Genomic characterization of Listeria monocytogenes recovered from dairy facilities in British Columbia, Canada from 2007 to 2017.

Listeria monocytogenes is a foodborne pathogen of concern in dairy processing facilities, with the potential to cause human illness and trigger regulatory actions if found in the product. Monitoring for Listeria spp. through environmental sampling is recommended to prevent establishment of these microorganisms in dairy processing environments, thereby reducing the risk of product contamination. To inform on L. monocytogenes diversity and transmission, we analyzed genome sequences of L. monocytogenes strains (n = 88) obtained through the British Columbia Dairy Inspection Program. Strains were recovered from five different dairy processing facilities over a 10 year period (2007-2017). Analysis of whole genome sequences (WGS) grouped the isolates into nine sequence types and 11 cgMLST types (CT). The majority of isolates (93%) belonged to lineage II. Within each CT, single nucleotide polymorphism (SNP) differences ranged from 0 to 237 between isolates. A highly similar (0-16 SNPs) cluster of over 60 isolates, collected over 9 years within one facility (#71), was identified suggesting a possible persistent population. Analyses of genome content revealed a low frequency of genes associated with stress tolerance, with the exception of widely disseminated cadmium resistance genes cadA1 and cadA2. The distribution of virulence genes and mutations within internalin genes varied across the isolates and facilities. Further studies are needed to elucidate their phenotypic effect on pathogenicity and stress response. These findings demonstrate the diversity of L. monocytogenes isolates across dairy facilities in the same region. Findings also showed the utility of using WGS to discern potential persistence events within a single facility over time.

Experiences of physical and emotional intimate partner violence during the COVID-19 pandemic: a comparison of prepandemic and pandemic data in a longitudinal study of Australian mothers.

OBJECTIVE: There is a lack of longitudinal population-based research comparing women's experiences of intimate partner violence (IPV) prior to and during the COVID-19 pandemic. Using data from the Mothers' and Young People's Study, the prevalence of physical and emotional IPV in the first year of the pandemic is compared with earlier waves of data. DESIGN: A prospective pregnancy cohort of first-time mothers in Melbourne, Australia was followed up over the first decade of motherhood, with a quick response study conducted during the COVID-19 pandemic. 422 women completed the primary exposure measure (IPV; Composite Abuse Scale) in the 1st, 4th and 10th year postpartum and the additional pandemic survey (June 2020-April 2021). OUTCOME MEASURES: Depressive symptoms; anxiety symptoms; IPV disclosure to a doctor, friends or family, or someone else. RESULTS: Maternal report of emotional IPV alone was higher during the pandemic (14.4%, 95% CI 11.4% to 18.2%) than in the 10th (9.5%, 95% CI 7.0% to 12.7%), 4th (9.2%, 95% CI 6.8% to 12.4%) and 1st year after the birth of their first child (5.9%, 95% CI 4.0% to 8.6%). Conversely, physical IPV was lowest during the pandemic (3.1%, 95% CI 1.8% to 5.0%). Of women experiencing IPV during the pandemic: 29.7% were reporting IPV for the first time, 52.7% reported concurrent depressive symptoms and just 6.8% had told their doctor. CONCLUSIONS: Findings suggest that the spike in IPV-related crime statistics following the onset of the pandemic (typically incidents of physical violence) is the tip of the iceberg for women's IPV experiences. There is a need to increase the capacity of health practitioners to recognise emotional as well as physical IPV, and IPV ought to be considered where women present with mental health problems.

WormBase 2024: status and transitioning to Alliance infrastructure.

WormBase has been the major repository and knowledgebase of information about the genome and genetics of C. elegans and other nematodes of experimental interest for over two decades. We have three goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable. Here we discuss the current state of WormBase as well as progress and plans for moving core WormBase infrastructure to the Alliance of Genome Resources (the Alliance). As an Alliance member, WormBase will continue to interact with the C. elegans community, develop new features as needed, and curate key information from the literature and large-scale projects.

The Childhood Resilience Study: Resilience and emotional and behavioural wellbeing experienced by Australian Aboriginal and Torres Strait Islander boys and girls aged 5-9 years.

