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Extant odontocetes (toothed whales) exhibit differences in body size and brain mass, biosonar mode, feeding strategies, and diving and habitat adaptations. Strong selective pressures associated with these factors have likely contributed to the morphological diversification of their skull. Here, we used 3D landmark geometric morphometric data from the skulls of 60 out of ~ 72 extant odontocete species and a well-supported phylogenetic tree to test whether size and shape variation are associated with ecological adaptations at an interspecific scale. Odontocete skull morphology exhibited a significant phylogenetic signal, with skull size showing stronger signal than shape. After accounting for phylogeny, significant associations were detected between skull size and biosonar mode, body length, brain and body mass, maximum and minimum prey size, and maximum peak frequency. Brain mass was also strongly correlated with skull shape together with surface temperature and average and minimum prey size. When asymmetric and symmetric components of shape were analysed separately, a significant correlation was detected between sea surface temperature and both symmetric and asymmetric components of skull shape, and between diving ecology and the asymmetric component. Skull shape variation of odontocetes was strongly influenced by evolutionary allometry but most of the associations with ecological variables were not supported after phylogenetic correction. This suggests that ecomorphological feeding adaptations vary more between, rather than within, odontocete families, and functional anatomical patterns across odontocete clades are canalised by size constraints.

Increasing numbers of women with HIV are experiencing menopause. We use data from a large, representative sample of women with HIV to describe the prevalence and clustering of menopausal symptoms amongst pre-, peri- and post-menopausal women using hierarchical agglomerative cluster analysis. Of the 709 women included, 21.6%, 44.9% and 33.6% were pre-, peri- and post-menopausal, respectively. Joint pain (66.4%) was the most commonly reported symptom, followed by hot flashes (63.0%), exhaustion (61.6%) and sleep problems (61.4%). All symptoms were reported more commonly by peri- and post-menopausal women compared to pre-menopausal women. Psychological symptoms and sleep problems clustered together at all menopausal stages. Somatic and urogenital symptom clusters emerged more distinctly at peri- and post-menopause. We recommend regular and proactive assessment of menopausal symptoms in midlife women with HIV, with an awareness of how particular patterns of symptoms may evolve over the menopausal transition.

Poor engagement in HIV care is associated with poorer health outcomes and increased mortality. Our survey examined experiential and circumstantial factors associated with clinic attendance among women (n = 250) and men (n = 106) in London with heterosexually-acquired HIV. While no associations were found for women, among men, sub-optimal attendance was associated with insecure immigration status (25.6% vs. 1.8%), unstable housing (32.6% vs. 10.2%) and reported effect of HIV on daily activities (58.7% vs. 40.0%). Among women and men on ART, it was associated with missing doses of ART (OR = 2.96, 95% CI:1.74–5.02), less belief in the necessity of ART (OR = 0.56, 95% CI:0.35–0.90) and more concern about ART (OR = 3.63, 95% CI:1.45–9.09). Not wanting to think about being HIV positive was the top reason for ever missing clinic appointments. It is important to tackle stigma and the underlying social determinants of health to improve HIV prevention, and the health and well-being of people living with HIV.

The false killer whale (Pseudorca crassidens (Owen, 1846)) is a globally distributed delphinid that shows geographical differentiation in its skull morphology. We explored cranial morphological variation in a sample of 85 skulls belonging to a mixed sex population stranded in the Moray Firth, Scotland, in 1927. A three-dimensional digitizer (Microscribe 2GX) was used to record 37 anatomical landmarks on the cranium and 25 on the mandible to investigate size and shape variation and to explore sexual dimorphism using geometric morphometric. Males showed greater overall skull size than females, whereas no sexual dimorphism could be identified in cranial and mandibular shape. Allometric skull changes occurred in parallel for both males and females, supporting the lack of sexual shape dimorphism for this particular sample. Also, fluctuating asymmetry did not differ between crania of males and females. This study confirms the absence of sexual shape dimorphism and the presence of a sexual size dimorphism in this false killer whale population.

