Revealing the short-range structure of the mirror nuclei 3H and 3He.

When protons and neutrons (nucleons) are bound into atomic nuclei, they are close enough to feel significant attraction, or repulsion, from the strong, short-distance part of the nucleon-nucleon interaction. These strong interactions lead to hard collisions between nucleons, generating pairs of highly energetic nucleons referred to as short-range correlations (SRCs). SRCs are an important but relatively poorly understood part of nuclear structure1-3, and mapping out the strength and the isospin structure (neutron-proton (np) versus proton-proton (pp) pairs) of these virtual excitations is thus critical input for modelling a range of nuclear, particle and astrophysics measurements3-5. Two-nucleon knockout or 'triple coincidence' reactions have been used to measure the relative contribution of np-SRCs and pp-SRCs by knocking out a proton from the SRC and detecting its partner nucleon (proton or neutron). These measurements6-8 have shown that SRCs are almost exclusively np pairs, but they had limited statistics and required large model-dependent final-state interaction corrections. Here we report on measurements using inclusive scattering from the mirror nuclei hydrogen-3 and helium-3 to extract the np/pp ratio of SRCs in systems with a mass number of three. We obtain a measure of the np/pp SRC ratio that is an order of magnitude more precise than previous experiments, and find a marked deviation from the near-total np dominance observed in heavy nuclei. This result implies an unexpected structure in the high-momentum wavefunction for hydrogen-3 and helium-3. Understanding these results will improve our understanding of the short-range part of the nucleon-nucleon interaction.

The asymmetry of antimatter in the proton.

The fundamental building blocks of the proton-quarks and gluons-have been known for decades. However, we still have an incomplete theoretical and experimental understanding of how these particles and their dynamics give rise to the quantum bound state of the proton and its physical properties, such as its spin1. The two up quarks and the single down quark that comprise the proton in the simplest picture account only for a few per cent of the proton mass, the bulk of which is in the form of quark kinetic and potential energy and gluon energy from the strong force2. An essential feature of this force, as described by quantum chromodynamics, is its ability to create matter-antimatter quark pairs inside the proton that exist only for a very short time. Their fleeting existence makes the antimatter quarks within protons difficult to study, but their existence is discernible in reactions in which a matter-antimatter quark pair annihilates. In this picture of quark-antiquark creation by the strong force, the probability distributions as a function of momentum for the presence of up and down antimatter quarks should be nearly identical, given that their masses are very similar and small compared to the mass of the proton3. Here we provide evidence from muon pair production measurements that these distributions are considerably different, with more abundant down antimatter quarks than up antimatter quarks over a wide range of momenta. These results are expected to revive interest in several proposed mechanisms for the origin of this antimatter asymmetry in the proton that had been disfavoured by previous results4, and point to future measurements that can distinguish between these mechanisms.

Novel Measurement of the Neutron Magnetic Form Factor from A=3 Mirror Nuclei.

The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6

The Lived Experience of Informal Caregivers of People Who Have Severe Mental Illness and Coexisting Long-Term Conditions: A Qualitative Study.

BACKGROUND: People with severe mental illness (SMI) experience higher rates and poorer outcomes of physical long-term conditions (LTCs). The management of SMI and LTCs is highly complex and many people with SMI rely on informal carers for support, which may lead to high levels of caregiver burden, and caregiver burnout. Caregiver burnout can result in poor health outcomes for informal carers and a reduction in the quality of care they are able to provide. Therefore, it is important to understand the caring experience to identify and address factors that contribute to burden and burnout. METHODS: This paper reports a secondary qualitative analysis of semistructured interviews and focus groups conducted with informal carers of people who have coexisting SMI and LTCs. We recruited 12 informal carers in England between December 2018 and April 2019. The transcripts were coded and analysed thematically. RESULTS: We identified two overarching themes and five subthemes. The themes included 'Fighting on all fronts: Mounting strain between demands and resources', which described the challenge of providing care in the context of coexisting SMI and LTCs, and 'Safekeeping: The necessity of chronic hypervigilance', which captured how informal carers' roles were defined by managing high-risk situations, leading to hypervigilance and paternalistic approaches to care. CONCLUSION: The experience of informal carers for people with SMI and coexisting LTCs is marked by limited access to support and the management of significant risk, which could contribute to high caregiver burden. Further primary research is needed to understand how the experiences of the caregiver role for people with SMI and LTCs influence caregiver burden. PATIENT OR PUBLIC CONTRIBUTION: Our PPI panel DIAMONDS Voice provided guidance on this study from conception, design and development of interview guides and recruitment materials to final write-up. DIAMONDS Voice consists of service users and carers who have experience of SMI and LTCs. Three carer members reviewed the final manuscript, and two are credited as authors.

Why We Want Our Students to Learn about Poverty and Health Care: Sharing Our Own Experiences from Poverty Simulations.

Poverty is a leading cause of numerous health and social inequities in the United States. Educators are increasingly searching for ways to create meaningful learning opportunities about poverty and its profound effect on individuals and communities. In this narrative, we explore our own perspectives as faculty who guide students through a simulated poverty experience. This essay unfolds primarily as a dialogue among us as we make sense of and clarify why we participate in the coordination and facilitation of poverty simulations on our campus and their anticipated benefits for future health care professionals and social service providers.

Why We Want Our Students to Learn about Poverty and Healthcare: Sharing Our Students' Experiences from Poverty Simulations.

Poverty contributes to acute illness, chronic disease and health inequity among millions of Americans, yet health care providers often do not understand the daily experiences of those who live below the poverty line and how it affects their interactions with the health care system. In this narrative, we share healthcare students' stories and reflect on how they account for their experiences of participating in a poverty simulation. Their words come from reflection assignments, and when we read their words, that for a moment, many of our students understand that as a healthcare practitioner, they can make a difference in the life of someone living in poverty. We believe that this experience will inspire our students to make meaningful change as future healthcare professionals. We also believe that the impact on these students goes toward our collective goal as teachers of future healthcare providers to make a difference in our world.

Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study.

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.

Measurement of the Nucleon F_{2}

The ratio of the nucleon F_{2} structure functions, F_{2}^{n}/F_{2}^{p}, is determined by the MARATHON experiment from measurements of deep inelastic scattering of electrons from ^{3}H and ^{3}He nuclei. The experiment was performed in the Hall A Facility of Jefferson Lab using two high-resolution spectrometers for electron detection, and a cryogenic target system which included a low-activity tritium cell. The data analysis used a novel technique exploiting the mirror symmetry of the two nuclei, which essentially eliminates many theoretical uncertainties in the extraction of the ratio. The results, which cover the Bjorken scaling variable range 0.19

Evaluation of data imputation strategies in complex, deeply-phenotyped data sets: the case of the EU-AIMS Longitudinal European Autism Project.

An increasing number of large-scale multi-modal research initiatives has been conducted in the typically developing population, e.g. Dev. Cogn. Neur. 32:43-54, 2018; PLoS Med. 12(3):e1001779, 2015; Elam and Van Essen, Enc. Comp. Neur., 2013, as well as in psychiatric cohorts, e.g. Trans. Psych. 10(1):100, 2020; Mol. Psych. 19:659-667, 2014; Mol. Aut. 8:24, 2017; Eur. Child and Adol. Psych. 24(3):265-281, 2015. Missing data is a common problem in such datasets due to the difficulty of assessing multiple measures on a large number of participants. The consequences of missing data accumulate when researchers aim to integrate relationships across multiple measures. Here we aim to evaluate different imputation strategies to fill in missing values in clinical data from a large (total N = 764) and deeply phenotyped (i.e. range of clinical and cognitive instruments administered) sample of N = 453 autistic individuals and N = 311 control individuals recruited as part of the EU-AIMS Longitudinal European Autism Project (LEAP) consortium. In particular, we consider a total of 160 clinical measures divided in 15 overlapping subsets of participants. We use two simple but common univariate strategies-mean and median imputation-as well as a Round Robin regression approach involving four independent multivariate regression models including Bayesian Ridge regression, as well as several non-linear models: Decision Trees (Extra Trees., and Nearest Neighbours regression. We evaluate the models using the traditional mean square error towards removed available data, and also consider the Kullback-Leibler divergence between the observed and the imputed distributions. We show that all of the multivariate approaches tested provide a substantial improvement compared to typical univariate approaches. Further, our analyses reveal that across all 15 data-subsets tested, an Extra Trees regression approach provided the best global results. This not only allows the selection of a unique model to impute missing data for the LEAP project and delivers a fixed set of imputed clinical data to be used by researchers working with the LEAP dataset in the future, but provides more general guidelines for data imputation in large scale epidemiological studies.

The lived experience of severe mental illness and long-term conditions: a qualitative exploration of service user, carer, and healthcare professional perspectives on self-managing co-existing mental and physical conditions.

BACKGROUND: People with severe mental illness (SMI), such as schizophrenia, have higher rates of physical long-term conditions (LTCs), poorer health outcomes, and shorter life expectancy compared with the general population. Previous research exploring SMI and diabetes highlights that people with SMI experience barriers to self-management, a key component of care in long-term conditions; however, this has not been investigated in the context of other LTCs. The aim of this study was to explore the lived experience of co-existing SMI and LTCs for service users, carers, and healthcare professionals. METHODS: A qualitative study with people with SMI and LTCs, their carers, and healthcare professionals, using semi-structured interviews, focused observations, and focus groups across the UK. Forty-one interviews and five focus groups were conducted between December 2018 and April 2019. Transcripts were coded by two authors and analysed thematically. RESULTS: Three themes were identified, 1) the precarious nature of living with SMI, 2) the circularity of life with SMI and LTCs, and 3) the constellation of support for self-management. People with co-existing SMI and LTCs often experience substantial difficulties with self-management of their health due to the competing demands of their psychiatric symptoms and treatment, social circumstances, and access to support. Multiple long-term conditions add to the burden of self-management. Social support, alongside person-centred professional care, is a key facilitator for managing health. An integrated approach to both mental and physical healthcare was suggested to meet service user and carer needs. CONCLUSION: The demands of living with SMI present a substantial barrier to self-management for multiple co-existing LTCs. It is important that people with SMI can access person-centred, tailored support for their LTCs that takes into consideration individual circumstances and priorities.

Diabetes management during cardiac surgery in the UK: A survey.

AIM: To determine current practice regarding the diabetes management of people undergoing cardiac surgery in the UK. METHODS: We conducted an online survey of UK cardiothoracic surgeons. All cardiothoracic surgeons listed in the Society of Cardiothoracic Surgery membership directory were invited to participate. The survey, compiled using SurveyMonkey software, comprised 15 closed and open-ended questions about the management of people with diabetes pre- and peri-operatively. RESULTS: Sixty-two cardiothoracic surgeons from all 33 UK cardiac centres completed the survey. Of these, 44% responded that they routinely measure HbA1c preoperatively for all patients, 19% had an HbA1c threshold above which they would not operate and 21% currently undertake a point-of-care HbA1c measurement during the cardiothoracic outpatient visit. A total of 74% of respondents reported that it was 'easy' or 'very easy' to obtain a diabetes team review; diabetes nurse specialists were the members of the diabetes team working most closely with cardiac surgeons. Up to a third of the surgeons did not provide physical activity recommendations prior to admission and over 80% did not have a different preoperative or surgical diabetes protocol. Inconsistency in the responses within centres suggests that differences in practice may depend on individual surgeons rather than local policy. CONCLUSIONS: The study demonstrates there is only limited peri-operative management of diabetes in people undergoing cardiac surgery in the UK. There is an opportunity for greater involvement of the diabetes specialist team both before and during admission for surgery to improve outcomes. (Trial registration: ISRCTN10170306).

