Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia.

Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.02). Further, in patients with CD3+ T cell counts between 51 and 300 cells/µL, there was a higher proliferative response with the PHA flow assay compared to the 3H-T assay (p < 0.0001), suggesting that the method of analysis influences the resolution and interpretation of PHA results. Importantly, we observed many SCID patients with profound T cell lymphopenia having normal T cell proliferation when assessed by flow cytometry. We recommend this test be considered only as supportive in the diagnosis of typical SCID.

Multicomponent perinatal breastfeeding support in women with BMI >25: The Latch On multi-centre randomised trial.

OBJECTIVE: To investigate the effectiveness of a multicomponent breastfeeding support intervention on breastfeeding prevalence at 3 months among women with a body mass index (BMI) >25 kg/m2 . DESIGN: Multicentre multicomponent randomised controlled trial. SETTING: Four maternity centres in Ireland. POPULATION: A total of 225 primiparous women and their nominated support partners. Participants were aged 18 years and over, with BMI ≥25 kg/m2 , carrying a singleton pregnancy and without contraindication for breastfeeding. METHODS: The intervention included an antenatal group breastfeeding education session for participants and their support partners, followed by a planned postnatal breastfeeding assessment and telephone support for up to 6 weeks by a lactation consultant. MAIN OUTCOME MEASURES: Any breastfeeding at 3 months postpartum. RESULTS: Any breastfeeding prevalence was 68.7% (n = 68) in the intervention group and 62.1% (n = 59) in the control group at 3 months postpartum (odds ratio 1.33, 95% confidence interval 0.72-2.46, p = 0.36). Any and exclusive breastfeeding rates did not significantly differ at any other time point. More women in the control group accessed support from private lactation consultants (intervention 23.5% [n = 12], control 45.3% [n = 24], p = 0.02). CONCLUSIONS: The control group had higher than expected breastfeeding rates, and the study found no evidence of effect on the primary outcome. Providing comprehensive education and support for women intending to breastfeed remains of paramount importance.

How Can People Become Happier? A Systematic Review of Preregistered Experiments.

Can happiness be reliably increased? Thousands of studies speak to this question. However, many of them were conducted during a period in which researchers commonly "p-hacked," creating uncertainty about how many discoveries might be false positives. To prevent p-hacking, happiness researchers increasingly preregister their studies, committing to analysis plans before analyzing data. We conducted a systematic literature search to identify preregistered experiments testing strategies for increasing happiness. We found surprisingly little support for many widely recommended strategies (e.g., performing random acts of kindness). However, our review suggests that other strategies-such as being more sociable-may reliably promote happiness. We also found strong evidence that governments and organizations can improve happiness by providing underprivileged individuals with financial support. We conclude that happiness research stands on the brink of an exciting new era, in which modern best practices will be applied to develop theoretically grounded strategies that can produce lasting gains in life satisfaction.

Use of a Data Repository to Identify Delirium as a Presenting Symptom of COVID-19 Infection in Hospitalized Adults: Cross-Sectional Cohort Pilot Study.

