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Objective To investigate associations between markers of social functioning (trouble with social eating and social contact), depression and health-related quality of life (QOL) among head and neck cancer survivors. Methods This cross-sectional analysis included individuals with oral cavity, oropharynx, larynx, salivary gland and thyroid cancers from Head and Neck 5000 alive at 12 months. Trouble with social eating and social contact were measured using items from EORTC QLQ-HN responses were converted into a score of 0-100, with a higher score equalling more trouble or better QOL. A HADS subscale score of ≥8 was considered significant depression. Associations between tertiles of trouble with social eating and social contact and depression and QoL were assessed using multivariable logistic and linear regression (with robust errors), respectively. Results Of 2561 survivors, 23% reported significant depression. The median QOL score was 75.0 (interquartile range 58.3-83.3). For trouble with social eating, after confounder adjustment, those in the intermediate and highest tertiles had higher odds of depression (intermediate: OR = 4.5, 95% CI 3.19-6.45; high: OR = 21.8, 15.17-31.18) and lower QOL (intermediate:β = -8.7, 95% CI -10.35 to -7.14; high: β = -24.8, -26.91 to -22.77). Results were similar for trouble with social contact. Conclusion We found strong clinically important associations between markers of social functioning and depression and QOL. More effective interventions addressing social eating and contact are required. These may help survivors regain their independence, reduce levels of isolation and loneliness, and depression, and improve QOL outcomes generally.

INTRODUCTION The mulberry tree (Morus alba L.) is a prolific source of biologically active compounds. There is considerable growing interest in probing M. alba twigs as a source of disruptive antioxidant lead candidates for cosmetic skin care product development. OBJECTIVE An integrated approach using high-performance liquid chromatography (HPLC) coupled with either chemical detection (CD) or high-resolution mass spectrometry (HRMS) was applied to the hydroalcoholic extract of M. alba to detect and identify lead antioxidant compounds, respectively. MATERIAL AND METHODS The twigs were weighed, powdered and homogenized using a mill and the extract was prepared using 70% aqueous ethanol. The antioxidant metabolites were detected with HPLC coupled with CD (based on the ORAC assay) and their structural identification was carried out using a Q-Exactive Orbitrap MS instrument. RESULTS Using this approach, 13 peaks were detected as overall contributors to the antioxidant activity of M. alba, i.e. mulberrosides (A & E), oxyresveratrol & its derivatives, moracin & its derivatives and a dihydroxy-octadecadienoic acid, which together accounted for >90% of the antioxidant activity, highlighting the effectiveness of the integrated approach based on HPLC-CD and HPLC-HRMS. Additionally, a (3,4-dimethoxyphenyl-1-O-β-D-apiofuranosyl-(1″ → 6')-O-β-D-glucopyranoside was also discovered for the first time from the twig extract and is presented here. CONCLUSION To our knowledge, this is the first report from M. alba twigs using HPLC-CD and HPLC-HRMS that identifies key compounds responsible for the antioxidant property of this native Chinese medicinal plant.

This chapter focuses on public health in Wales and the context within which it is delivered. As a devolved service, health policy and the wider public policy legislative framework are the responsibility of the devolved Welsh Government tasked under the Government of Wales Act 2006 with developing and implementing policy, exercising executive functions, and making subordinate legislation. The chapter outlines the organisations involved and the context of the policy in Wales. It also explores the political drive for more collaboration between different organisations as a mechanism for the delivery of better services. The chapter then examines a unique piece of legislation in Wales, the Well-Being of Future Generations Act 2015 (WFG Act), and identifies how this may influence the work of local authorities and other organisations in relation to health and its social determinants. It draws on the available evidence on how this is working so far and looks at two key policy areas jointly driven by the Cymru Well Wales partnership: 'Adverse Childhood Experiences' and 'The first 1,000 days'.

Background: \ud Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer–BioNtech, hearafter referred to as BNT).\ud \ud Methods: \ud COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY) control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.\ud \ud Findings: \ud Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44–61) in the younger age group and 76 years (73–78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41–59) in the younger age group and 78 years (75–82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5–2·3) in the half VLA group to 32·3 (24·8–42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7–1·6) for ChAd to 3·6 (2·4–5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0–1·5) in the half VLA group to 11·5 (9·4–14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7–1·6) for half VLA to 4·7 (3·1–7·1) for m1273. The results were similar between those aged 30–69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30–69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.\ud \ud Interpretation: \ud All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.\ud \ud Funding: \ud UK Vaccine Taskforce and National Institute for Health Research.

Introduction Recent guidelines have stated transoral laser microsurgery be recommended for the management of T1a glottic carcinoma over radiotherapy. If radiotherapy offered superior quality of life (QoL) outcomes, this guidance would need revisiting. There is a paucity of good quality evidence on QoL outcomes. Design This prospective cohort study aims to assess generic and disease specific patient reported QoL in patients treated with either surgery or RT for T1a glottic carcinoma. Participants Participants were recruited as part of the multicentre, prospective Head and Neck 5000 cohort between 2011 and 2014. Main outcome measures Baseline demographic data were collected. All participants completed the EORTC QLQ C30 and EORTC QLQ H&N35 questionnaires at baseline, 4 months, 12 months, and after 36 months. Results 123 participants received radiotherapy only (n=68) or surgery only (n=55). Overall QoL scores were similar between both groups. The median (IQR) EORTC QLQ C30 summary scores at 12 months were 89.3 (79.1, 95.7) and 92.6 (74.4, 97.9) for the radiotherapy and surgery groups respectively. The equivalent summary scores for the EORTC QLQ H&N35 were 91.9 (83.8, 94.9) and 90.4 (85.5, 94.9). There was a modest difference in some QoL subscales between the groups but no differences existed beyond 4 months. Conclusions Patient reported QoL is similar following either radiotherapy or surgery for T1a glottic carcinoma. This data supports current guidance recommended TLM for this disease.

Background A key challenge for most systems is how to provide effective access to urgent and emergency care across rural and urban populations. Tensions about the placement and scope of hospital emergency services are longstanding in Irish political life and there has been recent reform to centralise hospital services in some regions. The focus of this paper is a system approach to examine the geographic variation in resourcing and utilisation of such care across GP practices, out-of-hours care, ambulance services, Emergency Departments and Local Injury Units in Ireland. Methods We used a cross-sectional study design to evaluate variation in resource allocation by aggregating geographic funding to various elements of the urgent and emergency care system and assessing patterns in hospital resource utilisation across the population. Expenditure, staffing, access and activity data were gathered from government sources, individual facilities and service providers, health professional bodies, private firms and central statistics. Data on costs and activity in 2014 are collated and presented at both county and regional levels. Analyses focus on resources spent on urgent and emergency care across geographic areas, the role of population concentration in allocation, the relationship between pre-hospital spending and in-hospital spending, and the utilisation of hospital-based emergency care resources by residents of each county. Results An array of funding mechanisms exists, resulting in a fragmented approach to the resourcing of urgent and emergency care. There are large differences in spending per capita at the county-level, ranging from between €50 and €200 per capita; however, these are less pronounced regionally. Distribution of hospital emergency care resources is highly skewed to the North East of the country, and away from the recently reconfigured South and Mid-West regions. Conclusions This analysis advances the traditional approach of evaluating individual services or hospital resourcing. There are notable differences in utilisation of hospital-based emergency care resources at the regional level, indicating that populations within those regions which have been reconfigured have lower utilisation of hospital resources. There is a clear case for more integration in decision-making around funding and consideration of key principles, such as equity, to guide that process.