BACKGROUND: Resilience is a process of drawing on internal or external strengths to regain, sustain or improve adaptive outcomes despite adversity. Using a child resilience measure co-designed with Aboriginal and Torres Strait Islander communities, we investigate: 1) children's personal, family, school and community strengths; 2) gender differences; and 3) associations between resilience and wellbeing. METHODS: 1132 parent/caregivers of children aged 5-12 years were recruited to the Childhood Resilience Study, including through the Aboriginal Families Study. The Aboriginal Families Study is a population-based cohort of 344 mothers of an Aboriginal and/or Torres Strait Islander child. This paper focuses on the wave 2 survey data on child resilience at age 5-9 years (n = 231). Resilience was assessed with the Child Resilience Questionnaire-parent/caregiver report (CRQ-P/C), categorised into tertiles of low, moderate and high scores. Child emotional/behavioural wellbeing and mental health competence was assessed with the parent-report Strengths and Difficulties Questionnaire. All Tobit regression models adjusted for child age. OUTCOMES: Aboriginal and Torres Strait Islander girls had higher resilience scores compared to boys (Adj.ß = 0·9, 95%CI 0·9-1·4), with higher School Engagement, Friends and Connectedness to language scale scores. Resilience scores were strongly associated with wellbeing and high mental health competence. A higher proportion of girls with low resilience scores had positive wellbeing than did boys (73.3% versus 49.0%). High resilience scores were associated with lower SDQ total difficulties score after adjusting for child age, gender, maternal age and education and family location (major city, regional, remote) (Adj.ß = -3.4, 95%CI -5.1, -1.7). Compared to the Childhood Resilience Study sample, Aboriginal Families Study children had higher mean CRQ-P/C scores in the personal and family domains. INTERPRETATION: High family strengths can support Aboriginal and Torres Strait Islander children at both an individual and cultural level. Boys may benefit from added scaffolding by schools, family and communities to support their social and academic connectedness.

A Systematic Scoping Review of Indigenous People's Experience of Healing and Recovery from Child Sexual Abuse.

Child sexual abuse is a form of violence that occurs across nations and cultures. Collective efforts are being made to address this issue within many Indigenous communities. In Australia, Aboriginal and Torres Strait Islander communities have expressed the need for cultural models of healing child sexual abuse. A preliminary exploration of the relevant literature shows a lack of synthesis with regard to the current evidence base. This protocol outlines the methods and background for a scoping review that aims to explore and collate the broad scope of literature related to healing from child sexual abuse within an Indigenous context. The proposed review utilises a 'population, concept, and context structure' from the Joanna Briggs Institute to explore the broad scope of the literature within a scoping review framework. The target population is Indigenous survivors of child sexual abuse, including Indigenous populations from six distinct regions: Aboriginal and Torres Strait Islander peoples from Australia; Maori peoples from Aotearoa (New Zealand); First Nations, Inuit and Métis peoples from Canada; Native American peoples from North America; Native peoples from Alaska; and the Sámi peoples of the Sápmi region in Northern Europe. The concept within the review is healing from an Indigenous perspective, which includes a broad range of processes related to both recovery and personal growth. The contexts explored within this review are any context in which healing from child sexual abuse can occur. This may include processes related to disclosure and accessing services, specific interventions or programs for survivors of child sexual abuse, as well as broader non-specific healing programs and personal experiences of healing without intervention. The scoping review will use search strings with broad inclusion and exclusion criteria to capture the potential breadth of perspectives. The search will be conducted across several academic databases and will also include an extensive search for grey literature. This protocol establishes the proposed benefits of this scoping review.

Understanding cannabis use and mental health difficulties in context with women's experiences of stressful events and social health issues in pregnancy: The Aboriginal Families Study.

