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Objective ANCA-associated vasculitis (AAV) is a relapsing-remitting disease, resulting in incremental tissue injury. The gold-standard relapse definition (Birmingham Vasculitis Activity Score, BVAS>0) is often missing or inaccurate in registry settings, leading to errors in ascertainment of this key outcome. We sought to create a computable phenotype (CP) to automate retrospective identification of relapse using real-world data in the research setting.Methods We studied 536 patients with AAV and >6 months follow-up recruited to the Rare Kidney Disease registry (a national longitudinal, multicentre cohort study). We followed five steps: (1) independent encounter adjudication using primary medical records to assign the ground truth, (2) selection of data elements (DEs), (3) CP development using multilevel regression modelling, (4) internal validation and (5) development of additional models to handle missingness. Cut-points were determined by maximising the F1-score. We developed a web application for CP implementation, which outputs an individualised probability of relapse.Results Development and validation datasets comprised 1209 and 377 encounters, respectively. After classifying encounters with diagnostic histopathology as relapse, we identified five key DEs; DE1: change in ANCA level, DE2: suggestive blood/urine tests, DE3: suggestive imaging, DE4: immunosuppression status, DE5: immunosuppression change. F1-score, sensitivity and specificity were 0.85 (95% CI 0.77 to 0.92), 0.89 (95% CI 0.80 to 0.99) and 0.96 (95% CI 0.93 to 0.99), respectively. Where DE5 was missing, DE2 plus either DE1/DE3 were required to match the accuracy of BVAS.Conclusions This CP accurately quantifies the individualised probability of relapse in AAV retrospectively, using objective, readily accessible registry data. This framework could be leveraged for other outcomes and relapsing diseases.

Immunosuppressive treatment in patients with rheumatic diseases can maintain disease remission but also increase risk of infection. Their response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is frequently blunted. In this study we evaluated the effect of immunosuppression exposure on humoral and T cell immune responses to SARS-CoV-2 infection and vaccination in two distinct cohorts of patients; one during acute SARS-CoV-2 infection and 3 months later during convalescence, and another prior to SARS-CoV-2 vaccination, with follow up sampling 6 weeks after vaccination. Results were compared between rituximab-exposed (in previous 6 months), immunosuppression-exposed (in previous 3 months), and non-immunosuppressed groups. The immune cell phenotype was defined by flow cytometry and ELISA. Antigen specific T cell responses were estimated using a whole blood stimulation interferon-γ release assay. A focused post-vaccine assessment of rituximab-treated patients using high dimensional spectral cytometry was conducted. Acute SARS-CoV-2 infection was characterised by T cell lymphopenia, and a reduction in NK cells and naïve CD4 and CD8 cells, without any significant differences between immunosuppressed and non-immunosuppressed patient groups. Conversely, activated CD4 and CD8 cell counts increased in non-immunosuppressed patients with acute SARS-CoV-2 infection but this response was blunted in the presence of immunosuppression. In rituximab-treated patients, antigen-specific T cell responses were preserved in SARS-CoV-2 vaccination, but patients were unable to mount an appropriate humoral response.

Bees are important pollinators of agricultural crops, but their populations are at risk when pesticides are used. One of the largest risks bees face is poisoning of floral nectar and pollen by insecticides. Studies of bee detection of neonicotinoids have reported contradictory evidence about whether bees can taste these pesticides in sucrose solutions and hence avoid them. Here, we use an assay for the detection of food aversion combined with single-sensillum electrophysiology to test whether the mouthparts of the buff-tailed bumblebee (Bombus terrestris) detect the presence of pesticides in a solution that mimicked the nectar of oilseed rape (Brassica napus). Bees did not avoid consuming solutions containing concentrations of imidacloprid, thiamethoxam, clothianidin, or sulfoxaflor spanning six orders of magnitude, even when these solutions contained lethal doses. Only extremely high concentrations of the pesticides altered spiking in gustatory neurons through a slight reduction in firing rate or change in the rate of adaptation. These data provide strong evidence that bumblebees cannot detect or avoid field-relevant concentrations of pesticides using information from their mouthparts. As bees rarely contact floral nectar with other body parts, we predict that they are at high risk of unwittingly consuming pesticides in the nectar of pesticide-treated crops.

In higher education (HE), collaborative activities that revolve around a core idea, practice, or knowledge base, such as learning circles, communities of practice or inquiry, peer observation, and peer-assisted teaching, are known to support professional learning. This paper explores the experiences of eight HE scholars from Australia and New Zealand, across four years, as they recognized a new means of collaborative professional development that transcends known approaches and extends beyond an immediate focal point. The group originally formed to support the development of HE fellowship applications, but evolved to what they now consider a community for practice (CfP), where the purpose of collaboration has changed to meet the unique learning needs of each member. During their four years of collaboration, meeting discussions were recorded, and individual and community narrative reflections about participation in the group were created. A thematic analysis of these collective data sources revealed the group’s evolution, and the authors draw on their experiences to tell their story with an aim to enhance professional learning in HE. The study highlights that individuals’ distinct and varied needs can be developed and supported through scholarly, collegial engagements such as a CfP, which does not necessarily require an immediate point of practice.

