Qualitative interviews with mentor mothers living with HIV: potential impacts of role and coping strategies.

IntroductionIn South Africa where HIV prevalence is high, mentor mother programmes have been used to promote the health and wellbeing of women enrolled in government programmes preventing vertical transmission. The Masihambisane Project trained mentors to be educators and facilitators as "expert patients" in self-help groups. While this and other similar interventions demonstrate positive outcomes for mothers and their children, the long-term repercussions for mentors delivering the intervention are seldom considered. This article explores the personal impact of being a mentor, the potentially traumatizing effects of repeatedly sharing their experiences of living with HIV and the coping strategies they adopt.ResultsTowards the end of the Masihambisane intervention, 10 semi-structured qualitative interviews were conducted with locally recruited mentors living with HIV and were thematically analysed. Mentors found the repeated telling of their stories a painful reminder of adverse personal experiences. In some cases, retelling caused a physical reaction. Mentors relied on coping strategies like taking breaks, writing their experiences down and debriefing sessions. Despite the difficulties associated with their role, some mentors found being advisors and the group sessions therapeutic and empowering.ConclusionsThese findings indicate that the inclusion of peer mentors comes with certain responsibilities. While the mentors were resilient and some found the experience therapeutic and empowering found creative ways to cope with secondary trauma, the negative implications cannot be ignored. To effectively deliver a mentor-driven intervention to mothers enrolled in a programme to prevent vertical transmission, the possibilities of secondary trauma should be considered and mentors provided with ongoing counselling, training on coping skills and regular debriefing sessions

Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. Results: The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. Conclusions: ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function

Duration and urgency of transfer in births planned at home and in freestanding midwifery units in England: secondary analysis of the Birthplace national prospective cohort study

Background: In England, there is a policy of offering healthy women with straightforward pregnancies a choice of birth setting. Options may include home or a freestanding midwifery unit (FMU). Transfer rates from these settings are around 20%, and higher for nulliparous women. The duration of transfer is of interest because of the potential for delay in access to specialist care and is also of concern to women. We aimed to estimate the duration of transfer in births planned at home and in FMUs and explore the effects of distance and urgency on duration. Methods: This was a secondary analysis of data collected in a national prospective cohort study including 27,842 ‘low risk’ women with singleton, term, ‘booked’ pregnancies, planning birth in FMUs or at home in England from April 2008 to April 2010. We described transfer duration using the median and interquartile range, for all transfers and those for reasons defined as potentially urgent or non-urgent, and used cumulative distribution curves to compare transfer duration by urgency. We explored the effect of distance for transfers from FMUs and described outcomes in women giving birth within 60 minutes of transfer. Results: The median overall transfer time, from decision to transfer to first OU assessment, was shorter in transfers from home compared with transfers from FMUs (49 vs 60 minutes; p < 0.001). The median duration of transfers before birth for potentially urgent reasons (home 42 minutes, FMU 50 minutes) was 8–10 minutes shorter compared with transfers for non-urgent reasons. In transfers for potentially urgent reasons, the median overall transfer time from FMUs within 20 km of an OU was 47 minutes, increasing to 55 minutes from FMUs 20-40 km away and 61 minutes in more remote FMUs. In women who gave birth within 60 minutes after transfer, adverse neonatal outcomes occurred in 1-2% of transfers. Conclusions: Transfers from home or FMU commonly take up to 60 minutes from decision to transfer, to first assessment in an OU, even for transfers for potentially urgent reasons. Most transfers are not urgent and emergencies and adverse outcomes are uncommon, but urgent transfer is more likely for nulliparous women

Bureaucracy as a Lens for Analyzing and Designing Algorithmic Systems

Scholarship on algorithms has drawn on the analogy between algorithmic systems and bureaucracies to diagnose shortcomings in algorithmic decision-making. We extend the analogy further by drawing on Michel Crozier’s theory of bureaucratic organizations to analyze the relationship between algorithmic and human decision-making power. We present algorithms as analogous to impartial bureaucratic rules for controlling action, and argue that discretionary decision-making power in algorithmic systems accumulates at locations where uncertainty about the operation of algorithms persists. This key point of our essay connects with Alkhatib and Bernstein’s theory of ’street-level algorithms’, and highlights that the role of human discretion in algorithmic systems is to accommodate uncertain situations which inflexible algorithms cannot handle. We conclude by discussing how the analysis and design of algorithmic systems could seek to identify and cultivate important sources of uncertainty, to enable the human discretionary work that enhances systemic resilience in the face of algorithmic errors.Peer reviewe

Learning together for and with the Martuwarra Fitzroy River

Co-production across scientific and Indigenous knowledge systems has become a cornerstone of research to enhance knowledge, practice, ethics, and foster sustainability transformations. However, the profound differences in world views and the complex and contested histories of nation-state colonisation on Indigenous territories, highlight both opportunities and risks for Indigenous people when engaging with knowledge co-production. This paper investigates the conditions under which knowledge co-production can lead to improved Indigenous adaptive environmental planning and management among remote land-attached Indigenous peoples through a case study with ten Traditional Owner groups in the Martuwarra (Fitzroy River) Catchment in Western Australia’s Kimberley region. The research team built a 3D map of the river and used it, together with an interactive table-top projector, to bring together both scientific and Indigenous spatial knowledge. Participatory influence mapping, aligned with Traditional Owner priorities to achieve cultural governance and management planning goals set out in the Fitzroy River Declaration, investigated power relations. An analytical framework, examining underlying mechanisms of social learning, knowledge promotion and enhancing influence, based on different theories of change, was applied to unpack the immediate outcomes from these activities. The analysis identified that knowledge co-production activities improved the accessibility of the knowledge, the experiences of the knowledge users, strengthened collective identity and partnerships, and strengthened Indigenous-led institutions. The focus on cultural governance and management planning goals in the Fitzroy River Declaration enabled the activities to directly affect key drivers of Indigenous adaptive environmental planning and management—the Indigenous-led institutions. The nation-state arrangements also gave some support to local learning and decision-making through a key Indigenous institution, Martuwarra Fitzroy River Council. Knowledge co-production with remote land-attached Indigenous peoples can improve adaptive environmental planning and management where it fosters learning together, is grounded in the Indigenous-led institutions and addresses their priorities

Early ultrasound surveillance of newly-created haemodialysis arteriovenous fistula

IntroductionWe assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.MethodsConsenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.ResultsOf 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9–77.3]; elbow, 66.7% [48.9–84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan’s findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data.ConclusionEarly ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc