What happens in the Lab: Applying Midstream Modulation to Enhance Critical Reflection in the Laboratory

In response to widespread policy prescriptions for responsible innovation, social scientists and engineering ethicists, among others, have sought to engage natural scientists and engineers at the ‘midstream’: building interdisciplinary collaborations to integrate social and ethical considerations with research and development processes. Two ‘laboratory engagement studies’ have explored how applying the framework of midstream modulation could enhance the reflections of natural scientists on the socio-ethical context of their work. The results of these interdisciplinary collaborations confirm the utility of midstream modulation in encouraging both first- and second-order reflective learning. The potential for second-order reflective learning, in which underlying value systems become the object of reflection, is particularly significant with respect to addressing social responsibility in research practices. Midstream modulation served to render the socio-ethical context of research visible in the laboratory and helped enable research participants to more critically reflect on this broader context. While lab-based collaborations would benefit from being carried out in concert with activities at institutional and policy levels, midstream modulation could prove a valuable asset in the toolbox of interdisciplinary methods aimed at responsible innovation

Functional Restoration of CFTR Nonsense Mutations in Intestinal Organoids

Background: Pharmacotherapies for people with cystic fibrosis (pwCF) who have premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are under development. Thus far, clinical studies focused on compounds that induce translational readthrough (RT) at the mRNA PTC location. Recent studies using primary airway cells showed that PTC functional restoration can be achieved through combining compounds with multiple mode-of-actions. Here, we assessed induction of CFTR function in PTC-containing intestinal organoids using compounds targeting RT, nonsense mRNA mediated decay (NMD) and CFTR protein modulation. Methods: Rescue of PTC CFTR protein was assessed by forskolin-induced swelling of 12 intestinal organoid cultures carrying distinct PTC mutations. Effects of compounds on mRNA CFTR level was assessed by RT-qPCRs. Results: Whilst response varied between donors, significant rescue of CFTR function was achieved for most donors with the quintuple combination of a commercially available pharmacological equivalent of the RT compound (ELX-02-disulfate or ELX-02ds), NMD inhibitor SMG1i, correctors VX-445 and VX-661 and potentiator VX-770. The quintuple combination of pharmacotherapies reached swelling quantities higher than the mean swelling of three VX-809/VX-770-rescued F508del/F508del organoid cultures, indicating level of rescue is of clinical relevance as VX-770/VX-809-mediated F508del/F508del rescue in organoids correlate with substantial improvement of clinical outcome. Conclusions: Whilst variation in efficacy was observed between genotypes as well as within genotypes, the data suggests that strong pharmacological rescue of PTC requires a combination of drugs that target RT, NMD and protein function

The evolution of socioeconomic status-related inequalities in maternal health care utilization: evidence from Zimbabwe, 1994-2011

Background: Inequalities in maternal health care are pervasive in the developing world, a fact that has led to questions about the extent of these disparities across socioeconomic groups. Despite a growing literature on maternal health across Sub-Saharan African countries, relatively little is known about the evolution of these inequalities over time for specific countries. This study sought to quantify and explain the observed differences in prenatal care use and professional delivery assistance in Zimbabwe. Methods: The empirical analysis uses four rounds of the nationwide Zimbabwe Demographic and Health Survey administered in 1994, 1999, 2005/06 and 2010/11. Two binary indicators were used as measures of maternal health care utilization; (1) the receipt of four or more antenatal care visits and (2) receiving professional delivery assistance for the most recent pregnancy. We measure inequalities in maternal health care use using the Erreygers corrected concentration index. A decomposition analysis was conducted to determine the underlying drivers of the measured disparities. Results: The computed concentration indices for professional delivery assistance and prenatal care reveal a mostly pro-rich distribution of inequalities between 1994 and 2011. Particularly, the concentration index [95% confidence interval] for the receipt of prenatal care was 0.111 [0.056, 0.171] in 2005/06 and 0.094 [0.057, 0.138] in 2010/11. For professional delivery assistance, the concentration index stood at 0.286 [0.244, 0.329] in 2005/06 and 0.324 [0.283, 0.366] in 2010/11. The pro-rich inequality was also increasing in both rural and urban areas over time. The decomposition exercise revealed that wealth, education, religion and information access were the underlying drivers of the observed inequalities in maternal health care. Conclusions: In Zimbabwe, socioeconomic disparities in maternal health care use are mostly pro-rich and have widened over time regardless of the location of residence. Overall, we established that inequalities in wealth and education are amongst the top drivers of the observed disparities in maternal health care. These findings suggest that addressing inequalities in maternal health care utilization requires coordinated public policies targeting the more poor and vulnerable segments of the population in Zimbabwe