Objective To investigate the recovery trajectory and predictors of outcome for swallowing difficulties following head and neck cancer treatment in a large prospective cohort. Materials and methods Data from 5404 participants of the Head and Neck 5000 study were collected from 2011 to 2014. Patient-reported swallowing was measured using the EORTC HN35, recorded at baseline (pre-treatment) and 4 and 12 months post-baseline. Mixed-effects linear multivariable regression was used to investigate time trends, compare cancer sites, and identify associations between clinical, socio-demographic and lifestyle variables. Results 2458 participants with non-recurrent oral (29%) oropharyngeal (46%) and laryngeal (25%) cancer were included in the analysis. There was a clinically significant deterioration in scores between baseline and four months for swallowing (11.7 points; 95% CI 10.7–12.8) and trouble with social eating (17.9 points; 95% CI 16.7–19.2), but minimal difference between baseline and 12 months. Predictors of better swallowing and social eating were participants with larynx cancer, early-stage disease, treatment type, age, gender, co-morbidity, socio-economic status, smoking behaviour and cohabitation. Conclusion Swallowing problems persist up to a year after head and neck cancer treatment. These findings identify disease and demographic characteristics for particularly vulnerable groups, supporting the need for holistic interventions to help improve swallowing outcomes. People diagnosed with head and neck cancer at risk of severe eating and drinking problems following treatment can be identified earlier in the pathway, receive more accurate information about early and late post-treatment side-effects, which can inform shared decision-making discussions.

This paper compares health policy responses to COVID-19 in Canada, Ireland, the United Kingdom and United States of America (US) from January to November 2020, with the aim of facilitating cross-country learning. Evidence is taken from the COVID-19 Health System Response Monitor, a joint initiative of the European Observatory on Health Systems and Policies, the WHO Regional Office for Europe, and the European Commission, which has documented country responses to COVID-19 using a structured template completed by country experts. We show all countries faced common challenges during the pandemic, including difficulties in scaling-up testing capacity, implementing timely and appropriate containment measures amid much uncertainty and overcoming shortages of health and social care workers, personal protective equipment and other medical technologies. Country responses to address these issues were similar in many ways, but dissimilar in others, reflecting differences in health system organization and financing, political leadership and governance structures. In the US, lack of universal health coverage have created barriers to accessing care, while political pushback against scientific leadership has likely undermined the crisis response. Our findings highlight the importance of consistent messaging and alignment between health experts and political leadership to increase the level of compliance with public health measures, alongside the need to invest in health infrastructure and training and retaining an adequate domestic health workforce. Building on innovations in care delivery seen during the pandemic, including increased use of digital technology, can also help inform development of more resilient health systems longer-term.

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta, Author summary Squamous cell carcinomas are specific type of cancer that can arise in multiple organs of the aerodigestive tract including the lung, oral cavity, oropharynx, larynx and esophagus. Previous studies have shown that aerodigestive squamous cell carcinomas share common environmental risk factors (tobacco smoking and alcohol intake). Here, we investigate genetic factors involved in the risk of aerodigestive squamous cell carcinomas as a group in a large genetic association study involving 13,887 cancer cases and 61,961 controls. We identified one genome-wide significant region within 2q33.1 and 3 other suggestive regions at 1q32.1, 5q31.2 and 19p13.11. Gene-based analyses also identify a list of SqCC-related genes that are involved in DNA damage response and epigenetic regulation. Our results suggest some overlap in the genetic factors influencing the risk of aerodigestive squamous cell carcinomas in European populations and highlights the importance of cross-cancer studies.

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC., Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

BACKGROUND: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity. METHODS: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements. FINDINGS: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p

The current climate is one of uncertainty and immeasurable tragedy for people afflicted by the pandemic of SARS-CoV-2 virus infection. As professionals, we have a duty of care towards all patients especially the vulnerable and those suffering with life-threatening illnesses such as oral cancer. We present a safe & objective triaging method for afflicted with this disease in the prevailing morbid situation., Highlights • Objective method. • Safe triaging system. • Risk assessment in COVID-19 climate.

