Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

Surface and Subsurface Decontamination Technology

A number of proven technologies applicable to the chemical and physical decontamination of radioactive and non-radioactive contaminants within the environmental remediation and radiological waste management sectors exist. Previous work generally acknowledges that these methods have limitations such as production of large volumes of waste, destruction of the substrate, complex safety considerations [1a] and application of special precautions to meet disposal acceptance criteria [2]. A method that removes a variety of contaminants from the surface and subsurface of porous materials, with minimal contaminated waste arisings, is highly desirable. TechXtract® is a patented, sequential chemical extraction process developed to remove radionuclides, PCBs, and other hazardous organic and inorganic substances from solid materials such as concrete, brick, steel, and exotic metals [3]. The technology uses multifarious task-specific chemical formulations and engineered applications to achieve surface penetration and removal of the contaminants from the atomic voids of metals and other substrates, or the capillaries and gel pores of concretes. TechXtract® is proven to remove a variety of contaminants from various substrates, allowing free release of the substrate as waste for disposal, or re-use, whilst producing minimal secondary waste. Data from testing of TechXtract’s capabilities and evidencing the technology’s efficacy during site based applied research and development is presented here.</jats:p

Independently testing prosocial interventions: Methods and recommendations from 31 researchers

There is a growing need for independent, ecologically valid research on prosocial design interventions within online platforms. Platform design has a significant impact on user interactions, yet independent researchers often lack access to live platforms, limiting the ecological validity of studies testing the effectiveness of prosocial interventions. In response, thirty-one experts from academia, industry and civil society gathered for a workshop focused on understanding methods that enable effective research on design interventions that lead to prosocial outcomes, such as healthy interactions and individual safety, well-being and dignity. We synthesize the workshop findings to guide researchers and practitioners in advancing prosocial design and to provide stakeholders - platforms, advocacy groups and regulators - with evidence-based tools to promote healthy online behavior. First, we present a review of the dominant research methods in the field. Second, we highlight the challenges that researchers agreed were most prominent, such as the constant 'reinvention of the wheel' for testing interventions, and recommend ways to address them. Finally, we propose specific future actions to address the challenges in the areas of knowledge sharing, events, and supporting infrastructure that experts consider most worth pursuing, and set out an agenda for future online prosocial research and investment

Independently testing prosocial interventions: Methods and recommendations from 31 researchers

There is a growing need for independent, ecologically valid research on prosocial design interventions within online platforms. Platform design has a significant impact on user interactions, yet independent researchers often lack access to live platforms, limiting the ecological validity of studies that test the effectiveness of prosocial interventions. In response, thirty-one experts from academia, industry, and civil society gathered for a workshop focused on understanding methods that enable effective research on design interventions that result in prosocial outcomes, such as healthy interactions and individual safety, wellbeing, and dignity. This paper synthesizes the workshop findings to guide researchers and practitioners in advancing prosocial design and to provide stakeholders—platforms, advocacy groups, and regulators—with evidence-based tools to promote healthy online behavior. First, we present an in-depth review of the dominant research methods in the field as identified in the workshop. Second, we highlight challenges that workshop participants agreed were most prominent, such as the constant 'reinvention of the wheel' for intervention testing, and recommend how to deal with them. Finally, we propose specific future actions to address challenges in the areas of knowledge sharing, events, and supporting infrastructure that experts consider most worth pursuing, laying out an agenda for future online prosocial research and investment