Non-attendance at diabetes outpatient appointments: a systematic review.

BACKGROUND: Non-attendance at diabetes outpatient appointments is a sizeable problem worldwide and has been associated with suboptimal health outcomes. We aimed to describe the characteristics, health outcomes and reasons given for non-attendance at doctor- or nurse-led diabetes appointments, and interventions to improve attendance. METHODS: PubMed, EMBASE, CINAHL and PsychInfo were searched from database inception to February 2019. Included articles were peer-reviewed, published in English, related to adults or young people with type 1 or type 2 diabetes, and addressed one of the above aspects of non-attendance. Studies were excluded if reporting on other types of diabetes or reviewing attendance at structured education, retinal screening, paediatric, antenatal, podiatry or dietetic clinics. RESULTS: Thirty-four studies of varied designs were identified (15 observational, 1 randomized control trial, 9 qualitative, 5 surveys, 4 service improvements). The definition of non-attendance varied. Younger adults, smokers and those with financial pressures were less likely to attend. Non-attendance was associated with higher HbA1c ; other outcomes were varied but typically worse in non-attenders. Reasons for non-attendance in qualitative studies fell into three categories: balancing the costs and benefits of attendance, coping strategies, and the relationships between the person with diabetes and healthcare professionals. Interventions included appointment management strategies, service improvements, patient navigators and WebCam appointments. CONCLUSIONS: Non-attendance is only partially explained by logistical issues. Qualitative studies suggest complex psychosocial factors are involved. Interventions have progressed from simple appointment reminders in an attempt to address some of the psycho-social determinants, but more work is needed to improve attendance.

Diabetes in the UK: 2019.

AIM: Diabetes impairs the quality of life of people living with the condition and is a major public health concern. The aim of this paper is to create a state of the nation report of diabetes in the UK. METHODS: Diabetes UK collates information about diabetes from diverse sources. This paper synthesizes these data to create a national report. RESULTS: Some 7% of the UK population are now living with diabetes; approximately one million people have undiagnosed type 2 diabetes, 40 000 children have diabetes and more than 3000 children are diagnosed every year. Forty-nine per cent of people with type 1 diabetes were offered structured education, but only 7.6% attended; the corresponding figures for type 2 diabetes were 90% and 10.4%, respectively. Among people with diabetes, 28% reported having issues obtaining medication or equipment for self-management. Fifty-seven per cent of people with type 1 diabetes and 42% with type 2 diabetes do not receive all eight annual health checks. Around 40% of people with diabetes have diminished psychological well-being. One-third of people have a microvascular complication at the time of diagnosis of type 2 diabetes. Diabetes is responsible for 530 myocardial infarctions and 175 amputations every week. The National Health Service spends at least £10 billion a year on diabetes, equivalent to 10% of its budget; 80% is spent treating complications. One in six hospital inpatients has diabetes. CONCLUSION: Diabetes continues to place a significant burden on the individual with diabetes and wider UK society. This report will be updated annually to understand how diabetes is changing across the UK.

How 25 years of psychosocial research has contributed to a better understanding of the links between depression and diabetes.

This narrative review of the literature provides a summary and discussion of 25 years of research into the complex links between depression and diabetes. Systematic reviews have shown that depression occurs more frequently in people with type 1 or type 2 diabetes compared with people without diabetes. Currently, it remains unclear whether depression is also more common in people with impaired glucose metabolism or undiagnosed type 2 diabetes compared with people without diabetes. More prospective epidemiological research into the course of depression and an exploration of mechanisms in individuals with diabetes are needed. Depression in diabetes is associated with less optimal self-care behaviours, suboptimal glycaemic control, impaired quality of life, incident micro- and macrovascular diseases, and elevated mortality rates. Randomized controlled trails concluded that depression in diabetes can be treated with antidepressant medication, cognitive-behavioural therapy (individual, group-based or web-based), mindfulness-based cognitive therapy and stepped care. Although big strides forward have been made in the past 25 years, scientific evidence about depression in diabetes remains incomplete. Future studies should investigate mechanisms that link both conditions and test new diabetes-specific web- or app-based interventions for depression in diabetes. It is important to determine whether treatment or prevention of depression prevents future diabetes complications and lowers mortality rates.