Background Head and neck cancer (HNC) is an important cause of morbidity and mortality globally. Radical treatment methods may result in facial disfigurement and/or functional difficulties with subsequent adverse impacts on health-related quality of life (HRQoL). Guidelines suggest that HRQoL should be measured repeatedly throughout treatment to enable refined treatment protocols and tailored follow-up support but questionnaires are often long and burdensome. We compared condition-specific and generic metrics to assess HRQoL for people with this condition. Methods We used data from the prospective Head and Neck 5000 clinical cohort study - 5511 participants with a new diagnosis of HNC between 2011 and 2014. HRQoL data were collected at baseline from 2065 people who completed both the condition-specific EORTC-QLQ-C30 and the shorter, generic EQ-5D-5L questionnaires. Results There was strong evidence of association between comparable scales on each questionnaire at baseline: higher levels of functioning and lower levels of reported symptoms assessed with EQ-5D-5L were associated with lower EORTC-QLQ-C30 symptom scores. A moderate relationship (0.61) was found between overall QoL in the EQ-5D-5L index and self-perceived health (EQ VAS). Conclusions HRQoL data collected from the generic EQ-5D-5L and cancer-specific EORTC-QLQ-C30 questionnaires are comparable at baseline for people diagnosed with HNC. This would allow a reduced burden of data collection but the EQ-5D-5L may not be sensitive to some condition-specific symptoms. Clinicians and researchers must clarify their aims and outcomes of interest before choosing their HRQoL measures. Further work is required to examine the ability to detect change in these measures over time.

Extra-intestinal pathogenic E. coli (ExPEC) is one of the leading causes of bacteraemia and urinary tract infections (UTI) worldwide. At present, there is no licensed vaccine available and with the increasing incidence of multidrug resistance (MDR) the demand for developing alternatives to antibiotics is paramount. We have developed in vitro functional antibody assays to fast track screening of patient convalescent sera from ExPEC infections to identify potential vaccine antigens. A functional immunological assay will also facilitate the assessment of vaccine candidates against the many disease-causing serotypes circulating in the population. Outer membrane vesicles (OMVs) purified from a mutant (ΔlpxM) MDR O25 (ST131) strain were used to immunise mice to raise antiserum against the bacterial strain. Immunised mice were protected in a mouse model of E. coli bacteraemia. The antiserum from protected animals was used to develop an antibody-mediated bacterial killing assay and a complement deposition assay (CDA). The antiserum mediated killing with human IgG and IgM-depleted plasma as the complement source, and also showed deposition of C3b and C5b-9 onto the bacterial surface determined by flow cytometry. This may be a useful screening tool for mining for new antigens and in assessing the antisera raised against the candidates for cross serotype protection.

In this paper we examine the proposition of de-risking through life and the guidance offered by TDFs in the decumulation phase following retirement. Using both Monte Carlo methods along with actual historical experience we investigate the withdrawal experience associated with Glidepath Investing in the US since 1925 for conventional bond-equity portfolios. We find two very powerful and practical conclusions. First, that smoothing the returns on individual assets by simple absolute momentum or trend following techniques is a potent tool to enhance withdrawal rates, often by as much as 50% per annum. And, perhaps of even greater social relevance is that it removes the ‘left-tail’ of unfortunate withdrawal rate experiences, that is, the bad luck of a poor sequence of returns early in decumulation. We show that diversifying assets over time by switching between a risky asset and cash in a systematic way is potentially more important for the retirement income experience than diversifying one’s portfolio across a range of risky asset classes. In particular the willingness to tactically de-risk and re-risk allows the investor to stay exposed to equities in selective calendar fashion for far longer with reduced potential for painful drawdowns and raised potential for higher withdrawal rates. Second, and very importantly, we also show that Glidepath Investing is indeed a very sensible strategy within a few years of the target date. This finding provides succour to enthusiasts for target date investing in the face of the growing hostility in the literature

