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Complex trauma is associated with complex-posttraumatic stress disorder (CPTSD). While dissociative processes, developmental factors and systemic factors are implicated in the development of CPTSD, there are no existing systematic reviews examining the underlying pathways linking complex trauma and CPTSD. This study aims to systematically review evidence of mediating factors linking complex trauma exposure in childhood (birth to eighteen years of age) and subsequent development of CPTSD (via self-reports and diagnostic assessments). All clinical, at-risk and community-sampled articles on three online databases (PsycINFO, MedLine and Embase) were systematically searched, along with grey literature from ProQuest. Fifteen articles were eligible for inclusion according to pre-determined eligibility criteria and a search strategy. Five categories of mediating processes were identified: 1) dissociative processes; 2) relationship with self; 3) emotional developmental processes; 4) social developmental processes; and 5) systemic and contextual factors. Further research is required to examine the extent to which targeting these mediators may act as mechanisms for change in supporting individuals to heal from complex trauma.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022346152.

Abstract Background Thailand has achieved global acclaim for its response to HIV/AIDS. However, the success of some of the country’s most well-known initiatives was by no means a foregone conclusion. Policy entrepreneurs on the periphery of power had to achieve buy-in from stakeholders in state and society to scale and mainstream their ideas. This paper offers a comparative and historical understanding the process by which three of the country’s most well-known initiatives came into being: a civil society campaign to promote condom usage; a Ministry of Public Health program that aimed to prevent the spread of Human Immunodeficiency Virus (HIV) by targeting high-risk populations (the 100% condom program); and a universal Prevention of Mother-To-Child Transmission (PMTCT) program. Methods The research relied on existing literature and interviews with high-ranking ministerial officials, representatives from international and non-governmental organizations, professors, and philanthropic organizations, in addition to a review of the existing literature. Taking a comparative and historical approach that is common within political science and sociology, we analysed the in-depth qualitative interviews in relation to the literatures and used an inductive cross-case analysis aimed to draw out critical features that the initiatives shared in common. Results Common factors in HIV/AIDS prevention that cut across the three key cases include policy entrepreneurs who championed the programs, successful demonstration projects that produced a credible evidence base for policy adoption, and a diverse set of institutional partners that played critical roles in helping to mainstream their initiatives into national HIV/AIDS policy and scale programs nationally. The findings from this comparative research project have implications not only for the building of understanding related to one single project, but for broader theoretical understanding related to the mainstreaming of health policy from peripheral spaces of power. Conclusions This analysis draws out the role that demonstration projects played in building a credible evidence base for policy adoption and the role that a diverse set of institutional partners played in elevating the profile of policy entrepreneurs’ ideas and helping to scale them nationally as state policy. Success was contingent on entrepreneurs first identifying and then taking advantage of different political opportunities that arose during each of the historical periods. Over time, these initiatives have evolved from vertical programs into an integrated program, in parallel with the evolution of the HIV/AIDS landscape at the global level.

Insecticide treated nets (ITNs) are an important part of malaria control in Africa and WHO targets aim for 80% coverage. This study estimates the spatio-temporal access and use of ITNs in Africa from 2000-2020, and shows that both metrics have improved over time but access remains below WHO targets.

To what extent is the normative commitment of STS to the democratization of science a product of the democratic contexts where it is most often produced? STS scholars have historically offered a powerful critical lens through which to understand the social construction of science, and seminal contributions in this area have outlined ways in which citizens have improved both the conduct of science and its outcomes. Yet, with few exceptions, it remains that most STS scholarship has eschewed study of more problematic cases of public engagement of science in rich, supposedly mature Western democracies, as well as examination of science-making in poorer, sometimes non-democratic contexts. How might research on problematic cases and dissimilar political contexts traditionally neglected by STS scholars push the field forward in new ways? This paper responds to themes that came out of papers from two Eastern Sociological Society Presidential Panels on Science and Technology Studies in an Era of Anti-Science. It considers implications of the normative commitment by sociologists working in the STS tradition to the democratization of science.