BACKGROUND: Delirium, an acute confusional state highlighted by inattention, has been reported to occur in 10% to 50% of patients with COVID-19. People hospitalized with COVID-19 have been noted to present with or develop delirium and neurocognitive disorders. Caring for patients with delirium is associated with more burden for nurses, clinicians, and caregivers. Using information in electronic health record data to recognize delirium and possibly COVID-19 could lead to earlier treatment of the underlying viral infection and improve outcomes in clinical and health care systems cost per patient. Clinical data repositories can further support rapid discovery through cohort identification tools, such as the Informatics for Integrating Biology and the Bedside tool. OBJECTIVE: The specific aim of this research was to investigate delirium in hospitalized older adults as a possible presenting symptom in COVID-19 using a data repository to identify neurocognitive disorders with a novel group of International Classification of Diseases, Tenth Revision (ICD-10) codes. METHODS: We analyzed data from 2 catchment areas with different demographics. The first catchment area (7 counties in the North-Central Florida) is predominantly rural while the second (1 county in North Florida) is predominantly urban. The Integrating Biology and the Bedside data repository was queried for patients with COVID-19 admitted to inpatient units via the emergency department (ED) within the health center from April 1, 2020, and April 1, 2022. Patients with COVID-19 were identified by having a positive COVID-19 laboratory test or a diagnosis code of U07.1. We identified neurocognitive disorders as delirium or encephalopathy, using ICD-10 codes. RESULTS: Less than one-third (1437/4828, 29.8%) of patients with COVID-19 were diagnosed with a co-occurring neurocognitive disorder. A neurocognitive disorder was present on admission for 15.8% (762/4828) of all patients with COVID-19 admitted through the ED. Among patients with both COVID-19 and a neurocognitive disorder, 56.9% (817/1437) were aged ≥65 years, a significantly higher proportion than those with no neurocognitive disorder (P<.001). The proportion of patients aged <65 years was significantly higher among patients diagnosed with encephalopathy only than patients diagnosed with delirium only and both delirium and encephalopathy (P<.001). Most (1272/4828, 26.3%) patients with COVID-19 admitted through the ED during our study period were admitted during the Delta variant peak. CONCLUSIONS: The data collected demonstrated that an increased number of older patients with neurocognitive disorder present on admission were infected with COVID-19. Knowing that delirium increases the staffing, nursing care needs, hospital resources used, and the length of stay as previously noted, identifying delirium early may benefit hospital administration when planning for newly anticipated COVID-19 surges. A robust and accessible data repository, such as the one used in this study, can provide invaluable support to clinicians and clinical administrators in such resource reallocation and clinical decision-making.

The UBC State Social Connection Scale: Factor Structure, Reliability, and Validity.

Social connection plays a central role in people's everyday lives. Although researchers have traditionally focused on the benefits of experiencing an enduring sense of social connection, recent research has also begun to explore the contextual factors that shape momentary feeling of social connection. To date, however, no psychological scales have been developed to measure state social connection. To address this gap, we developed the 10-item UBC State Social Connection Scale (UBC-SSCS). In Study 1, we generated and refined our initial pool of items and confirmed our hypothesized factor structure in a large university sample. In Studies 2 to 3, we established several forms of validity. We provide foundational evidence that the UBC-SSCS is a reliable and valid instrument for assessing momentary feelings of social connection. Our exploratory findings also suggest that researchers can substantially increase their statistical power using state (vs. trait) measures to capture fluctuations in feelings of social connection.

Are People Generous When the Financial Stakes Are High?

How generous are people when making consequential financial decisions in the real world? We took advantage of a rare opportunity to examine generosity among a diverse sample of adults who received a gift of U.S. $10,000 from a pair of wealthy donors, with nearly no strings attached. Two-hundred participants were drawn from three low-income countries (Indonesia, Brazil, and Kenya) and four high-income countries (Australia, Canada, the United Kingdom, and the United States) as part of a preregistered study. On average, participants spent over $6,400 on purchases that benefited others, including nearly $1,700 on donations to charity, suggesting that humans exhibit remarkable generosity even when the stakes are high. To address whether generosity was driven by reputational concerns, we asked half the participants to share their spending decisions publicly on Twitter, whereas the other half were asked to keep their spending private. Generous spending was similar between the groups, in contrast to our preregistered hypothesis that enhancing reputational concerns would increase generosity.

A systematic review of the strength of evidence for the most commonly recommended happiness strategies in mainstream media.

We conducted a systematic review of the evidence underlying some of the most widely recommended strategies for increasing happiness. By coding media articles on happiness, we first identified the five most commonly recommended strategies: expressing gratitude, enhancing sociability, exercising, practising mindfulness/meditation and increasing nature exposure. Next, we conducted a systematic search of the published scientific literature. We identified well-powered, pre-registered experiments testing the effects of these strategies on any aspect of subjective wellbeing (that is, positive affect, negative affect and life satisfaction) in non-clinical samples. A total of 57 studies were included. Our review suggests that a strong scientific foundation is lacking for some of the most commonly recommended happiness strategies. As the effectiveness of these strategies remains an open question, there is an urgent need for well-powered, pre-registered studies investigating strategies for promoting happiness.

Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p<0·0001), age 3·5 months or older at HCT (2·12, 1·38-3·24; p=0·001), Black or African-American race (2·33, 1·56-3·46; p<0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43-1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival. INTERPRETATION: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID. FUNDING: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences.

The diagnosis of severe combined immunodeficiency: Implementation of the PIDTC 2022 Definitions.

BACKGROUND: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortium's (PIDTC's) prospective and retrospective studies of SCID. OBJECTIVE: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed. METHODS: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes. RESULTS: According to PIDTC 2022 Definitions, 18 of 353 patients eligible per 2014 Criteria were considered not to have SCID, whereas 11 of 26 patients ineligible per 2014 Criteria were determined to have SCID. Of note, very low numbers of autologous T cells (<0.05 × 109/L) characterized typical SCID under the 2022 Definitions. Pathogenic variant(s) in SCID-associated genes was identified in 93% of patients, with 7 genes (IL2RG, RAG1, ADA, IL7R, DCLRE1C, JAK3, and RAG2) accounting for 89% of typical SCID. Three genotypes (RAG1, ADA, and RMRP) accounted for 57% of cases of leaky/atypical SCID; there were 13 other rare genotypes. Patients with leaky/atypical SCID were more likely to be diagnosed at more than age 1 year than those with typical SCID lacking maternal T cells: 20% versus 1% (P < .001). Although repeat testing proved important, an initial CD3 T-cell count of less than 0.05 × 109/L differentiated cases of typical SCID lacking maternal cells from leaky/atypical SCID: 97% versus 7% (P < .001). CONCLUSIONS: The PIDTC 2022 Definitions describe SCID and its subtypes more precisely than before, facilitating analyses of SCID characteristics and outcomes.

The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 Definitions.

Severe combined immunodeficiency (SCID) results from defects in the differentiation of hematopoietic stem cells into mature T lymphocytes, with additional lymphoid lineages affected in particular genotypes. In 2014, the Primary Immune Deficiency Treatment Consortium published criteria for diagnosing SCID, which are now revised to incorporate contemporary approaches. Patients with typical SCID must have less than 0.05 × 109 autologous T cells/L on repetitive testing, with either pathogenic variant(s) in a SCID-associated gene, very low/undetectable T-cell receptor excision circles or less than 20% of CD4 T cells expressing naive markers, and/or transplacental maternally engrafted T cells. Patients with less profoundly impaired autologous T-cell differentiation are designated as having leaky/atypical SCID, with 2 or more of these: low T-cell numbers, oligoclonal T cells, low T-cell receptor excision circles, and less than 20% of CD4 T cells expressing naive markers. These patients must also have either pathogenic variant(s) in a SCID-associated gene or reduced T-cell proliferation to certain mitogens. Omenn syndrome requires a generalized erythematous rash, absent transplacentally acquired maternal engraftment, and 2 or more of these: eosinophilia, elevated IgE, lymphadenopathy, hepatosplenomegaly. Thymic stromal defects and other causes of secondary T-cell deficiency are excluded from the definition of SCID. Application of these revised Primary Immune Deficiency Treatment Consortium 2022 Definitions permits precise categorization of patients with T-cell defects but does not imply a preferred treatment strategy.

Wealth redistribution promotes happiness.

How much happiness could be gained if the world's wealth were distributed more equally? Despite decades of research investigating the relationship between money and happiness, no experimental work has quantified this effect for people across the global economic spectrum. We estimated the total gain in happiness generated when a pair of high-net-worth donors redistributed US$2 million of their wealth in $10,000 cash transfers to 200 people. Our preregistered analyses offer causal evidence that cash transfers substantially increase happiness among economically diverse individuals around the world. Recipients in lower-income countries exhibited happiness gains three times larger than those in higher-income countries. Still, the cash provided detectable benefits for people with household incomes up to $123,000.

