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The current study reports the results of a randomized controlled trial examining the impact of the Getting Ready parent-engagement intervention on expressive language skills of children (N = 267) with developmental concerns upon entry into preschool. Latent growth for expressive language and moderating roles of parental stress and parental involvement in learning at home were analyzed using a structural equation modeling framework. Probing of interaction effects indicates that when families report below-average levels of stress or involvement in learning at home, children in the intervention group demonstrate accelerated growth in expressive language skills compared with peers in the comparison condition. Getting Ready is most salient when families report low to moderate levels of stress and can serve as a buffer for families who report low to moderate levels of involvement in learning at preschool entry. Results have implications for connections between families and educators across the preschool period.

Abstract Backgrounds Team leadership skills of physicians working in high-performing medical teams are directly related to outcome. It is currently unclear how these skills can best be developed. Therefore, in this multi-national cross-sectional prospective study, we explored the development of these skills in relation to physician-, organization- and training characteristics of Helicopter Emergency Medicine Service (HEMS) physicians from services in Europe, the United States of America and Australia. Methods Physicians were asked to complete a survey regarding their HEMS service, training, and background as well as a full Leader Behavior Description Questionnaire (LBDQ). Primary outcomes were the 12 leadership subdomain scores as described in the LBDQ. Secondary outcome measures were the association of LBDQ subdomain scores with specific physician-, organization- or training characteristics and self-reported ways to improve leadership skills in HEMS physicians. Results In total, 120 HEMS physicians completed the questionnaire. Overall, leadership LBDQ subdomain scores were high (10 out of 12 subdomains exceeded 70% of the maximum score). Whereas physician characteristics such as experience or base-specialty were unrelated to leadership qualities, both organization- and training characteristics were important determinants of leadership skill development. Attention to leadership skills during service induction, ongoing leadership training, having standards in place to ensure (regular) scenario training and holding structured mission debriefs each correlated with multiple LBDQ subdomain scores. Conclusions Ongoing training of leadership skills should be stimulated and facilitated by organizations as it contributes to higher levels of proficiency, which may translate into a positive effect on patient outcomes. Trial registration Not applicable.

Abstract Off-grid photovoltaic systems have been proposed as a panacea for economies with poor electricity access, offering a lower-cost “leapfrog” over grid infrastructure used in higher-income economies. Previous research examining pathways to electricity access may understate the role of off-grid photovoltaics as it has not considered reliability and carbon pricing impacts. We perform high-resolution geospatial analysis on universal household electricity access in Sub-Saharan Africa that includes these aspects via least-cost pathways at different electricity demand levels. Under our “Tier 3" demand reference scenario, 24% of our study’s 470 million people obtaining electricity access by 2030 do so via off-grid photovoltaics. Including a unit cost for unmet demand of 0.50 US dollars ($)/kWh, to penalise poor system reliability increases this share to 41%. Applying a carbon price (around $80/tonne CO2-eq) increases it to 38%. Our results indicate considerable diversity in the level of policy intervention needed between countries and suggest several regions where lower levels of policy intervention may be effective.

Low-level jets (LLJs) occur under a variety of atmospheric conditions and influence the available wind resource for wind energy projects. In 2020, lidar-mounted buoys owned by the US Department of Energy (DOE) were deployed off the California coast in two wind energy lease areas administered by the Bureau of Ocean Energy Management: Humboldt and Morro Bay. The wind profile observations from the lidars and collocated near-surface meteorological stations (4–240 m) provide valuable year-long analyses of offshore LLJ characteristics at heights relevant to wind turbines. At Humboldt, LLJs were associated with flow reversals and north-northeasterly winds, directions that are more aligned with terrain influences than the predominant northerly flow. At Morro Bay, coastal LLJs were observed primarily during northerly flow as opposed to the predominant north-northwesterly flow. LLJs were observed more frequently in colder seasons within the lowest 250 m a.s.l. (above sea level), in contrast with the summertime occurrence of the higher-altitude California coastal jet influenced by the North Pacific High, which typically occurs at heights of 300–400 m. The lidar buoy observations also validate LLJ representation in atmospheric models that estimate potential energy yield of offshore wind farms. The European Centre for Medium-Range Weather Forecasts Reanalysis version 5 (ERA5) was unsuccessful at identifying all observed LLJs at both buoy locations within the lowest 200 m. An extension of the National Renewable Energy Laboratory (NREL) 20-year wind resource dataset for the Outer Continental Shelf off the coast of California (CA20-Ext) yielded marginally greater captures of observed LLJs using the Mellor–Yamada–Nakanishi–Niino (MYNN) planetary boundary layer (PBL) scheme than the 2023 National Offshore Wind dataset (NOW-23), which uses the Yonsei University (YSU) scheme. However, CA20-Ext also produced the most LLJ false alarms, which are instances when a model identified an LLJ but no LLJ was observed. CA20-Ext and NOW-23 exhibited a tendency to overestimate the duration of LLJ events and underestimate LLJ core heights.

Abstract Background Recruiting large cohorts efficiently can speed the translation of findings into care across a range of scientific disciplines and medical specialties. Recruitment can be hampered by factors such as financial barriers, logistical concerns, and lack of resources for patients and clinicians. These and other challenges can lead to underrepresentation in groups such as rural residents and racial and ethnic minorities. Here we discuss the implementation of various recruitment strategies for enrolling participants into a large, prospective cohort study, assessing the need for adaptations and making them in real-time, while maintaining high adherence to the protocol and high participant satisfaction. Methods While conducting a large, prospective trial of a multi-cancer early detection blood test at Geisinger, an integrated health system in central Pennsylvania, we monitored recruitment progress, adherence to the protocol, and participants’ satisfaction. Tracking mechanisms such as paper records, electronic health records, research databases, dashboards, and electronic files were utilized to measure each outcome. We then reviewed study procedures and timelines to list the implementation strategies that were used to address barriers to recruitment, protocol adherence and participant satisfaction. Results Adaptations to methods that contributed to achieving the enrollment goal included offering multiple recruitment options, adopting group consenting, improving visit convenience, increasing the use of electronic capture and the tracking of data and source documents, staffing optimization via leveraging resources external to the study team when appropriate, and integrating the disclosure of study results into routine clinical care without adding unfunded work for clinicians. We maintained high protocol adherence and positive participant experience as exhibited by a very low rate of protocol deviations and participant complaints. Conclusion Recruiting rapidly for large studies – and thereby facilitating clinical translation – requires a nimble, creative approach that marshals available resources and changes course according to data. Planning a rigorous assessment of a study’s implementation outcomes prior to study recruitment can further ground study adaptations and facilitate translation into practice. This can be accomplished by proactively and continuously assessing and revising implementation strategies.

Abstract. Introduction:. Traditionally, stiff hypertrophic nonunions have been managed with open preparation of the nonunion site, which is then secured with internal fixation. Alternative surgical options are available including distraction osteogenesis with an external fixator. There is currently a limited amount of literature pertaining to the use of distraction osteogenesis in the management of hypertrophic nonunion. The aim of this systematic review was to collate and assess the effectiveness of distraction osteogenesis (DO) in the management of hypertrophic nonunions and to evaluate the complications that are commonly reported in the literature. Methods:. We searched for articles pertaining to the treatment of hypertrophic nonunion using distraction osteogenesis. Several electronic bibliographic databases and clinical trial registries were searched using the MeSH terms “hypertrophic non-union,” “distraction osteogenesis,” “stiff non-union,” and “External Fixation” in various combinations to return the maximal number of studies for review. We performed a systematic review and identified a total of 11 studies eligible for review. Results:. The review of the literature demonstrated that this technique is highly effective in achieving bony union with minimal complications. The most common complication is mild superficial pin site infections, usually managed with oral antibiotics and effective wound hygiene. Other complications reported were deep pin tract infections, broken hardware, and deformity recurrence due to collapse of regenerate bone. Conclusion:. The use of distraction osteogenesis with external fixator devices is an effective and safe method for producing bony union in hypertrophic nonunions. There were minimal associated complications.

