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Abstract In this study, optical photothermal infrared (O-PTIR) spectroscopy combined with machine learning algorithms were used to evaluate 46 tissue cores of surgically resected cervical lymph nodes, some of which harboured oral squamous cell carcinoma nodal metastasis. The ratios obtained between O-PTIR chemical images at 1252 cm−1 and 1285 cm−1 were able to reveal morphological details from tissue samples that are comparable to the information achieved by a pathologist’s interpretation of optical microscopy of haematoxylin and eosin (H&E) stained samples. Additionally, when used as input data for a hybrid convolutional neural network (CNN) and random forest (RF) analyses, these yielded sensitivities, specificities and precision of 98.6 ± 0.3%, 92 ± 4% and 94 ± 5%, respectively, and an area under receiver operator characteristic (AUC) of 94 ± 2%. Our findings show the potential of O-PTIR technology as a tool to study cancer on tissue samples.

Abstract Background Estimation of prognosis of oral squamous cell carcinoma (OSCC) is inaccurate prior to surgery, only being effected following subsequent pathological analysis of the primary tumour and excised lymph nodes. Consequently, a proportion of patients are overtreated, with an increase in morbidity, or undertreated, with inadequate margins and risk of recurrence. We hypothesise that it is possible to accurately characterise clinical outcomes from infrared spectra arising from diagnostic biopsies. In this first step, we correlate survival with IR spectra derived from the primary tumour. Methods Infrared spectra were collected from tumour tissue from 29 patients with OSCC and subject to classification modelling. Results The model had a median AUROC of 0.89 with regard to prognosis, a median specificity of 0.83, and a hazard ratio of 6.29 in univariate Cox proportional hazard modelling. Conclusion The data suggest that FTIR spectra may be a useful early biomarker of prognosis in OSCC.

Background Home working has increased since the Coronavirus Disease 2019 (COVID-19) pandemic’s onset with concerns that it may have adverse health implications. We assessed the association between home working and social and mental wellbeing among the employed population aged 16 to 66 through harmonised analyses of 7 UK longitudinal studies. Methods and findings We estimated associations between home working and measures of psychological distress, low life satisfaction, poor self-rated health, low social contact, and loneliness across 3 different stages of the pandemic (T1 = April to June 2020 –first lockdown, T2 = July to October 2020 –eased restrictions, T3 = November 2020 to March 2021 –second lockdown) using modified Poisson regression and meta-analyses to pool results across studies. We successively adjusted the model for sociodemographic characteristics (e.g., age, sex), job characteristics (e.g., sector of activity, pre-pandemic home working propensities), and pre-pandemic health. Among respectively 10,367, 11,585, and 12,179 participants at T1, T2, and T3, we found higher rates of home working at T1 and T3 compared with T2, reflecting lockdown periods. Home working was not associated with psychological distress at T1 (RR = 0.92, 95% CI = 0.79 to 1.08) or T2 (RR = 0.99, 95% CI = 0.88 to 1.11), but a detrimental association was found with psychological distress at T3 (RR = 1.17, 95% CI = 1.05 to 1.30). Study limitations include the fact that pre-pandemic home working propensities were derived from external sources, no information was collected on home working dosage and possible reverse association between change in wellbeing and home working likelihood. Conclusions No clear evidence of an association between home working and mental wellbeing was found, apart from greater risk of psychological distress during the second lockdown, but differences across subgroups (e.g., by sex or level of education) may exist. Longer term shifts to home working might not have adverse impacts on population wellbeing in the absence of pandemic restrictions but further monitoring of health inequalities is required. Jacques Wels and colleagues investigate the relationship between working from home and different indicators of mental and social wellbeing in the UK. Author summary Why was this study done? ➢ The number of workers working from home drastically increased during the Coronavirus Disease 2019 (COVID-19) pandemic. ➢ Little is known about the relationship between home working and mental and social wellbeing before and during the pandemic. ➢ As some home working schemes are likely to remain post-pandemic, understanding this association is important. What did the researchers do and find? ➢ We analysed data from 7 UK-based population surveys to better understand the relationship between working from home (partially or fully) and different indicators of mental and social wellbeing. ➢ We analysed these relationships over 3 time points—i.e., April to June 2020 (T1), July to October 2020 (T2), and November 2020 to March 2021 (T3)—and controlled for sociodemographic (e.g., age, sex, and ethnicity) and job characteristics (e.g., sector of activity, key worker status). ➢ We found that home working was not associated with psychological distress at T1 or T2, but at T3 it was associated with increased psychological distress (relative risk = 1.17, 95% CI = 1.05 to 1.30). No other meaningful associations were found. ➢ We stratified these associations by sex, education level, age, and full-time versus part-time employment and found that home working was associated with greater psychological distress in those with lower than degree level education. What do these findings mean? ➢ We found no clear evidence of a lasting association between home working, mental health, and social wellbeing which may indicate that, during the pandemic, home working was not detrimental nor beneficial for workers’ wellbeing. ➢ Differences across subgroups may exist and specific impacts by sex, age, and education level need to be investigated further.