Abstract Background The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin. We hypothesised that prolonged periods of low ambient UVB (and by extension vitD deficiency) are associated with the granulomatous form of the disease and an increased risk of AAV relapse. Methods Patients with AAV recruited to the Irish Rare Kidney Disease (RKD) (n = 439) and UKIVAS (n = 1961) registries were studied. Exposure variables comprised latitude and measures of ambient vitD-UVB, including cumulative weighted UVB dose (CW-D-UVB), a well-validated vitD proxy. An n-of-1 study design was used to examine the relapse risk using only the RKD dataset. Multi-level models and logistic regression were used to examine the effect of predictors on AAV relapse risk, phenotype and serotype. Results Residential latitude was positively correlated (OR 1.41, 95% CI 1.14–1.74, p = 0.002) and average vitD-UVB negatively correlated (0.82, 0.70–0.99, p = 0.04) with relapse risk, with a stronger effect when restricting to winter measurements (0.71, 0.57–0.89, p = 0.002). However, these associations were not restricted to granulomatous phenotypes. We observed no clear relationship between latitude, vitD-UVB or CW-D-UVB and AAV phenotype or serotype. Conclusion Our findings suggest that low winter ambient UVB and prolonged vitD status contribute to AAV relapse risk across all phenotypes. However, the development of a granulomatous phenotype does not appear to be directly vitD-mediated. Further research is needed to determine whether sufficient vitD status would reduce relapse propensity in AAV.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease. There is a need for interoperable national registries to enable reporting of real-world long-term outcomes and their predictors in AAV. Methods: The Irish National Rare Kidney Disease (RKD) registry was founded in 2012. To date, 842 patients with various forms of vasculitis have been recruited across eight nephrology, rheumatology and immunology centres. We focus here on patient- and disease- characteristics, treatment and outcomes of the 397 prospectively recruited patients with AAV. Results: Median age was 64 years (IQR 55–73), 57.9% were male, 58.9% had microscopic polyangiitis and 85.9% had renal impairment. Cumulative one- and five-year patient survival was 94% and 77% respectively. Median follow-up was 33.5 months (IQR 10.7–52.7). After controlling for age, baseline renal dysfunction (p = 0.04) and the burden of adverse events (p

Summary: The sense of taste permits the recognition of valuable nutrients and the avoidance of potential toxins. Previously, we found that bumblebees have a specialized mechanism for sensing sugars whereby two gustatory receptor neurons (GRNs) within the galeal sensilla of the bees’ mouthparts exhibit bursts of spikes. Here, we show that the temporal firing patterns of these GRNs separate sugars into four distinct groups that correlate with sugar nutritional value and palatability. We also identified a third GRN that responded to stimulation with relatively high concentrations of fructose, sucrose, and maltose. Sugars that were nonmetabolizable or toxic suppressed the responses of bursting GRNs to sucrose. These abilities to encode information about sugar value are a refinement to the bumblebee’s sense of sweet taste that could be an adaptation that enables precise calculations of the nature and nutritional value of floral nectar.

Abstract Data surrounding sex-specific differences in ANCA-associated vasculitis glomerulonephritis (ANCA-GN) outcomes is sparse. We hypothesised that the previously observed increased risk of end-stage kidney disease (ESKD) in males is driven by sex-specific variation in immunosuppression dosing. Patients were recruited to the Irish Rare Kidney Disease Registry or followed by the Royal Free Hospital vasculitis team (2012–2020). Inclusion criteria: prior diagnosis of ANCA-GN (biopsy proven pauci-immune glomerulonephritis) and positive serology for anti-MPO or -PR3 antibodies. Renal and patient survival, stratified by sex and Berden histological class, was analysed. The cumulative- and starting dose/kilogram of induction agents and prednisolone, respectively, was compared between sexes. 332 patients were included. Median follow-up was time 40.2 months (IQR 17.3–69.2). 73 (22%) reached ESKD and 47 (14.2%) died. Overall 1- and 5-year renal survival was 82.2% and 76.7% in males and 87.1% and 82.0% in females, respectively (p 0.13). The hazard ratio for ESKD in males versus females, after adjustment for age, ANCA serology, baseline creatinine and histological class was 1.07 (95% CI 0.59–1.93). There was no difference between sexes in the dose/kilogram of any induction agent. We did not observe a strong impact of sex on renal outcome in ANCA-GN. Treatment intensity does not vary by sex.

Abstract Background Intimate partner violence (IPV) is the most common form of gender-based violence affecting women and girls worldwide and is exacerbated in humanitarian crises. There is evidence that substance use is associated with male perpetration of IPV. Consumption of khat —a plant containing amphetamines traditionally chewed in the horn of Africa and legal in some countries including Ethiopia—may increase risk of IPV toward women. This analysis aimed to assess perceptions on khat use among Somali refugees in Dollo Ado, Ethiopia and its association with IPV to inform an IPV and HIV prevention intervention. Methods A descriptive qualitative study comprising individual interviews (n = 30) and focus group discussions (n = 10) was conducted in Bokolmayo refugee camp in Dollo Ado, Ethiopia in October 2016. A purposive sample of male and female Somali refugees, religious and community leaders, and service providers (n = 110 individuals; 44 women and 66 men) was included. Trained interviewers from the camp conducted the interviews and discussion, which were audio recorded, transcribed and translated. A content analysis was conducted on coded excerpts from the transcripts to identify factors contributing to IPV toward women, including khat use. Results Participants reported that displacement has resulted in limited employment opportunities for men and increased idle time, which has led to increased khat use among men as a coping mechanism. Male khat use was perceived to be associated with perpetration of physical and sexual IPV through several mechanisms including increased anger and aggression and enhanced sexual desire. Khat use also contributes to intra-marital conflict as money allocated for a household is spent on purchasing khat. Conclusion Khat use should be addressed as part of IPV prevention programming in this context. Livelihood interventions and other strategies to improve economic conditions, should be explored in collaboration with refugee camp authorities and community leaders as a potential avenue to mitigate the impact of khat use on women and families.

