Tracing the paths: a systematic review of mediators of complex trauma and complex post-traumatic stress disorder.

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 registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022346152.

Experience of an NIHR Clinical Lectureship (medical/dental) and the determining factors for a clinical academic career post lectureship: a mixed-method evaluation.

OBJECTIVES: The objective of this study is to investigate early-to-late postdoctoral clinical academic progression and the experiences of NIHR Clinical Lectureship (CL) fellows, considering enablers and barriers to success, and identifying the factors associated with immediate progression to a clinical academic role following completion of the award. SETTING: Datasets of CL awardees across the UK. PARTICIPANTS: For semistructured interviews, n=40 CL awardees that had finished their award within the previous 5 years. For quantitative analysis, n=1226 completed or currently active CL awardees. OUTCOME MEASURES: The responses from the semistructured interviews to the defined questions on experiences during the award, postaward progression, and enablers and barriers to academic progression. Other primary outcome measures were quantitative data on first destinations postaward, demographic data, and whether an awardee had previously held an NIHR Academic Clinical Fellowship (ACF) or was a recipient of the Academy of Medical Sciences (AMS) Starter Grant. RESULTS: CL awardees identified numerous benefits to the award, with the majority achieving their aims. Most awardees progressed to a clinical academic role; however, some returned to a clinical only position, citing concerns around the time pressure associated with balancing clinical and academic responsibilities, and the competition to attain further postdoctoral awards. The region of the award partnership, year of award end and success in applying for an AMS Starter Grant were associated with progression to a clinical academic role. Gender, holding an ACF and having a craft or non-craft specialty had no independent statistical association with clinical academic progression. CONCLUSIONS: The CL is a valued element of the Integrated Academic Pathway. By addressing issues around later postdoctoral progression opportunities, responding to challenges experienced by CLs, and by understanding the factors identified in this study associated with clinical academic progression, it should be possible to increase the proportion of CLs that become fully independent clinical academic research leaders. PARTICIPANTS: 1226 NIHR CLs active or completed on the award between 2006 and 2020.

Trends in treatment-seeking for fever in children under five years old in 151 countries from 1990 to 2020.

Access to medical treatment for fever is essential to prevent morbidity and mortality in individuals and to prevent transmission of communicable febrile illness in communities. Quantification of the rates at which treatment is accessed is critical for health system planning and a prerequisite for disease burden estimates. In this study, national data on the proportion of children under five years old with fever who were taken for medical treatment were collected from all available countries in Africa, Latin America, and Asia (n = 91). We used generalised additive mixed models to estimate 30-year trends in the treatment-seeking rates across the majority of countries in these regions (n = 151). Our results show that the proportions of febrile children brought for medical treatment increased steadily over the last 30 years, with the greatest increases occurring in areas where rates had originally been lowest, which includes Latin America and Caribbean, North Africa and the Middle East (51 and 50% increase, respectively), and Sub-Saharan Africa (23% increase). Overall, the aggregated and population-weighted estimate of children with fever taken for treatment at any type of facility rose from 61% (59-64 95% CI) in 1990 to 71% (69-72 95% CI) in 2020. The overall population-weighted average for fraction of treatment in the public sector was largely unchanged during the study period: 49% (42-58 95% CI) sought care at public facilities in 1990 and 47% (44-52 95% CI) in 2020. Overall, the findings indicate that improvements in access to care have been made where they were most needed, but that despite rapid initial gains, progress can plateau without substantial investment. In 2020 there remained significant gaps in care utilisation that must be factored in when developing control strategies and deriving disease burden estimates.

Evaluating COVID-19-Related Disruptions to Effective Malaria Case Management in 2020-2021 and Its Potential Effects on Malaria Burden in Sub-Saharan Africa.

The COVID-19 pandemic has led to far-reaching disruptions to health systems, including preventative and curative services for malaria. The aim of this study was to estimate the magnitude of disruptions in malaria case management in sub-Saharan Africa and their impact on malaria burden during the COVID-19 pandemic. We used survey data collected by the World Health Organization, in which individual country stakeholders reported on the extent of disruptions to malaria diagnosis and treatment. The relative disruption values were then applied to estimates of antimalarial treatment rates and used as inputs to an established spatiotemporal Bayesian geostatistical framework to generate annual malaria burden estimates with case management disruptions. This enabled an estimation of the additional malaria burden attributable to pandemic-related impacts on treatment rates in 2020 and 2021. Our analysis found that disruptions in access to antimalarial treatment in sub-Saharan Africa likely resulted in approximately 5.9 (4.4-7.2 95% CI) million more malaria cases and 76 (20-132) thousand additional deaths in the 2020-2021 period within the study region, equivalent to approximately 1.2% (0.3-2.1 95% CI) greater clinical incidence of malaria and 8.1% (2.1-14.1 95% CI) greater malaria mortality than expected in the absence of the disruptions to malaria case management. The available evidence suggests that access to antimalarials was disrupted to a significant degree and should be considered an area of focus to avoid further escalations in malaria morbidity and mortality. The results from this analysis were used to estimate cases and deaths in the World Malaria Report 2022 during the pandemic years.

Common factors in HIV/AIDS prevention success: lessons from Thailand.

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.

Benchmarking Information Scrambling.

Information scrambling refers to the rapid spreading of initially localized information over an entire system, via the generation of global entanglement. This effect is usually detected by measuring a temporal decay of the out-of-time order correlators. However, in experiments, decays of these correlators suffer from fake positive signals from various sources, e.g., decoherence due to inevitable couplings to the environment, or errors that cause mismatches between the purported forward and backward evolutions. In this Letter, we provide a simple and robust approach to single out the effect of genuine scrambling. This allows us to benchmark the scrambling process by quantifying the degree of the scrambling from the noisy backgrounds. We also demonstrate our protocol with simulations on IBM cloud-based quantum computers.

Elastic anisotropy in the reduced Landau-de Gennes model.

We study the effects of elastic anisotropy on Landau-de Gennes critical points, for nematic liquid crystals, on a square domain. The elastic anisotropy is captured by a parameter, L 2 , and the critical points are described by 3 d.f. We analytically construct a symmetric critical point for all admissible values of L 2 , which is necessarily globally stable for small domains, i.e. when the square edge length, λ , is small enough. We perform asymptotic analyses and numerical studies to discover at least five classes of these symmetric critical points-the WORS , Ring ± , C o n s t a n t and p W O R S solutions, of which the WORS , Ring + and C o n s t a n t solutions can be stable. Furthermore, we demonstrate that the novel C o n s t a n t solution is energetically preferable for large λ and large L 2 , and prove associated stability results that corroborate the stabilizing effects of L 2 for reduced Landau-de Gennes critical points. We complement our analysis with numerically computed bifurcation diagrams for different values of L 2 , which illustrate the interplay of elastic anisotropy and geometry for nematic solution landscapes, at low temperatures.

Opposing effects on regulated insulin secretion of acute vs chronic stimulation of AMP-activated protein kinase.