Purpose: Patients with conjunctival squamous cell carcinoma that present with persisting disease or recurrence following topical chemotherapy and/or surgery especially when invading the sclera are challenging to treat. Herein, we describe the use of high-dose-rate (HDR), FDA-cleared, yttrium-90 (90Y) plaque brachytherapy for such lesions. Observation: Three cases of invasive conjunctival squamous cell carcinoma that had exhibited a poor response or recurrence following topical chemotherapy and/or surgery are described. As treatment, HDR 90Y beta-radiation was applied to the tumor and margins for a single, continuous duration. In contrast to low-dose-rate (LDR) plaque, HDR 90Y brachytherapy did not require episcleral sutures, amniotic membrane buffering of the cornea, a Gunderson flap, outpatient dwell time, or second surgery. Radiation safety was improved by eliminating LDR-implant related post-operative radiation exposure to health care personnel, the community, family, and pets. Follow-up examination at one month revealed complete tumor resolution in all patients. At last follow-up (8, 11 and 18 months) all patients remained clinically tumor-free as confirmed by slit-lamp biomicroscopy, anterior segment optical coherence tomography, and high-frequency ultrasound imaging. There were no acute complications (e.g., corneal edema, iridocyclitis, scleropathy, keratopathy or cataract). Conclusion and Importance: 90Y brachytherapy demonstrated efficacy as a single-surgery, minimally invasive, outpatient irradiation for squamous carcinoma of the ocular surface. While short-term results were promising, long-term follow-up monitoring for side-effects and recurrence are essential.

The motivation to socially connect with peers increases during adolescence in parallel with changes in neurodevelopment. These changes in social motivation create opportunities for experiences that can impact risk for psychopathology, but the specific motivational presentations that confer greater psychopathology risk are not fully understood. To address this issue, we used a latent profile analysis to identify the multidimensional presentations of self-reported social goals in a sample of 220 girls (9-15 years old, M = 11.81, SD = 1.81) that was enriched for internalizing symptoms, and tested the association between social goal profiles and psychopathology. Associations between social goals and brain network connectivity were also examined in a subsample of 138 youth. Preregistered analyses revealed four unique profiles of social goal presentations in these girls. Greater psychopathology was associated with heightened social goals such that higher clinical symptoms were related to a greater desire to attain social competence, avoid negative feedback and gain positive feedback from peers. The profiles endorsing these excessive social goals were characterized by denser connections among social-affective and cognitive control brain regions. These findings thus provide preliminary support for adolescent-onset changes in motivating factors supporting social engagement that may contribute to risk for psychopathology in vulnerable girls.

We present an auxiliary learning task for the problem of neuron segmentation in electron microscopy volumes. The auxiliary task consists of the prediction of local shape descriptors (LSDs), which we combine with conventional voxel-wise direct neighbor affinities for neuron boundary detection. The shape descriptors capture local statistics about the neuron to be segmented, such as diameter, elongation, and direction. On a study comparing several existing methods across various specimen, imaging techniques, and resolutions, auxiliary learning of LSDs consistently increases segmentation accuracy of affinity-based methods over a range of metrics. Furthermore, the addition of LSDs promotes affinity-based segmentation methods to be on par with the current state of the art for neuron segmentation (flood-filling networks), while being two orders of magnitudes more efficient-a critical requirement for the processing of future petabyte-sized datasets.

The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored.

Over the past decade, targeted therapy for oncogene-driven NSCLC and immune checkpoint inhibitors for non-oncogene-driven NSCLC, respectively, have greatly improved the survival and quality of life for patients with unresectable NSCLC. Increasingly, these biomarker-guided systemic therapies given before or after surgery have been used in patients with early-stage NSCLC. In March 2022, the US FDA granted the approval of neoadjuvant nivolumab and chemotherapy for patients with stage IB-IIIA NSCLC. Several phase II/III trials are evaluating the clinical efficacy of various neoadjuvant immune checkpoint inhibitor combinations for non-oncogene-driven NSCLC and neoadjuvant molecular targeted therapies for oncogene-driven NSCLC, respectively. However, clinical application of precision neoadjuvant treatment requires a paradigm shift in the biomarker testing and multidisciplinary collaboration at the diagnosis of early-stage NSCLC. In this comprehensive review, we summarize the current diagnosis and treatment landscape, recent advances, new challenges in biomarker testing and endpoint selections, practical considerations for a timely multidisciplinary collaboration at diagnosis, and perspectives in emerging neoadjuvant precision systemic therapy for patients with resectable, early-stage NSCLC. These biomarker-guided neoadjuvant therapies hold the promise to improve surgical and pathological outcomes, reduce systemic recurrences, guide postoperative therapy, and improve cure rates in patients with resectable NSCLC.

BackgroundLong-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking.ObjectivesWe conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae.MethodsParticipants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method.ResultsFifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index

Anxiety sensitivity, or fear of anxious arousal, is cross-sectionally associated with a wide array of adverse posttraumatic neuropsychiatric sequelae, including symptoms of posttraumatic stress disorder, depression, anxiety, sleep disturbance, pain, and somatization. The current study utilizes a large-scale, multi-site, prospective study of trauma survivors presenting to emergency departments. Hypotheses tested whether elevated anxiety sensitivity in the immediate posttrauma period is associated with more severe and persistent trajectories of common adverse posttraumatic neuropsychiatric sequelae in the eight weeks posttrauma. Participants from the AURORA study (n = 2,269 recruited from 23 emergency departments) completed self-report assessments over eight weeks posttrauma. Associations between heightened anxiety sensitivity and more severe and/or persistent trajectories of trauma-related symptoms identified by growth mixture modeling were analyzed. Anxiety sensitivity assessed two weeks posttrauma was associated with severe and/or persistent posttraumatic stress, depression, anxiety, sleep disturbance, pain, and somatic symptoms in the eight weeks posttrauma. Effect sizes were in the small to medium range in multivariate models accounting for various demographic, trauma-related, pre-trauma mental health-related, and personality-related factors. Anxiety sensitivity may be a useful transdiagnostic risk factor in the immediate posttraumatic period identifying individuals at risk for the development of adverse posttraumatic neuropsychiatric sequelae. Further, considering anxiety sensitivity is malleable via brief intervention, it could be a useful secondary prevention target. Future research should continue to evaluate associations between anxiety sensitivity and trauma-related pathology.