Abstract Background Child and forced marriage have negative health consequences including increased risk of intimate partner violence (IPV) for women and girls. War and humanitarian crises may impact decision-making around marriage and risks of IPV for displaced populations. A qualitative study was conducted among Somali refugees in Dollo Ado, Ethiopia to understand the interplay of factors that contribute to IPV and to inform an intervention. This secondary analysis aims to explore the influence of displacement on marital practices and associated IPV risk. Methods Interviews and focus group discussions were conducted in 2016 in Dollo Ado, Ethiopia, among Somali women and men living in Bokolmayo refugee camp, host community members, non-governmental staff and service providers, stakeholders, and community and religious leaders (N = 110). Data were transcribed, translated to English, and coded and analyzed thematically using Dedoose software and a codebook developed a priori. Results Findings reveal numerous displacement-related factors that led to perceived shifts in marital practices among refugees, including reductions in child and forced marriages. NGO awareness-raising programs and Ethiopian laws prohibiting child marriage as well as increased access to education for girls were reported to have contributed to these changes, despite continued economic hardship and high perceived risk of non-partner sexual violence within the camp and host community. Polygamy was also perceived to have decreased, primarily due to worsening economic conditions. Forced marriage, polygamy and dowry were reported to contribute to physical IPV, and sexual IPV was reported as common in all types of marital unions. However, there was no evidence that changes in these marital practices contributed to any perceived declines in IPV within this context. Conclusion Safe access to education for girls should be prioritized in humanitarian settings. Interventions to address child and forced marriage should address gender and social norms. Intimate partner violence prevention programming should include specialized content taking into account marital practices including child and forced marriage and polygamy. Laws recognizing sexual IPV within marital relationships are needed to reduce sexual IPV.

Abstract Planktic and benthic foraminiferal iodine (I) to calcium (Ca) molar ratios have been proposed as an exciting new proxy to assess subsurface and bottom water oxygenation in the past. Compared to trace metals, the analysis of iodine in foraminiferal calcite is more challenging, as iodine is volatile in acid solution. Here, we compare previous analyses that use tertiary amine with alternative analyses using tetramethylammonium hydroxide (TMAH) and ammonium hydroxide (NH4OH) to stabilize iodine in solution. In addition, we assess the effect of sample size and cleaning on planktic and benthic foraminiferal I/Ca. Our stabilization experiments with TMAH and NH4OH show similar trends as those using tertiary amine, giving relatively low I/Ca ratios for planktic and benthic foraminifera samples from poorly oxygenated waters, and high ratios for well‐oxygenated waters. This suggests that both alternative methods are suitable to stabilize iodine initially dissolved in acid. Samples that contain 5–10 specimens show a wide spread in I/Ca. Samples containing 20 specimens or more show more centered I/Ca values, indicating that a larger sample size is more representative of the average planktic foraminifera community. The impact of cleaning on planktic and benthic foraminifera I/Ca ratios is very similar to Mg/Ca, with the largest effect occurring during the clay removal step. The largest iodine contaminations were recorded at locations characterized by moderate to high organic carbon contents. In those circumstances, we recommend doubling the oxidative cleaning steps (4 instead of 2 repetitions) to ensure that all organic material is removed.

Aspergillus fumigatus is a human fungal pathogen that can cause devastating pulmonary infections, termed "aspergilloses," in individuals suffering immune imbalances or underlying lung conditions. As rapid adaptation to stress is crucial for the outcome of the host-pathogen interplay, here we investigated the role of the versatile posttranslational modification (PTM) persulfidation for both fungal virulence and antifungal host defense. We show that an A. fumigatus mutant with low persulfidation levels is more susceptible to host-mediated killing and displays reduced virulence in murine models of infection. Additionally, we found that a single nucleotide polymorphism (SNP) in the human gene encoding cystathionine γ-lyase (CTH) causes a reduction in cellular persulfidation and correlates with a predisposition of hematopoietic stem cell transplant recipients to invasive pulmonary aspergillosis (IPA), as correct levels of persulfidation are required for optimal antifungal activity of recipients' lung resident host cells. Importantly, the levels of host persulfidation determine the levels of fungal persulfidation, ultimately reflecting a host-pathogen functional correlation and highlighting a potential new therapeutic target for the treatment of aspergillosis.