The global demand to increase food production from underperforming, water and nutrient limited soils is increasing, which has resulted in an increased dependency on water for irrigation. As fresh water is a finite resource, the increase in irrigation use has resulted in competition between water used for municipal purposes and that used for food and fibre production for an increasing global population. An opportunity exists to improve the efficiency of both urban and agricultural systems by taking green waste compost generated in urban centres and incorporating it into agricultural soils with poor water retention, thereby increasing the ability of these soils to efficiently retain irrigation water for plant use and also to capture a greater volume of water from rainfall. Addition of amendments to soil changes the pore space. The magnitude and cause for this change depends on amendment type, application rate, soil type and climatic conditions. The aim of this research was to determine if the incorporation of municipal compost (MC) can increase the quantity (total volume) and concentration (total volume per unit volume) of soil pores that hold readily available water (defined as macro-mesopores of 30–3 μm diameter) and plant available water (defined as mesopores of 30–0.3 μm diameter). We hypothesised that increases in total porosity would be positively correlated with MC application rate and increases in water holding porosity (macro-mesoporosity and mesoporosity) would be positively correlated with decreasing MC particle size due to the creation of inter-particle pore spaces < 30 μm in diameter. The MC was screened to three different maximum particle sizes – MC4 (

Background: The Enhanced Recovery After Surgery (ERAS) programme is an approach to the perioperative care of patients which aims to improve outcomes and speed up recovery after surgery. Although the evidence base appears strong for this programme, the implementation of ERAS has been slow. This study aimed to gain an understanding of the facilitating factors and challenges of implementing the programme with a view to providing additional contextual information to aid implementation. The study had a particular focus on the nutritional elements as these have been highlighted as important. Methods: The study employed qualitative research methods, guided by the Normalisation Process Theory (NPT) to explore the experiences and opinions of 26 healthcare professionals from a range of disciplines implementing the programme. Results: This study identified facilitating factors to the implementation of ERAS: alignment with evidence based practice, standardising practice, drawing on the evidence base of other specialties, leadership, teamwork, ERAS meetings, patient involvement and education, a pre-operative assessment unit, staff education, resources attached to obtaining The Commissioning for Quality and Innovation (CQUIN) money, the ward layout, data collection and feedback, and adapting the care pathway. A number of implementation challenges were also identified: resistance to change, standardisation affecting personalised patient care, the buy-in of relevant stakeholders, keeping ERAS visible, information provision to patients, resources, palatability of nutritional drinks, aligning different ward cultures, patients going to non-ERAS departments, spreading the programme within the hospital, differences in health issue, and utilising a segmental approach. Conclusions: The findings presented here provide useful contextual information from diverse surgical specialties to inform healthcare providers when implementing ERAS in practice. Addressing the challenges and utilising the facilitating factors identified in this study, could speed up the rate at which ERAS is adopted, implemented and embedded.

[This corrects the article DOI: 10.1371/journal.pone.0167250.].

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers. Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through the grant X01HG007492-0. Corina Lesseur undertook this work during the tenure of a Postdoctoral Fellowship awarded by the International Agency for Research on Cancer. The funders did not participate in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all of the participants involved in this research and the funders and support. We thank Dr. Leticia Fernandez (Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba) for her contribution to the IARC ORC multicenter study. We are also grateful to Sergio Koifman (Escola Nacional de Saúde Pública, Rio de Janeiro, Brazil) for his contribution to the IARC Latin America multicenter study (Sergio Koifman passed away in May 2014) and to Xavier Castellsagué from the ARCAGE Barcelona Center who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19 CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission’s 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222).The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to SB, and Fondazione Veronesi to SB. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by European Commission’s INCO-COPERNICUS Program (IC15-CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28.The IARC Oral Cancer Multicenter study was funded by: grant S06 96 202489 05F02 from Europe against Cancer; Grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; UICC Yamagiwa-Yoshida Memorial International Cancer Study; National Cancer Institute of Canada; Italian Association for Research on Cancer; and the Pan American Health Organization. The coordination of EPIC study is financially supported