AIMS/HYPOTHESIS: Although targeted in extrapancreatic tissues by several drugs used to treat type 2 diabetes, the role of AMP-activated protein kinase (AMPK) in the control of insulin secretion is still debatable. Previous studies have used pharmacological activators of limited selectivity and specificity, and none has examined in primary pancreatic beta cells the actions of the latest generation of highly potent and specific activators that act via the allosteric drug and metabolite (ADaM) site. METHODS: AMPK was activated acutely in islets isolated from C57BL6/J mice, and in an EndoC-ßH3 cell line, using three structurally distinct ADaM site activators (991, PF-06409577 and RA089), with varying selectivity for ß1- vs ß2-containing complexes. Mouse lines expressing a gain-of-function mutation in the γ1 AMPK subunit (D316a) were generated to examine the effects of chronic AMPK stimulation in the whole body, or selectively in the beta cell. RESULTS: Acute (1.5 h) treatment of wild-type mouse islets with 991, PF-06409577 or RA089 robustly stimulated insulin secretion at high glucose concentrations (p<0.01, p<0.05 and p<0.001, respectively), despite a lowering of glucose-induced intracellular free Ca2+ dynamics in response to 991 (AUC, p<0.05) and to RA089 at the highest dose (25 µmol/l) at 5.59 min (p<0.05). Although abolished in the absence of AMPK, the effects of 991 were observed in the absence of the upstream kinase, liver kinase B1, further implicating 'amplifying' pathways. In marked contrast, chronic activation of AMPK, either globally or selectively in the beta cell, achieved using a gain-of-function mutant, impaired insulin release in vivo (p<0.05 at 15 min following i.p. injection of 3 mmol/l glucose) and in vitro (p<0.01 following incubation of islets with 17 mmol/l glucose), and lowered glucose tolerance (p<0.001). CONCLUSIONS/INTERPRETATION: AMPK activation exerts complex, time-dependent effects on insulin secretion. These observations should inform the design and future clinical use of AMPK modulators.

Ten years of NIHR research training: who got an award? A retrospective cohort study.

OBJECTIVE: In 2017, the National Institute for Health Research (NIHR) academy produced a strategic review of training, which reported the variation in application characteristics associated with success rates. It was noted that variation in applicant characteristic was not independent of one another. Therefore, the aim of this secondary analysis was to investigate the inter-relationships in order to identify factors (or groups of factors) most associated with application numbers and success rates. DESIGN: Retrospective data were gathered from 4388 applications to NIHR Academy between 2007 and 2016. Multinominal logistic regression models quantified the likelihood of success depending on changes in the explanatory factors; relative risk ratios with 95% CIs. A classification tree analysis was built using exhaustive χ2 automatic interaction detection to better understand the effect of interactions between explanatory variables on application success rates. RESULTS: 936 (21.3%) applications were awarded. Applications from males and females were equally likely to be successful (p=0.71). There was an overall reduction in numbers of applications from females as award seniority increased from predoctoral to professorship. Applications from institutions with a medical school had a 2.6-fold increase in likelihood of success (p<0.001). Classification tree analysis revealed key predictors of application success: award level, type of programme, previous NIHR award experience and applying form a medical school. CONCLUSION: Success rates did not differ according to gender, and doctors were not more likely to be successful than applications from other professions. Taken together, these findings suggest an essential fairness in how the quality of a submitted application is assessed, but they also raise questions about variation in the opportunity to submit a high-quality application. The companion qualitative study (Burkshaw et al. (2021) BMJ Open) provides valuable insight into potential candidate mechanisms and discusses how research capacity development initiatives might be targeted in the future.

Universal healthcare does not look the same everywhere: Divergent experiences with the private sector in Brazil and Thailand.

How does the private sector structure the trajectory of a country's universal healthcare programme? Social scientists have long pointed to the importance of path dependence in shaping health reform. Yet, rarely have middle-income countries' experience with the private sector under Universal Health Coverage (UHC) been examined from comparative perspective. In this paper, we explore the changing landscape of the health sector in Brazil and Thailand before UHC reform and after. We find path-dependent processes at work that have pushed two countries that both adopted UHC reforms in divergent directions. In Brazil, a comparatively large and entrenched private sector that existed before reform has grown over time, and a sizable private health insurance industry has exerted powerful influence on health policy, weakening the public sector. In Thailand, constraints on private health insurance growth and sustained investment in public health infrastructure and governance have helped check the growth of private sector influence, although battles over health policy still remain contentious. The experiences of these countries offer lessons for policymakers seeking to achieve and maintain robust UHC programmes in other contexts.

Is there still a role for the oesophageal Doppler in cardiac output monitoring?

The oesophageal Doppler monitor received early endorsement as an effective emerging medical technology, although numerous alternatives have since been widely adopted. This article examines the evidence supporting the continued use of the oesophageal Doppler.

Total intravenous anaesthesia.