Background: As constant figures in children's lives, parents are key in protecting children from sexual abuse. One barrier to reaching parents is that the topic can be difficult to broach and is sensitive in nature. Such barriers can interfere with implementation and fidelity of evidence-based prevention strategies that are focused on reducing rates of childhood sexual abuse (CSA). Aims: In this exploratory study, we examine provider attitudes about delivering CSA-specific content in an evidence-based prevention module and their self-efficacy. Method: Thirty-three providers participated in three surveys: prior to a skills-oriented training on how to deliver the CSA prevention module (pretraining), immediately posttraining, and 6 months posttraining. Changes in self-reported willingness to deliver content, beliefs about parents' role in CSA prevention, and confidence about their ability to deliver content were assessed over time. Open-ended questions were coded thematically to reinforce quantitative findings. Results: Prior to training, providers were worried that parents would respond negatively to CSA content and were concerned about their comfort level discussing victimization and sexual development. Findings suggest that skill-oriented training and provision scripts effectively supported providers and improved confidence in delivering CSA prevention content. Discussion: Provider self-efficacy is an important element of implementation fidelity. This exploratory study demonstrated that, though providers may approach CSA content with wariness and trepidation, adequate skills-oriented training can reduce negative attitudes and increase perceived efficacy in the actual delivery of CSA content that persists through implementation. Conclusion: Skills-based training can significantly enhance fidelity in the delivery of difficult content included in parent-focused preventative interventions.

Abstract Marine scientific trawl surveys are commonly used to assess the distribution and population size of fisheries‐related species, yet the method is effort‐intensive and can be environmentally destructive. Sequencing environmental DNA (eDNA) from water samples can reveal the presence of organisms in a community without capturing them; however, we expect the detectability of taxa to differ between eDNA and trawl surveys, and understanding how species traits and population variables contribute to detection differences can help calibrate our expectations from each form of sampling. Here, we coupled eDNA metabarcoding and capture trawl surveys in British Columbia, Canada, to examine species traits that explain recurrent differences in detectability between the two methods, including habitat, body size, and biomass. At the regional scale, 17 of 23 fish species (74%) captured by the trawl were detected by eDNA metabarcoding, and 39 additional species were detected by eDNA sampling only. We found that eDNA metabarcoding disproportionately detected trawl‐caught species with greater local biomass (i.e., greater biomass in the adjacent trawl). Fish detected only in eDNA had a greater range of body lengths and a broader range of habitat preferences outside the trawls' target size and sampling areas. Our results suggest that with our level of sampling, eDNA metabarcoding can adequately recapitulate detection of fish communities detected by trawl surveys, but with a bias toward fish of high population biomass and greater inclusion of fish from outside the trawled area.