BACKGROUND: Few population-based data sources fully recognise the intersections between stressful events, social health issues, and cannabis use in pregnancy, and little is known about sequelae for women's mental health. METHODS: We draw on two waves of population-based data for 344 families participating in the Aboriginal Families Study longitudinal cohort. We examine women's mental health in the first year postpartum and when children were aged 5-9 years in context with life experiences and use of cannabis in pregnancy. OUTCOMES: One in five women (19·5%) used cannabis during pregnancy (with or without co-use of tobacco). Within this group of women, 88·3% experienced 3 or more (3+) stressful events or social health issues. Psychological distress (Kessler-5 scale, K-5) in the year postpartum was substantially higher amongst women who had used cannabis or experienced 3+ stressful events or social health issues. High proportions of women met criteria for support and referral for depression and/or anxiety (52·5% of women who had used cannabis compared to 20·9% amongst women who had neither used cannabis nor tobacco; 43·2% of women who had experienced 3+ stressful events or social health issues compared to 15·6% amongst women who had not indicated these experiences). Similar patterns of psychological distress, depressive (9-item adapted Personal Health Questionnaire, aPHQ-9) and anxiety symptoms (7-item Generalised Anxiety Disorder score, GAD-7) were evident when the study children were aged 5-9 years. INTERPRETATION: Amongst women who had used cannabis in pregnancy, a high burden of psychological distress, depression, and anxiety is evident in the postpartum period and as their children turn 5-9 years. The overlay of stressful events and social health issues and the high proportion of women meeting criteria for referral for mental health assessment and support indicate an urgent need to offer women opportunities for safe disclosure of cannabis use and opportunities to access sustained holistic services. Reducing the harms of cannabis use on Aboriginal and Torres Strait Islander families must be coupled with culturally safe ways of addressing the social, historical, and structural determinants of mental health distress and harmful use of substances.

Homelessness Among Acute Care Patients Within a Large Health Care System in Northern California.

The impacts of homelessness on health and health care access are detrimental. Intervention and efforts to improve outcomes and increase availability of affordable housing have mainly originated from the public health sector and government. The role that large community-based health systems may play has yet to be established. This study characterizes patients self-identified as homeless in acute care facilities in a large integrated health care system in Northern California to inform the development of collaborative interventions addressing unmet needs of this vulnerable population. The authors compared sociodemographic characteristics, clinical conditions, and health care utilization of individuals who did and did not self-identify as homeless and characterized their geographical distribution in relation to Sutter hospitals and homeless resources. Between July 1, 2019 and June 30, 2020, 5% (N = 20,259) of the acute care settings patients had evidence of homelessness, among which 51.1% age <45 years, 66.4% males, and 24% non-Hispanic Black. Patients experiencing homelessness had higher emergency department utilization and lower utilization of outpatient and urgent care services. Mental health conditions were more common among patients experiencing homelessness. More than half of the hospitals had >5% of patients who identified as homeless. Some hospitals with higher proportions of patients experiencing homelessness are not located near many shelter resources. By understanding patients who self-identify as homeless, it is possible to assess the role of the health system in addressing their unmet needs. Accurate identification is the first step for the health systems to develop and deliver better solutions through collaborations with nonprofit organizations, community partners, and government agencies.

Creating shared goals and experiences as a pathway to peace.

Glowacki offers many new directions for understanding and even eliminating the problem of war, especially creating positive interdependencies with out-group members. We develop Glowacki's intriguing proposition that in-group dynamics provide a route to peace by describing a prosocial motivational system, the caregiving system, that aligns individual interests and eliminates the need to use coercion to achieve mutually beneficial outcomes.

Pre-pandemic adversity and maternal mental health during the COVID-19 pandemic: the mediating role of pandemic stress and family relationships.

BACKGROUND: The COVID-19 pandemic was a time of increased stress for families. Parents with a history of adversity may have been at higher risk of experiencing mental health problems during this time. The current study aims to investigate the relationship between pre-pandemic adversity pandemic related stressors and maternal mental health outcomes during the pandemic. METHODS: Data was drawn from the Mothers' and Young People's Study (MYPS), a longitudinal of first time mothers and their children. Participants were 418 mothers who completed the MYPS COVID-19 sub-study. Data was collected during pregnancy, at 1, 4, 10 years postpartum, and during the COVID-19 pandemic (approximately 14 years postpartum). Path-analysis was used to test the relationship indirect relationship between pre-pandemic adversity and maternal depressive and anxiety symptoms, via family functioning and pandemic related stress. RESULTS: The hypothesised model was a good fit to the data accounting for 34 % and 33 % of the variance in maternal depressive and anxiety scores, respectively. A significant indirect effect was found between pre-pandemic adversity and both maternal anxiety and depressive systems via family relationships during the pandemic and pandemic related stress. LIMITATIONS: MYPS participants who took part in the COVID-19 sub-study were more likely to be older, have a higher level of education, and speak English as a first language, compared to the total MYPS sample. CONCLUSIONS: Family inclusive service responses which aim to strengthen family relationships may be particularly important for families where there is a history of adversity to support parental mental health.