BACKGROUND Women with HIV face challenges in engaging in HIV care post partum. We aimed to examine changes in engagement in HIV care through clinic attendance before, during, and after pregnancy, compared with matched women with HIV who had never had a recorded pregnancy. METHODS In this cohort study, we describe changes in engagement in HIV care before, during, and after pregnancy among women with HIV from the UK Collaborative HIV Cohort (CHIC) study from 25 HIV clinics in the UK with a livebirth reported to the National Surveillance of HIV in Pregnancy and Childhood between Jan 1, 2000, and Dec 31, 2017. To investigate whether changes were specific to HIV, we compared these changes to those over equivalent periods among non-pregnant women with HIV in the UK CHIC study matched for ethnicity, year of conception, age, CD4 cell count, viral suppression, and antiretroviral therapy use. Analyses were via logistic regression using generalised estimated equations with an interaction between case-control status (pregnant women vs non-pregnant women) and pregnancy or pseudo pregnancy (for non-pregnant women) stage. FINDINGS 1116 matched pairs of pregnant and non-pregnant women were included (median age 34 years [IQR 30-38], 80·1% Black African, 12·5% white). 69 330 person-months of follow-up were recorded, 25 412 in the before stage, 18 897 during, and 25 021 after pregnancy or pseudo pregnancy stages. Among pregnant women, the proportion of time engaged in care increased during pregnancy (8477 [90·5%] of 9371 person-months) and after pregnancy (10 501 [84·6%] of 12 407), compared with before pregnancy (9979 [78·5%] of 12 707). Among non-pregnant women in the control group, engagement in HIV care remained stable across the three equivalent stages (9688 [76·3%] of 12 705 person-months before pseudo pregnancy; 7463 [78·3%] of 9526 during pseudo pregnancy; and 9892 [78·4%] of 12 614 after pseudo pregnancy). The association of engagement in HIV care with pregnancy or pseudo pregnancy stage differed significantly by case-control status (pinteraction

Background:It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).Methods:CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART.Results:In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj = 0.048 and padj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals.Conclusions:All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.Funding:This work was supported by ZonMw (09120011910035) and FP7 Health (305522).

Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. © 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

OBJECTIVES The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts

HD 54662 AB is one of the three O + OB binaries known so far with orbital period longer than 1000 d, offering the opportunity to test scenarios of massive star formation and models of single stellar evolution. Here, we present a detailed study of this system based on new high-resolution spectra and data. A disentangling method is used to recover the individual spectra of the primary and secondary components, which are classified as O6.5 V(n)z and O7.5 Vz, respectively. Combining radial velocity measurements and astrometric data, a new absolute orbit with a period of 2113 ± 9 d and an eccentricity of 0.062 ± 0.008 is determined, confirming previous findings. However, absolute masses of 23.8 ± 1.1 M¿ for the primary and 20.3 ± 1.1 M¿ for the secondary are obtained, differing from previous determinations but in reasonable agreement with the spectral types of the stars. Primary and secondary components show remarkably different projected rotational velocities (160 and ¿40 $\rm km\, s^{-1}$, respectively), which is probably related to the formation process of the binary. Contrary to previously interpretations, the star with broader spectral features is the most massive object in the system. Stellar and wind parameters of both stars are derived through quantitative spectroscopic analysis of the disentangled spectra using fastwind models, and they are consistent with the current calibrations for O-type stars. Evolutionary masses and ages are also computed with the bonnsai tool. Ages below 2.5 Ma are obtained, in agreement with the youth expected from their Vz nature., With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737)

This article presents 24-h wind speed forecasting for the city of La Serena in Chile and a methodology to explore forecasting effects on the production of wind turbine power. To that end, we used meteorological data from a weather station located in the southern zone of the hyper-arid Atacama Desert. In this area, energy resources are economically and environmentally important, and wind speed forecasting plays a vital role in the management and marketing processes of wind potential via wind farms. To contribute to the development of this energy, we propose carrying out the short-term prediction of 12 and 24 h ahead (identified as Ws( t + 12) and Ws( t + 24), respectively) using an artificial neural network with backpropagation approach. Hourly time series of wind speed, temperature, and relative humidity (from 2003 to 2006) were considered to characterize the artificial neural network in the training phase, while we used data from the year 2007 to check the efficiency of our prediction. For artificial neural network Ws( t + 12) and Ws( t + 24) models, we obtained similar performance of wind speed prediction with root mean square error of around 0.7 m s−1 and with maximum and minimum residuals of +4 and ‒4 m s−1, respectively. Based on the results, we gain a reliable tool to characterize wind speed properties in the range of 1 day within 20% of uncertainty. Moreover, this tool becomes useful to study the effects of our artificial neural network Ws( t + 12) and Ws( t + 24) models on the generation of wind energy from a wind power turbine parametrization.