Background Arising in blood and lymph-forming tissues, haematological malignancies (leukaemias, lymphomas and myelomas) are the fifth most common group of cancers. Around 60% are currently incurable and follow a chronic, remitting–relapsing pathway often initially managed by ‘watch & wait’. This involves hospital-based monitoring, followed by treatment if the cancer progresses (which not all do) and then further observation, in a process that may continually repeat. New treatments are constantly emerging, survival is improving and prevalence is rising, but population-based data documenting entire care pathway are sparse. Hence, empirically-based incidence and prevalence estimates about various treatment states (watch and wait, first-line treatment, observation, second-line treatment, etc.) and patterns of healthcare activity are lacking. Likewise, despite complex trajectories, anxiety-provoking watch and wait, and therapies that impede quality of life and incur marked healthcare costs, evidence about patient preferences for information sharing and treatment decisions is scant. Objectives Primary – to generate high-quality, evidence-based information about the care pathways of the general population of patients with chronic haematological malignancies. Secondary – to produce information resources suitable for testing in routine National Health Service practice. Design Population-based cohort of ≈ 8000 patients with chronic haematological malignancies, incorporating five nested work packages, each with its own individual design: (1) exploration of patient experiences: information and treatment decisions; (2) population-based analyses; (3) health economics; (4) development of information resources to support decision-making; and (5) patient well-being and decision-making survey. Setting This programme is predicated on the infrastructure of the United Kingdom’s Haematological Malignancy Research Network (www.hmrn.org); which provides ‘real-world’, robust, generalisable data to inform research and clinical practice, nationally and internationally. Set in Yorkshire and Humberside, the Haematological Malignancy Research Network’s catchment population of ≈ 4 million has a comparable sex, age, urban/rural, and area-based deprivation (Index of Multiple Deprivation, income domain) distribution to the United Kingdom as a whole; and in terms of ethnic diversity the region is centrally ranked, with around 80% of residents identifying as White British, 9% as Asian and 2% as black. Within the Haematological Malignancy Research Network, clinical practice adheres to national guidelines, and all patients with blood cancers are centrally diagnosed (≈ 2500 each year), tracked through their treatment pathways and linked to national databases (deaths, cancer registrations and Hospital Episode Statistics). Linked to the same national databases, the Haematological Malignancy Research Network also contains an age- and sex-matched general-population cohort. Participants Patients aged ≥ 18 years, resident in the study region, and diagnosed with chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Methods Core Haematological Malignancy Research Network data were used to compare the hospital activity of patients with chronic lymphocytic leukaemia, follicular lymphoma and myeloma with that of the general population. Following additional linkages to genetic and clinical data, follicular lymphoma prognostic factors were examined. Two self-administered questionnaires addressing (1) quality of life and well-being and (2) decision-making were iteratively developed, piloted and deployed. Linkage to quality of life, clinical information and Hospital Episode Statistics enabled economic (myeloma) model development. In-depth interviews were conducted with 35 patients (10 alongside relatives). Results Trajectories of ≈ 8000 patients were mapped, and patient-pathway visualisations summarising individual and aggregate information were developed. As expected, patients with chronic blood cancers experienced higher levels of hospital activity than their general population counterparts, the largest effects being for myeloma. Following survey deployment, 3153 patients were recruited across 14 hospitals, 1282 with chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Over half of the questionnaires were completed by patients on watch and wait; the remainder were completed during treatment or post-chemotherapy monitoring. Information gathered, coupled with in-depth interviews, demonstrated patients’ marked anxiety and fluctuating preferences for information sharing and decision-making, contingent on complex, inter-related factors. In turn, prognostic and microsimulation economic models were used to predict individual-level trajectories across multiple treatment lines, examining associated overall survival, costs and quality-adjusted life-years. Limitations Survey mapping to individual care pathways could not be completed because the COVID-19 pandemic delayed clinical data collection. Patients who attended clinics and participated in the survey were more likely than non-attenders to have had first-line chemotherapy, be slightly younger and live in more affluent areas. Conclusions This programme collated high-quality, population-based evidence. Previously lacking, this, coupled with new findings on preferences for information sharing and treatment decisions, provides the foundation for future research. Future work The translation of information accrued into resources suitable for testing in routine NHS practice is key. In this regard, COVID-19 has changed the communication landscape. The visualisations developed by this programme require further refinement/testing using participatory co-design with stakeholder groups. Underpinned by a suitable protocol applied within a single multidisciplinary team setting, prior to further evaluation within/outside the region, such outputs require testing in a cluster-randomised trial. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: RP-PG-0613-20002) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 5. See the NIHR Funding and Awards website for further award information. Plain language summary Around half of all blood cancers (leukaemias, lymphomas and myeloma) are chronic and incurable. Management often involves ‘watch and wait’, which begins with hospital-based monitoring and is followed by treatment if the cancer progresses. This typically leads to further observation and treatment in an ongoing process over time. Patients often experience anxiety and distress about not being treated at diagnosis and also because of uncertainty about ‘if’ and ‘when’ chemotherapy might be needed. Information is critical if patients are to (1) understand what may happen to them in the future and (2) be involved treatment decisions. However, evidence about the care pathways most patients follow is lacking. This programme was designed to fill this gap, tracking all patients with chronic blood cancers through their care pathways. We collected information about diagnosis, treatment and outcome on approximately 8000 patients. These data were used to develop models that could be used to examine outcomes and costs. When compared with the general population, patients with blood cancer were confirmed to have more healthcare activity (e.g. hospital appointments and admissions). Computer programs were developed to electronically generate visual care-pathway ‘maps’ that revealed key similarities and differences between patient groups. Two questionnaires exploring quality of life and involvement in treatment decisions were developed and completed by 3153 patients in 14 hospitals. Thirty-five patients were interviewed about their preferences for information sharing and decision-making; needs were found to differ between patients and over time, and treatment recommendations from clinical staff were generally preferred. Emotional difficulties associated with uncertain trajectories were also clearly described. Yielding new information about the pathways of patients with chronic haematological malignancies, findings from this programme can be built on to improve future care. Final information resources could not be developed or tested in practice due to COVID-19, which continues to impact how health care is delivered. Scientific summary Background Population-based data are required to inform aetiological hypotheses, plan healthcare services and monitor the impact of therapeutic change in the general patient population. This need for data is particularly pertinent in fast-moving areas such as haemato-oncology, where treatments change rapidly and ‘gold-standard’ randomised controlled trials are absent or restricted to specific subgroups (often younger patients with fewer comorbidities), to specific time points (commonly first-line treatment) or by factors such as socioeconomic status, gender or ethnicity. Arising in blood and lymph-forming tissues, haematological malignancies (leukaemias, lymphomas and myelomas) are, collectively, the fifth most common cancer. With diverse aetiologies, treatments and outcomes, more than 100 subtypes are currently recognised by the World Health Organization. Although the incidence of these cancers is stable in high-income countries such as the UK, prevalence is increasing due to population ageing and the development of new multifaceted regimens (e.g. chemotherapies, radiotherapy, stem cell transplants, novel targeted agents). However, around 60% of blood cancers remain incurable, with management often beginning with regular hospital-based monitoring, known as ‘watch & wait’ (W&W). While some patients may never need treatment, others often experience a remitting–relapsing care pathway, requiring treatment at progression interspersed with further monitoring. As with many chronic conditions, there are often uncertainties regarding how individual trajectories will progress, and variations are evident in the need for (and response to) treatment; the most effective regimen; the time when treatment is required (if ever); and the impact of treatment (and non-treatment) on quality of life. Despite such complex trajectories, many of which are associated with anxiety-provoking W&W, and therapies that impede quality of life and incur marked healthcare costs, empirically-based incidence and prevalence estimates relating to treatment states (W&W, first-line treatment, second-line treatment, etc.) are lacking, and granular population-based evidence to guide treatment decisions is sparse. Importantly, new data-gathering measures to redress this deficit have been introduced in the UK but are presently insufficiently mature to guide decisions, and the rapidly evolving nature of haemato-oncology means that generic sources may never be adequate for assessing particular therapies and their impact on individuals. Furthermore, most health economic models have been developed to reflect specific (often static) decision problems, despite effective clinical management being dynamic, involving treatment, monitoring and therapy switching, and depending on treatment response and disease evolution. To summarise, there is a dearth of accessible, reliable information to guide clinicians and patients about treatment and associated healthcare activities, physical health (e.g. disruption to daily life), psychosocial well-being, quality of life and life expectancy. This situation, which is particularly difficult for patients who face uncertain pathways and unresolved anxiety about the future, is compounded by the fact that little is known about preferences for information sharing and the desire to engage in treatment decisions. Objectives This programme sought to address the deficits described above, the premise being that the provision of personalised evidence-based information at key decision points would facilitate treatment decisions, support clinical practice and improve patient experiences. The objectives were as follows: primary – to generate high-quality, longitudinal, real-world information about the care pathways of the general population of patients with chronic haematological malignancies, incorporating data on healthcare costs, and patient preferences for information sharing and engagement in treatment decisions secondary – to produce accessible information resources suitable for testing in routine NHS practice. Design This was a population-based cohort of ≈ 8000 patients with chronic haematological malignancies, incorporating 5 distinct, but inter-related, nested work packages with individual designs, including longitudinal studies, cross-sectional surveys, data linkage and qualitative investigation of patient experiences, as follows: in-depth exploration of patient experiences: information and decision-making population-based analyses health economics development of information resources to support decision-making patient well-being and decision-making survey. Setting This programme is predicated on the established expertise and infrastructure of the UK’s Haematological Malignancy Research Network (HMRN; www.hmrn.org), which was initiated in 2004 to provide robust, generalisable data to inform research and clinical practice. Set in Yorkshire and Humberside, HMRN’s population of ≈ 4 million people has a comparable sex, age, urban/rural and area-based deprivation (Index of Multiple Deprivation, income domain) distribution to that of the UK. Within HMRN, clinical practice adheres to national guidelines, and all patients are centrally diagnosed (≈ 2500 each year), tracked through their care pathways and linked to nationwide health administrative databases (deaths, cancer registrations and Hospital Episode Statistics). HMRN also contains a general-population cohort linked to the same nationwide administrative databases as the patient cohort. HMRN has ethics approval (Leeds West Research Ethics Committee 04/Q1205/69) and Section 251 support [NHS Act 2006: Patient Information and Advisory Group 1-05(h)2007], which provides the legal basis for data collection/linkage. Research building on HMRN’s infrastructure requires supplementary approvals, granted for this programme by the London, City and East Committee (Research Ethics Committee 16/LO/0740). Participants Participants were patients aged ≥ 18 years resident in the study area and diagnosed with one of the three commonest chronic haematological malignancies: chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Patient public involvement and engagement Patient and public involvement and engagement is integral to HMRN, and lay individuals are routinely involved in all research activities via the Patient Partnership, which was established in 2009 and is overseen by a Partnership Committee comprising patients, relatives/carers and researchers. The Partnership includes several hundred people who have agreed to further contact for research purposes, including directing HMRN’s activities and participating in surveys and individual/group discussions. HMRN also benefits from a group that act as a ‘sounding board’, ensuring that all our research is patient-centred and relevant. Patients and relatives were involved in the current programme as applicants and participants. Discussions preceding our application identified issues for investigation, based on patient experiences. Information was considered an area requiring improvement because of widespread concern about W&W and the anxiety and distress that this was said to instil due to uncertainty about ‘if’ and ‘when’ treatment may be required, and its likely impact. Such stories underpinned this programme, alongside our ability (via HMRN) to provide information, mapped to pathways. Changes to programme Following piloting, the survey instrument was split and the content expanded. Questionnaire 1 focused on quality of life and was to be completed pre appointment, and questionnaire 2 targeted treatment decisions and was to be completed post appointment. The number of in-depth interviews was finalised at 35 as the purposeful sampling strategy identified ‘information-rich’ sources and high-quality data. Finally, the secondary objective was curtailed by the COVID-19 pandemic (see Conclusions). Results Patient characteristics and treatment pathways With a median diagnostic age of 71 years, chronic lymphocytic leukaemia and myeloma occur more frequently in men than in women. By contrast, with a younger median age of 65.5 years, follicular lymphoma has a slight preponderance among female patients. First-line management varied markedly by subtype; 84.7% of chronic lymphocytic leukaemia patients were monitored via W&W, compared with 40.9% with follicular lymphoma and 20.2% with myeloma. Furthermore, with a 5-year relative survival of 47.7%, patients with myeloma fared less well than those with chronic lymphocytic leukaemia (5-year relative survival 84.1%) or follicular lymphoma (5-year relative survival 88.1%). To quantify/visualise the data, two software applications were developed. First, a tree-based approach aggregated patients into pathway subgroups, beginning with the initial management or event (chemotherapy, observation or death) and ending with the last. Diversity by cancer subtype was clearly evident: among those diagnosed between 2004 and 2010 who were initially managed by W&W, 40.6% (419/1031) with chronic lymphocytic leukaemia, 38.4% (93/242) with follicular lymphoma and 26.5% (90/339) with myeloma were still on W&W at the end of follow-up (5–11 years later). Second, a patient pathway generator was developed in-house from a Data-Driven Documents (D3) JavaScript library (https://d3js.org/), followed by an iterative graphical restructuring algorithm that displayed visualisations of entire pathways that included all diagnoses, investigations, treatments/responses and hospital activity in real time (generation < 1 second). Population-based analysis and prognostic model Facilitating the identification of patients requiring alternative treatment strategies and separating those at high-risk of disease progression and/or transformation from those who are not is important for clinicians and patients. With a view to incorporating genetic data into conventional prognostic models and the future development of novel targeted treatments, we examined the mutational data of patients newly diagnosed with follicular lymphoma. The molecular investigations undertaken determined that aberrant somatic hypermutations played a leading role in the genetic substructure of follicular lymphoma, with a small number of key genetic mutations, including STAT6, having a marked impact on prognosis. These clusters have implications both for understanding pathogenesis and for potential future treatment strategies. However, separation of follicular lymphoma according to mutational status despite being linked to apparent underlying mechanistic differences provides only limited prognostic information in conventionally treated patients. Hospital activity patterns Patients often question the difference their disease, or treatment, is likely to have on their survival, future healthcare needs and quality of life. As expected, inpatient and outpatient Hospital Episode Statistics activity post diagnosis was considerably higher among patients with chronic haematological malignancies than in the general population, the largest differences being for myeloma. For all three diagnoses, hospital activity peaks around the time of diagnosis, outpatient activity remaining high but levelling around 12 months after diagnosis, and inpatient activity around 8 months post diagnosis for chronic lymphocytic leukaemia and 36 months for follicular lymphoma. Health economics A microsimulation model was developed for myeloma to reflect multiple lines of treatment, post-treatment surveillance and overall survival. The model was used to predict long-term costs, and quality-adjusted life-years to enable future assessment of the expected impact of new treatments and policies. Input parameters were estimated by analysing individual-level time-to-event data (to represent patients’ trajectories), the EuroQol-5 Dimensions, five-level version (to derive quality-adjusted life-years), and HMRN treatment data (to model treatment sequences). Healthcare costs were estimated from Hospital Episode Statistics, based on national tariffs. The model is flexible enough to incorporate evidence from other sources, including clinical trials. Results were based on 2687 patients with myeloma, diagnosed 2004–15 and followed up until December 2017. Patient survey Two questionnaires for use in haemato-oncology outpatient clinics were developed in-house and piloted: questionnaire 1 (health-related quality of life) was to be completed before the clinic appointment, and questionnaire 2 (treatment decisions) was to be completed after. The survey was successfully implemented in all 14 HMRN hospitals, 2016–8, with 3153 patients participating, 1282 with chronic lymphocytic leukaemia, follicular lymphoma or myeloma. Providing information across the pathway, over half of patients completed questionnaires while on W&W; the remainder either received chemotherapy or were monitored post treatment. Survey distribution and data collection were found to be simple and effective, and patients said that they appreciated the opportunity to ‘give back’ via taking part in research. Patient preferences for information sharing and engagement in treatment decisions Interviews were conducted with 35 patients who had experienced varying treatment pathways, and 10 relatives. A large, rich data set generated multifaceted findings. The unpredictable nature of chronic haematological malignancies was confirmed, as were the challenges of coping with uncertain pathways. This caused prolonged anxiety, which could be more distressing than any physical symptoms and difficult to resolve because of infrequent clinic visits and an absence of definitive information. Preferences for information (timing, content, depth and format) varied markedly, both between patients and across individual pathways over time. Regarding treatment decisions, most interviewees said that they preferred a discussion about options, but did not wish, or felt ill-equipped, to make choices themselves. Finally, individual access to a support network (e.g. family, friends or clinical staff) was found to impact positively on experiences and preferences. Conclusions Enhancing understanding about the pathways of the general population of patients with chronic haematological malignancies, this programme has accrued an abundance of new evidence. Data collection instruments have been developed, pathway visualisation programmes have been written, and detailed quantitative and qualitative information, to an extent not previously captured, are now available. We have demonstrated that it is possible to distribute questionnaires and collect longitudinal data in hospital settings, and assemble, summarise and visualise longitudinal pathways, including data on diagnostics, prognostics, treatments, transformations/progressions, hospital episodes, outcomes and costs. Regarding health economics, we have shown the utility of using longitudinal data to estimate how many patients are on each treatment line, post treatment after each line, receiving palliative care, and so on, thereby facilitating cost calculations and resource planning. Such models could potentially be used by commissioners and healthcare managers to simulate the impact of novel policies, treatments and pathway changes prior to their introduction. The marked, ongoing anxiety experienced by some patients due to uncertain pathways suggests that benefits could be accrued from increased awareness about the extent and impact of this, alongside interventions to counteract such difficulties. Addressing varied preferences for information (content, depth, format and timing) would require a broad range and depth of material (from a basic overview to detailed options), complexity (from simple terminology to more complicated graphs) and methods for sharing (verbal, written or electronic), thereby enabling patients to access what they want to know, when they want to know it. As most (but not all) people reported a preference for clinicians to make treatment recommendations, this should also be considered. Changing preferences means that strategies for patient engagement with information-sharing and treatment decisions may need to be tailored to individual needs over time, assessed by routine clinician monitoring. Clinicians might also explore the social infrastructure and support network available to patients, so that they are aware of gaps that could be addressed. Based on several thousand patients, and exceeding any evidence previously generated, this programme collated, assessed and successfully mapped high-quality evidence-based information about the pathways of the general population of patients with chronic haematological malignancies. Previously lacking, these data, coupled with new evidence on preferences for information-sharing and treatment decisions garnered directly from patients, provide the foundation to improve clinical practice. Unfortunately, the final part of the programme could not be completed due to the COVID-19 pandemic; hence, the key future priority is the translation of the data accrued into accessible information resources suitable for testing in routine NHS practice. These would need to be responsive to both the rapidly changing haemato-oncology landscape and the varying needs of clinicians and patients at different points on the pathway. Building on the foundations of the present programme, future research, in collaboration with clinicians and patients, could include: co-refinement of electronic visualisations for use in multidisciplinary team settings co-design of resources for use in clinician–patient consultations development of cluster randomised trial protocols to test resources developed in (1) and (2) across a single multidisciplinary team area using the data collection instruments developed, prior to further evaluation within/outside the region. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref: RP-PG-0613-20002) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 5. See the NIHR Funding and Awards website for further award information.

Traumatic brain injury (TBI) causes a prolonged inflammatory response in the central nervous system (CNS) driven by microglia. Microglial reactivity is exacerbated by stress, which often provokes sleep disturbances. We have previously shown that sleep fragmentation (SF) stress after experimental TBI increases microglial reactivity and impairs hippocampal function 30 days post-injury (DPI). The neuroimmune response is highly dynamic the first few weeks after TBI, which is also when injury induced sleep-wake deficits are detected. Therefore, we hypothesized that even a few weeks of TBI SF stress would synergize with injury induced sleep-wake deficits to promote neuroinflammation and impair outcome. Here, we investigated the effects of environmental SF in a lateral fluid percussion model of mouse TBI. Half of the mice were undisturbed, and half were exposed to 5 h of SF around the onset of the light cycle, daily, for 14 days. All mice were then undisturbed 15–30 DPI, providing a period for SF stress recovery (SF-R). Mice exposed to SF stress slept more than those in control housing 7–14 DPI and engaged in more total daily sleep bouts during the dark period. However, SF stress did not exacerbate post-TBI sleep deficits. Testing in the Morris water maze revealed sex dependent differences in spatial reference memory 9–14 DPI with males performing worse than females. Post-TBI SF stress suppressed neurogenesis-related gene expression and increased inflammatory signaling in the cortex at 14 DPI. No differences in sleep behavior were detected between groups during the SF stress recovery period 15–30 DPI. Microscopy revealed cortical and hippocampal IBA1 and CD68 percent-area increased in TBI SF-R mice 30 DPI. Additionally, neuroinflammatory gene expression was increased, and synaptogenesis-related gene expression was suppressed in TBI-SF mice 30 DPI. Finally, IPA canonical pathway analysis showed post-TBI SF impaired and delayed activation of synapse-related pathways between 14 and 30 DPI. These data show that transient SF stress after TBI impairs recovery and conveys long-lasting impacts on neuroimmune function independent of continuous sleep deficits. Together, these finding support that even limited exposure to post-TBI SF stress can have lasting impacts on cognitive recovery and regulation of the immune response to trauma.