The health system in northern Iraq has been weakened by conflict and the internal displacement of over three million people. Mobile phone-based interventions (mHealth) may improve maternal and neonatal health outcomes by enabling emergency referrals, facilitating communication between patients and providers, and improving patient data management; however, they have not been sufficiently studied in conflict-affected settings. We explored stakeholders' perspectives on challenges to obstetric referrals and the feasibility and acceptability of a mobile phone-based application to reduce delays in reaching emergency obstetric care in order to inform its development. We conducted a qualitative study in the Kurdistan region of northern Iraq from May to July, 2018. Using purposive sampling, we carried out 15 semi-structured interviews with coordination actors including healthcare management staff, government health officials, non-government health program managers and ambulance staff. The interviews explored obstetric care delivery, referral processes, mobile phone usage and mHealth implementation strategies. Eleven focus group discussions, which incorporated participatory activities on similar topics, were conducted with ambulance drivers, hospital and primary health center staff. Audio-recorded, transcribed and translated data were coded iteratively to identify emerging concepts, and analyzed thematically. Sixty-eight stakeholders (36 women and 32 men) participated. Challenges regarding the referral system included resource limitations, security concerns, costs and women's reluctance to be transported in male-staffed ambulances. In terms of obstetric care and decision-making, participants noted gaps in communication and coordination of services with the current paper-based system between health care providers, ambulance drivers, and hospital staff. Ambulance drivers reported incurring delays through lack of patient information, poor road conditions, and security issues. A prototype mobile phone application was found to be acceptable based on perceived usefulness to address some of the challenges to safe obstetric care and focused on phone usage, access to information, Global Positioning System (GPS), connectivity, cost, and user-friendliness. However, the feasibility of the innovation was considered in relation to implementation challenges that were identified, including poor connectivity, and digital literacy. Implementation of the app would need to account for the humanitarian context, cultural and gender norms regarding obstetric care, and would require substantial commitment and engagement from policymakers and practitioners.

Abstract The COVID-19 outbreak has been declared a global pandemic and cases are being reported among displaced populations that are particularly vulnerable to infection. Humanitarian workers on the frontlines of the response are working in some of the most challenging contexts and also face elevated risk of contracting COVID-19 and potential stigmatization or violence in the community. Women humanitarians may be at even greater risk, but their protection is dependent on organization-specific policies and procedures. Without gender balance in leadership positions, the specific needs of women may not be prioritized and women may not be included in decision-making or design of responses. Ensuring gender equitable access to personal protective equipment and information is imperative, but additional measures must be put into place to ensure the protection of women on the frontlines while reducing COVID-19 deaths and adverse health effects among displaced populations.

Fifty-two maternal deaths occurred between September 2017 and August 2018 in the Rohingya refugee camps in Ukhia and Teknaf Upazilas, Cox’s Bazar District, Bangladesh. Behind every one of these lives lost is a complex narrative of historical, social, and political forces, which provide an important context for reproductive health programming in Rohingya camps. Rohingya women and girls have experienced human rights violations in Myanmar for decades, including government-sponsored sexual violence and population control efforts. An extension of nationalist, anti-Rohingya policies, the attacks of 2017 resulted in the rape and murder of an unknown number of women. The socio-cultural context among Rohingya and Bangladeshi host communities limits provision of reproductive health services in the refugee camps, as does a lack of legal status and continued restrictions on movement. In this review, the historical, political, and social contexts have been overlaid below on the Three Delays Model, a conceptual framework used to understand the determinants of maternal mortality. Attempts to improve maternal mortality among Rohingya women and girls in the refugee camps in Bangladesh should take into account these complex historical, social and political factors in order to reduce maternal mortality.

Abstract Background There is limited evidence regarding the ways in which displacement disrupts social norms, expectations and trajectories for adolescent girls and young women and the resulting impacts on their risks of violence. This knowledge gap is especially marked with regards to Syrian adolescent girls and young women seeking refuge in Turkey. We explored risks of gender-based violence against Syrian adolescent girls and young women in Turkey and examined how these risks were shaped by their displacement. Methods Data were collected in August 2016 in Izmir, Turkey through five sex-specific focus group discussions with Syrian adolescents and young people (aged 15–25 years) and two mixed gender focus group discussions with Syrian adults (18 years and older). Group discussions covered the issues facing Syrian adolescents and young women in Turkey, and how these were influenced by their displacement. Discussions in Arabic were audio-recorded, transcribed and translated into English. Data were coded inductively, and analysed thematically. Results Syrian adolescent girls and young women expressed an increased sense of vulnerability to violence since their displacement. Due to financial strains and limited educational opportunities, they were often encouraged by parents to work or marry, both of which they perceived to increase the risks of violence. In contrast, some adults suggested that marriage could protect adolescent girls and young women from risks of violence associated with working. Being alone outside the home was viewed as risky by all participants due to pervasive sexual, verbal and physical harassment, aggression, and even kidnapping attempts. To limit these risks, many parents reported keeping adolescent girls and young women at home, or ensuring that they were accompanied by male relatives when in public. Conclusions Syrian adolescent girls and young women face multiple risks of violence following displacement related to altered social trajectories. Some family-based strategies to protect young women from violence could reinforce restrictive gender norms and increase risks of violence. Interventions to address violence should include providing safe spaces, access to education and safe transport for young women, and financial support for families as well as community-based interventions to address the daily risks of sexual harassment in public spaces.