Outcomes After Respiratory Extracorporeal Life Support in Teens and Young Adults: An Extracorporeal Life Support Organization Registry Analysis.

OBJECTIVES: A recent study from Germany found that survival after respiratory extracorporeal life support (ECLS) was lower among patients 10-20 years old than 20-30 years old. The objective of this study was to compare survival between teenage and young adult patients who receive respiratory ECLS. DESIGN: Retrospective cohort study. SETTING: Extracorporeal Life Support Organization registry, an international prospective quality improvement database. PATIENTS: All patients ages 16-30 years cannulated for respiratory indications from 1990 to 2020 were included. Patients were divided into two groups, teens (16-19 yr old) and young adults (20-30 yr old). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was survival to discharge. Variables were considered for the multivariate logistic regression model if there was both a statistically significant difference (p ≤ 0.05) and a clinically meaningful absolute difference between the groups. A total of 5,751 patients were included, of whom 1,653 (29%) were teens and 4,098 (71%) were young adults. Survival to discharge was higher in young adults than teens, 69% versus 63% (p < 0.001). Severity of illness was higher among teens; however, survival within each stratum defined by Pao2/Fio2 ratio was higher in young adults than in teens. Use of venoarterial ECLS was higher in teens than in young adults, 15% versus 7%, respectively. Teens were more likely to receive high-frequency oscillatory ventilation and this therapy was associated with a longer time from admission to ECLS initiation. After adjusting for variables that differ significantly between the groups, the odds ratio for survival in young adults compared with teens was 1.14 (95% CI, 1.004-1.3). CONCLUSIONS: In this large multicenter retrospective study, mortality was higher in teens than in young adults who received respiratory ECLS. This difference persisted after adjusting for multiple variables and the mechanism underlying these findings remains unclear.

The Pediatric Data Science and Analytics Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network: Use of Supervised Machine Learning Applications in Pediatric Critical Care Medicine Research.

OBJECTIVE: Perform a scoping review of supervised machine learning in pediatric critical care to identify published applications, methodologies, and implementation frequency to inform best practices for the development, validation, and reporting of predictive models in pediatric critical care. DESIGN: Scoping review and expert opinion. SETTING: We queried CINAHL Plus with Full Text (EBSCO), Cochrane Library (Wiley), Embase (Elsevier), Ovid Medline, and PubMed for articles published between 2000 and 2022 related to machine learning concepts and pediatric critical illness. Articles were excluded if the majority of patients were adults or neonates, if unsupervised machine learning was the primary methodology, or if information related to the development, validation, and/or implementation of the model was not reported. Article selection and data extraction were performed using dual review in the Covidence tool, with discrepancies resolved by consensus. SUBJECTS: Articles reporting on the development, validation, or implementation of supervised machine learning models in the field of pediatric critical care medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5075 identified studies, 141 articles were included. Studies were primarily (57%) performed at a single site. The majority took place in the United States (70%). Most were retrospective observational cohort studies. More than three-quarters of the articles were published between 2018 and 2022. The most common algorithms included logistic regression and random forest. Predicted events were most commonly death, transfer to ICU, and sepsis. Only 14% of articles reported external validation, and only a single model was implemented at publication. Reporting of validation methods, performance assessments, and implementation varied widely. Follow-up with authors suggests that implementation remains uncommon after model publication. CONCLUSIONS: Publication of supervised machine learning models to address clinical challenges in pediatric critical care medicine has increased dramatically in the last 5 years. While these approaches have the potential to benefit children with critical illness, the literature demonstrates incomplete reporting, absence of external validation, and infrequent clinical implementation.

Protection against lung pathology during obesity-accelerated ageing in mice by the parasitic worm product ES-62.

Mice develop pathology in the lungs as they age and this may be accelerated by a high calorie diet (HCD). ES-62 is a protein secreted by the parasitic worm Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties. In this study, we show that weekly treatment of C57BL/6J mice with ES-62 protected against pathology in the lungs in male but not female mice fed a HCD from 10 weeks of age as shown by reductions in cellular infiltration and airway remodelling, particularly up to 160 days of age. ES-62 also reduced gene expression of the cytokines IL-4 and IL-17 and in addition the TLR/IL-1R adaptor MyD88, in the lungs of male mice although HCD-induced increases in these inflammatory markers were not detected until between 340 and 500 days of age. A combination of two drug-like ES-62 PC-based small molecule analogues (SMAs), produced broadly similar protective effects in the lungs of male mice with respect to both lung pathology and inflammatory markers, in addition to a decrease in HCD-induced IL-5 expression. Overall, our data show that ES-62 and its SMAs offer protection against HCD-accelerated pathological changes in the lungs during ageing. Given the targeting of Th2 cytokines and IL-17, we discuss this protection in the context of ES-62's previously described amelioration of airway hyper-responsiveness in mouse models of asthma.