Aims Psychiatric illnesses are common in the perinatal period and many women are treated with psychotropic medications. Prescribing psychotropic medications often raises concern among patients and clinicians, because of a lack of information and no license to prescribe during pregnancy. This project aimed to evaluate the interventions offered in a perinatal clinic against the Perinatal College Centre for Quality Improvement standards. This included evaluating medications prescribed in the antenatal and postnatal periods; counselling regarding medication risks and benefits, provision of verbal and written information and psychosocial interventions. Methods Data of 60 patients (30 antenatal and 30 postnatal) attending perinatal outpatient clinics covering two cities in Midlands, England, consecutively from November 1st 2023 were collected from electronic clinical notes and clinic letters. Patients who did not attend their appointment were excluded. Results The mean age of the sample was 30.3 ± 5.2 (range 19–41). Average gestational age was 6.5 ± 2.1 months (range 2.0–9.5) for antenatal women, and average postnatal duration was 6.5 ± 5.0 months (range 0.1–22.0) at the time of review. All women had psychiatric diagnosis, except one who was discharged back to primary care. The most common diagnoses were mixed anxiety and depression (38.3%), emotionally unstable personality disorder (38.3%), and postnatal depression (20%). The majority (75.0%) were prescribed psychotropic drugs. Antidepressants were prescribed in 66.7% of antenatal and 76.7% postnatal patients; most commonly prescribed overall were sertraline (33.3%) and citalopram (23.3%). Antipsychotics were prescribed in 30.0% of antenatal and 46.7% of postnatal patients. Aripiprazole and quetiapine were most commonly prescribed in the antenatal (both 13.3%) and postnatal (both 20%) periods. A larger proportion (40.0%) of women had as required medications; promethazine (20.0% vs 30.0%), diazepam (6.7% vs 13.3%) and zopiclone (3.3% vs 13.3%) were most frequently prescribed, with figures indicating prescription rates in the ante- versus postnatal period. None of the medications were prescribed above licensed limits nor met criteria for high dose antipsychotic monitoring. Verbal and written information about medications was provided in 78.3% and 35.0% of all cases respectively. Most (65.0%) women were offered psychological therapies, and of these, 69.2% received it. Conclusion Most women in the perinatal period were prescribed psychotropic drugs, with higher proportions in the postnatal period. The findings suggested areas of improvement, such as offering written information, documenting the discussion of medication counselling, and to increase the psychotherapeutic support. It also suggests developing manualised educational interventions to improve information sharing with patients, and perinatal care.

Aims To improve the quality of junior doctor handover in the Tyrone and Fermanagh hospital. The hospital is spread across a number of inpatient sites making it difficult to complete an in-person handover. Each day the handover is completed on a Word document and sent via trust email to relevant staff. Issues were identified with the quality of information shared and how the outstanding tasks were handed over. Methods A PDSA cycle was implemented to explore outstanding issues with the handover and consider how change might be implemented. Junior doctors identified various issues including the lack of a common format, the amounts and relevancy of information shared and identifying an individual or team to conduct the outstanding tasks. A baseline audit for a 3 month period (July–September 2023) was completed. Results were reviewed and a driver diagram was established. Suggestions identified for improvement included the use of new template and an in-person handover. A new template for recording information was drawn up and agreed by the group. It included basic demographic prompts such as staff member on shift and the date of handover. The template included prompts for key patient information identified from initial audit as frequently forgotten. The template was emailed to doctors on the rota and was also highlighted to new staff at junior doctor changeover points. This new template was the intervention chosen for re-audit between November 2023 and January 2024. Results Following the application of our intervention, completion of the handover improved. From an information governance perspective the identification of staff and shift dates improved (to 98% & 99% respectively). The security of information shared improved through use of password (69% to 91%). The quality of information sharing also improved with the percentage improvement of key demographics increasing, such as patient initials (29.4%), Healthcare number (9.2%), MHO status (15.46%), patient summary (19.76%) and working diagnosis (34.91%) and finally an increase of 88.74% in identifying the person for following up outstanding tasks. Conclusion The use of a handover template has improved the quality of information shared across a number of key areas. The identification of person for handover has improved significantly with this tool and is felt to represent an improvement in patient safety. Following re-audit cycle, other areas were identified for further changes such as adjusting prompts on the template and a secure folder for storing the handover. These changes could be easily implemented in a subsequent audit cycle.

BackgroundLymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds of mass drug administration (MDA). In certain scenarios, including when elimination targets have not been met with two-drug MDA, triple-drug MDA (using ivermectin, diethylcarbamazine and albendazole) is recommended. In this study, we report on antigen (Ag) and microfilaria (Mf) prevalence in eight primary sampling units (PSUs) in Samoa 4.5 years after one round of triple-drug MDA.MethodologyIn 2023, community surveys were conducted in eight PSUs that had been surveyed previously in 2018 (between 1.5 and 3.5 months post triple-drug MDA) and 2019 (six to eight-months post triple-drug MDA). Fifteen houses were randomly selected in each PSU with household members aged ≥ 5 years invited to participate. Blood samples were tested for Ag and Mf.Principal findingsAg-positive participants were observed in six of the eight PSUs, and Ag prevalence was significantly above the 1% threshold in four PSUs. The presence of Mf-positive participants in five PSUs confirms the presence of residual active infections.Conclusions/significanceThis study provides evidence of persistent LF transmission in Samoa 4.5 years after one round of triple-drug MDA, confirming that one round was insufficient for interruption of transmission in this setting. Our findings highlight the negative impact of delaying MDA rounds, for example, due to public health emergencies.