Abstract Background Theories, models, and frameworks (TMF) are foundational for generalizing implementation efforts and research findings. However, TMF and the criteria used to select them are not often described in published articles, perhaps due in part to the challenge of selecting from among the many TMF that exist in the field. The objective of this international study was to develop a user-friendly tool to help scientists and practitioners select appropriate TMF to guide their implementation projects. Methods Implementation scientists across the USA, the UK, and Canada identified and rated conceptually distinct categories of criteria in a concept mapping exercise. We then used the concept mapping results to develop a tool to help users select appropriate TMF for their projects. We assessed the tool’s usefulness through expert consensus and cognitive and semi-structured interviews with implementation scientists. Results Thirty-seven implementation scientists (19 researchers and 18 practitioners) identified four criteria domains: usability, testability, applicability, and familiarity. We then developed a prototype of the tool that included a list of 25 criteria organized by domain, definitions of the criteria, and a case example illustrating an application of the tool. Results of cognitive and semi-structured interviews highlighted the need for the tool to (1) be as succinct as possible; (2) have separate versions to meet the unique needs of researchers versus practitioners; (3) include easily understood terms; (4) include an introduction that clearly describes the tool’s purpose and benefits; (5) provide space for noting project information, comparing and scoring TMF, and accommodating contributions from multiple team members; and (6) include more case examples illustrating its application. Interview participants agreed that the tool (1) offered them a way to select from among candidate TMF, (2) helped them be explicit about the criteria that they used to select a TMF, and (3) enabled them to compare, select from among, and/or consider the usefulness of combining multiple TMF. These revisions resulted in the Theory Comparison and Selection Tool (T-CaST), a paper and web-enabled tool that includes 16 specific criteria that can be used to consider and justify the selection of TMF for a given project. Criteria are organized within four categories: applicability, usability, testability, and acceptability. Conclusions T-CaST is a user-friendly tool to help scientists and practitioners select appropriate TMF to guide implementation projects. Additionally, T-CaST has the potential to promote transparent reporting of criteria used to select TMF within and beyond the field of implementation science.

ABSTRACT There is an urgent need to develop novel antifungals to tackle the threat fungal pathogens pose to human health. Here, we have performed a comprehensive characterization and validation of the promising target methionine synthase (MetH). We show that in Aspergillus fumigatus the absence of this enzymatic activity triggers a metabolic imbalance that causes a reduction in intracellular ATP, which prevents fungal growth even in the presence of methionine. Interestingly, growth can be recovered in the presence of certain metabolites, which shows that metH is a conditionally essential gene and consequently should be targeted in established infections for a more comprehensive validation. Accordingly, we have validated the use of the tetOFF genetic model in fungal research and improved its performance in vivo to achieve initial validation of targets in models of established infection. We show that repression of metH in growing hyphae halts growth in vitro, which translates into a beneficial effect when targeting established infections using this model in vivo. Finally, a structure-based virtual screening of methionine synthases reveals key differences between the human and fungal structures and unravels features in the fungal enzyme that can guide the design of novel specific inhibitors. Therefore, methionine synthase is a valuable target for the development of new antifungals. IMPORTANCE Fungal pathogens are responsible for millions of life-threatening infections on an annual basis worldwide. The current repertoire of antifungal drugs is very limited and, worryingly, resistance has emerged and already become a serious threat to our capacity to treat fungal diseases. The first step to develop new drugs is often to identify molecular targets in the pathogen whose inhibition during infection can prevent its growth. However, the current models are not suitable to validate targets in established infections. Here, we have characterized the promising antifungal target methionine synthase in great detail, using the prominent fungal pathogen Aspergillus fumigatus as a model. We have uncovered the underlying reason for its essentiality and confirmed its druggability. Furthermore, we have optimized the use of a genetic system to show a beneficial effect of targeting methionine synthase in established infections. Therefore, we believe that antifungal drugs to target methionine synthase should be pursued and additionally, we provide a model that permits gaining information about the validity of antifungal targets in established infections.

Abstract Background Sexual violence is prevalent in conflict-affected settings and may result in sexual violence-related pregnancies (SVRPs). There are limited data on how women with SVRPs make decisions about pregnancy continuation or termination, especially in contexts with limited or restricted access to comprehensive reproductive health services. Methods A qualitative study was conducted in Bukavu, Democratic Republic of the Congo (DRC) as part of a larger mixed methods study in 2012. Utilizing respondent-driven sampling (RDS), adult women who self-reported sexual violence and a resultant SVRP were enrolled into two study subgroups: 1) women currently raising a child from an SVRP (parenting group) and 2) women who terminated an SVRP (termination group). Trained female research assistants conducted semi-structured interviews with a subset of women in a private setting and responses were manually recorded. Interview notes were translated and uploaded to a qualitative software program, coded, and thematic content analysis was conducted. Results A total of 55 women were interviewed: 38 in the parenting group and 17 in the termination group. There were a myriad of expressed attitudes, beliefs, and emotional responses toward SVRPs and the termination of SVRPs with three predominant influences on decision-making, including: 1) the biologic, ethnic, and social identities of the fetus and/or future child; 2) social reactions, including fear of social stigmatization and/or rejection; and 3) the power of religious beliefs and moral considerations on women’s autonomy in the decision-making process. Conclusion Findings from women who continued and women who terminated SVRPs reveal the complexities of decision-making related to SVRPs, including the emotional reasoning and responses, and the social, moral, and religious dimensions of the decision-making processes. It is important to consider these multi-faceted influences on decision-making for women with SVRPs in conflict-affected settings in order to improve provision of health services and to offer useful insights for subsequent programmatic and policy decisions.