Introduction Liver transplantation is an important measure of burden from hepatitis C virus (HCV)-associated liver disease. Aims To describe transplant rates and survival in individuals with HCV infection from 2008 to 2017 in England through data linkage. Methods This is a retrospective observational cohort study. Laboratory reports of HCV infection were linked to the Liver Transplant Registry for individuals aged 15 years and over, first diagnosed between 1998 and 2017. We estimated age-sex standardised incidence rates and used Poisson regression to investigate predictors of liver transplantation and test for a change in incidence after introduction of direct-acting antivirals (DAAs) in 2014. Kaplan-Meier survival analysis was used to calculate post-transplant survival rates. Results Of 124,238 individuals diagnosed with HCV infection, 1,480 were registered and 1,217 received a liver transplant. Of individuals registered, 1,395 had post-HCV cirrhosis and 636 had hepatocellular carcinoma (618 also had post-HCV cirrhosis). Median time from HCV diagnosis to transplant was 3.4 years (interquartile range: 1.3–6.8 years). Liver transplant rates were lower 2014–17 compared with 2011–13 (incidence rate ratio: 0.64; 95% confidence interval: 0.55–0.76). Survival rates were 93.4%, 79.9% and 67.9% at 1, 5 and 10 years, respectively. Data linkage showed minimal under-reporting of HCV in the transplant registry. Conclusion In the post-DAA era, liver transplant rates have fallen in individuals with HCV infection, showing early impact of HCV treatment scale-up; but the short time from HCV diagnosis to liver transplant suggests late diagnosis is a problem.

Summary of data collection at each timepoint (Phase 2 â trial). (DOCX 41 kb)

Summary of data collection at each timepoint (Phase 1 â observational study). (DOCX 14 kb)

OBJECTIVES Transmission of drug-resistant HIV-1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013. METHODS Resistance tests conducted in antiretroviral treatment (ART)-naive individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society-USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs. RESULTS TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)-related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first-line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART-naive. CONCLUSIONS We observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first-line ART, including integrase inhibitors, remained reassuringly low.

Background:Response to treatment in psoriatic arthritis (PsA) can be captured using the OMERACT PsA Magnetic Resonance Imaging Score (PsAMRIS). While reliable and valid, PsAMRIS interpretation requires a trained reader to assess inflammatory lesions such as synovitis and flexor tenosynovitis on a discrete scale ranging from 0 to 3, which might not have sufficient sensitivity to capture early and subtle changes in inflammation in small cohorts.Objectives:To propose a novel computer-assisted imaging quantitative methodology to assess early response to treatment on a continuous scale and compare its results with those of PsAMRIS.Methods:Patients with active PsA in the hand and wrist were treated with apremilast 30 mg twice daily after a 5-day titration period. A total of 29 patients underwent MRI scans at baseline and months 3, 6, and 12. Images were scored for synovitis using the PsAMRIS interpreted by an experienced reader and were read in blinded sequences. Images for 13 patients with involvement of the wrist and metacarpophalangeal (MCP) joints and MRI available at baseline, 3 months, and 6 months were further processed using a novel computer-assisted imaging quantitative methodology. Images were scored concurrently, with the reader blinded to the order of visits. An experienced reader pre-defined regions of interest (ROIs) around the wrist, MCP joints (MCP-2 to MCP-5), and flexor and extensor tendons of the fingers and wrist (as applicable) with adjacent blood vessels and possible artifacts excluded from ROIs. From these ROIs, the normalized volume of inflammation (NormI) was calculated in each joint and tendon. This was done by automatically counting the pixels that were enhanced above the intensity level of a muscle. Each enhanced pixel was given a weight corresponding to the degree of enhancement, allowing differentiation of areas of residual inflammation and high perfusion. This method has been validated, tested, and implemented in the CE/FDA510-cleared software package Dynamika (IAG, Image Analysis Group). PsAMRIS responses were compared with those of the computer-assisted imaging quantitative methodology at baseline, 3 months, and 6 months. A heat map of normalized intensities was produced, highlighting areas of perfusion higher than that of healthy muscle. Changes from baseline were tested for significance using at-test. Patients with non-missing data were included in the final statistical analysis.Results:The generated NormI map highlighted a reduction in wrist inflammation activity after 3 and 6 months of treatment with apremilast. In all cases, a downward trend in inflammatory activity in the wrist and MCP joints was observed at 3 months, indicating a reduction following treatment with apremilast (Figures 1 and 2). Similar improvements were observed in tenosynovitis (Figures 1 and 2).Conclusion:In this pilot assessment, apremilast was associated with improvements in synovitis and tenosynovitis over a period of 6 months using PsAMRIS. Assessment of images using NormI, a methodology allowing quantification of inflammatory activity within a joint or tendon, demonstrated the same trends over 6 months. Further studies are planned to determine the sensitivity of this novel computer-assisted imaging quantitative methodology relative to that of PsAMRIS and whether it could be used to provide early indications of treatment response in small cohorts of patients.Disclosure of Interests:Paul Bird Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer – advisor, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Mark Hinton: None declared, Eser Sanverdi Employee of: Image Analysis Group – employment, Romiesa Hagoug Employee of: Image Analysis Group – employment, Christoper Sabin Employee of: Image Analysis Group – employment, Priscila Nakasato Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Benoit Guerette Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Olga Kubassova Shareholder of: IAG, Image Analysis Group, Consultant of: Novartis, Takeda, Lilly, Employee of: IAG, Image Analysis Group