Background: There is an increasing emphasis on promoting women’s autonomy in reproductive decision-making, particularly given global efforts to increase contraceptive access and uptake. Scales to quantify autonomy have inconsistently included the effect of external influences and focused primarily on influences of partners. Objectives: This study aimed to gain greater depth in understanding how influences including and beyond a woman’s partner affect her contraceptive decision-making, as well as how external influences can overlap and further complicate contraceptive decision-making. Design: A phenomenological, qualitative study in which in-depth interviews were conducted in three phases from May 2021 to February 2022 with women living in northwest Tanzania who had varying histories of contraceptive use or non-use. Methods: One-on-one, in-depth interviews were conducted in Swahili, the national language of Tanzania, by trained female interviewers. Interviews were digitally recorded, transcribed, translated into English, and independently coded by three investigators. Analysis was conducted using NVivo. The codes developed from the transcripts were grouped into overarching themes with supporting illustrative quotes. Results: A total of 72 women were interviewed. Partners were the most influential in women’s family planning decision-making, followed by friends, relatives, community religious leaders, and healthcare providers. Out of the 52 women with a partner who had ever used family planning, 76.9% had discussed their desire to use family planning with their partner and nearly all reported strong pressures to use or not to use family planning from partners, family, and friends. Rarely, participants stated that they were devoid of any influence. Conclusion: In rural Tanzania, women’s decision-making about family planning was highly impacted by external influences, including not only partners but also family, friends, and community. Indicators of women’s reproductive autonomy and measurements of interventions to promote contraceptive use should incorporate measures of these external influences.

Summary: Mechanisms by which Porphyromonas gingivalis (P. gingivalis) infection enhances oral tumor growth or resistance to cell death remain elusive. Here, we determined that P. gingivalis infection mediates therapeutic resistance via inhibiting lethal mitophagy in cancer cells and tumors. Mechanistically, P. gingivalis targets the LC3B-ceramide complex by associating with LC3B via bacterial major fimbriae (FimA) protein, preventing ceramide-dependent mitophagy in response to various therapeutic agents. Moreover, ceramide-mediated mitophagy is induced by Annexin A2 (ANXA2)-ceramide association involving the E142 residue of ANXA2. Inhibition of ANXA2-ceramide-LC3B complex formation by wild-type P. gingivalis prevented ceramide-dependent mitophagy. Moreover, a FimA-deletion mutant P. gingivalis variant had no inhibitory effects on ceramide-dependent mitophagy. Further, 16S rRNA sequencing of oral tumors indicated that P. gingivalis infection altered the microbiome of the tumor macroenvironment in response to ceramide analog treatment in mice. Thus, these data provide a mechanism describing the pro-survival roles of P. gingivalis in oral tumors.

This reflective, autoethnographic piece provides some insights into our involvement with a program that promotes a value-driven approach to community development work. As a 'conversation' between a lecturer and a graduate, or Educator of Informal Educators and Informal Educator, we discuss the process of teaching and learning about values within day-to-day community development practice. We emphasise that a value-driven approach enables informal educators to celebrate cultural diversity, which can be complex in community settings. As the educator of informal educators (Louise), I reflect on the need to explore and demonstrate what value-driven practice looks like in day-to-day practice within community work and not simply state that values are important. This was prompted by self-reflection and the realisation that my teaching failed to illuminate how to bring values to life in all aspects of community work to achieve anti-discriminatory, inclusive and empowering practice. As an informal educator (Matthew), I consider how community development theories and values translate into meaningful practice that celebrates cultural diversity. Reflections are influenced by theories from Paulo Freire, with a focus on his notion that 'educators should respect the autonomy of the students and respect cultural identities'. An example of Freirean dialogue, the article discusses our critical consciousness through praxis as educator and informal educator. Acknowledging that we are never fully complete--we are always 'becoming'--we hope the article will be of interest to both Educators of Informal Educators and Informal Educators alike.

Gut microbiome studies have documented depletion of butyrate-producing taxa in type 2 diabetes. We analyzed associations between butyrate-producing taxa and detailed measures of insulin homeostasis, whose dysfunction underlies diabetes in 224 non-Hispanic Whites and 129 African Americans, all of whom completed an oral glucose tolerance test. Stool microbiome was assessed by whole-metagenome shotgun sequencing with taxonomic profiling. We examined associations among 36 butyrate-producing taxa (n = 7 genera and 29 species) and insulin sensitivity, insulin secretion, disposition index, insulin clearance, and prevalence of dysglycemia (prediabetes plus diabetes, 46% of cohort), adjusting for age, sex, BMI, and race. The genus Coprococcus was associated with higher insulin sensitivity (β = 0.14; P = 0.002) and disposition index (β = 0.12; P = 0.012) and a lower rate of dysglycemia (odds ratio [OR] 0.91; 95% CI 0.85-0.97; P = 0.0025). In contrast, Flavonifractor was associated with lower insulin sensitivity (β = -0.13; P = 0.004) and disposition index (β = -0.11; P = 0.04) and higher prevalence of dysglycemia (OR 1.22; 95% CI 1.08-1.38; P = 0.0013). Species-level analyses found 10 bacteria associated with beneficial directions of effects and two bacteria with adverse associations on insulin homeostasis and dysglycemia. Although most butyrate producers analyzed appear to be metabolically beneficial, this is not the case for all such bacteria, suggesting that microbiome-directed therapeutic measures to prevent or treat diabetes should be targeted to specific butyrate-producing taxa rather than all butyrate producers.

ObjectivesTo investigate several basic psychometric properties, including construct, convergent and discriminant validity, of the tablet-based Rapid Assessment of Cognitive and Emotional Regulation (RACER) among children aged 4-6 years in Ghana.MethodsWe investigated whether RACER tasks administered to children in Ghana could successfully reproduce expected patterns of performance previously found in high-income countries on similar tasks assessing inhibitory control (e.g., slower responses on inhibition trials), declarative memory (e.g., higher accuracy on previously seen items), and procedural memory (e.g., faster responses on sequence blocks). Next, we assessed the validity of declarative memory and inhibitory control scores by examining associations of these scores with corresponding paper-based test scores and increasing child age. Lastly, we examined whether RACER was more sensitive than paper-based tests to environmental risk factors common in low- and middle-income countries (LMICs).ResultsOf the 966 children enrolled, more than 96% completed the declarative memory and inhibitory control tasks; however, around 30% of children were excluded from data analysis on the procedural memory task due to missing more than half of trials. The performance of children in Ghana replicated previously documented patterns of performance. RACER inhibitory control accuracy score was significantly correlated with child age (r (929) = .09, p = .007). However, our findings did not support other hypotheses.ConclusionsThe high task completion rates and replication of expected patterns support that certain RACER sub-tasks are feasible for measuring child cognitive development in LMIC settings. However, this study did not provide evidence to support that RACER is a valid tool to capture meaningful individual differences among children aged 4-6 years in Ghana.

Increasing interest in three-dimensional nanostructures adds impetus to electron microscopy techniques capable of imaging at or below the nanoscale in three dimensions. We present a reconstruction algorithm that takes as input a focal series of four-dimensional scanning transmission electron microscopy (4D-STEM) data. We apply the approach to a lead iridate, PbIrO, and yttrium-stabilized zirconia, YZrO, heterostructure from data acquired with the specimen in a single plan-view orientation, with the epitaxial layers stacked along the beam direction. We demonstrate that Pb-Ir atomic columns are visible in the uppermost layers of the reconstructed volume. We compare this approach to the alternative techniques of depth sectioning using differential phase contrast scanning transmission electron microscopy (DPC-STEM) and multislice ptychographic reconstruction.