Pathogen-pathogen interactions in polymicrobial infections are known to directly impact, often to worsen, disease outcomes. For example, co-infection with Pseudomonas aeruginosa and Aspergillus fumigatus, respectively the most common bacterial and fungal pathogens isolated from cystic fibrosis (CF) airways, leads to a worsened prognosis. Recent studies of in vitro microbial cross-talk demonstrated that P. aeruginosa-derived volatile sulfur compounds (VSCs) can promote A. fumigatus growth in vitro. However, the mechanistic basis of such cross-talk and its physiological relevance during co-infection remains unknown. In this study we combine genetic approaches and GC-MS-mediated volatile analysis to show that A. fumigatus assimilates VSCs via cysteine (CysB)- or homocysteine (CysD)-synthase. This process is essential for utilization of VSCs as sulfur sources, since P. aeruginosa-derived VSCs trigger growth of A. fumigatus wild-type, but not of a ΔcysBΔcysD mutant, on sulfur-limiting media. P. aeruginosa produces VSCs when infecting Galleria mellonella and co-infection with A. fumigatus in this model results in a synergistic increase in mortality and of fungal and bacterial burdens. Interestingly, the increment in mortality is much greater with the A. fumigatus wild-type than with the ΔcysBΔcysD mutant. Therefore, A. fumigatus’ ability to assimilate P. aeruginosa derived VSCs significantly triggers a synergistic association that increases the pathobiology of infection. Finally, we show that P. aeruginosa can promote fungal growth when growing on substrates that resemble the lung environment, which suggests that this volatile based synergism is likely to occur during co-infection of the human respiratory airways.

Abstract Background By 2017, more than 500,000 Syrian refugees had passed through Greece seeking safety and asylum. Understanding how their health needs evolved over the refugee crisis in Greece and in relation to changing migration policy, and exploring the challenges involved in delivering their healthcare is timely as non-governmental organizations (NGOs) transition health service provision to the Greek health authorities. Methods We conducted a qualitative study to explore stakeholders’ perspectives on delivering health services to Syrian refugees over the course of the humanitarian response in Greece from 2015 to 2017. Twenty-five in-depth interviews were conducted face-to-face or by Skype with healthcare providers, NGO staff, and organizational and government representatives involved in coordinating and managing healthcare for the Syrian refugee population in Greece. Following informed consent, interviews were audio-recorded or detailed summaries were manually recorded. Data were coded inductively to identify emerging themes. Results Following the implementation of the European Union-Turkey agreement in 2016, healthcare providers in refugee camps reported a shift from acute physical health issues to mental health disorders, and heightened risks of gender-based violence among Syrian refugees. Key challenges to service delivery included a narrow model of healthcare provision and insufficient referral mechanisms for social support and mental health services. Language and gender differences between refugees and healthcare providers, and a lack of privacy and space in clinics impeded the quality of care. Stakeholders observed deterioration in refugees’ mental health in relation to longer periods spent in the camps. Many also emphasized that services for gender-based violence and mental health should be prioritized. Conclusion This study provides stakeholders’ perspectives on changes in refugee health needs over the course of the humanitarian response in Greece. With protracted encampment resulting from migration policy, addressing mental health disorders and gender-based violence should be prioritized, including psychosocial training for healthcare providers and strengthening referral mechanisms for specialized care. The findings also emphasize the importance of providing human-centered care and gender concordant services by incorporating female healthcare providers and interpreters into medical teams. Strategic communication and coordination is needed between NGOs and Greek health authorities to facilitate the transition of health service delivery to the Greek healthcare system and to improve access and quality of care for refugees.

Introduction: Little is known about the anticipated disease course for individuals who present with renal-limited antineutrophil cytoplasmic antibody (ANCA)−associated vasculitis but who lack inflammation on a kidney biopsy. The impact of immunosuppression on renal and overall survival is unknown. Methods: Patients were recruited from 2005 to 2016 from 8 centers worldwide (N = 16) for this descriptive study. All had positive ANCA, elevated serum creatinine with active urine sediment, histologic evidence of pauci-immune glomerulonephritis without active lesions, and had no evidence of extrarenal vasculitis. We describe the characteristics of this cohort and the differences in the clinical, histologic, and therapeutic parameters of those who developed primary outcomes of end-stage renal disease (ESRD) and vasculitis relapse. Results: The cohort was 63% Caucasian, and 75% were men, with a median age of 62 years. At entry, the mean ± SD estimated glomerular filtration rate (eGFR) was 24 ± 20 ml/min per 1.73 m2, and 5 patients required dialysis. Twelve patients received immunosuppressive therapy, 25% experienced disease relapse, and 38% developed ESRD. Patients who developed ESRD had lower baseline eGFRs (8 ± 5 ml/min per 1.73 m2 vs. 35 ± 18 ml/min per 1.73 m2; P = 0.001) and more often required dialysis at presentation (83% vs. 0%; P = 0.001). Patients who relapsed were less likely to receive immunosuppression (25% for the relapsed group vs. 92% for the nonrelapsed group; relative risk: 0.27, risk difference: 67%; P = 0.03). Conclusion: Among these patients, lower initial eGFR and dialysis dependence at presentation might increase the risk for ESRD. Immunosuppression did not affect renal outcomes in this sample of patients but was associated with a reduced risk for vasculitis relapse. More information is needed on factors that predict treatment response in this high-risk group. Keywords: ANCA-associated vasculitis, glomerulonephritis, renal limited vasculitis