The World Health Organization in its recommendations for the care of preterm infants has drawn attention to the need to address issues related to family involvement and support, including education, counseling, discharge preparation, and peer support. A failure to address these issues may translate into poor outcomes that extend across the lifespan. In this paper, we review the often far-reaching impact of preterm birth on the health and wellbeing of the parents and highlight the ways in which psychological stress may have a negative long-term impact on the parent-child interaction, attachment, and the styles of parenting. This paper addresses the following topics: (1) neurodevelopmental outcomes in preterm infants, including cognitive, sensory, and motor difficulties, (2) long-term mental health issues in premature infants that include elevated rates of anxiety and depressive disorders, autism, and somatization, which may affect social relationships and quality of life, (3) adverse mental health outcomes for parents that include elevated rates of depression, anxiety, and symptoms of post-traumatic stress, as well as increased rates of substance abuse, and relationship strain, (4) negative impacts on the parent-infant relationship, potentially mediated by maternal sensitivity, parent child-interactions, and attachment, and (5) impact on the parenting behaviors, including patterns of overprotective parenting, and development of Vulnerable Child Syndrome. Greater awareness of these issues has led to the development of programs in neonatal mental health and developmental care with some data suggesting benefits in terms of shorter lengths of stay and decreased health care costs.

Ethnic inequities in COVID-19 vaccine hesitancy have been reported in the United Kingdom (UK), and elsewhere. Explanations have mainly focused on differences in the level of concern about side effects, and in lack of trust in the development and efficacy of vaccines. Here we propose that racism is the fundamental cause of ethnic inequities in vaccine hesitancy. We introduce a theoretical framework detailing the mechanisms by which racism at the structural, institutional, and interpersonal level leads to higher vaccine hesitancy among minoritised ethnic groups. We then use data from Wave 6 of the UK Household Longitudinal Study COVID-19 Survey (November to December 2020) to empirically examine these pathways, operationalised into institutional, community, and individual-level factors. We use the Karlson–Holm–Breen method to formally compare the relationship between ethnicity and vaccine hesitancy once age and gender, sociodemographic variables, and institutional, community, and individual-level factors are accounted for. Based on the Average Partial Effects we calculate the percentage of ethnic inequities explained by each set of factors.Findings show that institutional-level factors (socioeconomic position, area-level deprivation, overcrowding) explained the largest part (42%) of the inequity in vaccine hesistancy for Pakistani or Bangladeshi people, and community-level factors (ethnic density, community cohesion, political efficacy, racism in the area) were the most important factors for Indian and Black groups, explaining 35% and 15% of the inequity, respectively.Our findings suggest that if policy intervened on institutional and community-level factors – shaped by structural and institutional racism - considerable success in reducing ethnic inequities might be achieved.

