An IgE antibody targeting HER2 identified by clonal selection restricts breast cancer growth via immune-stimulating activities.

Background: Tumor-targeting IgE antibodies have elicited potent tumor-restricting effects by recruiting immune effector mechanisms. However, a dedicated platform for the generation, selection and evaluation of novel IgEs based on target antigen recognition and functional profiles has not been reported.

Methods: By establishing an IgE class antibody therapeutic design platform to allow selection of lead candidates, we generated a panel of IgEs recognising the human epidermal growth factor receptor 2 (HER2), overexpressed in 15-20% of breast cancers.

Metabolomic and transcriptomic remodeling of bone marrow myeloid cells in response to maternal obesity.

Maternal obesity puts the offspring at high risk of developing obesity and cardiometabolic diseases in adulthood. Here, we utilized a mouse model of maternal high-fat diet (HFD)-induced obesity that recapitulates metabolic perturbations seen in humans. We show increased adiposity in the offspring of HFD-fed mothers (Off-HFD) when compared with the offspring of regular diet-fed mothers (Off-RD).

The role of economic evaluation in modelling public health and social measures for pandemic policy: a systematic review.

Background: Dynamic transmission models are often used to provide epidemiological guidance for pandemic policy decisions. However, how economic evaluation is typically incorporated into this technique to generate cost-effectiveness estimates of pandemic policy responses has not previously been reviewed.

Methods: We systematically searched the Embase, PubMed and Scopus databases for dynamic epidemiological modelling studies that incorporated economic evaluation of public health and social measures (PHSMs), with no date restrictions, on 7 July 2024.

Metabolomic and transcriptomic remodeling of bone marrow myeloid cells in response to maternal obesity.

Maternal obesity puts the offspring at high risk of developing obesity and cardio-metabolic diseases in adulthood. Here, using a mouse model of maternal high-fat diet (HFD)-induced obesity, we show that whole body fat content of the offspring of HFD-fed mothers (Off-HFD) increases significantly from very early age when compared to the offspring regular diet-fed mothers (Off-RD). We have previously shown significant metabolic and immune perturbations in the bone marrow of newly-weaned offspring of obese mothers.

Variations and value improvement in back pain care in one area of England.

The pursuit of value and equity have been put on a legal footing in the NHS with the arrival of the legal duty for all in the NHS to improve health and well-being of the population served, to provide fair access to high quality healthcare, and to use resources sustainably and efficiently. Recognising this we used analysis of variation to help us understand the degree to which we were fulfilling our new duty for people with back pain in Mid-Nottinghamshire and where there might be opportunities for value improvement.MSK Together is a group of clinical and managerial representatives from providers, purchasers, local government, and patients who work collectively to optimise the use of resources for people with MSK conditions in Mid-Nottinghamshire.

The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results.

Approved antibody-drug conjugates (ADCs) for HER2-positive breast cancer include trastuzumab emtansine and trastuzumab deruxtecan. To develop a differentiated HER2 ADC, we chose an antibody that does not compete with trastuzumab or pertuzumab for binding, conjugated to a reduced potency PBD (pyrrolobenzodiazepine) dimer payload. PBDs are potent cytotoxic agents that alkylate and cross-link DNA.

Assessing the potential of portable X-ray fluorescence (XRF) as a rapid, onsite screening tool in the assessment of cadmium surface decontamination effectiveness.

Portable X-ray fluorescence has successfully been used to effectively evaluate occupational exposure to airborne and surface metal contaminants nondestructively. Traditional methods of assessing metal surface contamination involve the costly, time-consuming collection and laboratory analysis of wipe samples, making portable X-ray fluorescence an attractive alternative method for screening worksites by reducing delays in risk assessment decision-making. Existing research into this use of portable X-ray fluorescence has primarily been centered on the analysis of airborne and surface lead contamination.

Economic effects for citizens and the government of a country-level tobacco endgame strategy: a modelling study.

Background: Aotearoa-New Zealand (A/NZ) was the first country to pass a comprehensive commercial tobacco endgame strategy into law. Key components include the denicotinisation of smoked tobacco products and a major reduction in tobacco retail outlets. Understanding the potential long-term economic impacts of such measures is important for government planning.

The total health gains and cost savings of eradicating cold housing in Australia.

Background: Cold indoor temperature (<18 °C) is associated with hypertension-related and respiratory disease, depression, and anxiety. We estimate total health, health expenditure and income impacts of permanently lifting the temperature in living areas of the home to 18 °C in cold homes in South-eastern Australia (N = 17 million).

Methods: A proportional multistate lifetable model was used to estimate health adjusted life years (HALYs), health expenditure and income earnings, over the remainder of the lifespan of the population alive in 2021 (3% discount rate).

Unwarranted variations in end-of-life care and the impact of using an electronic coordination system.