Abstract Background Sexual violence is prevalent in eastern Democratic Republic of Congo (DRC) and has potentially devastating psychosocial consequences. Previous studies have reported on sexual violence and its impact on the mental health of survivors, but there are few studies conducted among women with sexual violence-related pregnancies (SVRPs). Women with SVRPs may be at greater risk of complex psychosocial outcomes, including social stigmatization. This study aimed to describe psychosocial outcomes among this subgroup of sexual violence survivors in order to inform future interventions. Methods A mixed methods study was conducted in Bukavu, DRC in 2012 among adult women who self-reported an SVRP and either (1) were currently raising a child from an SVRP (parenting group) or (2) had terminated an SVRP (termination group). This manuscript presents qualitative findings from the mixed methods study. Participants were recruited using respondent-driven sampling and a proportion engaged in semi-structured qualitative interviews conducted by trained female interviewers. Thematic content analysis was conducted and key themes were identified. Results In total, 55 women were interviewed, of whom 38 were in the parenting group and 17 in the termination group. Women with SVRPs experienced a myriad of emotional responses as they navigated their social environments following the SVRPs. Negative reactions, including social stigmatization and/or social rejection, toward women with SVRPs and toward children born from SVRPs were important influences on psychological well-being. Women expressed both internalized emotionality intertwined with externalized experiences in the social environment. Many women demonstrated resilience, or what could be termed post-traumatic growth, identifying avenues of agency to advance the social conditions for women. Conclusions The findings from the qualitative study, and in particular, the respondents’ needs and suggested strategies, may be useful to inform future research, programs, and policies for women with SVRPs in eastern DRC. Future research could move beyond cross-sectional assessments to utilize innovative research methodologies to assess processes of psychological adaptation among women with SVRPs. Multi-dimensional psychosocial programs for women with SVRPs should consider basic needs such as shelter, food, and health care within the broader framework of trauma-informed care. Participatory programming, guided by beneficiaries, could provide further avenues for agency to advance social conditions for women with SVRPs in eastern DRC.

Zika virus (ZIKV) can persist in human semen and sperm, which can result in sexual transmission. Here, Griffinet al. show that a DNA vaccine, expressing ZIKV pre-membrane and envelope proteins, protects mice from infection-associated damage to testes and sperm, and prevents viral persistence in testes.

Introduction: Patients who require invasive mechanical ventilation (IMV) often represent a sequence of care between the emergency department (ED) and intensive care unit (ICU). Despite being the most populous state, little information exists to define patterns of IMV use within the state of California. Methods: We examined data from the masked Patient Discharge Database of California’s Office of Statewide Health Planning and Development from 2000-2009. Adult patients who received IMV during their stay were identified using the International Classification of Diseases 9th Revision and Clinical Modification procedure codes (96.70, 96.71, 96.72). Patients were divided into age strata (18-34yr, 35-64yr, and >65yr). Using descriptive statistics and regression analyses, for IMV discharges during the study period, we quantified the number of ED vs. non-ED based admissions; changes in patient characteristics and clinical outcome; evaluated the marginal costs for IMV; determined predictors for prolonged acute mechanical ventilation (PAMV, i.e. IMV>96hr); and projected the number of IMV discharges and ED-based admissions by year 2020. Results: There were 696,634 IMV discharges available for analysis. From 2000–2009, IMV discharges increased by 2.8%/year: n=60,933 (293/100,000 persons) in 2000 to n=79,868 (328/100,000 persons) in 2009. While ED-based admissions grew by 3.8%/year, non-ED-based admissions remained stable (0%). During 2000-2009, fastest growth was noted for 1) the 35–64 year age strata; 2) Hispanics; 3) patients with non-Medicare public insurance; and 4) patients requiring PAMV. Average total patient cost-adjusted charges per hospital discharge increased by 29% from 2000 (from $42,528 to $60,215 in 2014 dollars) along with increases in the number of patients discharged to home and skilled nursing facilities. Higher marginal costs were noted for younger patients (ages 18-34yr), non-whites, and publicly insured patients. Some of the strongest predictors for PAMV were age 35-64 years (OR=1.12; 95% CI [1.09-1.14], p

Introduction Since its’ inception in May 2015, the Public Benefit and Privacy Panel has provided a centralised, simplified and truly national Information Governance scrutiny process. It has successfully harnessed expertise across NHS Scotland health boards implementing a collaborative approach which contributes to consistency and continued capacity development across the sector. Objectives and Approach Over the last 3 years PBPP developed several procedures within its’ operations to become more efficient and achieve consistent decision making to ensure there is adequate information sharing amongst both Tier 1 and Tier 2 PBPP members. These components include: • Integrated working with eDRIS team to support applicants pre submission • Established an operational group with action plan • Monthly reporting to NHS Boards Information Governance colleagues • Annual learning and sharing workshop • Annual audit of Tier 1 Proportionate Governance approved applications • Documented Case Law • Information Sheets on categories of applications to aid consistent decision making Results Tier 1 panel members have noted that the quality of applications is noticeably improved when assistance is provided pre-submission aiding the speed of their proportionate review and that reference documents provide valuable information on the foundations of previous decisions. As a result of this and other improvements 90% of all applications are approved by Tier 1. Only those deemed highly complex or novel proposals are usually referred to Tier 2 at which 8% are reviewed and approved out of committee via email and the remaining 2% are heard at a Full Committee meeting. Whilst the average “clocked” days for an application is approximately 31 days. Conclusion/Implications PBPP needs to continue to evolve in order to continue providing efficient and pragmatic IG assessments for new technologies, more complex, voluminous data linkages and innovation. This is no mean feat in a fast paced environment and we have to ensure those involved are given sufficient time to do so.

At the heart of many computations in science and engineering lies the need to efficiently and accurately solve large sparse linear systems of equations. Direct methods are frequently the method of choice because of their robustness, accuracy and potential for use as black-box solvers. In the last few years, there have been many new developments, and a number of new modern parallel general-purpose sparse solvers have been written for inclusion within the HSL mathematical software library. In this paper, we introduce and briefly review these solvers for symmetric sparse systems. We describe the algorithms used, highlight key features (including bit-compatibility and out-of-core working) and then, using problems arising from a range of practical applications, we illustrate and compare their performances. We demonstrate that modern direct solvers are able to accurately solve systems of order 106 in less than 3 minutes on a 16-core machine.