Financial Sustainability of Novel Delivery Models in Behavioral Health Treatment.

BACKGROUND: In the US, much of the research into new intervention and delivery models for behavioral health care is funded by research institutes and foundations, typically through grants to develop and test the new interventions. The original grant funding is typically time-limited. This implies that eventually communities, clinicians, and others must find resources to replace the grant funding -otherwise the innovation will not be adopted. Diffusion is challenged by the continued dominance in the US of fee-for-service reimbursement, especially for behavioral health care. AIMS: To understand the financial challenges to disseminating innovative behavioral health delivery models posed by fee-for-service reimbursement, and to explore alternative payment models that promise to accelerate adoption by better addressing need for flexibility and sustainability. METHODS: We review US experience with three specific novel delivery models that emerged in recent years. The models are: collaborative care model for depression (CoCM), outpatient based opioid treatment (OBOT), and the certified community behavioral health clinic (CCBHC) model. These examples were selected as illustrating some common themes and some different issues affecting diffusion. For each model, we discuss its core components; evidence on its effectiveness and cost-effectiveness; how its dissemination was funded; how providers are paid; and what has been the uptake so far. RESULTS: The collaborative care model has existed for longest, but has been slow to disseminate, due in part to a lack of billing codes for key components until recently. The OBOT model faced that problem, and also (until recently) a regulatory requirement requiring physicians to obtain federal waivers in order to prescribe buprenorphine. Similarly, the CCBHC model includes previously nonbillable services, but it appears to be diffusing more successfully than some other innovations, due in part to the approach taken by funders. DISCUSSION: A common challenge for all three models has been their inclusion of services that were not (initially) reimbursable in a fee-for-service system. However, even establishing new procedure codes may not be enough to give providers the flexibility needed to implement these models, unless payers also implement alternative payment models. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: For providers who receive time-limited grant funding to implement these novel delivery models, one key lesson is the need to start early on planning how services will be sustained after the grant ends. IMPLICATIONS FOR HEALTH POLICY: For research funders (e.g., federal agencies), it is clearly important to speed up the process of obtaining coverage for each novel delivery model, including the development of new billable service codes, and to plan for this as early as possible. Funders also need to collaborate with providers early in the grant period on sustainability planning for the post-grant environment. For payers, a key lesson is the need to fold novel models into stable existing funding streams such as Medicaid and commercial insurance coverage, rather than leaving them at the mercy of revolving time-limited grants, and to provide pathways for contracting for innovations under new payment models. IMPLICATIONS FOR FURTHER RESEARCH: For researchers, a key recommendation would be to pay greater attention to the payment environment when designing new delivery models and interventions.

Diversity, equity, and inclusion correlates of racial/ethnic harassment and discrimination in the U.S. military.

As one of the most racially/ethnically diverse workplaces in the United States, the Department of Defense (DoD) has been on the forefront in driving diversity initiatives. Yet, racial/ethnic harassment and discrimination (REHD) in the military persist and threaten mission readiness. Despite this, limited research exists identifying factors that influence REHD in the U.S. military that could be leveraged for prevention and intervention. In this study, we sought to identify how diversity, equity, and inclusion (DEI) factors in the workplace are associated with REHD in order to identify potential targets for prevention and policy efforts to improve racial/ethnic relations in the U.S. military. Using the 2017 Workplace and Equal Opportunity Survey of Active Duty Members, we found military, leadership, and unit DEI climate factors were the top predictors of REHD, though the relative importance of each predictor varied by racial/ethnic minority status. In particular, we found military and leadership attention to REHD to be the top predictors for Racial/Ethnic Minority active duty members whereas workplace hostility was the top predictor for non-Hispanic White active duty members. Implications for programs and policies surrounding REHD in the U.S. military are discussed.

Intimate partner violence exposure during infancy and social functioning in middle childhood: An Australian mother and child cohort study.

