Feasibility and acceptability of implementing early infant diagnosis of HIV in Papua New Guinea at the point of care: a qualitative exploration of health worker and key informant perspectives

Introduction: Early infant diagnosis (EID) of HIV and timely initiation of antiretroviral therapy can significantly reduce morbidity and mortality among HIV-positive infants. Access to EID is limited in many low-income and middle-income settings, particularly those in which standard care involves dried blood spots (DBS) sent to centralised laboratories, such as in Papua New Guinea (PNG). We conducted a qualitative exploration of the feasibility and acceptability of implementing a point-of-care (POC) EID test (Xpert HIV-1 Qualitative assay) among health workers and key stakeholders working within the prevention of mother-to-child transmission of HIV (PMTCT) programme in PNG. Methods: This qualitative substudy was conducted as part of a pragmatic trial to investigate the effectiveness of the Xpert HIV-1 Qualitative test for EID in PNG and Myanmar. Semistructured interviews were undertaken with 5 health workers and 13 key informants to explore current services, experiences of EID testing, perspectives on the Xpert test and the feasibility of integrating and scaling up POC EID in PNG. Coding was undertaken using inductive and deductive approaches, drawing on existing acceptability and feasibility frameworks. Results: Health workers and key informants (N=18) felt EID at POC was feasible to implement and beneficial to HIV-exposed infants and their families, staff and the PMTCT programme more broadly. All study participants highlighted starting HIV-positive infants on treatment immediately as the main advantage of POC EID compared with standard care DBS testing. Health workers identified insufficient resources to follow up infants and caregivers and space constraints in hospitals as barriers to implementation. Participants emphasised the importance of adequate human resources, ongoing training and support, appropriate coordination and a sustainable supply of consumables to ensure effective scale-up of the test throughout PNG. Conclusions: Implementation of POC EID in a low HIV prevalence setting such as PNG is likely to be both feasible and beneficial with careful planning and adequate resources

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers. While vaccination of seropositive individuals resulted in robust recall of humoral and T cell immunity, recall of vaccine-elicited responses was delayed and variable in magnitude during breakthrough infections and depended on the infecting variant of concern. While the delayed kinetics of immune recall provides a potential mechanism for the lack of early control of viral replication, the recall of antibodies coincided with viral clearance and likely underpins the protective effects of vaccination against severe COVID-19

Gaia Data Release 2: Calibration and mitigation of electronic offset effects in the data

The European Space Agency Gaia satellite was launched into orbit around L2 in December 2013. This ambitious mission has strict requirements on residual systematic errors resulting from instrumental corrections in order to meet a design goal of sub-10 microarcsecond astrometry. During the design and build phase of the science instruments, various critical calibrations were studied in detail to ensure that this goal could be met in orbit. In particular, it was determined that the video-chain offsets on the analogue side of the analogue-to-digital conversion electronics exhibited instabilities that could not be mitigated fully by modifications to the flight hardware. We provide a detailed description of the behaviour of the electronic offset levels on microsecond timescales, identifying various systematic effects that are known collectively as offset non-uniformities. The effects manifest themselves as transient perturbations on the gross zero-point electronic offset level that is routinely monitored as part of the overall calibration process. Using in-orbit special calibration sequences along with simple parametric models, we show how the effects can be calibrated, and how these calibrations are applied to the science data. While the calibration part of the process is relatively straightforward, the application of the calibrations during science data processing requires a detailed on-ground reconstruction of the readout timing of each charge-coupled device (CCD) sample on each device in order to predict correctly the highly time-dependent nature of the corrections. We demonstrate the effectiveness of our offset non-uniformity models in mitigating the effects in Gaia data. We demonstrate for all CCDs and operating instrument and modes on board Gaia that the video-chain noise-limited performance is recovered in the vast majority of science samples

Moving towards public policy-ready science: philosophical insights on the social-ecological systems perspective for conservation science