Abstract Background The Malaria Atlas Project (MAP) has worked to assemble and maintain a global open-access database of spatial malariometric data for over a decade. This data spans various formats and topics, including: geo-located surveys of malaria parasite rate; global administrative boundary shapefiles; and global and regional rasters representing the distribution of malaria and associated illnesses, blood disorders, and intervention coverage. MAP has recently released malariaAtlas, an R package providing a direct interface to MAP’s routinely-updated malariometric databases and research outputs. Methods and results The current paper reviews the functionality available in malariaAtlas and highlights its utility for spatial epidemiological analysis of malaria. malariaAtlas enables users to freely download, visualise and analyse global malariometric data within R. Currently available data types include: malaria parasite rate and vector occurrence point data; subnational administrative boundary shapefiles; and a large suite of rasters covering a diverse range of metrics related to malaria research. malariaAtlas is here used in two mock analyses to illustrate how this data may be incorporated into a standard R workflow for spatial analysis. Conclusions malariaAtlas is the first open-access R-interface to malariometric data, providing a new and reproducible means of accessing such data within a freely available and commonly used statistical software environment. In this way, the malariaAtlas package aims to contribute to the environment of data-sharing within the malaria research community.

Multi-compartment microfluidic devices have become valuable tools for experimental neuroscientists, improving the organization of neurons and access to their distinct subcellular microenvironments for measurements and manipulations. While murine neurons are extensively used within these devices, there is a growing need to culture and maintain human neurons differentiated from stem cells within multi-compartment devices. Human neuron cultures have different metabolic demands and require longer culture times to achieve synaptic maturation. We tested different channel heights (100 μm, 400 μm, and open) to determine whether greater exposure to media for nutrient exchange might improve long-term growth of NIH-approved H9 embryonic stem cells differentiated into glutamatergic neurons. Our data showed an opposite result with both closed channel configurations having greater synaptic maturation compared to the open compartment configuration. These data suggest that restricted microenvironments surrounding neurons improve growth and maturation of neurons. We next tested whether covalently bound poly-D-lysine (PDL) might improve growth and maturation of these neurons as somata tend to cluster together on PDL adsorbed surfaces after long culture periods (>30 days). We found that covalently bound PDL greatly improved the differentiation and maturation of stem cell-derived neurons within the devices. Lastly, experimental paradigms using the multi-compartment platform show that axons of human stem cell derived neurons intrinsically regenerate in the absence of inhibitory cues and that isolated axons form presynaptic terminals when presented with synaptic targets.

Professor Sophus Bugge is internationally probably still the most famous Norwegian scholar in the humanities of any period - and that more than a century after his death in 1907. Today it is difficult to image any single scholar staking a significant claim to such a variety of learned fields, including Indo-European and Scandinavian linguistics and philology, mythology and runology, classics, folklore, Celtic, and even the non-Indo-European Etruscan - and I have probably overlooked some. Not only was his range superhuman, but so was the quantity of his output, as a look at the bibliography in his memorial volume confirms (Olsen 1908: 285-294) - containing by rough count 230 free-standing titles and Magnus Olsen's reminder (n. 1) that Bugge frequently published within other scholar's works, for example, within the ballad collection of his friend Svend Grundtvig. Bugge plainly belongs to those nineteenth-century gen­iuses who were also workaholics. Looking into Bugge's life a while back, I found no full biography, though many good short accounts shed light on his career (an especially good one, Holm-Olsen 1981) or on a section of his work, such as the fine appreciation of his ballad scholarship by Bengt R. Jonsson (1992). Perhaps no modern biographer has yet been fully prepared to evaluate that formidable oeuvre and also to take account of Bugge's friendships and social connections generally. In any case, the handsome three-volume edition of his letters within Scandinavia firmly places him at the center of a lively epistolary social network.

Abstract Background This paper identifies differences in all-cancer incidence and mortality between Pakistani-born (PB), Bangladeshi-born (BB), their descendants, and the White British (WB) in England and Wales. Pakistanis and Bangladeshis are the most marginalised and disadvantaged groups in England and Wales yet, are found to have low cancer mortality and low all-cause mortality. Previous studies though have not looked at generational differences, applied individual-level data nor separated Pakistanis and Bangladeshis from each other and other Asian groups. Methods We use the Office for National Statistics Longitudinal Study of England and Wales which is a 1% representative sample of the population. We apply event history analysis on a study period from 1971 to 2016, following individuals from age 20 until a first cancer incidence, censoring at emigration or death. We observe 10,885,500 person-years and 71,926 cancer incidences for WB; 125,700 person-years and 295 events for PB; 53,900 person-years and 113 events for BB and 26,900 person-years and 24 events for descendants. Following incidence, we study a maximum of ten years until a death from cancer, or censoring. In this second analysis on mortality our sample has 329,700 person-years and 31,689 cancer deaths for WB; 1,200 person-years and 104 events for PB; 400 person-years and 50 events for BB and 100 person-years and 10 events for descendants. Results Results from the fully adjusted models show that the risk of cancer incidence is lower for PB, BB and descendants compared to the WB native group. Estimated hazard ratio (HR) equals 0.42 for PB (95% confidence interval (CI): 0.38–0.47), for BB HR is 0.38 (CI: 0.32–0.46) and, for descendants HR is 0.36 (CI: 0.24–0.54). Results for cancer mortality after incidence show HR for PB is 0.93 (CI: 0.76–1.12), for BB it is 0.95 (CI: 0.72–1.25) and for descendants HR equals 1.62 (CI: 0.87–3.02 - significant at 90%). Conclusions Using high quality representative data, we show that lower incidence of cancer and not better survival is the driver of the low cancer mortality previously found. This advantage persists across immigrant generations, but all-cancer mortality following incidence may be elevated for descendants.

Abstract Background Given that the majority of suicide decedents visit primary care in the year preceding death, primary care has been identified as a key setting in which to engage patients at risk for suicide in mental health services. The objective of this research was to identify barriers and facilitators to engagement in mental health services among primary care patients at risk for suicide to inform the development of strategies to increase engagement. Methods Seventy-four semi-structured qualitative interviews were conducted with primary care patients (n = 20), primary care (n = 18) and behavioral health (n = 12) clinicians, mental health intake coordinators (n = 4), and health system and clinic leaders (n = 20). Patients who had been referred for mental health services from primary care and reported an elevated score (≥ 1) on item 9 on the Patient Health Questionnaire at the time of referral were eligible to participate. Eligible clinicians and leaders were employed in a primary care or behavioral health setting in a single large health system with an integrated mental health program. Interviews typically lasted 30–60 min, were completed over video conference or phone, and were coded by members of the research team using a rapid qualitative analysis procedure. Results Participants were primarily female (64.9%), white (70.3%) and non-Hispanic/Latine (91.9%). The most identified barriers to mental health care engagement were waitlists, capacity limits, insurance, patient characteristics, communication, collaboration, and/or difficulties surrounding travel. The most commonly cited facilitators of engagement included telehealth, integrated care models, reminders, case management support, psychoeducation, motivational enhancement, and scheduling flexibility. Concrete suggestions for improving engagement in mental health services included increasing communication between providers, streamlining referral and intake processes, providing reminders and follow ups, and advocacy for increased reimbursement for suicide risk assessment. Conclusions Results underscore the myriad barriers patients at risk for suicide encounter when attempting to engage in mental health care in a primary care setting. Facilitators of engagement and suggestions for improving connections to care were also identified, which can inform the design of implementation strategies to improve engagement in mental health services among primary care patients at risk for suicide. Trial registration ClinicalTrials.gov Identifier: NCT05021224 (Registered August 19, 2021).