Social functioning of children with experiences of intimate partner violence (IPV) between caregivers in early childhood has received less attention than emotional-behavioral outcomes. Drawing on data from 1507 ten-year-old Australian-born children and their mothers participating in a community-based longitudinal study, this study examined the associations between IPV exposure during infancy and social development during middle childhood. IPV during the first 12 months of life was associated with lower social skills, higher peer problems, and peer victimization at age 10 years, while accounting for concurrent IPV. This study provides evidence for the long-term impacts of early-life IPV exposure on children's social functioning, and the importance of prevention and early intervention programs focused on social development following experiences of IPV.

Social and emotional wellbeing of Aboriginal and Torres Strait Islander peoples in Aboriginal controlled social housing.

BACKGROUND: Little is known about the wellbeing and aspirations of Aboriginal and Torres Strait Islander peoples living in social housing. Aboriginal and Torres Strait Islander peoples living in social housing face common social housing challenges of low income, higher incidence of mental health issues and poorer health along with specific challenges due to the impacts of colonisation and its ongoing manifestations in racism and inequity. A greater understanding of social and emotional wellbeing needs and aspirations is essential in informing the provision of appropriate support. METHODS: Surveys of social and emotional wellbeing (SEWB) were completed by 95 Aboriginal people aged 16 years and older living in Aboriginal Housing Victoria social housing in 2021. The survey addressed a range of domains reflecting social and emotional wellbeing, as defined by Aboriginal and Torres Strait Islander peoples. RESULTS: Most respondents demonstrated a strong sense of identity and connection to family however 26% reported having 6 or more health conditions. Ill health and disability were reported to be employment barriers for almost a third of people (32%). Improving health and wellbeing (78%) was the most cited aspiration. Experiences of racism and ill health influenced engagement with organisations and correspondingly education and employment. CONCLUSION: Strong connections to identity, family and culture in Aboriginal peoples living in social housing coexist along with disrupted connections to mind, body and community. Culturally safe and appropriate pathways to community services and facilities can enhance these connections. Research aimed at evaluating the impact of strengths-based interventions that focus on existing strong connections will be important in understanding whether this approach is effective in improving SEWB in this population. TRIAL REGISTRATION: This trial was retrospectively registered with the ISRCTN Register on the 12/7/21 with the study ID:ISRCTN33665735.

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma.

BACKGROUND: Pembrolizumab is approved for the treatment of advanced and resected melanoma and was originally licensed as a three-weekly infusion (Q3W). In April 2019, a six-weekly infusion schedule (Q6W) was also approved. We retrospectively reviewed pembrolizumab prescribing for patients with melanoma across multiple United Kingdom (UK) centres to compare the safety and efficacy of Q6W with Q3W in real-world clinical practice. METHODS: Case notes for melanoma patients treated with pembrolizumab between April 2019 and August 2020 at eight UK centres were reviewed. Prespecified baseline characteristics of the Q3W and Q6W cohorts were compared, as well as toxicity and efficacy outcomes. Prescribers were surveyed about their prescribing practice. RESULTS: Two hundred seventy-seven patients were included: 116 commenced Q3W and 161 commenced Q6W pembrolizumab. The proportion of Q6W prescriptions varied by the centre (range 32-88%). Patient factors associated with an increased likelihood of receiving Q3W over Q6W were preexisting autoimmune comorbidity (odds ratio [OR] 0.33; 95% confidence interval [CI] 0.12-0.82) and treatment for advanced (versus resected) disease (OR 0.54; 95%CI 0.33-0.90). Toxicity outcomes were broadly similar for Q6W and Q3W: 14.9% versus 15.5% ≥ grade 3 Common Terminology Criteria for Adverse Events. Estimated 12-month recurrence-free survival for adjuvantly treated patients was 78.9% for Q6W and 74.2% for Q3W (hazard ratio [HR] 0.93; 95%CI 0.50-1.73). Estimated 12-month progression-free survival for advanced patients was 41.8% for Q6W and 55.9% for Q3W (HR 1.21, 95%CI 0.67-2.18). CONCLUSIONS: Q6W is an appropriate option for administering pembrolizumab, given the opportunity to reduce the health service resource burden.

Hypothalamic volume is associated with body mass index.