The social-ecological systems (SES) perspective stems from the need to rethink the ways humans relate to the environment, given the evidence that conventional conservation and management approaches are often ineffective in dealing with complex socio-environmental problems. The SES approach conceives non-scientific and scientific knowledge as equally necessary in the process of management and public policy formation. Thus, the adoption of the SES approach must also serve to make better decisions about what kind of science and technology would be ‘public policy-ready’ (as well as also ‘policy-relevant’); that is, a science oriented and conceived to provide concrete solutions to societal needs and demands. Here we review and reinterpret the SES perspective as a real paradigm change for conservation science. Under the lenses of philosophy, we try to untangle some weak points of the SES approach in order to advance to a conservation science closer to the process of science-based public policy creation and to enhance the intertwining with other types of knowledge. In this sense, we discuss how co-production of knowledge and decision-making process under the SES perspective are a huge step forward towards fulfilling the need to bring increasingly closer the spheres of science and policy, narrowing its interface.Fil: Sala, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Torchio, Gabriela María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentin

Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study

OBJECTIVE: To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS: CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2-17 years), ERA (12-17 years), or PsA (12-17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. RESULTS: 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. CONCLUSIONS: ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings

On-orbit performance of the Gaia CCDs at L2

The European Space Agency's Gaia satellite was launched into orbit around L2 in December 2013 with a payload containing 106 large-format scientific CCDs. The primary goal of the mission is to repeatedly obtain high-precision astrometric and photometric measurements of one thousand million stars over the course of five years. The scientific value of the down-linked data, and the operation of the onboard autonomous detection chain, relies on the high performance of the detectors. As Gaia slowly rotates and scans the sky, the CCDs are continuously operated in a mode where the line clock rate and the satellite rotation spin-rate are in synchronisation. Nominal mission operations began in July 2014 and the first data release is being prepared for release at the end of Summer 2016. In this paper we present an overview of the focal plane, the detector system, and strategies for on-orbit performance monitoring of the system. This is followed by a presentation of the performance results based on analysis of data acquired during a two-year window beginning at payload switch-on. Results for parameters such as readout noise and electronic offset behaviour are presented and we pay particular attention to the effects of the L2 radiation environment on the devices. The radiation-induced degradation in the charge transfer efficiency (CTE) in the (parallel) scan direction is clearly diagnosed; however, an extrapolation shows that charge transfer inefficiency (CTI) effects at end of mission will be approximately an order of magnitude less than predicted pre-flight. It is shown that the CTI in the serial register (horizontal direction) is still dominated by the traps inherent to the manufacturing process and that the radiation-induced degradation so far is only a few per cent. Finally, we summarise some of the detector effects discovered on-orbit which are still being investigated.Comment: Published in A&A Gaia special featur

Exposure to animals and risk of oligoarticular juvenile idiopathic arthritis: a multicenter case-control study

<p>Abstract</p> <p>Background</p> <p>An inverse association between early contact with microbial compounds and respiratory allergies is well established. The protective effect of infant contact with animals was also shown for inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE). We aimed to test the association between animal contact in infancy and oligoarticular juvenile idiopathic arthritis (OA JIA).</p> <p>Methods</p> <p>Parents of children with OA JIA registered at the Hospital for Pediatric Rheumatology in Garmisch-Partenkirchen were asked to complete a questionnaire. Children who underwent strabismus surgery at six referral centers for ophthalmology served as controls. Children age 6 to 18 years born in Germany without malformations were included (238 cases; response 89% and 832 controls; response 86%). Data were analyzed using logistic regression models after adjusting for potential confounders.</p> <p>Results</p> <p>Neither place of living (urban vs. rural area), living on a farm, nor regular farm animal (adjusted odds ratio 0.79; 95% confidence interval 0.42-1.47) or pet contact (0.79; 0.55-1.14) during infancy were clearly related to case status. Allergic rhinitis was inversely related to OA JIA (0.57; 0.34-0.95).</p> <p>Neither place of living (urban vs. rural area), living on a farm, nor regular farm animal (adjusted odds ratio 0.79; 95% confidence interval 0.42-1.47) or pet contact (0.79; 0.55-1.14) during infancy were related to case status. Allergic rhinitis was inversely related to OA JIA (0.57; 0.34-0.95).</p> <p>Conclusions</p> <p>Contact with farm environments in infancy might not be associated with OA JIA. This finding is consistent with previous findings for diabetes mellitus type 1 but contradicts results for IBD and SLE.</p