Are the benefits of prosocial spending and buying time moderated by age, gender, or income?

In the last two decades, social psychologists have identified several key spending strategies that promote happiness such as making time-saving purchases (buying time) and spending money on others (prosocial spending). Although the emotional benefits of these two spending strategies are well-documented in the current literature, it is unclear whether the effectiveness of these strategies vary depending on individual characteristics. To address this research gap, we surveyed an economically diverse sample of 15,545 Americans about their subjective well-being, spending behavior, personal values and beliefs, as well as demographics including age, gender, and income. Across demographic groups, spending money on others was robustly related to happiness. Spending money on others was also associated with greater happiness regardless of whether participants believed that they would be happier spending money on others. In contrast, the relationship between buying time and happiness was somewhat less reliable. Although gender and personal income did not moderate the relationship between buying time and happiness, the relationship was only marginally significant for men, and non-significant within each income bracket. Our results also indicated that those who valued money over time were significantly happier when they used money to buy time, whereas those who valued time over money reported similar levels of happiness whether or not they bought time. Taken together, the present research shows that the relationship between prosocial spending, buying time, and subjective well-being is largely consistent across the different demographic groups we examined.

Policy stringency and mental health during the COVID-19 pandemic: a longitudinal analysis of data from 15 countries.

BACKGROUND: To date, public health policies implemented during the COVID-19 pandemic have been evaluated on the basis of their ability to reduce transmission and minimise economic harm. We aimed to assess the association between COVID-19 policy restrictions and mental health during the COVID-19 pandemic. METHODS: In this longitudinal analysis, we combined daily policy stringency data from the Oxford COVID-19 Government Response Tracker with psychological distress scores and life evaluations captured in the Imperial College London-YouGov COVID-19 Behaviour Tracker Global Survey in fortnightly cross-sections from samples of 15 countries between April 27, 2020, and June 28, 2021. The mental health questions provided a sample size of 432 642 valid responses, with an average of 14 918 responses every 2 weeks. To investigate how policy stringency was associated with mental health, we considered two potential mediators: observed physical distancing and perceptions of the government's handling of the pandemic. Countries were grouped on the basis of their response to the COVID-19 pandemic as those pursuing an elimination strategy (countries that aimed to eliminate community transmission of SARS-CoV-2 within their borders) or those pursuing a mitigation strategy (countries that aimed to control SARS-CoV-2 transmission). Using a combined dataset of country-level and individual-level data, we estimated linear regression models with country-fixed effects (ie, dummy variables representing the countries in our sample) and with individual and contextual covariates. Additionally, we analysed data from a sample of Nordic countries, to compare Sweden (that pursued a mitigation strategy) to other Nordic countries (that adopted a near-elimination strategy). FINDINGS: Controlling for individual and contextual variables, higher policy stringency was associated with higher mean psychological distress scores and lower life evaluations (standardised coefficients ß=0·014 [95% CI 0·005 to 0·023] for psychological distress; ß=-0·010 [-0·015 to -0·004] for life evaluation). Pandemic intensity (number of deaths per 100 000 inhabitants) was also associated with higher mean psychological distress scores and lower life evaluations (standardised coefficients ß=0·016 [0·008 to 0·025] for psychological distress; ß=-0·010 [-0·017 to -0·004] for life evaluation). The negative association between policy stringency and mental health was mediated by observed physical distancing and perceptions of the government's handling of the pandemic. We observed that countries pursuing an elimination strategy used different policy timings and intensities compared with countries pursuing a mitigation strategy. The containment policies of countries pursuing elimination strategies were on average less stringent, and fewer deaths were observed. INTERPRETATION: Changes in mental health measures during the first 15 months of the COVID-19 pandemic were small. More stringent COVID-19 policies were associated with poorer mental health. Elimination strategies minimised transmission and deaths, while restricting mental health effects. FUNDING: None.

