Brain cell reservoirs of latent virus in presymptomatic HIV-infected individuals

We detected HIV-1 DNA in pure populations of perivascular macrophages, parenchymal microglia, and astrocytes, isolated using laser microdissection from brain tissue of five untreated individuals who died in the presymptomatic stage of infection from non-HIV causes. HIV-1 DNA was detected in the three cell populations, most consistently in perivascular macrophages, without evidence of productive infection. The percentage of PCR reactions detecting HIV-1 DNA in perivascular macrophages correlated inversely with peripheral blood CD4 counts. These findings demonstrate that brain cell reservoirs of latent HIV-1 exist before pathological HIV encephalitis and suggest that perivascular macrophage trafficking of latent virus into the brain increases with immunosuppression

The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake

The erythrocyte and plasma fatty acid compositions of children with autism were compared in a case-control study with typically developing (TD) children and with children showing developmental delay (DD). Forty-five autism subjects were age-matched with TD controls and thirty-eight with DD controls. Fatty acid data were compared using paired t tests. In addition, blood fatty acids from treatment-naive autism subjects were compared with autism subjects who had consumed fish oil supplements by two-sample t tests. Relatively few differences were seen between erythrocyte fatty acids in autism and TD subjects although the former had an increased arachidonic acid (ARA):EPA ratio. This ratio was also increased in plasma samples from the same children. No changes in n-3 fatty acids or ARA:EPA ratio were seen when comparing autism with DD subjects but some SFA and MUFA were decreased in the DD subjects, most notably 24 : 0 and 24 : 1, which are essential components of axonal myelin sheaths. However, if multiple comparisons are taken into account, and a stricter level of significance applied, most of these values would not be significant. Autism subjects consuming fish oil showed reduced erythrocyte ARA, 22 : 4n-6, 22 : 5n-6 and total n-6 fatty acids and increased EPA, 22 : 5n-3, 22 : 6n-3 and total n-3 fatty acids along with reduced n-6:n-3 and ARA:EPA ratios. Collectively, the autism subjects did not have an underlying phospholipid disorder, based on erythrocyte fatty acid compositions, although the increased ARA:EPA ratio observed suggested that an imbalance of essential highly unsaturated fatty acids may be present in a cohort of autism subjects

The transition into veterinary practice: Opinions of recent graduates and final year students

Background The transition from veterinary student to member of the veterinary profession is known to be challenging. This study aimed to determine and compare the opinions of final year veterinary students and recent graduates on graduate attributes that ease this transition. Methods The study was carried out across 3 veterinary schools in the United Kingdom. Paper based or electronic surveys were used. Final year students in the 3 schools were surveyed either electronically (school A) or on paper (schools B and C). Student cohort sizes were 112, 227 and 102 respectively. Recent graduates were contacted either at a reunion event (school A) or electronically from database records (school B and school C). Cohort sizes of contacted graduates were 80, 175 and 91 respectively. Respondents were asked to rate 42 individual attributes on a 5 point Likert scale. Focus groups with final year students and recent graduates and telephone interviews with recent graduates were carried out. Data were analysed by two researchers through a combination of manual coding and thematic analysis. Data were grouped into broad themes then sorted into narrower themes. Data were then searched for counter examples. Results Response rates for final year students were 34% (school A), 36% (school B) and 40% (school C). Response rates for recent graduates were 56% (school A), 20% (school B) and 11% (school C). There was a high level of agreement between the cohorts with respect to communication skills, problem solving and decision making skills, recognition of own limitations and the ability to cope with pressure all rated unanimously important or very important. Business acumen, knowledge of veterinary practice management and research skills were the 3 attributes ranked at the bottom of the list. Nine attributes were identified with a significantly different (p < 0.05) ranking between the cohorts. Final year students ranked veterinary clinical knowledge, knowledge of veterinary public health and zoonotic issues, veterinary legislation and veterinary practice management, commitment to continuing professional development and ability to evaluate information higher than recent graduates. Recent graduates ranked the attributes of integrity, friendliness and compassion higher than final year students. Conclusions Recent graduates and final year students rate highly the attributes which help foster the client/veterinarian relationship. Recent graduates reflect that a focus on knowledge based attributes is less important once in practice when compared to final year. The study confirms the importance to recent graduates and final year students of attributes considered as non-technical in the transition to working in the veterinary profession

Early Release Science of the exoplanet WASP-39b with JWST NIRCam

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution, and high precision that, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0 - 4.0 $\mu$m, exhibit minimal systematics, and reveal well-defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous H$_2$O in the atmosphere and place an upper limit on the abundance of CH$_4$. The otherwise prominent CO$_2$ feature at 2.8 $\mu$m is largely masked by H$_2$O. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100$\times$ solar (i.e., an enrichment of elements heavier than helium relative to the Sun) and a sub-stellar carbon-to-oxygen (C/O) ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation or disequilibrium processes in the upper atmosphere.Comment: 35 pages, 13 figures, 3 tables, Nature, accepte