Farr and Mandel reanalyse our data, finding initial-mass-function slopes for high mass stars in 30 Doradus that agree with our results. However, their reanalysis appears to underpredict the observed number of massive stars. Their technique results in more precise slopes than in our work, strengthening our conclusion that there is an excess of massive stars above $30\,\mathrm{M}_\odot$ in 30 Doradus., Comment: Authors' version of a response to a technical comment published in Science; 8 pages, 1 figure

Objectives In persons with hepatitis C virus (HCV) infection, HIV coinfection leads to faster progression to advanced liver disease. The aim of our study was to estimate diagnosed HIV prevalence among people with evidence of current HCV infection (polymerase chain reaction positive) and examine predictors of coinfection. Methods Adults (≥ 15 years old) with a current HCV infection reported to the Public Health England (PHE) sentinel surveillance of blood-borne viruses were linked to the PHE national HIV database using a deterministic methodology. Descriptive and multivariate analyses were conducted. Results Between 2008 and 2014, 5.0% (999/20 088) of adults with a current HCV infection were diagnosed with HIV coinfection. The majority acquired HIV through sex between men (441; 64.9%), followed by injecting drug use (153; 22.5%) and heterosexual contact (84; 12.4%). Of persons who were coinfected, 65.5% had been diagnosed with HIV infection > 6 months before their HCV diagnosis, 41.4% of whom had a negative anti-HCV test between their HIV and HCV diagnoses. In a multivariable model among persons with current HCV infection, an HIV diagnosis was more likely among men [adjusted odds ratio (aOR) 3.29; 95% confidence interval (CI) 2.60-4.16] and persons of black ethnicity (aOR 3.19; 95% CI 1.36-7.46), and less likely among older adults (aOR 0.85 per 10-year increase; 95% CI 0.79-0.92) and persons of Asian ethnicity (aOR 0.59; 95% CI 0.41-0.86). Conclusions Our results indicate that the majority of diagnosed HIV and current HCV coinfections are among men who have sex with men. Safer sex campaigns should include awareness of transmission of HCV among MSM living with HIV.

This dataset contains d13C and d15N stable isotope data from northern hemisphere rorqual whale (Balaenoptera) baleen taken from our collections. This includes data from the baleen of the Hintze Hall blue whale. The data has been used in various research papers. Additional data allow the analyses in these papers to be carried out and mostly encompass environmental datasets or the outputs of various simulation models. **Note that if trying to link these data to analyses in GitHub, an update to this site has changed all "." in column headers to "_". These will need to be changed before the code will work. Apologies.**

Data from the paper: **What can cetacean stranding records tell us? A study of UK and Irish cetacean diversity over the past 100 years**. Ellen J. Coombs et al. 2019. *Marine Mammal Science*, DOI: [https://doi.org/10.1111/mms.12610](https://doi.org/10.1111/mms.12610). This dataset contains information on cetaceans stranded in the UK and Ireland between 1913 and 2015. It also contains yearly data on various environmental variables believed to influence strandings. The full strandings datasets are available from: * UK (1913 - 1989): NHM Data Portal: [https://doi.org/10.5519/0028204](https://doi.org/10.5519/0028204). * UK (1990 - 2015): CSIP http://data.ukstrandings.org * Irish records (1990 - 2015): Irish Whale and Dolphin group (contact them for access).