Abstract Background Complications after major surgery are a significant cause of morbidity and mortality. Neck dissection is one of the most commonly performed major operations in Head and Neck Surgical Oncology. Significant surgical complications occur in approximately 10–20% of all patients, increasing to 40% in patients who have had previous treatment to the area or have multiple co-morbidities and/or polypharmacy. Current evidence suggests that fibrin sealants (FS) may have potential clinical advantages in Head and Neck Surgery through the reduction of complications, volume of wound drainage and retention time of the drains. However, a paucity of high-quality trial-based evidence means that a surgical trial to determine the effectiveness of FS in reducing the rate and severity of complications in patients undergoing lateral neck dissection is warranted. The DEFeND randomised external pilot trial will address critical questions on how well key components of the proposed study design work together as well as the feasibility of a future phase III trial. Methods The study design that is being piloted is that of a two-arm, parallel group, superiority trial with block randomisation in a 1:1 allocation ratio. The interventional arm will constitute the application of FS (Artiss, Baxter Healthcare Ltd.) to the surgical wound following completion of a neck dissection procedure, in addition to standard of care (SOC). The control arm will constitute SOC alone. Eligible patients will include patients who require a lateral neck dissection with a minimum of three cervical nodal levels. Patients who require bilateral neck procedures or undergoing immediate reconstruction with free or regional flaps will be excluded. The outcomes being assessed will be recruitment rate, screened to randomisation rate, fidelity of blinding process using blinding indices, number of missing or incomplete data entries, number of protocol deviations and number of losses to follow-up. Suitability of the outcome measures proposed for the future phase III trial will also be assessed. Discussion The anticipated challenges for this study will be recruitment, complexity of the intervention and adherence to the protocol. The outcomes will inform the design, feasibility and conduct of a future phase III surgical trial. Trial registration First participant randomised: November 06, 2018; UKCRN Portfolio ID: 37896; ISRCTN99181100 .

Background: Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic. Methods: Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: ‘no suicidality’ controls (N = 83,557); ‘thoughts that life was not worth living’ (N = 21,063); ‘ever contemplated self-harm’ (N = 13,038); ‘act of deliberate self-harm in the past’ (N = 2498); and ‘previous suicide attempt’ (N = 2666). Outcomes: We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81). Interpretation: These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level. Fund: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217). MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. UKRI Innovation Fellowship (MR/R024774/1).

Abstract Background Sedentary behaviour is related to poorer health independently of time spent in moderate to vigorous physical activity. The aim of this study was to investigate whether wellbeing or symptoms of anxiety or depression predict sedentary behaviour in older adults. Method Participants were drawn from the Lothian Birth Cohort 1936 (LBC1936) (n = 271), and the West of Scotland Twenty-07 1950s (n = 309) and 1930s (n = 118) cohorts. Sedentary outcomes, sedentary time, and number of sit-to-stand transitions, were measured with a three-dimensional accelerometer (activPAL activity monitor) worn for 7 days. In the Twenty-07 cohorts, symptoms of anxiety and depression were assessed in 2008 and sedentary outcomes were assessed ~ 8 years later in 2015 and 2016. In the LBC1936 cohort, wellbeing and symptoms of anxiety and depression were assessed concurrently with sedentary behaviour in 2015 and 2016. We tested for an association between wellbeing, anxiety or depression and the sedentary outcomes using multivariate regression analysis. Results We observed no association between wellbeing or symptoms of anxiety and the sedentary outcomes. Symptoms of depression were positively associated with sedentary time in the LBC1936 and Twenty-07 1950s cohort, and negatively associated with number of sit-to-stand transitions in the LBC1936. Meta-analytic estimates of the association between depressive symptoms and sedentary time or number of sit-to-stand transitions, adjusted for age, sex, BMI, long-standing illness, and education, were β = 0.11 (95% CI = 0.03, 0.18) and β = − 0.11 (95% CI = − 0.19, −0.03) respectively. Conclusion Our findings indicate that depressive symptoms are positively associated with sedentary behavior. Future studies should investigate the causal direction of this association.