Early Release Science of the exoplanet WASP-39b with JWST NIRISS

Transmission spectroscopy provides insight into the atmospheric properties and consequently the formation history, physics, and chemistry of transiting exoplanets. However, obtaining precise inferences of atmospheric properties from transmission spectra requires simultaneously measuring the strength and shape of multiple spectral absorption features from a wide range of chemical species. This has been challenging given the precision and wavelength coverage of previous observatories. Here, we present the transmission spectrum of the Saturn-mass exoplanet WASP-39b obtained using the SOSS mode of the NIRISS instrument on the JWST. This spectrum spans $0.6 - 2.8 \mu$m in wavelength and reveals multiple water absorption bands, the potassium resonance doublet, as well as signatures of clouds. The precision and broad wavelength coverage of NIRISS-SOSS allows us to break model degeneracies between cloud properties and the atmospheric composition of WASP-39b, favoring a heavy element enhancement ("metallicity") of $\sim 10 - 30 \times$ the solar value, a sub-solar carbon-to-oxygen (C/O) ratio, and a solar-to-super-solar potassium-to-oxygen (K/O) ratio. The observations are best explained by wavelength-dependent, non-gray clouds with inhomogeneous coverage of the planet's terminator.Comment: 48 pages, 12 figures, 2 tables. Under review at Natur

A roadmap to the efficient and robust characterization of temperate terrestrial planet atmospheres with JWST

Ultra-cool dwarf stars are abundant, long-lived, and uniquely suited to enable the atmospheric study of transiting terrestrial companions with JWST. Amongst them, the most prominent is the M8.5V star TRAPPIST-1 and its seven planets, which have been the favored targets of eight JWST Cycle 1 programs. While Cycle 1 observations have started to yield preliminary insights into the planets, they have also revealed that their atmospheric exploration requires a better understanding of their host star. Here, we propose a roadmap to characterize the TRAPPIST-1 system -- and others like it -- in an efficient and robust manner. We notably recommend that -- although more challenging to schedule -- multi-transit windows be prioritized to constrain stellar heterogeneities and gather up to 2$\times$ more transits per JWST hour spent. We conclude that in such systems planets cannot be studied in isolation by small programs, thus large-scale community-supported programs should be supported to enable the efficient and robust exploration of terrestrial exoplanets in the JWST era

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Like gold dust these days’: domestic violence fact-finding hearings in child contact cases

Fact-finding hearings may be held to determine disputed allegations of domestic violence in child contact cases in England and Wales, and can play a vital role for mothers seeking protection and autonomy from violent fathers. Drawing on the author’s empirical study, this article examines the implications for the holding of fact-finding hearings of judges’ and professionals’ understandings of domestic violence and the extent to which they perceive it to be relevant to contact. While more judges and professionals are developing their understanding of domestic violence, the ambit of when and how it is considered relevant to contact has grown increasingly narrow, which suggests that many disputed allegations of domestic violence are disregarded and women and children continue to be put at risk from violent fathers. This bifurcated approach is likely to have significant implications for recent developments in this area of family law which are considered in this article

Identification of carbon dioxide in an exoplanet atmosphere

Carbon dioxide (CO2) is a key chemical species that is found in a wide range of planetary atmospheres. In the context of exoplanets, CO2 is an indicator of the metal enrichment (that is, elements heavier than helium, also called ‘metallicity’), and thus the formation processes of the primary atmospheres of hot gas giants. It is also one of the most promising species to detect in the secondary atmospheres of terrestrial exoplanets. Previous photometric measurements of transiting planets with the Spitzer Space Telescope have given hints of the presence of CO2, but have not yielded definitive detections owing to the lack of unambiguous spectroscopic identification. Here we present the detection of CO2 in the atmosphere of the gas giant exoplanet WASP-39b from transmission spectroscopy observations obtained with JWST as part of the Early Release Science programme. The data used in this study span 3.0–5.5 micrometres in wavelength and show a prominent CO2 absorption feature at 4.3 micrometres (26-sigma significance). The overall spectrum is well matched by one-dimensional, ten-times solar metallicity models that assume radiative–convective–thermochemical equilibrium and have moderate cloud opacity. These models predict that the atmosphere should have water, carbon monoxide and hydrogen sulfide in addition to CO2, but little methane. Furthermore, we also tentatively detect a small absorption feature near 4.0 micrometres that is not reproduced by these models