The electrochemical, structural and photoelectrochemical properties of blend of a low-viscosity IL 1-ethyl 3-methyl imidazolium dicynamide (EMIM DCA, viscosity 17 cP) in poly(vinylidene fluoride-hexafluoropropylene) (PVdF-HFP) are presented in detail. The blending of low-viscous IL provides charge carriers with higher mobility which are significantly observed in ionic conductivity measurement. The incorporation of IL provides more amorphous region within polymer matrix which is known as a beneficial condition for conductivity enhancement and are affirmed by our DSC and XRD measurements. The fabricated supercapacitor with configuration MWCNT/PVdF-HFP +IL/MWCN shows promising results.

Objectives We sought to compare all‐cause mortality of people living with HIV and accessing care in Canada and the UK. Methods Individuals from the Canadian Observational Cohort (CANOC) collaboration and UK Collaborative HIV Cohort (UK CHIC) study who were aged ≥ 18 years, had initiated antiretroviral therapy (ART) for the first time between 2000 and 2012 and who had acquired HIV through sexual transmission were included in the analysis. Cox regression was used to investigate the difference in mortality risk between the two cohort collaborations, accounting for loss to follow‐up as a competing risk. Results A total of 19 960 participants were included in the analysis (CANOC, 4137; UK CHIC, 15 823). CANOC participants were more likely to be older [median age 39 years (interquartile range (IQR): 33, 46 years) vs. 36 years (IQR: 31, 43 years) for UK CHIC participants], to be male (86 vs. 73%, respectively), and to report men who have sex with men (MSM) sexual transmission risk (72 vs. 56%, respectively) (all P < 0.001). Overall, 762 deaths occurred during 98 798 person‐years (PY) of follow‐up, giving a crude mortality rate of 7.7 per 1000 PY [95% confidence interval (CI): 7.1, 8.3 per 1000 PY]. The crude mortality rates were 8.6 (95% CI: 7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study participants, respectively. No statistically significant difference in mortality risk was observed between the cohort collaborations in Cox regression accounting for loss to follow‐up as a competing risk (adjusted hazard ratio 0.86; 95% CI: 0.72–1.03). Conclusions Despite differences in national HIV care provision and treatment guidelines, mortality risk did not differ between CANOC and UK CHIC study participants who acquired HIV through sexual transmission.

Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 +/- 1 months, (2) 6 +/- 1 months, and (3) 9-12 +/- 1 months. We used inverseprobability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -25.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

On the basis of the Galactic O Star Spectroscopic Survey (GOSSS), we present a detailed systematic investigation of the O Vz stars. The currently used spectral classification criteria are rediscussed, and the Vz phenomenon is recalibrated through the addition of a quantitative criterion based on the equivalent widths of the He i λ4471, He ii λ4542, and He ii λ4686 spectral lines. The GOSSS O Vz and O V populations resulting from the newly adopted spectral classification criteria are comparatively analyzed. The locations of the O Vz stars are probed, showing a concentration of the most extreme cases toward the youngest star-forming regions. The occurrence of the Vz spectral peculiarity in a solar-metallicity environment, as predicted by the fastwind code, is also investigated, confirming the importance of taking into account several processes for the correct interpretation of the phenomenon., Instituto de Astrofísica de La Plata, Facultad de Ciencias Astronómicas y Geofísicas

Objectives Current British HIV Association (BHIVA) guidelines recommend that all patients with a CD4 count