Background: Social contact, including remote contact (by telephone, email, letter or text), could help reduce social inequalities in depressive symptoms and loneliness among older adults. Methods: Data were from the 8th wave of the English Longitudinal Study of Aging (2016/17), stratified by age (n = 1578 aged

This study investigates if cyberbullying is associated with wellbeing independently of traditional bullying and if social support and eating family meals together promotes resilience by buffering adolescents against the consequences of both types of bullying. Data for 5286 eleven, thirteen and fifteen year olds participating in the cross-sectional 2018 Scottish Health Behaviour in School-aged Children study were analysed. Adolescent self-report measures were used to assess traditional bullying, cyberbullying, classmate and teacher support and frequency of family meals together. Psychological wellbeing was assessed with the 5-item World Health Organization Wellbeing index. Analyses were conducted separately by gender with multilevel models, adjusting for sociodemographic factors. Resilience to bullying and cyberbullying was operationalised using statistical interactions. For both genders, cyberbullying and traditional bullying measures were associated with reduced wellbeing and all social support indicators were associated with increased wellbeing. In models containing both bullying measures, frequent traditional bullying victimisation was associated with a 7.2 (95% CI: 3.4–10.1) reduction in wellbeing score for boys and a 7.2 (95% CI: 4.5–10.0) reduction for girls, while cyberbullying was associated with 10.5 (95% CI: 5.8–15.1) reduction in wellbeing score for boys and 11.1 (95% CI: 6.7–15.5) reduction for girls. For both genders adjusting for classmate support explained away the relationships between traditional bullying and wellbeing, but cyberbullying was associated negatively with wellbeing independent of social support. Only one of 12 interaction tests provided any evidence of resilience. Cyberbullying was associated with a 7.8 (95% CI: 0.2–15.4) reduction in wellbeing score for girls who ate with their family every day, and 17.3 (95% CI: 10.5–24.1) reduction for girls who ate with their families less than weekly. In conclusion, cyberbullying is a strong, albeit rare, threat to adolescent wellbeing. Social support is important for wellbeing, but its ability to buffer adolescents against the consequences of bullying may be limited. Keywords: Cyberbullying, Bullying, Wellbeing, Resilience, Social support

BackgroundPoor physical health in severe mental illness (SMI) remains a major issue for clinical practice.AimsTo use electronic health records of routinely collected clinical data to determine levels of screening for cardiometabolic disease and adverse health outcomes in a large sample (n = 7718) of patients with SMI, predominantly schizophrenia and bipolar disorder.MethodWe linked data from the Glasgow Psychosis Clinical Information System (PsyCIS) to morbidity records, routine blood results and prescribing data.ResultsThere was no record of routine blood monitoring during the preceding 2 years for 16.9% of the cohort. However, monitoring was poorer for male patients, younger patients aged 16–44, those with schizophrenia, and for tests of cholesterol, triglyceride and glycosylated haemoglobin. We estimated that 8.0% of participants had diabetes and that lipids levels, and use of lipid-lowering medication, was generally high.ConclusionsElectronic record linkage identified poor health screening and adverse health outcomes in this vulnerable patient group. This approach can inform the design of future interventions and health policy.

Objective: The aim of this study was to examine a cohort of unaccompanied refugee minors (URMs) by means of psycholinguistic methods in order to obtain a more subtle picture of their degree of traumatization. Methods: Twenty-eight participants were included in the Stress-Inducing Speech Task (SIST) consisting of a free association (FA) and a stress (STR) condition. Narratives were examined by means of (1) quantitative parameters (word count); (2) psycholinguistic variables (temporal junctures, TJs), narrative structure, referential activity (RA)—a measure of emotional expressivity; and (3) content analysis ratings. Results: Word count was significantly lower than in age-matched norms. In the FA condition, TJs were lower, but in the STR condition, rates were comparable. RA was significantly higher in both conditions. Content analysis ratings showed that the experiences described by these youths were potentially traumatic in nature. Conclusions: This pattern of narrative shows a mixture of fulfilling the task demand, while containing an emotionally charged narrative. Narrative structure was absent in the FA condition, but preserved in the STR condition, as URMs struggled with the description of non-normative events. This indicates that these youths have not yet emotionally dealt with and fully integrated their trauma experiences.