Investigation into the cause of spontaneous emulsification of a free steel droplet : validation of the chemical exchange pathway

Small Fe-based droplets have been heated to a molten phase suspended within a slag medium to replicate a partial environment within the basic oxygen furnace (BOF). The confocal scanning laser microscope (CSLM) has been used as a heating platform to interrogate the effect of impurities and their transfer across the metal/slag interface, on the emulsification of the droplet into the slag medium. The samples were then examined through X-ray computer tomography (XCT) giving the mapping of emulsion dispersion in 3D space, calculating the changing of interfacial area between the two materials, and changes of material volume due to material transfer between metal and slag. Null experiments to rule out thermal gradients being the cause of emulsification have been conducted as well as replication of the previously reported study by Assis et al.[1] which has given insights into the mechanism of emulsification. Finally chemical analysis was conducted to discover the transfer of oxygen to be the cause of emulsification, leading to a new study of a system with undergoing oxygen equilibration

The Western Australian regional forest agreement: economic rationalism and the normalisation of political closure

This article explores the constraints imposed by economic rationalism on environmental policy-making in light of Western Australia\u27s (WA) Regional Forest Agreement (RFA) experience. Data derived from interviews with WA RFA stakeholders shed light on their perceptions of the RFA process and its outcomes. The extent to which involvement of science and the public RFA management enabled is analysed. The findings point to a pervasive constrainedness of WA\u27s RFA owing to a closing of the process by the administrative decision-making structures. A dominant economic rationality is seen to have normalised and legitimised political closure, effectively excluding rationalities dissenting from an implicit economic orthodoxy. This article argues for the explication of invisible, economic constraints affecting environmental policy and for the public-cum-political negotiation of the points of closure within political processes

Wolbachia Infections in Anopheles gambiae Cells: Transcriptomic Characterization of a Novel Host-Symbiont Interaction

The endosymbiotic bacterium Wolbachia is being investigated as a potential control agent in several important vector insect species. Recent studies have shown that Wolbachia can protect the insect host against a wide variety of pathogens, resulting in reduced transmission of parasites and viruses. It has been proposed that compromised vector competence of Wolbachia-infected insects is due to up-regulation of the host innate immune system or metabolic competition. Anopheles mosquitoes, which transmit human malaria parasites, have never been found to harbor Wolbachia in nature. While transient somatic infections can be established in Anopheles, no stable artificially-transinfected Anopheles line has been developed despite numerous attempts. However, cultured Anopheles cells can be stably infected with multiple Wolbachia strains such as wAlbB from Aedes albopictus, wRi from Drosophila simulans and wMelPop from Drosophila melanogaster. Infected cell lines provide an amenable system to investigate Wolbachia-Anopheles interactions in the absence of an infected mosquito strain. We used Affymetrix GeneChip microarrays to investigate the effect of wAlbB and wRi infection on the transcriptome of cultured Anopheles Sua5B cells, and for a subset of genes used quantitative PCR to validate results in somatically-infected Anopheles mosquitoes. Wolbachia infection had a dramatic strain-specific effect on gene expression in this cell line, with almost 700 genes in total regulated representing a diverse array of functional classes. Very strikingly, infection resulted in a significant down-regulation of many immune, stress and detoxification-related transcripts. This is in stark contrast to the induction of immune genes observed in other insect hosts. We also identified genes that may be potentially involved in Wolbachia-induced reproductive and pathogenic phenotypes. Somatically-infected mosquitoes had similar responses to cultured cells. The data show that Wolbachia has a profound and unique effect on Anopheles gene expression in cultured cells, and has important implications for mechanistic understanding of Wolbachia-induced phenotypes and potential novel strategies to control malaria