Objective: To assess the genotypic determinants of the virological response to didanosine (ddI) in HIV-infected patients.Methods: The Forum database on ddI was randomly divided into a derivation set (n=1000) and a validation set (n=453). Linear regression models and bootstrap sampling were used to select resistance mutations and to estimate their resistance scores. Linear regression models, accounted for the censoring of viral load measurements due to assay lower limits, of the week 8 reduction in viral load from baseline were adjusted for baseline viral load, the exact number of weeks between baseline and the week 8 viral load measurements, and the Stanford genotypic sensitivity score.Results: The ddI resistance mutations and their resistance scores based on the derivation set were as follows: M41L (score of 14), T69D (24), D123S (40), T139M (54), I180V (53), M184V (-12), V1891 (55), Q207K (37), L210W (25), and T215Y (eight). The total score is obtained by adding the individual scores. Viruses with scores of 19 or less, 20-59, and 60 or more are considered sensitive, intermediate, and resistant, respectively. In the validation set, respectively, 58.7, 36.9, and 4.4% of viruses were predicted to be sensitive, intermediate, and resistant to ddI. The observed viral load reductions at week 8 were, respectively, 1.51 log(10)copies/ml [interquartile range (IQR) 1.26-1.76] (P=0.0001 versus resistant), 1.11 (0.94-1.30) (P=0.0077 versus sensitive), and 0.46 (0.32-0.74) (P=0.0079 versus intermediate).Conclusion: We developed a genotypic resistance score for didanosine including four mutations never previously used. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Life expectancy (LE) is an important indicator of health used widely by government and healthcare agencies to monitor trends over time and to determine resource allocation, as well as by insurance companies and pension providers. LE of the HIV-positive population has increased dramatically since the introduction of combination antiretroviral therapy (cART); indeed, it is now believed that LE may be similar to that of the general population in some subgroups. There are, however, specific subgroups in which LE remains substantially impaired. The impact of HIV and of cART on mortality may be expressed in several ways. LE itself provides an estimate of the average additional number of years that an individual would be expected to live beyond a particular age. However, the detrimental impact of HIV may also be described in terms of the number of years of life lost or the gains in LE if HIV were to be eliminated as a cause of morbidity in the population. My presentation will start with a description of the different methods that researchers have used to describe the mortality outcomes of those with HIV, and the impact of cART on these. I will then consider how LE in the HIV-positive population has changed over time and will describe the impact of demographic factors (e.g. gender, age, ethnic group) on LE. To investigate the circumstances under which LE may return to normal levels, I will also consider the potential impact of timely diagnosis and linkage into care, continued engagement with care, optimal initiation of cART and maintenance of viral suppression on LE. Finally, I will discuss some of the limitations of the approaches used to estimate LE, with particular emphasis on the confounding effects of lifestyle and behavioural factors when making any comparison with LE in the general population.

We identified predictors of clinical complexity based on data collected in the UK CHIC Study. All subjects under established care (>1 year) from 2000-2010 were included. Each subject’s follow-up (1 year after study entry to last clinic visit, death or 31/12/2010) was stratified into a series of 6-monthly periods and his/her status was assessed at the start of each. Using Poisson regression (with generalised estimating equations to allow for multiple entries per subject), we studied associations between demographic/clinical factors, CD4 count/percent, viral load (VL), calendar year and measures of prior/current antiretroviral (ART) use, and the development of a new AIDS event or death during each period. A complexity score was derived from the coefficients of the final model; subjects were categorised into ten equally sized groups based on the score, and event rates were calculated for each group. The 31,338 eligible subjects had a median (interquartile range) age of 36 (10, 42) years at baseline. Ethnicity was white (55%), black African (27%), black other (5%), other (9%) and unknown (4%). Mode of acquisition was sex between men (52%), heterosexual sex (37%), other (5%) and unknown (5%). Subjects contributed a total of 377,284 periods of follow-up (181,170 person-years [PY]) of which 5796 included a clinical event (rate/1000 PY: 3.20 [95% confidence interval 3.12, 3.28], 4322 AIDS events, 1534 deaths). As an active AIDS-defining event in the past 6 months was the dominant predictor of a new clinical event (relative rate 41.55), subjects with an active event were excluded from further analysis. Risk factors for a clinical event in patients without an active AIDS event (Table 1) were earlier calendar year, non-white ethnicity, older age, lower CD4 count, >80 CD4 cell drop from previous visit, being off ART or on ART with a VL >10,000 copies/ml. Hepatitis co-infection and previous experience of immune suppression were associated with lower clinical risk. A score based on this model discriminated reasonably well between subjects who did/did not develop an endpoint over the next 6 months (approximate C-statistic: 0.72), with event rates increasing from 0.49/100 PY in the lowest score group to 7.16/100 PY in the highest. A score based on clinical markers may provide a means to identify those who will experience clinical progression over the next 6 months, allowing this group to be targeted for closer monitoring and funds for HIV care to be distributed appropriately. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Sabin C and Delpech V. Journal of the International AIDS Society 2012, 15 (Suppl 4):18133 http://www.jiasociety.org/index.php/jias/article/view/18133 | http://dx.doi.org/10.7448/IAS.15.6.18133