Advances in pharmacokinetic understanding have popularised the safe and effective use of total intravenous anaesthesia delivered by continuous infusion. This article explores why the practical and outcome benefits have made total intravenous anaesthesia an increasingly accepted alternative to use of inhalational agents.

Tailored nematic and magnetization profiles on two-dimensional polygons.

We study dilute suspensions of magnetic nanoparticles in a nematic host, on two-dimensional polygons. These systems are described by a nematic order parameter and a spontaneous magnetization, in the absence of any external fields. We study the stable states in terms of stable critical points of an appropriately defined free energy, with a nemato-magnetic coupling energy. We numerically study the interplay between the shape of the regular polygon, the size of the polygon, and the strength of the nemato-magnetic coupling for the multistability of this prototype system. Our notable results include (1) the coexistence of stable states with domain walls and stable interior and boundary defects, (2) the suppression of multistability for positive nemato-magnetic coupling, and (3) the enhancement of multistability for negative nemato-magnetic coupling.

Maps and metrics of insecticide-treated net access, use, and nets-per-capita in Africa from 2000-2020.

Insecticide-treated nets (ITNs) are one of the most widespread and impactful malaria interventions in Africa, yet a spatially-resolved time series of ITN coverage has never been published. Using data from multiple sources, we generate high-resolution maps of ITN access, use, and nets-per-capita annually from 2000 to 2020 across the 40 highest-burden African countries. Our findings support several existing hypotheses: that use is high among those with access, that nets are discarded more quickly than official policy presumes, and that effectively distributing nets grows more difficult as coverage increases. The primary driving factors behind these findings are most likely strong cultural and social messaging around the importance of net use, low physical net durability, and a mixture of inherent commodity distribution challenges and less-than-optimal net allocation policies, respectively. These results can inform both policy decisions and downstream malaria analyses.

Modification of the Priority Risk Index: Adapting to Emergency Management Accreditation Program standards for institutes of higher learning hazard mitigation plans.

The Priority Risk Index is increasingly used as a methodology for quantifying jurisdictional risk for hazard mitigation planning purposes, and it can evolve to meet specific community needs. The index incorporates probability, impact, spatial extent, warning time, and duration when assessing each hazard, but it does not explicitly integrate a vulnerability and consequence analysis into its final scoring. To address this gap, a new index was developed-the Enhanced Priority Risk Index (EPRI). The new index adds a sixth category, vulnerability, calculated from a vulnerability and consequence analysis of the impacts on seven sectors identified in Standard 4.1.2 of the Emergency Management Accreditation Program (EMAP). To obtain a vulnerability score, impacts are ranked by sector from low (1) to very high (4), then a weighting factor is applied to each sector. The vulnerability score is added to the EPRI and provides risk levels based on the number of exploitable weaknesses and countermeasures identified within a specific jurisdiction. The vulnerability score and resulting EPRI are scalable and can be applied across jurisdictions, providing a transferable methodology that improves the hazard identification and risk assessment process and provides an approach for meeting EMAP accreditation standards.

Indirect effects of the COVID-19 pandemic on malaria intervention coverage, morbidity, and mortality in Africa: a geospatial modelling analysis.