The Anti-Proliferative Effect of PI3K/mTOR and ERK Inhibition in Monolayer and Three-Dimensional Ovarian Cancer Cell Models.

Most ovarian cancer patients are diagnosed with advanced stage disease, which becomes unresponsive to chemotherapeutic treatments. The PI3K/AKT/mTOR and the RAS/RAF/MEK/ERK kinase signaling pathways are attractive targets for potential therapeutic inhibitors, due to the high frequency of mutations to PTEN, PIK3CA, KRAS and BRAF in several ovarian cancer subtypes. However, monotherapies targeting one of these pathways have shown modest effects in clinical trials. This limited efficacy of the agents could be due to upregulation and increased signaling via the adjacent alternative pathway. In this study, the efficacy of combined PI3K/mTOR (BEZ235) and ERK inhibition (SCH772984) was investigated in four human ovarian cancer cell lines, grown as monolayer and three-dimensional cell aggregates. The inhibitor combination reduced cellular proliferation in a synergistic manner in OV-90 and OVCAR8 monolayers and in OV-90, OVCAR5 and SKOV3 aggregates. Sensitivity to the inhibitors was reduced in three-dimensional cell aggregates in comparison to monolayers. OV-90 cells cultured in large spheroids were sensitive to the inhibitors and displayed a robust synergistic antiproliferative response to the inhibitor combination. In contrast, OVCAR8 spheroids were resistant to the inhibitors. These findings suggest that combined PI3K/mTOR and ERK inhibition could be a useful strategy for overcoming treatment resistance in ovarian cancer and warrants further preclinical investigation. Additionally, in some cell lines the use of different three-dimensional models can influence cell line sensitivity to PI3K/mTOR and RAS/RAF/MEK/ERK pathway inhibitors.

Mental Health During the First Year of the COVID-19 Pandemic: A Review and Recommendations for Moving Forward.

COVID-19 has infected millions of people and upended the lives of most humans on the planet. Researchers from across the psychological sciences have sought to document and investigate the impact of COVID-19 in myriad ways, causing an explosion of research that is broad in scope, varied in methods, and challenging to consolidate. Because policy and practice aimed at helping people live healthier and happier lives requires insight from robust patterns of evidence, this article provides a rapid and thorough summary of high-quality studies available through early 2021 examining the mental-health consequences of living through the COVID-19 pandemic. Our review of the evidence indicates that anxiety, depression, and distress increased in the early months of the pandemic. Meanwhile, suicide rates, life satisfaction, and loneliness remained largely stable throughout the first year of the pandemic. In response to these insights, we present seven recommendations (one urgent, two short-term, and four ongoing) to support mental health during the pandemic and beyond.

Challenges for the disaster workforce during a compound hurricane-pandemic.

The COVID-19 pandemic has created new workforce considerations for emergency management community in addressing cumulative and cascading disasters. This research identifies how emergency management planning for both the changing dynamics of COVID-19 and the upcoming hurricane season may change under a compound threat. Many jurisdictions have faced challenges in providing adequate staffing of shelters before the pandemic. Now, fatigue among staff further exacerbates these challenges as resources are stretched thin. Six workshops, involving 265 national, state, and local leaders, staff, experts, and advocates from 22 states, and a range of disciplines (disaster planning, public health, social services, academia, and healthcare), were convened to identify concerns and potential strategies to address staffing, training, logistics, and support. Strategies proposed to increase the number and skill set of staff available involve increased reliance upon volunteers and nonprofit organizations. Mental health resources, personal protective equipment, sanitation supplies, and defining roles within emergency shelters were recommended to reduce fatigue and redistribute responsibilities. Findings illuminate additional research avenues regarding assessing the underlying stressors contributing to the planning process and effective means of implementing these interventions to bolster emergency management shelter operations during a prolonged pandemic and in the future.

A Virtual Approach to Promote Inter-Professional Learning (IPL) Between Biomedical Science and Medicine in Higher Education for the Benefit of Patient Care.