We recently showed that a urine albumin/total protein ratio (uAPR) 0.4 identifies tubular pathology in proteinuric patients. In tubular disorders, proteinuria is usually of low molecular weight and contains relatively little albumin. We tested the hypothesis that uAPR is useful in identifying tubular pathology related to antiretroviral use in HIV-infected patients.We retrospectively identified urine protein/creatinine ratios (uPCRs) in HIV-infected patients. A subset of samples had uPCR and urine albumin/creatinie ratio (uACR) measured simultaneously. We classified proteinuric patients (uPCR 30 mg/mmol) into two groups: those with predominantly 'tubular' proteinuria (TP) (uAPR 0.4) and those with predominantly 'glomerular' proteinuria (GP) (uAPR ≥ 0.4).A total of 618 of 5244 samples from 1378 patients had uPCR ≥ 30 mg/mmol. uAPRs were available in 144 patients: 46 patients (32%) had TP and 21 (15%) GP; the remainder had uPCR 30 mg/mmol. The TP group had a higher fractional excretion of phosphate compared with the GP group (mean 27% vs. 16%, respectively; P0.01). Patients with TP were more likely to be on tenofovir and/or a boosted protease inhibitor compared with those with GP. In 18 patients with heavy proteinuria (uPCR 100 mg/mmol), a renal assessment was made; eight had a kidney biopsy. In all cases, the uAPR results correlated with the nephrological diagnosis.In HIV-infected patients, measuring uAPR may help to identify patients in whom a renal biopsy is indicated, and those in whom tubular dysfunction might be an important cause of proteinuria and which may be related to antiretroviral toxicity. We suggest that this would be useful as a routine screening procedure in patients with proteinuria.

The aim of the study was to estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV infection.Patients who reported smoking status and no previous CVD prior to enrolment in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were included in this study. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Time since stopping smoking was calculated for persons who had reported current smoking during follow-up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD: MI plus invasive coronary artery procedure or death from other CHD); CVD (CHD plus carotid artery endarterectomy or stroke); and all-cause mortality. Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow-up. Incidence rate ratios (IRRs) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral treatment.A total of 27 136 patients had smoking status reported, with totals of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events, respectively. The adjusted IRR of CVD in patients who stopped smoking during follow-up decreased from 2.32 within the first year of stopping to 1.49 after3 years compared with those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all-cause mortality.The risk of CVD events in HIV-positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV-positive patients.

The VLT-FLAMES Tarantula Survey (VFTS) is an ESO Large Programme that has obtained multi-epoch optical spectroscopy of over 800 massive stars in the 30 Doradus region of the Large Magellanic Cloud (LMC). Here we introduce our scientific motivations and give an overview of the survey targets, including optical and near-infrared photometry and comprehensive details of the data reduction. One of the principal objectives was to detect massive binary systems via variations in their radial velocities, thus shaping the multi-epoch observing strategy. Spectral classifications are given for the massive emission-line stars observed by the survey, including the discovery of a new Wolf-Rayet star (VFTS 682, classified as WN5h), 2' to the northeast of R136. To illustrate the diversity of objects encompassed by the survey, we investigate the spectral properties of sixteen targets identified by Gruendl & Chu from Spitzer photometry as candidate young stellar objects or stars with notable mid-infrared excesses. Detailed spectral classification and quantitative analysis of the O- and B-type stars in the VFTS sample, paying particular attention to the effects of rotational mixing and binarity, will be presented in a series of future articles to address fundamental questions in both stellar and cluster evolution., Accepted by A&A, 52 pages (main body: 19 pages, supplementary tables: 33 pages), v3: two classifications updated to match a parallel paper

Massive stars play a key role in environments with very different metallicities. To interpret the role of massive stars in these systems we have to know their properties at different metallicities. The Local Group offers an excellent laboratory to this aim.

