste está dominado por abanicos aluviales mientras que el del este es complejo, con depresiones de pie de escarpe bien desarrolladas, formas exhumadas y campos de dunas en algunos sectores

What qualities in a potential HIV pre-exposure prophylaxis service are valued by black men who have sex with men in London? A qualitative acceptability study.

Black men who have sex with men (BMSM) have higher HIV incidence and prevalence when compared to other MSM, despite similar levels of condom use and testing. Pre-exposure prophylaxis (PrEP) could be a useful intervention to reduce these inequalities. This research therefore aims to understand the dimensions of acceptability of a potential PrEP service for BMSM aged 18-45 years in London. In-depth semi-structured interviews were conducted with 25 PrEP-eligible BMSM between April and August 2016. Interviews were recorded and transcribed verbatim, then subject to a thematic framework analysis, informed by intersectionality theory. BMSM had distinct preferences for sexual health services, which have implications for PrEP service development. Three primary domains emerged in our analysis: proximity and anonymity; quality, efficiency and reassurance; and understanding, empathy and identity. These relate, respectively, to preferences regarding clinic location and divisions from community, features of service delivery and staff characteristics. Due to concerns about confidentiality, community-based services may not be useful for this group. Careful consideration in regards to components used in service development will facilitate ongoing engagement. Interpersonal skills of staff are central to service acceptability, particularly when staff are perceived to be from similar cultural backgrounds as their patients

STEM graduates in non STEM jobs (BIS Research Paper number 30)

"This report documents extensive new research, commissioned by the Department for Business, Innovation & Skills (BIS) in 2009, into the early careers and career decisions of STEM (Science, Technology, Engineering and Mathematics) students and graduates in order to understand why many elect not to enter STEM occupations and/or STEM employment sectors and what influences these career choices." - Page 13

Deprotonation by Dehydration: The Origin of Ammonium Sensing in the AmtB Channel

The AmtB channel passively allows the transport of NH(4) (+) across the membranes of bacteria via a “gas” NH(3) intermediate and is related by homology (sequentially, structurally, and functionally) to many forms of Rh protein (both erythroid and nonerythroid) found in animals and humans. New structural information on this channel has inspired computational studies aimed at clarifying various aspects of NH(4) (+) recruitment and binding in the periplasm, as well as its deprotonation. However, precise mechanisms for these events are still unknown, and, so far, explanations for subsequent NH(3) translocation and reprotonation at the cytoplasmic end of the channel have not been rigorously addressed. We employ molecular dynamics simulations and free energy methods on a full AmtB trimer system in membrane and bathed in electrolyte. Combining the potential of mean force for NH(4) (+)/NH(3) translocation with data from thermodynamic integration calculations allows us to find the apparent pK(a) of NH(4) (+) as a function of the transport axis. Our calculations reveal the specific sites at which its deprotonation (at the periplasmic end) and reprotonation (at the cytoplasmic end) occurs. Contrary to most hypotheses, which ascribe a proton-accepting role to various periplasmic or luminal residues of the channel, our results suggest that the most plausible proton donor/acceptor at either of these sites is water. Free-energetic analysis not only verifies crystallographically determined binding sites for NH(4) (+) and NH(3) along the transport axis, but also reveals a previously undetermined binding site for NH(4) (+) at the cytoplasmic end of the channel. Analysis of dynamics and the free energies of all possible loading states for NH(3) inside the channel also reveal that hydrophobic pressure and the free-energetic profile provided by the pore lumen drives this species toward the cytoplasm for protonation just before reaching the newly discovered site

What are the motivations and barriers to pre-exposure prophylaxis (PrEP) use among black men who have sex with men aged 18-45 in London? Results from a qualitative study.

BACKGROUND: Black men who have sex with men (BMSM) have higher HIV incidence and prevalence when compared with other men who have sex with men, despite similar risk profiles. New prevention technologies, including pre-exposure prophylaxis (PrEP), may be effective in responding to these inequalities, provided they are appropriately targeted and acceptable to their intended beneficiaries. This study aims to understand the motivations and barriers of BMSM aged 18-45 to PrEP uptake. METHODS: Twenty-five BMSM recruited through geolocation social networking apps took part in in-depth interviews between April and August 2016. Intersectionality theory was used as an organising principle. Interviews were transcribed verbatim and analysed using a thematic framework analysis. RESULTS: For BMSM with heterogeneous social groups, discussions about sexual health were challenging because of the intersection of ethnic background, family history and religion. This limited conversations about PrEP to gay male friends who often held stigmatising views of condomless anal intercourse. BMSM reported exclusion from gay male spaces (online and offline) which could serve to restrict exposure to PrEP messages. Stereotypes of BMSM intersected with negative conceptions of PrEP users, limiting acknowledgement of PrEP candidacy. For those who had attempted to or successfully accessed it, PrEP was framed as a strategy to mitigate risk and to guard against further stigma associated with HIV infection. DISCUSSION: BMSM operate within a complex set of circumstances related to the intersection of their sexual, ethnic, cultural and religious identities, which shape PrEP acceptability. Interventions which seek to facilitate uptake in this group must be attentive to these. Health promotion and clinical services could seek to facilitate nuanced discussions about the merits of PrEP for those at frequent risk, perhaps while also providing publicly visible PrEP role models for BMSM and other marginalised groups

Sexual selection, automata and ethics in George Eliot's The Mill on the Floss and Olive Schreiner's Undine and From Man to Man

This paper brings together two related areas of debate in the latter half of the nineteenth century. The first concerns how the courtship plot of the nineteenth-century novel responded to, and helped to shape, scientific ideas of sexual competition and selection. In The Mill on the Floss (1860), George Eliot strikingly prefigures Darwin's later work on sexual selection, drawing from her own extensive knowledge of the wider debates within which evolutionary theory developed. Maggie Tulliver's characterisation allows Eliot to explore the ethical complexities raised by an increasingly powerful scientific naturalism, where biology is seen to be embedded within morality in newly specific ways. The second strand of the paper examines the extension of scientific method to human mind and motivation which constituted the new psychology. It argues that there are crucial continuities of long-established ethical and religious ideas within this increasingly naturalistic view of human mind and motivation. The contention that such ideas persist and are transformed, rather than simply jettisoned, is illustrated through the example of Thomas Henry Huxley's 1874 essay on automata. Turning finally to focus on Olive Schreiner's Undine (1929) and From Man to Man (1926), the paper explores the importance of these persistent ethical and religious ideas in two novels which remained unpublished during her lifetime. It argues that they produce both difficulty and opportunity for imagining love plots within the context of increasingly assertive biological and naturalistic accounts of human beings