Abstract Background Primary care is an ideal setting to connect individuals at risk for suicide to follow-up care; however, only half of the patients referred from the primary care attend an initial mental health visit. We aim to develop acceptable, feasible, low-cost, and effective new strategies to increase treatment initiation among at-risk individuals identified in primary care. Methods We will conduct a multi-phase, mixed-methods study. First, we will conduct a chart review study by using administrative data, including medical records, to identify characteristics of primary care patients at risk for suicide who do or do not attend an initial mental health visit following a referral. Second, we will conduct a mixed methods study by using direct observations and qualitative interviews with key stakeholders (N = 65) to understand barriers and facilitators to mental health service initiation among at-risk individuals. Stakeholders will include patients with suicidal ideation referred from primary care who do and do not attend a first mental health visit, primary care and behavioral health providers, and individuals involved in the referral process. We also will collect preliminary self-report and behavioral data regarding potential mechanisms of behavior change (i.e., self-regulation and social support) from patients. Third, we will leverage these findings, relevant frameworks, and the extant literature to conduct a multi-arm, non-randomized feasibility trial. During this trial, we will rapidly prototype and test strategies to support attendance at initial mental health visits. Strategies will be developed with subject matter experts (N = 10) and iteratively pilot tested (~5 patients per strategy) and refined. Research will be completed in the Penn Integrated Care Program (PIC), which includes fourteen primary care clinics in Philadelphia that provide infrastructure for electronic referrals, patient communication, and data access. Discussion We will leverage frameworks and methods from behavioral economics and implementation science to develop strategies to increase mental health treatment initiation among individuals at risk for suicide identified in primary care. This project will lead to an evaluation of these strategies in a fully powered randomized trial and contribute to improvements in access to and engagement in mental health services for individuals at risk for suicide. Trial registration ClinicalTrials.gov Identifier: NCT05021224

Background: Previous work identifies conservative family behaviour amongst Pakistanis in the United Kingdom relative to natives, including earlier marriages, fewer dissolutions, and higher fertility. However, few studies have investigated how fertility and partnership are intertwined and interdependent. Objective: Our aims are, first, to identify differences between the family trajectories of Pakistanis and natives and, second, to determine if patterns are consistent across immigrant generations. Finally, we aim to identify how family trajectories vary across birth cohorts and education levels. Methods: We apply multichannel sequence analysis (MCSA) to data from the UK Household Longitudinal Study. We first use clustering methods to group similar individuals and then apply multinomial logistic regression to calculate the probability of belonging to a cluster based on individual characteristics. Results: The Pakistani population exhibits a higher likelihood of entering a direct marriage and having large families compared to natives. Cohabitation is rare amongst Pakistani population. These patterns have changed little between immigrant generations. Degree-level education is associated with a higher likelihood of adopting behaviours typical to ancestral natives; however, the effects are not large enough to indicate convergence. Contribution: We demonstrate the need to investigate partnership and fertility trajectories simultaneously and show the value of MCSA for identifying differences between migrant groups. The results improve our understanding of family formation patterns of Pakistani immigrants and their descendants in the United Kingdom.

Summary: RAS proteins function as highly regulated molecular switches that control cellular growth. In addition to regulatory proteins, RAS undergoes a number of posttranslational modifications (PTMs) that regulate its activity. Lysine 104, a hot spot for multiple PTMs, is a highly conserved residue that forms key interactions that stabilize the RAS helix-2(H2)/helix-3(H3) interface. Mutation at 104 attenuates interaction with guanine nucleotide exchange factors (GEFs), whereas ubiquitination at lysine 104 retains GEF regulation. To elucidate how ubiquitination modulates RAS function, we generated monoubiquitinated KRAS at 104 using chemical biology approaches and conducted biochemical, NMR, and computational analyses. We find that ubiquitination promotes a new dynamic interaction network and alters RAS conformational dynamics to retain GEF function. These findings reveal a mechanism by which ubiquitination can regulate protein function.