The Health And Wellbeing Of Children In The Early Years

Giving children the best start in life is by far the most effective way to address health inequalities in the long term. The wisest investment we can make to achieve the goal of a healthier population is during the first 1001 critical days of a child’s life. Good nutrition and safe environments supported by nurturing early relationships are the essential components of children’s cognitive, emotional and physical development. The importance of this age-range is acknowledged by the World Health Organisation’s Global Strategy for Women’s, Children’s and Adolescents’ Health, the UNICEF Baby Friendly Initiative and in England, both the NHS Long Term Plan and Public Health England’s 2016 guidance on ‘Giving every child the best start in life’. Covid-19 is having a continuing impact on babies born before and during the pandemic and children in the early years. The impact has been unequal for children, with a disproportionate number of BAME families, those living with poverty and children with SEND facing the greatest challenges. Parents and carers had less face-to-face interaction with health professionals and early years settings and studies reported families found it harder to stay active and access healthy food choices. In the UK, 14% of families with children experienced food insecurity during the first six months of the pandemic as opposed to 11.5% beforehand. There are now widespread and burgeoning concerns that Covid-19 has exacerbated nutritional problems linked to food insecurity including obesity, under-nourishment, nutrient deficiencies and mental health problems such as anxiety, low self-worth, and depression. Children have been subjected to violence and abuse at home as a corollary of lockdown whether as direct recipients or helpless observers. We are now reeling in the aftermath of such challenges as children’s emotional well-being and education faltered, instead of thriving. Children need to be put at the heart of any recovery plans to ensure Covid-19 is not the legacy of their future outcomes. It is probable that the true impact of the pandemic may not become clear for many years. Schools are already reporting an increasing number of their pupils requiring extra support with language and communication and personal social and emotional development. Early years settings were the one constant in the lives of young children providing a stable and safe space during Covid-19. They continue to play a central role in supporting parents, carers and young children in establishing lifelong healthy eating habits. Good quality early education has a positive impact on young children’s development and safe, excellent childcare enables parents and carers to work, while their children have the opportunity to interact with other children and be enriched by new challenges and experiences within a safe space. Nursery settings support children’s care and development from birth to five years and are a vital source of information, guidance and support for parents, carers and families. Early years providers continued to provide this support throughout the pandemic yet Covid-19 has impacted greatly on early years providers with over 2000 settings closing between January and May 2021. Staff from early years settings are at the forefront of providing support for our youngest children yet it is a resource that remains underfunded. There is a clear need to ensure training requirements for the early years’ workforce supports them to achieve the requirements set out in the Early Years Foundation Stage Framework. Children, families and the early years’ work force need to be at the heart of a national strategy to ensure children can enter adulthood with improved health and wellbeing outcomes. The recommendations that form this report highlight that we are already falling short of meeting children’s minimum requirements for nutrition, immunisation, education and emotional supportAdditional authors: Kathryn Peckham; Kristy Howells; Louise Pagden; Pamela Murray; Sonia Blandford; Wayne Veck; Helen Garnett; Jackie Harland; Jean Barlow; Julie Wharton; Kieran James; Margueritte Hunter Blair; Marian Greally; Nicola Calder; Francis McGlone; Keith Godfrey; Trudi Beswick; Viki Beale This report is the culmination of work from many sectors and considers where we are now as a society, as well as setting a roadmap for improving outcomes for children in the future

The Health And Wellbeing Of Children In The Early Years

Giving children the best start in life is by far the most effective way to address health inequalities in the long term. The wisest investment we can make to achieve the goal of a healthier population is during the first 1001 critical days of a child’s life. Good nutrition and safe environments supported by nurturing early relationships are the essential components of children’s cognitive, emotional and physical development. The importance of this age-range is acknowledged by the World Health Organisation’s Global Strategy for Women’s, Children’s and Adolescents’ Health, the UNICEF Baby Friendly Initiative and in England, both the NHS Long Term Plan and Public Health England’s 2016 guidance on ‘Giving every child the best start in life’. Covid-19 is having a continuing impact on babies born before and during the pandemic and children in the early years. The impact has been unequal for children, with a disproportionate number of BAME families, those living with poverty and children with SEND facing the greatest challenges. Parents and carers had less face-to-face interaction with health professionals and early years settings and studies reported families found it harder to stay active and access healthy food choices. In the UK, 14% of families with children experienced food insecurity during the first six months of the pandemic as opposed to 11.5% beforehand. There are now widespread and burgeoning concerns that Covid-19 has exacerbated nutritional problems linked to food insecurity including obesity, under-nourishment, nutrient deficiencies and mental health problems such as anxiety, low self-worth, and depression. Children have been subjected to violence and abuse at home as a corollary of lockdown whether as direct recipients or helpless observers. We are now reeling in the aftermath of such challenges as children’s emotional well-being and education faltered, instead of thriving. Children need to be put at the heart of any recovery plans to ensure Covid-19 is not the legacy of their future outcomes. It is probable that the true impact of the pandemic may not become clear for many years. Schools are already reporting an increasing number of their pupils requiring extra support with language and communication and personal social and emotional development. Early years settings were the one constant in the lives of young children providing a stable and safe space during Covid-19. They continue to play a central role in supporting parents, carers and young children in establishing lifelong healthy eating habits. Good quality early education has a positive impact on young children’s development and safe, excellent childcare enables parents and carers to work, while their children have the opportunity to interact with other children and be enriched by new challenges and experiences within a safe space. Nursery settings support children’s care and development from birth to five years and are a vital source of information, guidance and support for parents, carers and families. Early years providers continued to provide this support throughout the pandemic yet Covid-19 has impacted greatly on early years providers with over 2000 settings closing between January and May 2021. Staff from early years settings are at the forefront of providing support for our youngest children yet it is a resource that remains underfunded. There is a clear need to ensure training requirements for the early years’ workforce supports them to achieve the requirements set out in the Early Years Foundation Stage Framework. Children, families and the early years’ work force need to be at the heart of a national strategy to ensure children can enter adulthood with improved health and wellbeing outcomes. The recommendations that form this report highlight that we are already falling short of meeting children’s minimum requirements for nutrition, immunisation, education and emotional suppor