This study looks at the variations in end-of-life care in North-East Essex (eastern England) combining hospital records, official death records and the local electronic end-of-life coordination tool. These differences included dying in hospital (versus a general wish to die in the usual place of residence), and inequity in care provision: the place of death varying according to the cause of death (even for highly predictable conditions); and deprivation being associated with a greater likelihood of dying in hospital. There was a positive correlation between the use of an electronic end-of-life coordination system and dying in the preferred place of care.

Epidemiologic and economic modelling of optimal COVID-19 policy: public health and social measures, masks and vaccines in Victoria, Australia.

Background: Identifying optimal COVID-19 policies is challenging. For Victoria, Australia (6.6 million people), we evaluated 104 policy packages (two levels of stringency of public health and social measures [PHSMs], by two levels each of mask-wearing and respirator provision during large outbreaks, by 13 vaccination schedules) for nine future SARS-CoV-2 variant scenarios.

Tobacco endgame intervention impacts on health gains and Māori:non-Māori health inequity: a simulation study of the Aotearoa/New Zealand Tobacco Action Plan.

Background: The Aotearoa/New Zealand Government is aiming to end the tobacco epidemic and markedly reduce Māori:non-Māori health inequalities by legislating: (1) denicotinisation of retail tobacco, (2) 95% reduction in retail outlets and (c) a tobacco free-generation whereby people born after 2005 are unable to legally purchase tobacco. This paper estimates future smoking prevalence, mortality inequality and health-adjusted life year (HALY) impacts of these strategies.

Methods: We used a Markov model to estimate future yearly smoking and vaping prevalence, linked to a proportional multistate life table model to estimate future mortality and HALYs.

A framework for considering the utility of models when facing tough decisions in public health: a guideline for policy-makers.

The COVID-19 pandemic has brought the combined disciplines of public health, infectious disease and policy modelling squarely into the spotlight. Never before have decisions regarding public health measures and their impacts been such a topic of international deliberation, from the level of individuals and communities through to global leaders. Nor have models-developed at rapid pace and often in the absence of complete information-ever been so central to the decision-making process.

A log-odds system for waning and boosting of COVID-19 vaccine effectiveness.

Immunity to SARS-CoV-2 following vaccination wanes over time in a non-linear fashion, making modelling of likely population impacts of COVID-19 policy options challenging. We observed that it was possible to mathematize non-linear waning of vaccine effectiveness (VE) on the percentage scale as linear waning on the log-odds scale, and developed a random effects logistic regression equation based on UK Health Security Agency data to model VE against Omicron following two and three doses of a COVID-19 vaccine. VE on the odds scale reduced by 47% per month for symptomatic infection after two vaccine doses, lessening to 35% per month for hospitalisation.

The individual, place, and wellbeing - a network analysis.

Background: Previous research has examined individual-level and place characteristics as correlates of subjective wellbeing, with many studies concluding that individual factors (e.g. health, finances) are more strongly related to wellbeing.

Healthcare professional preferences in the health and fitness assessment and optimization of older patients facing colorectal cancer surgery.

Aim: There are few age- and fitness-specific, evidence-based guidelines for colorectal cancer surgery. The uptake of different assessment and optimization strategies is variable. The aim of this study was to explore healthcare professional opinion about these issues using a mixed methods design.

A universal power law for modelling the growth and form of teeth, claws, horns, thorns, beaks, and shells.

Background: A major goal of evolutionary developmental biology is to discover general models and mechanisms that create the phenotypes of organisms. However, universal models of such fundamental growth and form are rare, presumably due to the limited number of physical laws and biological processes that influence growth. One such model is the logarithmic spiral, which has been purported to explain the growth of biological structures such as teeth, claws, horns, and beaks.

EU-UK criminal justice and security cooperation after Brexit: A perspective.

The prospect of significantly reduced and potentially unstable EU-UK criminal justice cooperation under the 2020 Trade and Cooperation Agreement (TCA) unless criminal justice professionals and academics can help to shape its future development.Key wordsPost-Brexit readjustment process; The EU-UK Trade and Cooperation Agreement (TCA); EU-UK criminal justice cooperation.

Protocol for a multi-centre observational and mixed methods pilot study to identify factors predictive of poor functional recovery after major gastrointestinal surgery and strategies to enhance uptake of perioperative optimization: Optimizing the care and treatment pathways for older patients facing major gastrointestinal surgery (OCTAGON).

Introduction: National datasets report large variations in outcomes from older people (≥65 years) between different UK surgical units. This implies that not all patients receive the same level of care or access to resources, such as rehabilitation or allied health professional input. This might impact functional decline.

Do people living in disadvantaged circumstances receive different mental health treatments than those from less disadvantaged backgrounds?

Background: Socio-economic status (SES) has been linked to treatment outcomes for mental health problems, whilst little to no literature has explored the effects of SES on access to both medication and psychological therapy. The aim of this study was to explore whether access to mental health treatments differed by SES.

Methods: The North West Coast Household Health Survey (HHS) collected data from residents aged 18+ from across 20 disadvantaged and 8 less disadvantaged neighbourhoods in 2015, and from 20 disadvantaged neighbourhoods in 2018.