In the clinical setting, collaboration between multidisciplinary teams is core to providing effective patient care. The delivery of traditional interprofessional education is associated with a number of logistical challenges, which were heightened by the Covid-19 pandemic. This workshop was developed to bring together Biomedical Science and Medical students using an online platform. The workshop consisted of (1) defining interprofessional education, (2) introducing the role of the Pathology laboratory, (3) Professional registration with regulatory bodies and (4) an insight into Covid-19 laboratory diagnosis. The session was supported by mixed group breakout rooms and interactive polling. Thirty four percent of students completed a post-workshop online survey which included open and closed questions. Thematic analysis revealed a better understanding the role of the pathology laboratory in diagnosing disease, an increased awareness of the similarities and differences in the roles of a Biomedical Scientist and a Medic and the importance of a multi-disciplinary team in achieving effective patient care. Quantitative analysis of survey data revealed that the majority of students reported positive experiences of interprofessional education online. Approximately 90% of students agreed that the workshop enabled them to increase their understanding of their own roles within healthcare, in addition to increasing their understanding of the roles of other healthcare professionals. 74.3% of participants reported that working with students from a different programme provided an alternative perspective. Seventy nine percent of students agreed that the online format enabled interactivity and discussion of the tasks. Of the 204 students, 85% engaged with the four polls during the workshop. This online workshop enabled discussion between degree programmes, enabled interactivity and allowed the learning outcomes to be met. Universities should embrace online platforms to provide a novel, engaging and effective interprofessional educational experience.

Latch On: A protocol for a multi-centre, randomised controlled trial of perinatal support to improve breastfeeding outcomes in women with a raised BMI.

INTRODUCTION: Breastfeeding is associated with improved maternal and child outcomes. Women with a higher body mass index (BMI), who comprise about 50% of the population, are at increased risk of poorer breastfeeding practices and are a population who would benefit from breastfeeding. METHODS: This protocol is for a multi-centre, randomised controlled trial of perinatal breastfeeding support among primiparous women with a BMI >25 kg/m2, using a previously-tested, multi-component intervention. The primary outcome is any breastfeeding at 3 months. The intervention will support mothers and their partners and spans from late pregnancy to six weeks postpartum. Intervention components include group antenatal breastfeeding education, individual face-to-face education in the immediate postnatal period, professional support to six weeks' postpartum and weekly phone calls in the immediate postpartum period from an International Board Certified Lactation Consultant (IBCLC). The intervention will target attitudes towards breastfeeding, breastfeeding self-efficacy, and subjective norms around infant feeding with the aim to normalise the behaviour. RESULTS: We anticipate that the intervention will be well-accepted and feasible to carry out within four maternity units in the East of Ireland. Furthermore, essential formative qualitative work has been conducted to inform the intervention design and to ensure that it is contextually appropriate. CONCLUSION: The proposed intervention will be invaluable to policy-makers in providing insights into what specific interventions are effective in improving breastfeeding rates for women with a raised BMI.

Impact of sex on microvascular reactivity in a murine model of diet-induced obesity and insulin resistance.

The association of obesity with cardiovascular disease is well established. However, the interplay of obesity and vascular dysfunction in peripheral tissues such as skeletal muscle, which plays a key in role metabolic homeostasis, requires further study. In particular, there is a paucity of data with regard to sex-differences. Therefore, using a murine model (C57BL/6) of high-fat diet-induced obesity and insulin resistance, we investigated changes in vascular function in gluteus maximus muscle of female and male mice. Diet-induced obesity resulted in alterations in microvascular function. Obese male mice displayed impaired vasoconstriction in second order arterioles compared to lean, male mice, whereas arterioles of obese, female mice displayed significant impairments of both vasodilation and vasoconstrictor responses compared to lean, female mice. Overall, this study identifies distinct differences in how obesity impacts the female and male murine response to skeletal muscle vascular function. This work advances our understanding of sex-specific risk of metabolic complications of obesity and indicates the need for expansion of this study as well as detailed investigation of sex-specific differences in obesity pathology in the future.