Oral epithelial dysplasia (OED) is a histopathologically-defined, potentially premalignant condition of the oral cavity. The rate of transformation to frank carcinoma is relatively low (12% within 2 years) and prediction based on histopathological grade is unreliable, leading to both over- and under-treatment. Alternative approaches include infrared (IR) spectroscopy, which is able to classify cancerous and non-cancerous tissue in a number of cancers, including oral. The aim of this study was to explore the capability of FTIR (Fourier-transform IR) microscopy and machine learning as a means of predicting malignant transformation of OED. Supervised, retrospective analysis of longitudinally-collected OED biopsy samples from 17 patients with high risk OED lesions: 10 lesions transformed and 7 did not over a follow-up period of more than 3 years. FTIR spectra were collected from routine, unstained histopathological sections and machine learning used to predict malignant transformation, irrespective of OED classification. PCA-LDA (principal component analysis followed by linear discriminant analysis) provided evidence that the subsequent transforming status of these 17 lesions could be predicted from FTIR data with a sensitivity of 79 ± 5% and a specificity of 76 ± 5%. Six key wavenumbers were identified as most important in this classification. Although this pilot study used a small cohort, the strict inclusion criteria and classification based on known outcome, rather than OED grade, make this a novel study in the field of FTIR in oral cancer and support the clinical potential of this technology in the surveillance of OED.

Phage display was used to identify peptide mimics of an immunologically protective nematode glycan (CarLA) by screening a constrained C7C peptide library for ligands that bound to an anti-CarLA mAb (PAB1). Characterisation of these peptide mimotopes revealed functional similarities with an epitope that is defined by PAB1. Mimotope vaccinations of mice with three selected individual phage clones facilitated the induction of antibody responses that recognised the purified, native CarLA molecule which was obtained from Trichostrongylus colubriformis. Furthermore, these mimotopes are specifically recognised by antibodies in the saliva of animals that were immune to natural polygeneric nematode challenge. This shows that antibodies to the PAB1 epitope form part of the mucosal polyclonal anti-CarLA antibody response of nematode immune host animals. This demonstrates that the selected peptide mimotopes are of biological relevance. These peptides are the first to mimic the PAB1 epitope of CarLA, a defined larval glycan epitope which is conserved between many nematode species.

Nordic countries do not have the smallest health inequalities despite egalitarian social policies. A possible explanation for this is that drivers of class differences in health such as financial strain and labour force status remain socially patterned in Nordic countries.Our analyses used data for working age (25-59) men (n = 48,249) and women (n = 52,654) for 20 countries from five rounds (2002-2010) of the European Social Survey. The outcome was self-rated health in 5 categories. Stratified by gender we used fixed effects linear regression models and marginal standardisation to instigate how countries varied in the degree to which class inequalities were attenuated by financial strain and labour force status.Before adjustment, Nordic countries had large inequalities in self-rated health relative to other European countries. For example the regression coefficient for the difference in health between working class and professional men living in Norway was 0.34 (95% CI 0.26 to 0.42), while the comparable figure for Spain was 0.15 (95% CI 0.08 to 0.22). Adjusting for financial strain and labour force status led to attenuation of health inequalities in all countries. However, unlike some countries such as Spain, where after adjustment the regression coefficient for working class men was only 0.02 (95% CI -0.05 to 0.10), health inequalities persisted after adjustment for Nordic countries. For Norway the adjusted coefficient was 0.17 (95% CI 0.10 to 0.25). Results for women and men were similar. However, in comparison to men, class inequalities tended to be stronger for women and more persistent after adjustment.Adjusting for financial security and labour force status attenuates a high proportion of health inequalities in some counties, particularly Southern European countries, but attenuation in Nordic countries was modest and did not improve their relative position.