Molecular evolution and morphological speciation in North Atlantic brachiopods (Terebratulina spp.)

Morphological and molecular differentiation of western and eastern North Atlantic brachiopods were examined by morphometric analysis of six shell characteristics (<i>n</i>= 144), allozyme electrophoresis at six nuclear gene loci (<i>n</i>= 485), and estimation of nucleotide difference by digestion of mitochondrial DNA (mtDNA) with nine restriction endonucleases (<i>n</i>= 96)

Sequence Distances between env Genes of HIV-1 from Individuals Infected from the Same Source: Implications for the Investigation of Possible Transmission Events

AbstractPreviously described transmission studies have shown that HIV strains isolated from individuals infected from a common source are more homogeneous than HIV strains isolated from individuals with unrelated infections. This has been the basis, in at least four instances, for deciding whether apparently epidemiologically related cases represent actual transmissions. To date, HIV transmission studies have usually included sequence data from the most likely source of infection, and the probability of transmission from the donor to the recipient has been assessed by measuring sequence similarity against control data using likelihood analysis. We have recently studied a putative transmission involving a UK health care worker (CPHL1), a patient of CPHL1 (CPHL2), and CPHL3, a member of the same "sex circle" as CPHL2. We have used sequence distance and neighbour joining methods as well as likelihood analysis as means of determining genetic relatedness. Though no other source of infection was available our findings did not support the possibility that CPHL1 had infected CPHL2. Strain CPHL3 was closer to CPHL2 than to CPHL1. It is shown that control data from documented transmission events can be used to establish the source of infection in the absence of an index case. It is also shown that the C2-V3 region analysed in previous transmission studies is unreliable for accurate phylogenetic analysis. The results indicated that gp120 is a more informative region than C2-V3 for molecular transmission studies. Sequence distances between the env genes of related and unrelated infections have been derived in this work

Neutralizing antibody response during acute and chronic hepatitis C virus infection

Little is known about the role of Abs in determining the outcome of hepatitis C virus (HCV) infection. By using infectious retroviral pseudotypes bearing HCV glycoproteins, we measured neutralizing Ab (nAb) responses during acute and chronic HCV infection. In seven acutely infected health care workers, only two developed a nAb response that failed to associate with viral clearance. In contrast, the majority of chronically infected patients had nAbs. To determine the kinetics of strain-specific and crossreactive nAb emergence, we studied patient H, the source of the prototype genotype 1a H77 HCV strain. An early weak nAb response, specific for the autologous virus, was detected at seroconversion. However, neutralization of heterologous viruses was detected only between 33 and 111 weeks of infection. We also examined the development of nAbs in 10 chimpanzees infected with H77 clonal virus. No nAb responses were detected in three animals that cleared virus, whereas strain-specific nAbs were detected in six of the seven chronically infected animals after approximately 50 weeks of infection. The delayed appearance of high titer crossreactive nAbs in chronically infected patients suggests that selective mechanism(s) may operate to prevent the appearance of these Abs during acute infection. The long-term persistence of these nAbs in chronically infected patients may regulate viral replication

Public art today. How public art sheds light on the future of the theory of commons

Public art and common goods, although belonging to apparently distant realms of inquiry, share a long history and, inevitably, an evolving meaning. This chapter investigates the evolution of the practice of public art with the objective to obtain a viable understanding of how the value of public art is produced today. With a focus on the future of public art, this chapter investigates three public art cases. The results of the qualitative analysis of these public art experiences are interpreted from an institutional economics perspective. The combination of public art and the theory of commons sheds light on what seems to be the most important attributes of common goods in the current debate, that is the social practices that constitute the act of making the commons.</p

Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression

Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. Our knowledge of the host pathways that define susceptibility to infection and disease severity are limited. Hypoxia inducible factors (HIFs) define metabolic responses to low oxygen and regulate inflammatory responses in the lower respiratory tract. We demonstrate a role for HIFs to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors reduce the expression of the RSV entry receptor nucleolin and inhibit viral cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for this respiratory pathogen

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Young people’s perceptions of smartphone-enabled self-testing and online care for sexually transmitted infections: qualitative interview study