General practice makes a critical contribution to healthcare in Ireland. However, there is a weak understanding of the general practice workforce in Ireland. The aim of this study is to estimate the number of general practitioners (GPs) and practice nurses in Ireland. A variety of data sources was used to corroborate counts of general practitioners and practice nurses. Capture–recapture methods were used to estimate the hidden population of GPs not identified by the databases included. There are 2,954 general practitioners in Ireland, equivalent to 64.4 per 100,000 population. There are 1,700 practice nurses nationally, equivalent to 37.1 per 100,000 persons. There is substantial regional variation in the number of general practitioners and practice nurses per 100,000. To some extent, deficits in one discipline may be counterbalanced by a surplus in the other. In the absence of a centralised register, it is not possible to track the number of GPs or practice nurses working in Ireland at present. This is despite the fact that there are twice as many general practice visits per annum compared to hospital visits.

Aim There is evidence that preoperative carbohydrate drinks and postoperative nutritional supplements improve the outcome of colorectal surgery. There is little information on their individual contribution. Method A prospective four-arm double-blind controlled trial was carried out in which patients were randomized to carbohydrate or placebo drinks preoperatively and a polymeric supplement or placebo drink postoperatively. The primary outcome was insulin resistance (using the short insulin tolerance test and HOMA-IR). Secondary outcomes included handgrip strength, pulmonary function, intestinal permeability and postoperative complications. Results A total of 120 patients were randomized to four demographically well matched groups. Patients who received preoperative and postoperative supplements had better glucose homeostasis (P = 0.004), peak expiratory flow rate (P = 0.035), handgrip strength (P = 0.002) and less insulin resistance (P = 0.001) compared with those who only received placebo drinks. Conclusion Oral nutritional supplements given preoperatively and postoperatively improve postoperative handgrip strength, pulmonary function and insulin resistance. A weaker effect was seen in patients who received supplements either preoperatively or postoperatively. Oral nutritional supplements should be given both preoperatively and postoperatively.

The financial crisis that manifested itself in late 2007 resulted in a Europe-wide economic crisis by 2009. As the economic climate worsened, Governments and households were put under increased strain and more focus was placed on prioritising expenditures. Across European countries and their heterogeneous health care systems, this paper examines the initial responsiveness of health expenditures to the crisis and whether recession severity can be considered a predictor of health expenditure growth. In measuring severity we move away from solely gross domestic product (GDP) as a metric and construct a recession severity index predicated on a number of key macroeconomic indicators. We then regress this index on measures of total, public and private health expenditure to identify potential relationships. Analysis suggests that for 2009, the Baltic States, along with Ireland, Italy and Greece, experienced comparatively severe recessions. We find, overall, an initial counter-cyclical response in health spending (both public and private) across countries. However, our analysis finds evidence of a negative relationship between recession severity and changes in certain health expenditures. As a predictor of health expenditure growth in 2009, the derived index is an improvement over GDP change alone.

Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD. Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls. BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls. NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve - 29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation. When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p=0.0068) and NTHi-specific IgG1 (p=0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM. We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway. Furthermore, the NTHi+ve patients had significantly greater levels of IL-1? (p=0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients. This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi.