We investigated whether adverse responses to highly active antiretroviral therapy (HAART) associated with late HIV presentation are secondary to low CD4 cell count per se or other confounding factors.A longitudinal analysis of the UK Collaborative HIV Cohort (CHIC) Study of individuals starting HAART in 1998-2007 was carried out, comparing late presenters (presenting/starting HAART at a CD4 count200 cells/μL) with late starters (presenting at a CD4 count350 cells/μL; starting HAART at a CD4 count200 cells/μL), using 'ideal starters' (presenting at a CD4 count350 cells/μL; starting HAART at a CD4 count of 200-350 cells/μL) as a comparator. Virological, immunological and clinical (new AIDS event/death) outcomes at 48 and 96 weeks were analysed, with the analysis being limited to those remaining on HAART for3 months.A total of 4978 of 9095 individuals starting first-line HAART with HIV RNA500 HIV-1 RNA copies/mL were included in the analysis: 2741 late presenters, 947 late starters and 1290 ideal starters. Late presenters were more commonly female, heterosexual and Black African. Most started nonnucleoside reverse transcriptase inhibitors (NNRTIs); 48-week virological suppression was similar in late presenters and starters (and marginally lower than in ideal starters); by week 96 differences were reduced and nonsignificant. The median CD4 cell count increase in late presenters was significantly lower than that in late starters (weeks 48 and 96). During year 1, new clinical events were more frequent for late presenters [odds ratio (OR) 2.04; 95% confidence interval (CI) 1.19-3.51; P=0.01]; by year 2, event rates were similar in all groups.Amongst patients who initiate, and remain on, HAART, late presentation is associated with lower rates of virological suppression, blunted CD4 cell count increases and more clinical events compared with late starters in year 1, but similar clinical and immunological outcomes by year 2 to those of both late and ideal starters. Differences between late presenters and late starters suggest that factors other than CD4 cell count alone may be driving adverse treatment outcomes in late-presenting individuals.

Across Europe, almost a third of individuals infected with HIV do not enter health care until late in the course of their infection. Surveillance to identify the extent to which late presentation occurs remains inadequate across Europe and is further complicated by the lack of a common clinical definition of late presentation. The objective of this article is to present a consensus definition of late presentation of HIV infection.Over the past year, two initiatives have moved towards a harmonized definition. In spring 2009, they joined efforts to identify a common definition of what is meant by a 'late-presenting' patient.Two definitions were agreed upon, as follows. Late presentation: persons presenting for care with a CD4 count below 350 cells/μL or presenting with an AIDS-defining event, regardless of the CD4 cell count. Presentation with advanced HIV disease: persons presenting for care with a CD4 count below 200 cells/μL or presenting with an AIDS-defining event, regardless of the CD4 cell count.The European Late Presenter Consensus working group believe it would be beneficial if all national health agencies, institutions, and researchers were able to implement this definition (either on its own or alongside their own preferred definition) when reporting surveillance or research data relating to late presentation of HIV infection.

Background Our aim was to investigate the respective role of statistical methodology and patients' baseline characteristics in the selection of mutations included in genotypic resistance scores. Methods As an example, the FORUM database on didanosine including 1453 patients was used. We split this population into four samples based on countries of enrolment (France n = 474, Italy n = 440, USA/Canada n = 219, others n = 320). We used both a continuous outcome measure (the viral load reduction at week 8) and a binary outcome measure (viral load decline at week 8 or =0.6 log(10)) and both parametric and non-parametric methods for each outcome. Results Overall, 61 distinct mutations were selected by at least one method in at least one data set. The variability due to baseline characteristics varies from 79% to 88%, i.e. for a given method applied to the four data sets >80% of the mutations are selected only once. The variability induced by the methodology varies from 49% to 56%, i.e. for a given data set approximately 50% of the mutations are selected by at least two methods. Conclusions Baseline patient characteristics contribute more than the choice of statistical method to the variability of the mutations to be included in the genotypic resistance scores.

We examined the prevalence of hepatitis C virus (HCV) infection among HIV-positive individuals in the UK, trends in HCV testing and the impact of HCV on HIV treatment outcomes. Trends over time in HCV prevalence were calculated using each patient's most recent HCV status at the end of each calendar year. Logistic regression was used to identify factors associated with having a HCV antibody test, and Cox regression was used to determine whether HCV status was associated with the time to experiencing an immunological response to highly active antiretroviral treatment (HAART), time to virological response and viral rebound. Of the 31,765 HIV-positive individuals seen for care between January 1996 and September 2007, 20,365 (64.1%) individuals were tested for HCV, and 1807 (8.9%) had detectable HCV antibody. The proportion of patients in follow-up ever tested for HCV increased over time, from 782/8505 (9.2%) in 1996 to 14,280/17,872 (79.9%) in 2007. Nine thousand six hundred and sixty-nine individuals started HAART for the first time in or after January 2000, of whom, 396 (4.1%) were HCV positive. Presence of HCV infection did not affect initial virological response, virological rebound or immunological response. The cumulative prevalence of HCV in the UK CHIC Study is 8.9%. Despite UK guidelines, over 20% of HIV-positive individuals have not had their HCV status determined by 2007. HCV infection had no impact on HIV virological outcomes or immunological response to HIV treatment. The long-term impact on morbidity and mortality remain to be determined.