Background Control of sexually transmitted infections (STI) is a global public health priority. Despite the UK’s free, confidential sexual health clinical services, those at greatest risk of STIs, including young people, report barriers to use. These include: embarrassment regarding face-to-face consultations; the time-commitment needed to attend clinic; privacy concerns (e.g. being seen attending clinic); and issues related to confidentiality. A smartphone-enabled STI self-testing device, linked with online clinical care pathways for treatment, partner notification, and disease surveillance, is being developed by the eSTI2 consortium. It is intended to benefit public health, and could do so by increasing testing among populations which underutilise existing services and/or by enabling rapid provision of effective treatment. We explored its acceptability among potential users. Methods In-depth interviews were conducted in 2012 with 25 sexually-experienced 16–24 year olds, recruited from Further Education colleges in an urban, high STI prevalence area. Thematic analysis was undertaken. Results Nine females and 16 males participated. 21 self-defined as Black; three, mixed ethnicity; and one, Muslim/Asian. 22 reported experience of STI testing, two reported previous STI diagnoses, and all had owned smartphones. Participants expressed enthusiasm about the proposed service, and suggested that they and their peers would use it and test more often if it were available. Utilizing sexual healthcare was perceived to be easier and faster with STI self-testing and online clinical care, which facilitated concealment of STI testing from peers/family, and avoided embarrassing face-to-face consultations. Despite these perceived advantages to privacy, new privacy concerns arose regarding communications technology: principally the risk inherent in having evidence of STI testing or diagnosis visible or retrievable on their phone. Some concerns arose regarding the proposed self-test’s accuracy, related to self-operation and the technology’s novelty. Several expressed anxiety around the possibility of being diagnosed and treated without any contact with healthcare professionals. Conclusions Remote STI self-testing and online care appealed to these young people. It addressed barriers they associated with conventional STI services, thus may benefit public health through earlier detection and treatment. Our findings underpin development of online care pathways, as part of ongoing research to create this complex e-health intervention

Regional spread of HIV-1 M subtype B in middle-aged patients by random env-C2V4 region sequencing

A transmission cluster of HIV-1 M:B was identified in 11 patients with a median age of 52 (range 26–65) in North-East Germany by C2V4 region sequencing of the env gene of HIV-1, who—except of one—were not aware of any risky behaviour. The 10 male and 1 female patients deteriorated immunologically, according to their information made available, within 4 years after a putative HIV acquisition. Nucleic acid sequence analysis showed a R5 virus in all patients and in 7 of 11 a crown motif of the V3 loop, GPGSALFTT, which is found rarely. Analysis of formation of this cluster showed that there is still a huge discrepancy between awareness and behaviour regarding HIV transmission in middle-aged patients, and that a local outbreak can be detected by nucleic acid analysis of the hypervariable env region

Young women's decisions to accept chlamydia screening: influences of stigma and doctor-patient interactions

<p>Abstract</p> <p>Background</p> <p>An understanding of the factors that encourage young women to accept, and discourage them from accepting, STI (sexually transmitted infection) testing is needed to underpin opportunistic screening programs for the STI <it>Chlamydia trachomatis </it>(opportunistic screening involves healthcare professionals offering chlamydia tests to people while they are attending health services for reasons that are usually unrelated to their sexual health). We conducted a qualitative study to identify and explore: how young women would feel about being offered opportunistic tests for chlamydia?; how young women would like to be offered screening, and who they wanted to be offered screening by?; and what factors would influence young women's partner notification preferences for chlamydia (who they would notify in the event of a positive diagnosis of chlamydia, how they would want to do this).</p> <p>Methods</p> <p>Semi-structured interviews with 35 young women between eighteen and twenty nine years of age. The study was conducted in the Dublin and Galway regions of the Republic of Ireland. Young adults were recruited from General Practice (GP) practices, Third Level College health services, Family Planning clinics and specialist STI treatment services.</p> <p>Results</p> <p>Respondents were worried that their identities would become stigmatised if they accepted screening. Younger respondents and those from lower socio-economic backgrounds had the greatest stigma-related concerns. Most respondents indicated that they would accept screening if it was offered to them, however; accepting screening was seen as a correct, responsible action to engage in. Respondents wanted to be offered screening by younger female healthcare professionals. Respondents were willing to inform their current partners about positive chlamydia diagnoses, but were more ambivalent about informing their previous partners.</p> <p>Conclusions</p> <p>If an effort is not put into reducing young women's stigma-related concerns the population coverage of Chlamydia screening might be reduced.</p