A rising incidence of oropharyngeal squamous cell carcinoma (OPSCC) incidence has occurred throughout the developed world, where it has been attributed to an increasing impact of human papillomavirus (HPV) on disease etiology. This report presents the findings of a multicenter cross-sectional retrospective study aimed at determining the proportion of HPV-positive and HPV-negative OPSCC within the United Kingdom. Archival tumor tissue blocks from 1,602 patients previously diagnosed with OPSCC (2002–2011) were collated from 11 centers. HPV status was determined with three validated commercial tests to provide valid data for 1,474 cases in total. Corresponding national incidence data from the same decade were obtained from UK Cancer registries. The overall proportion of HPV+ OPSCC between 2002 and 2011 was 51.8% [95% confidence interval (CI), 49.3–54.4], and this remained unchanged throughout the decade [unadjusted RR = 1.00 (95% CI, 0.99–1.02)]. However, over the same period, the incidence of OPSCC in the broader UK population underwent a 2-fold increase [age-standardized rate 2002: 2.1 (95% CI, 1.9–2.2); 2011: 4.1 (95% CI, 4.0–4.3)]. Although the number of OPSCCs diagnosed within the United Kingdom from 2002 to 2011 nearly doubled, the proportion of HPV+ cases remained static at approximately 50%. Our results argue that the rapidly increasing incidence of OPSCC in the United Kingdom cannot be solely attributable to the influence of HPV. The parallel increase in HPV+ and HPV− cases we documented warrants further investigation, so that appropriate future prevention strategies for both types of disease can be implemented. Cancer Res; 76(22); 6598–606. ©2016 AACR.

Background International recruitment is a common strategy used by high-income countries to meet their medical workforce needs. Ireland, despite training sufficient doctors to meet its internal demand, continues to be heavily dependent on foreign-trained doctors, many of whom may migrate onwards to new destination countries. A cross-sectional study was conducted to measure and analyse the factors associated with the migratory intentions of foreign doctors in Ireland. Methods A total of 366 non-European nationals registered as medical doctors in Ireland completed an online survey assessing their reasons for migrating to Ireland, their experiences whilst working and living in Ireland, and their future plans. Factors associated with future plans – whether to remain in Ireland, return home or migrate to a new destination country – were tested by bivariate and multivariate analyses, including discriminant analysis. Results Of the 345 foreign doctors who responded to the question regarding their future plans, 16 % of whom were Irish-trained, 30 % planned to remain in Ireland, 23 % planned to return home and 47 % to migrate onwards. Country of origin, personal and professional reasons for migrating, experiences of training and supervision, opportunities for career progression, type of employment contract, citizenship status, and satisfaction with life in Ireland were all factors statistically significantly associated with the three migratory outcomes. Conclusion Reported plans may not result in enacted emigration. However, the findings support a growing body of evidence highlighting dissatisfaction with current career opportunities, contributing to the emigration of Irish doctors and onward migration of foreign doctors. Implementation of the WHO Global Code, which requires member states to train and retain their own health workforce, could also help reduce onward migration of foreign doctors to new destination countries. Ireland has initiated the provision of tailored postgraduate training to doctors from Pakistan, enabling these doctors to return home with improved skills of benefit to the source country. Electronic supplementary material The online version of this article (doi:10.1186/s12960-016-0121-z) contains supplementary material, which is available to authorized users.

Background Obesity has become a world-wide epidemic and is spreading to countries with emerging economies. Previously tested interventions are often too costly to maintain in the long term. This leaves a need for improved strategies for management of the epidemic. Nudge Theory presents a new collection of methods, deemed “nudges”, which have the potential for low-cost and broad application to guide healthier lifestyle choices without the need for restrictive regulation. There has not yet been a large-scale examination of the effectiveness of nudges, despite several policy making bodies now considering their use. Methods To address this gap in knowledge, an adapted systematic review methodology was used to collect and consolidate results from current Nudge papers and to determine whether Nudge strategies are successful in changing adults’ dietary choices for healthier ones. Results It was found that nudges resulted in an average 15.3 % increase in healthier dietary or nutritional choices, as measured by a change in frequency of healthy choices or a change in overall caloric consumption. All of the included studies were from wealthy nations, with a particular emphasis on the United States with 31 of 42 included experiments. Conclusions This analysis demonstrates Nudge holds promise as a public health strategy to combat obesity. More research is needed in varied settings, however, and future studies should aim to replicate previous results in more geographically and socioeconomically diverse countries. Electronic supplementary material The online version of this article (doi:10.1186/s12889-016-3272-x) contains supplementary material, which is available to authorized users.