A review of Latané, David E.. William Maginn and the British Press: A Critical Biography. London: Ashgate, 2013. 378 pp. £95.

The internet is becoming increasingly integral to children’s lives. Consequently, it is vital that children are educated in how to protect themselves online and how to become responsible online users. This action research study addresses significant gaps in existing research by exploring children’s online experiences, alongside their understandings of risk, from their own perspective, in order to inform a personalised and relevant internet safety curriculum within the research setting. The study utilises a mixed-methods approach, combining a comprehensive quantitative survey with a subsequent qualitative group interview with a sample of 14 participants. Findings suggest that, despite being proficient online users with an awareness of what constitutes online risk, many children largely fail to apply this knowledge to their own online practices. The study demonstrates the importance of educators and schools understanding children’s online activities in order to respond to their needs and concerns effectively. Based on the research findings, it is recommended that similar research is actioned across primary schools, and that schools appoint pupils as internet safety ambassadors to provide educators with insights into children’s current online activities, alongside providing peer guidance and support from a pupil perspective. These recommendations could be significant for the online safety education of children and young people in the wider context.

The Democratic Republic of the Congo (DRC) has experienced nearly two decades of civil conflict in the Eastern regions of North and South Kivu. This conflict has been notorious for the use of sexual violence as a weapon of war, leading in many cases to pregnancy after rape. The objectives of this analysis were: 1) to describe patterns of sexual violence-related pregnancy (SVRP) disclosure; 2) to consider why survivors chose to disclose to particular individuals; and 3) to examine the dialogue around SVRPs between women with SVRPs and their confidants. In South Kivu Province, Democratic Republic of Congo, two sub-groups of sexual violence survivors completed qualitative interviews, those currently raising a child from an SVRP (parenting group, N = 38) and those who had terminated an SVRP (termination group, N = 17). The findings show that a majority of SVRPs were conceived when participants were held in sexual captivity for prolonged periods of time. The SVRPs were disclosed to friends, family members, other sexual violence survivors, community members, spouses, health care providers, or perpetrators. The confidants were most often chosen because they were perceived by the participants as being discreet, trusted, and supportive. The confidants often provided advice about continuing or terminating the SVRP. Trust and discretion are the most important factors determining to whom women with SVRPs disclose their pregnancies. The vital role of confidants in giving support after disclosure cannot be overlooked. Providing opportunities for survivors to safely disclose their SVRPs, including to health care providers, is a necessary first step in allowing them to access safe and comprehensive post-assault care and services.

Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE.We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight 34 weeks with no adverse outcome.PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.

In 2009, the leadership of the Children’s University Medical Group (CUMG) embarked on an effort to answer the question, “What would it take to promote and foster a culture of service amongst the medical staff?” The challenge was to engage the physician group in leading patient and family experience improvements within Seattle Children’s. In this article, an innovative, physician-designed and led approach to improving the patient experience is described. The effort focuses on encouraging local, grass roots strategies rooted in readily available and validated best practices. In support of that effort, novel tools that were developed and deployed to elicit input, engagement and self-assessment are also described.

The Corneal limbus is a readily accessible region at the front of the eye, separating the cornea and sclera. Neural colonies (neurospheres) can be generated from adult corneal limbus in vitro. We have previously shown that these neurospheres originate from neural crest stem/progenitor cells and that they can differentiate into functional neurons in vitro. The aim of this study was to investigate whether mouse and human limbal neurosphere cells (LNS) could differentiate towards a retinal lineage both in vivo and in vitro following exposure to a developing retinal microenvironment. In this article we show that LNS can be generated from adult mice and aged humans (up to 97 years) using a serum free culture assay. Following culture with developing mouse retinal cells, we detected retinal progenitor cell markers, mature retinal/neuronal markers and sensory cilia in the majority of mouse LNS experiments. After transplantation into the sub-retinal space of neonatal mice, mouse LNS cells expressed photoreceptor specific markers, but no incorporation into host retinal tissue was seen. Human LNS cells also expressed retinal progenitor markers at the transcription level but mature retinal markers were not observed in vitro or in vivo. This data highlights that mouse corneal limbal stromal progenitor cells can transdifferentiate towards a retinal lineage. Complete differentiation is likely to require more comprehensive regulation; however, the accessibility and plasticity of LNS makes them an attractive cell resource for future study and ultimately therapeutic application.

Evangelical colleges and universities situated in rural communities are uniquely positioned to bridge the ever-widening cultural, economic, and political divide that threatens American democracy. However, success in this endeavor will require an appreciation for what it means to be a neighbor in this particular context. Thus, this article begins with a brief overview of how the common good has been conceptualized and pursued throughout the history of American higher education, followed by a description of features common to rural contexts. Next, a group of 31 member institutions of the Council for Christian Colleges and Universities is identified as rurally located, and their group characteristics are contrasted with their urban counterparts. Attention then turns to the contours of community engagement in the rural context, and the potential for rural evangelical colleges and universities to fulfill the place-based roles of stewarding and anchoring is explored. The article concludes by casting a vision for the common good in which Christian institutions of higher education partner with their surrounding communities to co-create a shared perspective, shared knowledge, and shared places.