The hypothalamus is an important neuroendocrine hub for the control of appetite and satiety. In animal studies it has been established that hypothalamic lesioning or stimulation causes alteration to feeding behaviour and consequently body mass, and exposure to high calorie diets induces hypothalamic inflammation. These findings suggest that alterations in hypothalamic structure and function are both a cause and a consequence of changes to food intake. However, there is limited in vivo human data relating the hypothalamus to obesity or eating disorders, in part due to technical problems relating to its small size. Here, we used a novel automated segmentation algorithm to exploratorily investigate the relationship between hypothalamic volume, normalised to intracranial volume, and body mass index (BMI). The analysis was applied across four independent datasets comprising of young adults (total n = 1,351 participants) spanning a range of BMIs (13.3 - 47.8 kg/m2). We compared underweight (including individuals with anorexia nervosa), healthy weight, overweight and obese individuals in a series of complementary analyses. We report that overall hypothalamic volume is significantly larger in overweight and obese groups of young adults. This was also observed for a number of hypothalamic sub-regions. In the largest dataset (the HCP-Young Adult dataset (n = 1111)) there was a significant relationship between hypothalamic volume and BMI. We suggest that our findings of a positive relationship between hypothalamic volume and BMI is potentially consistent with hypothalamic inflammation as seen in animal models in response to high fat diet, although more research is needed to establish a causal relationship. Overall, we present novel, in vivo findings that link elevated BMI to altered hypothalamic structure. This has important implications for study of the neural mechanisms of obesity in humans.

Trajectories of depression symptoms, anxiety symptoms and functional impairment during internet-enabled cognitive-behavioural therapy.

Underlying classes capture differences between patient symptom trajectories during psychological therapy. This has not been explored for one-to-one internet-delivered therapy or functional impairment trajectories. Patients experiencing depression or anxiety received cognitive-behavioural therapy with a therapist using an online chat platform (N = 52,029). Trajectory classes of depression symptoms (PHQ9), anxiety symptoms (GAD7) and functional impairment (WSAS) were investigated using growth mixture modelling. Multinomial regressions tested associations between baseline variables and trajectory class. A four-class trajectory model was selected for each outcome, and these were highly similar. Each outcome showed three classes with initially moderate-severe symptoms or impairment: one demonstrated no change, one gradual improvement and one fast improvement. A fourth class had mild baseline scores and minimal improvement. In the moderate-severe classes, patients in the two with improvement were more likely to be employed and not to have obsessive-compulsive disorder. Fast improvement was likelier than gradual improvement or no change for patients with older age, no disability (e.g., physical, learning), or lower comorbid symptom or impairment scores. Associations with functional impairment classes were more similar to associations with depression classes than anxiety classes. Results were largely consistent with findings from face-to-face therapy. This study is an important step towards personalising therapy in terms of suitability and continuation.

Results of a pilot risk-based lung cancer screening study: outcomes and comparisons to a Medicare eligible cohort.

PURPOSE: Risk-based lung cancer screening holds potential to detect more cancers and avert more cancer deaths than screening based on age and smoking history alone, but has not been widely assessed or implemented in the United States. The purpose of this study was to prospectively identify patients for lung cancer screening based on lung cancer risk using the PLCOm2012 model and to compare characteristics, risk profiles, and screening outcomes to a traditionally eligible screening cohort. METHODS: Participants who had a 6 year lung cancer risk score ≥ 1.5% calculated by the PLCOm2012 model and were ineligible for screening under 2015 Medicare guidelines were recruited from a lung cancer screening clinic. After informed consent, participants completed shared decision-making counseling and underwent a low-dose CT (LDCT). Characteristics and screening outcomes of the study population were compared to the traditionally eligible Medicare cohort with Fisher's Exact, t-tests, or Brown Mood tests, as appropriate. RESULTS: From August 2016 to July 2019, the study completed 48 baseline LDCTs. 10% of LDCTs recommended further pulmonary nodule evaluation (Lung-RADs 3 or 4) with two early-stage lung cancers diagnosed in individuals that had quit smoking > 15 years prior. The study population was approximately 5 years older (p = 0.001) and had lower pack years (p = 0.002) than the Medicare cohort. CONCLUSION: Prospective application of risk-based screening identifies screening candidates who are similar to a traditionally eligible Medicare cohort and future research should focus on the impact of risk calculators on lung cancer outcomes and optimal usability in clinical environments. This study was retrospectively registered on clinicaltrials.gov (NCT03683940) on 09/25/2018.