Acute tubulointerstitial nephritis in children- a retrospective case series in a UK tertiary paediatric centre.

BACKGROUND: Acute tubulointerstitial nephritis (AIN) is an uncommon cause of acute kidney injury in children, accounting for less than 10% of cases. There is limited information regarding the range of underlying diagnoses and how these may differ geographically. We undertook a retrospective case note review of consecutive cases of biopsy-proven AIN, presenting to a single UK tertiary paediatric centre, to describe the range of AIN in our caseload, define key characteristics and response to treatment, with the aim of informing paediatric nephrology practice. METHODS: Cases were identified retrospectively from departmental records. Data extracted included demographics, presenting clinical and biochemical features, renal biopsy histology, treatment and follow-up. RESULTS: Ten cases were identified over 8 years (2007-2014). Age range 6-16 years. Male:Female ratio 1:9. Final diagnoses included 6 tubulointerstitial nephritis and uveitis syndrome (TINU), 2 idiopathic, 1 sarcoidosis, 1 child with Streptococcal disease. Of the TINU cases, timing of eye symptoms varied in relation to AIN presentation. Cases had a varied investigative work-up. Median presenting plasma creatinine was 303 µmol/l (range 152-932 µmol/l). Renal function improved spontaneously in 1 idiopathic case and improved with antimicrobial treatment in a child with Streptococcal disease. Eight cases received immunosuppressive treatment with intravenous methylprednisolone (approximately 10 mg/kg for 3-5 days) and / or oral prednisolone (1-2 mg/kg initially, reducing over 7-28 days). At 1 month, median creatinine had fallen to 91 µmol/l (range 41-120 µmol/l) with median eGFR 61 ml/min/1.73m2 (range 51-103 ml/min/1.73m2). At last follow-up (median 18.5 months, range 2-70 months), median creatinine was 71 µmol/l (range 47-90 µmol/l) with median eGFR 80 ml/min/1.73m2, range 63 to 101 ml/min/1.73m2). Two patients received antihypertensives at diagnosis and 1 further patient at 1 month follow-up. Eight patients received electrolyte supplementation. Median time to discontinuing electrolyte supplementation was 3.5 months (range 1-12 months). CONCLUSION: To our knowledge, this is the only contemporary UK case series of biopsy-proven AIN in children. Our population has a high proportion of TINU. Treatment was accompanied by improvement of renal function, however 7/10 patients had an eGFR < 90 ml/min/1.73m2 at last follow-up. We suggest a standardised investigative work-up and recommend long-term follow-up.

Genetics of anophthalmia and microphthalmia. Part 1: Non-syndromic anophthalmia/microphthalmia.

Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause ocular growth and structural defects, such as anophthalmia and microphthalmia (A/M). A/M can be isolated or occur with systemic anomalies, when they may form part of a recognizable syndrome. Their etiology includes genetic and environmental factors; several hundred genes involved in ocular development have been identified in humans or animal models. In humans, around 30 genes have been repeatedly implicated in A/M families, although many other genes have been described in single cases or families, and some genetic syndromes include eye anomalies occasionally as part of a wider phenotype. As a result of this broad genetic heterogeneity, with one or two notable exceptions, each gene explains only a small percentage of cases. Given the overlapping phenotypes, these genes can be most efficiently tested on panels or by whole exome/genome sequencing for the purposes of molecular diagnosis. However, despite whole exome/genome testing more than half of patients currently remain without a molecular diagnosis. The proportion of undiagnosed cases is even higher in those individuals with unilateral or milder phenotypes. Furthermore, even when a strong gene candidate is available for a patient, issues of incomplete penetrance and germinal mosaicism make diagnosis and genetic counseling challenging. In this review, we present the main genes implicated in non-syndromic human A/M phenotypes and, for practical purposes, classify them according to the most frequent or predominant phenotype each is associated with. Our intention is that this will allow clinicians to rank and prioritize their molecular analyses and interpretations according to the phenotypes of their patients.