Six phenolic compounds namely, quercetin-3- O -rutinoside (1) , 3- O -caffeoylquinic acid (2) , luteolin-7- O -glucoside (3) , apigenin-7- O -rutinoside (4) , apigenin-7- O - β - d -glucopyranoside (5) and quercetin (6) were isolated from the whole plant of Pilea microphylla using conventional open-silica gel column chromatography and preparative HPLC. Further, these compounds were characterized by 1D, 2D NMR techniques and high-resolution LC–MS. Compounds 1–3 and 6 exhibited significant antioxidant potential in scavenging free radicals such as DPPH, ABTS and SOD with IC 50 of 3.3–20.4 μmol/L. The same compounds also prevented lipid peroxidation with IC 50 of 10.4–32.2 μmol/L. The compounds also significantly prevented the Fenton reagent-induced calf thymus DNA damage. Pre-treatment with compounds 1–3 and 6 in V79 cells attenuated radiation-induced formation of reactive oxygen species, lipid peroxidation, cytotoxicity and DNA damage, correlating the antioxidant activity of polyphenols with their radioprotective effects. Compounds 1 , 3 and 6 significantly inhibited lipid peroxidation, presumably due to 3′,4′-catechol ortho -dihydroxy moiety in the B-ring, which has a strong affinity for phospholipid membranes. Oxidation of flavonoids, with catechol structure on B-ring, yields a fairly stable ortho -semiquinone radical by facilitating electron delocalization, which is involved in antioxidant mechanism. Hence, the flavonoid structure, number and location of hydroxyl groups together determine the antioxidant and radioprotection mechanism.

Squamous cell carcinomas (SCC) of minor salivary gland origin are extremely rare. We present an unusual case of a 29-year-old female patient who presented with a well-differentiated SCC of minor salivary gland origin arising in the lower lip. Wedge resections of the lip, including bilateral mental nerve excision, were required to clear the tumor because of striking pathological evidence of perineural invasion distant from the primary tumor site.

A novel isoflavan-4-ol (pumilanol), ( re l)-3β-(2′-hydroxy-4′,5′-methylenedioxyphenyl)-6-methoxy-4α,7-dihydroxybenzo-3,4-dihydropyran ( 1 ) and two known flavonoids, tephrinone ( 2 ) and rotenone ( 3 ) together with lupeol and stigmasterol were isolated from the roots of Tephrosia pumila (Fabaceae) from a collection made in Andhra Pradesh, India. The structures of the compounds were determined by MS, 1D and 2D-NMR spectral analysis. Pumilanol ( 1 ) exhibited significant antiprotozoal activity against T. b. rhodensiense , T. cruzi and L. donovani with IC 50 of 3.7, 3.35 and 17.2 μg/mL, respectively, but displayed high toxicity towards L-6 (IC 50 of 17.12 μg/mL) rat skeletal myoblasts.

Human exposure to air pollutants is often characterized by measured or modeled outdoor concentrations. In Western societies, subjects spend about 90% of their time indoors, of which a large fraction in their own home. Hence indoor air quality is an important determinant of the true personal exposure for many components. Indoor air quality is affected both by infiltration of outdoor air in buildings and indoor sources such as smoking, gas cooking, and use of consumer products. In this chapter we separately describe the impact of indoor sources and outdoor air on indoor pollution. We first illustrate differences in outdoor and personal exposure using data on real-time particle number concentrations from a recent study in Augsburg, Germany. We then present a model of indoor PM concentrations, illustrating the factors that affect indoor air quality. We summarize empirical studies that have assessed indoor–outdoor relationships for particle mass, particle number, and specific components of particulate matter.