OBJECTIVE: Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk trauma populations. The authors conducted the largest prospective longitudinal biomarker study of persistent dissociation to date to determine its predictive capacity for adverse psychiatric outcomes following acute trauma. METHODS: All data were part of the Freeze 2 data release from the Advancing Understanding of Recovery After Trauma (AURORA) study. Study participants provided self-report data about persistent derealization (N=1,464), a severe type of dissociation, and completed a functional MRI emotion reactivity task and resting-state scan 2 weeks posttrauma (N=145). Three-month follow-up reports were collected of posttraumatic stress, depression, pain, anxiety symptoms, and functional impairment. RESULTS: Derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activation in the emotion reactivity task and decreased resting-state vmPFC connectivity with the cerebellum and orbitofrontal cortex. In separate analyses, brain-based and self-report measures of persistent derealization at 2 weeks predicted worse 3-month posttraumatic stress symptoms, distinct from the effects of childhood maltreatment history and current posttraumatic stress symptoms. CONCLUSIONS: The findings suggest that persistent derealization is both an early psychological and biological marker of worse later psychiatric outcomes. The neural correlates of trauma-related dissociation may serve as potential targets for treatment engagement to prevent posttraumatic stress disorder. These results underscore dissociation assessment as crucial following trauma exposure to identify at-risk individuals, and they highlight an unmet clinical need for tailored early interventions.

Individual-level studies with adjustment for important COVID-19 risk factors suggest positive associations of long-term air pollution exposure (particulate matter and nitrogen dioxide) with COVID-19 infection, hospitalisations and mortality. The evidence, however, remains limited and mechanisms unclear. We aimed to investigate these associations within UK Biobank, and to examine the role of underlying chronic disease as a potential mechanism. UK Biobank COVID-19 positive laboratory test results were ascertained via Public Health England and general practitioner record linkage, COVID-19 hospitalisations via Hospital Episode Statistics, and COVID-19 mortality via Office for National Statistics mortality records from March-December 2020. We used annual average outdoor air pollution modelled at 2010 residential addresses of UK Biobank participants who resided in England (n = 424,721). We obtained important COVID-19 risk factors from baseline UK Biobank questionnaire responses (2006-2010) and general practitioner record linkage. We used logistic regression models to assess associations of air pollution with COVID-19 outcomes, adjusted for relevant confounders, and conducted sensitivity analyses. We found positive associations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) with COVID-19 positive test result after adjustment for confounders and COVID-19 risk factors, with odds ratios of 1.05 (95% confidence intervals (CI) = 1.02, 1.08), and 1.05 (95% CI = 1.01, 1.08), respectively. PM 2.5 and NO 2 were positively associated with COVID-19 hospitalisations and deaths in minimally adjusted models, but not in fully adjusted models. No associations for PM10 were found. In analyses with additional adjustment for pre-existing chronic disease, effect estimates were not substantially attenuated, indicating that underlying chronic disease may not fully explain associations. We found some evidence that long-term exposure to PM2.5 and NO2 was associated with a COVID-19 positive test result in UK Biobank, though not with COVID-19 hospitalisations or deaths.

Background: The COVID-19 pandemic required many interventions to be conducted virtually. Building Resilience and Attachment in Vulnerable Adolescents (BRAVA) is a group intervention designed for adolescents and their caregivers to reduce adolescent suicidal ideation (SI). Objective: We aimed to adapt BRAVA for virtual delivery and evaluate its acceptability and feasibility. Methods: We conducted an 8-week pre?post trial between October and December 2020. Six adolescents and six primary caregivers were recruited from a pediatric hospital in Ontario, Canada. Families completed a virtual intake and exit assessment together and 6 weekly BRAVA group sessions separately. Satisfaction feedback was collected after each group session and during their exit, and clinical outcomes were collected at intake and exit. Weekly team meetings were conducted to gather clinician feedback. Results: The study uptake rate was 42.9% of eligible participants. There were no dropouts. Adolescent and caregiver attendance rates for group sessions were high (median?=?6). Most youth (83.4%) and caregivers (66.7%) reported that the virtual process worked well. All caregivers (100%) agreed they would participate in a virtual group session again, compared with youth (50%). Providers approved of the virtual adaptation but identified potential improvements (e.g., manual content, safety procedures). Adolescent SI decreased significantly post-treatment (Mpre?=?50.7, Mpost?=?29.7, p?=?0.002). Conclusions: Virtual delivery of BRAVA is acceptable and feasible and may help reduce SI in adolescents. Uptake, retention, and satisfaction were high for adolescents and caregivers. Feedback collected will improve BRAVA for future evaluations, including a randomized controlled trial.

Abstract Background and setting Domestic and family violence (DFV) is a significant societal problem that predominantly affects women and children. One behaviour that has been linked to DFV perpetration is coercive control. While various definitions have been proposed, it involves “acts of assault, threats, humiliation and intimidation or other abuse that is used to harm, punish, or frighten a victim” ranging from emotional to social and financial abuse. One potentially rich source of information on coercive control are police reports. In this paper we determine whether it is possible to automatically identify behaviours linked to coercive control from DFV police reports and present the prevalence of such behaviours by age and sex. Methods We modified an existing rule-based text mining method to identify 48 coercive control related behaviours from 406,196 DFV reports involving a single person of interest (POI) (i.e., an individual suspected or charged with a DFV offence) against a single victim from NSW Police Force records between 2009 and 2020. Results 223,778 (54.6%) DFV events had at least one identifiable coercive control behaviour with the most common behaviour being verbal abuse (38.9%) followed by property damage (30.0%). Financial (3.2%) and social abuse (0.4%) were the least common behaviours linked to coercive control. No major differences were found in the proportion of DFV events between male and female POIs or victims. The oldest POI group (≥ 65 years) had the largest proportion for behaviours related to verbal abuse (38.0%) while the youngest POI group reported the highest proportion of DFV involving property damage (45.5%). The youngest victim group (

Abstract Background For more than a century, Māori have experienced poorer health than non-Māori. In 2019 an independent Tribunal found the Government had breached Te Tiriti o Waitangi by “failing to design and administer the current primary health care system to actively address persistent Māori health inequities”. Many Māori (44%) have unmet needs for primary care. Seven models of primary care were identified by the funders and the research team, including Māori-owned practices. We hypothesised patient health outcomes for Māori would differ between models of care. Methods Cross-sectional primary care data were analysed at 30 September 2018. National datasets were linked to general practices at patient level, to measure associations between practice characteristics and patient health outcomes. Primary outcomes: polypharmacy (≥ 55 years), HbA1c testing, child immunisations, ambulatory sensitive hospitalisations (0–14, 45–64 years) and emergency department attendances. Regressions include only Māori patients, across all models of care. Results A total of 660,752 Māori patients were enrolled in 924 practices with 124,854 in 65 Māori-owned practices. Māori practices had: no significant association with HbA1c testing, ambulatory sensitive hospitalisations or ED attendances, and a significant association with lower polypharmacy (3.7% points) and lower childhood immunisations (13.4% points). Māori practices had higher rates of cervical smear and cardiovascular risk assessment, lower rates of HbA1c tests, and more nurse (46%) and doctor (8%) time (FTE) with patients. The average Māori practice had 52% Māori patients compared to 12% across all practices. Māori practices enrolled a higher percentage of children and young people, five times more patients in high deprivation areas, and patients with more multimorbidity. More Māori patients lived rurally (21.5% vs 15%), with a greater distance to the nearest ED. Māori patients were more likely to be dispensed antibiotics or tramadol. Conclusions Māori practices are an expression of autonomy in the face of enduring health system failure. Apart from lower immunisation rates, health outcomes were not different from other models of care, despite patients having higher health risk profiles. Across all models, primary care need was unmet for many Māori, despite increased clinical input. Funding must support under-resourced Māori practices and ensure accountability for the health outcomes of Māori patients in all models of general practice.