Unique Access to u-Channel Physics: Exclusive Backward-Angle Omega Meson Electroproduction.

Backward-angle meson electroproduction above the resonance region, which was previously ignored, is anticipated to offer unique access to the three quark plus sea component of the nucleon wave function. In this Letter, we present the first complete separation of the four electromagnetic structure functions above the resonance region in exclusive ω electroproduction off the proton, ep→e^{'}pω, at central Q^{2} values of 1.60, 2.45 GeV^{2}, at W=2.21 GeV. The results of our pioneering -u≈-u_{min} study demonstrate the existence of a unanticipated backward-angle cross section peak and the feasibility of full L/T/LT/TT separations in this never explored kinematic territory. At Q^{2}=2.45 GeV^{2}, the observed dominance of σ_{T} over σ_{L}, is qualitatively consistent with the collinear QCD description in the near-backward regime, in which the scattering amplitude factorizes into a hard subprocess amplitude and baryon to meson transition distribution amplitudes: universal nonperturbative objects only accessible through backward-angle kinematics.

Transforming mental well-being for people with diabetes: research recommendations from Diabetes UK's 2019 Diabetes and Mental Well-Being Workshop.

AIMS: To identify key gaps in the research evidence base that could help to improve the mental well-being of people with diabetes, and to provide recommendations to researchers and research funders on how best to address them. METHODS: A 2-day international research workshop was conducted, bringing together research experts in diabetes and in mental health, people living with diabetes and healthcare professionals. RESULTS: The following key areas needing increased financial investment in research were identified: understanding the mechanisms underlying depression; understanding the multifactorial impact of social stigma; improving the language used by healthcare professionals; supporting people who find it difficult to engage with their diabetes; supporting significant others; supporting people with diabetes and eating disorders; improving models of care by learning from best practice; the potential benefits of screening and managing diabetes distress in routine diabetes care pathways; primary prevention of mental health issues at the time of diagnosis of diabetes; establishing the effectiveness of diabetes therapies on mood and other mental health issues; and understanding the impact of current diabetes technologies on mental health. Research recommendations as to how to address each of these priority areas were also developed. CONCLUSIONS: This inaugural position statement outlines recommendations to address the urgent unmet need related to the mental well-being of people living with diabetes, and calls on the research community and funders to develop research programmes and strategies to reduce this need.

Fibrin-Targeted Polymerized Shell Microbubbles as Potential Theranostic Agents for Surgical Adhesions.

The development of new therapies for surgical adhesions has proven to be difficult as there is no consistently effective way to assess treatment efficacy in clinical trials without performing a second surgery, which can result in additional adhesions. We have developed lipid microbubble formulations that use a short peptide sequence, CREKA, to target fibrin, the molecule that forms nascent adhesions. These targeted polymerized shell microbubbles (PSMs) are designed to allow ultrasound imaging of early adhesions for diagnostic purposes and for evaluating the success of potential treatments in clinical trials while acting as a possible treatment. In this study, we show that CREKA-targeted microbubbles preferentially bind fibrin over fibrinogen and are stable for long periods of time (∼48 h), that these bound microbubbles can be visualized by ultrasound, and that neither these lipid-based bubbles nor their diagnostic-ultrasound-induced vibrations damage mesothelial cells in vitro. Moreover, these bubbles show the potential to identify adhesionlike fibrin formations and may hold promise in blocking or breaking up fibrin formations in vivo.