Exciton Spin Dynamics in Semiconductor Quantum Wells

In this paper we will review Exciton Spin Dynamics in Semiconductor Quantum Wells. The spin properties of excitons in nanostructures are determined by their fine structure. We will mainly focus in this review on GaAs and InGaAs quantum wells which are model systems.Comment: 55 pages, 27 figure

Intervention planning and modification of the BUMP intervention: a digital intervention for the early detection of raised blood pressure in pregnancy

Background: Hypertensive disorders in pregnancy, particularly pre-eclampsia, pose a substantial health risk for both maternal and foetal outcomes. The BUMP (Blood Pressure Self-Monitoring in Pregnancy) interventions are being tested in a trial. They aim to facilitate the early detection of raised blood pressure through self-monitoring. This article outlines how the self-monitoring interventions in the BUMP trial were developed and modified using the person-based approach to promote engagement and adherence. Methods: Key behavioural challenges associated with blood pressure self-monitoring in pregnancy were identified through synthesising qualitative pilot data and existing evidence, which informed guiding principles for the development process. Social cognitive theory was identified as an appropriate theoretical framework. A testable logic model was developed to illustrate the hypothesised processes of change associated with the intervention. Iterative qualitative feedback from women and staff informed modifications to the participant materials. Results: The evidence synthesis suggested women face challenges integrating self-monitoring into their lives and that adherence is challenging at certain time points in pregnancy (for example, starting maternity leave). Intervention modification included strategies to address adherence but also focussed on modifying outcome expectancies, by providing messages explaining pre-eclampsia and outlining the potential benefits of self-monitoring. Conclusions: With an in-depth understanding of the target population, several methods and approaches to plan and develop interventions specifically relevant to pregnant women were successfully integrated, to address barriers to behaviour change while ensuring they are easy to engage with, persuasive and acceptable

Decomposing socioeconomic inequality for binary health outcomes: an improved estimation that does not vary by choice of reference group

BACKGROUND Decomposition of concentration indices yields useful information regarding the relative importance of various determinants of inequitable health outcomes. But the two estimation approaches to decomposition in current use are not suitable for binary outcomes. FINDINGS The paper compares three estimation approaches for decomposition of inequality concentration indices: Ordinary Least Squares (OLS), probit, and the Generalized Linear Model (GLM) binomial distribution and identity link. Data are from the Thai Health and Welfare Survey 2003. The OLS estimates do not take into account the binary nature of the outcome and the probit estimates depend on the choice of reference groups, whereas the GLM binomial identity approach has neither of these problems. CONCLUSIONS The GLM with binomial distribution and identity link allows the inequality decomposition model to hold, and produces valid estimates of determinants that do not vary according to choice of reference groups. This GLM approach is readily available in standard statistical packages.The study was conducted under the auspices of the overarching project "The Thai Health-Risk Transition: a National Cohort Study", funded by the Wellcome Trust UK (GR071587 MA) and the Australian National Health and Medical Research Council (268055)

Clinical and Pathological Findings in SARS-CoV-2 Disease Outbreaks in Farmed Mink (Neovison vison)

SARS-CoV-2, the causative agent of COVID-19, caused respiratory disease outbreaks with increased mortality in 4 mink farms in the Netherlands. The most striking postmortem finding was an acute interstitial pneumonia, which was found in nearly all examined mink that died at the peak of the outbreaks. Acute alveolar damage was a consistent histopathological finding in mink that died with pneumonia. SARS-CoV-2 infections were confirmed by detection of viral RNA in throat swabs and by immunohistochemical detection of viral antigen in nasal conchae, trachea, and lung. Clinically, the outbreaks lasted for about 4 weeks but some animals were still polymerase chain reaction–positive for SARS-CoV-2 in throat swabs after clinical signs had disappeared. This is the first report of the clinical and pathological characteristics of SARS-CoV-2 outbreaks in mink farms

Equity and Geography: The Case of Child Mortality in Papua New Guinea

Background: Recent assessments show continued decline in child mortality in Papua New Guinea (PNG), yet complete subnational analyses remain rare. This study aims to estimate under-five mortality in PNG at national and subnational levels to examine the importance of geographical inequities in health outcomes and track progress towards Millennium Development Goal (MDG) 4