BACKGROUND: Substantial progress has been made in reducing the burden of malaria in Africa since 2000, but those gains could be jeopardised if the COVID-19 pandemic affects the availability of key malaria control interventions. The aim of this study was to evaluate plausible effects on malaria incidence and mortality under different levels of disruption to malaria control. METHODS: Using an established set of spatiotemporal Bayesian geostatistical models, we generated geospatial estimates across malaria-endemic African countries of the clinical case incidence and mortality of malaria, incorporating an updated database of parasite rate surveys, insecticide-treated net (ITN) coverage, and effective treatment rates. We established a baseline estimate for the anticipated malaria burden in Africa in the absence of COVID-19-related disruptions, and repeated the analysis for nine hypothetical scenarios in which effective treatment with an antimalarial drug and distribution of ITNs (both through routine channels and mass campaigns) were reduced to varying extents. FINDINGS: We estimated 215·2 (95% uncertainty interval 143·7-311·6) million cases and 386·4 (307·8-497·8) thousand deaths across malaria-endemic African countries in 2020 in our baseline scenario of undisrupted intervention coverage. With greater reductions in access to effective antimalarial drug treatment, our model predicted increasing numbers of cases and deaths: 224·1 (148·7-326·8) million cases and 487·9 (385·3-634·6) thousand deaths with a 25% reduction in antimalarial drug coverage; 233·1 (153·7-342·5) million cases and 597·4 (468·0-784·4) thousand deaths with a 50% reduction; and 242·3 (158·7-358·8) million cases and 715·2 (556·4-947·9) thousand deaths with a 75% reduction. Halting planned 2020 ITN mass distribution campaigns and reducing routine ITN distributions by 25%-75% also increased malaria burden to a total of 230·5 (151·6-343·3) million cases and 411·7 (322·8-545·5) thousand deaths with a 25% reduction; 232·8 (152·3-345·9) million cases and 415·5 (324·3-549·4) thousand deaths with a 50% reduction; and 234·0 (152·9-348·4) million cases and 417·6 (325·5-553·1) thousand deaths with a 75% reduction. When ITN coverage and antimalarial drug coverage were synchronously reduced, malaria burden increased to 240·5 (156·5-358·2) million cases and 520·9 (404·1-691·9) thousand deaths with a 25% reduction; 251·0 (162·2-377·0) million cases and 640·2 (492·0-856·7) thousand deaths with a 50% reduction; and 261·6 (167·7-396·8) million cases and 768·6 (586·1-1038·7) thousand deaths with a 75% reduction. INTERPRETATION: Under pessimistic scenarios, COVID-19-related disruption to malaria control in Africa could almost double malaria mortality in 2020, and potentially lead to even greater increases in subsequent years. To avoid a reversal of two decades of progress against malaria, averting this public health disaster must remain an integrated priority alongside the response to COVID-19. FUNDING: Bill and Melinda Gates Foundation; Channel 7 Telethon Trust, Western Australia.

MEG reveals preference specific increases of sexual-image-evoked responses in paedophilic sexual offenders and healthy controls.

OBJECTIVES: Paedophilic disorder is characterised by sexual attraction towards children. Classification of a counterpart as sexually attractive likely occurs rapidly, and involves both conscious and unconscious attentional and cognitive processes. Magnetoencephalography (MEG) is an imaging method especially well-suited to examine visual and attentional processes triggered by sexual images within the range of milliseconds. METHODS: We investigated brain responses to sexual images depicting adults (frequent) and children (infrequent stimulus) in seventeen paedophilic patients with a history of child sexual offending (P + CSO) and twenty healthy controls (HC) during a passive visual oddball paradigm. Event-related fields (ERF) were measured to extract the magnetic visual mismatch negativity (vMMNm), and how it relates to the processing of different classes of sexual stimuli. RESULTS: P + CSO exhibited significantly longer vMMNm latencies (100-180 ms post-stimulus) than HC. Moreover, P + CSO showed widespread increased amplitudes in response to child images starting from P3a and P3b components and lasting up to 400 ms post-stimulus presentation localised in frontal and temporal brain regions. CONCLUSIONS: This study uncovers the first MEG differences in automatic change detection between P + CSO and HC during the presentation of subliminal sexual images of adults and children, contributing towards a better understanding of the neurobiological processes of P + CSO.

Microscopy of Polyurea Grease.

Understanding the physical structure of greases can provide critical insight into improving the lubricating performance of a grease. Observation of the grease structure can be quite difficult depending on the type of grease and the length scale of the structure. Polyurea greases in previous reports have typically been examined by removal of the oil phase, which significantly changes the polyurea structure. This paper examines the effect of sample preparation conditions on the microstructure of polyurea greases. This study reveals new structures in the polyurea that have not been observed in the previous literature, including entangled fibers and nanotubes. Correlation is found between the observed polyurea microstructure coverage and grease stiffness.