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Hyalinizing clear cell carcinoma is an uncommon neoplasm arising in minor salivary glands. We present a rare case of hyalinizing clear cell carcinoma in the base of the tongue. We report a case of a 38-year-old female presented with a progressive history of hemoptysis and dysphagia over the course of 4 years. Examination revealed a mass originating from the base of the tongue with a biopsy confirmed as hyalinizing clear cell carcinoma . An Ovid MEDLINE and PubMed literature review was conducted due to the rarity of this type of tumor. The patient underwent surgical excision with immediate reconstruction with radial forearm free flap followed with adjuvant radiotherapy and was disease free at her most recent follow-up (12 months). Our review included a total of 13 new cases, including our case. The majority of the cases presented with dysphagia. Surgical excision is the mainstay of treatment, and overall these patients have a good prognosis. Our case highlights a rare presentation of hyalinizing clear cell carcinoma of the base of the tongue, successfully treated with surgical excision, free tissue reconstruction and adjuvant radiotherapy.

Background: Modeling is a cost-effective way to evaluate interventions pertaining to hospital infection acquisitions, such as staffing levels. Increasing the number of nurses in an intensive care unit affects rates of HAI transmission. The way compartmental models are often formulated assumes that there is a never-ending series of tasks for workers to perform. Our previous models used a baseline of 1:3 nurse:patient ratio, and we kept the number of tasks the same across staffing ratios. We wanted to understand how having a finite number of tasks, using this baseline number, across staffing levels affected HAI acquisitions. Methods: We used a stochastic mathematical model of methicillin-resistant Staphylococcus aureus (MRSA) to study the impact of changes in staffing and a finite pool of tasks on hospital-associated acquisitions. For a 15-bed intensive care unit (ICU), we have 1 intensivist, and we set the nurse:patient ratios at 1:1, 1:1.5, 1:2.5, 1:3, 1:5, and 1:7.5, to represent the extreme ends of staffing levels and more moderate values in line with critical care society guidelines. Each model was run 1,000 times. The outcome of each scenario is the median number of hospital-associated MRSA acquisitions in 1 year from those 1,000 runs. Results: Treating the 1:3 nurse:patient ratio as the baseline, with 45 MRSA acquisitions per year, increasing the number of nurses from 5 to 6 (moving to a 1:2.5 nurse:patient ratio) had a relative risk (RR) of 0.77, suggesting that a small change in nurse staffing levels might have an outsized impact on rates. More dramatic changes had correspondingly larger swings in MRSA acquisition rates, with 1:1 nurse:patient ratio scenarios having an RR of 0.17, and at the other extreme, a 1:7.5 nurse:patient ratio having an RR of 4.66. Comparing the infinite to finite models, the ratios with more nurses had lower acquisition rates, with decreases ranging from 20% to 50%. Ratios with fewer nurses in the ICU showed 100%–400% increases in the number of acquisitions. All results were statistically significant. Conclusions: As nurse:patient ratios go up, the burden of direct-care tasks fall on fewer people, which has a direct impact on HAI rates. Our model demonstrates this hypothesis. Therefore, appropriate staffing should be considered in infection control guidelines, and the cost of staffing should be weighed against its impact on infection prevention as well as other areas of patient care. In this study, we considered only the impact from changes in contact patterns emerging from different staffing levels. Further insights may exist when considering other outcomes that also accompany increased staffing.

BackgroundThe effects of the COVID-19 pandemic have been more pronounced for socially disadvantaged populations. We sought to determine how access to SARS-CoV-2 testing and the likelihood of testing positive for COVID-19 were associated with demographic factors, socioeconomic status (SES) and social determinants of health (SDH) in three Canadian provinces.MethodsAn observational population-based cross-sectional study was conducted for the provinces of Ontario, Manitoba and New Brunswick between March 1, 2020 and April 27, 2021, using provincial health administrative data. After excluding residents of long-term care homes, those without current provincial health insurance and those who were tested for COVID-19 out of province, records from provincial healthcare administrative databases were reviewed for 16,900,661 healthcare users. Data was modelled separately for each province in accordance to a prespecified protocol and follow-up consultations among provincial statisticians and collaborators. We employed univariate and multivariate regression models to examine determinants of testing and test results.ResultsAfter adjustment for other variables, female sex and urban residency were positively associated with testing, while female sex was negatively associated with test positivity. In New Brunswick and Ontario, individuals living in higher income areas were more likely to be tested, whereas in Manitoba higher income was negatively associated with both testing and positivity. High ethnocultural composition was associated with lower testing rates. Both high ethnocultural composition and high situational vulnerability increased the odds of testing positive for SARS-CoV-2.DiscussionWe observed that multiple demographic, income and SDH factors were associated with SARS-CoV-2 testing and test positivity. Barriers to healthcare access identified in this study specifically relate to COVID-19 testing but may reflect broader inequities for certain at-risk groups.

Abstract A retrospective risk-adjusted analysis was completed using data from the National Surgical Quality Improvement Program (NSQIP) to (1) compare the risks of post-operative hematoma for thyroid surgery using conventional cautery compared alternative energy devices (defined as LigaSure and Harmonic Scalpel), and (2) compare operative times for the same. The primary outcome variable was post-operative hematoma occurrence. The secondary outcome variable was operative time. The exposure variable was use of conventional or alternative sources of cautery. All adult patients who underwent a total thyroidectomy, subtotal thyroidectomy or completion thyroidectomy between 2016 and 2018 were included. Multivariable linear and logistic regression analyses were performed to control for potentially confounding variables. A total of 13,330 cases were analyzed; 4342 used conventional cautery, and 8988 used alternative sources. There was a statistically significant decrease in post-operative hematoma risk using alternative sources of cautery compared to conventional cautery (OR 0.75; 95% CI 0.58–0.98) (p = 0.04). Use of alternative sources of cautery added 4.95 min onto operative time (95% CI 2.45–7.45) which was statistically significant (p

Vaccine uptake is essential to managing the ongoing COVID-19 pandemic, and vaccine hesitancy is a persistent concern. At the same time, both decision-makers and the general population have high hopes for COVID-19 vaccination. Drawing from qualitative interview data collected in October 2020 as part of the pan-European SolPan study, this study explores early and anticipatory expectations, hopes and fears regarding COVID-19 vaccination across seven European countries. We find that stances towards COVID-19 vaccines were shaped by personal lived experiences, but participants also aligned personal and communal interests in their considerations. Trust, particularly in expert institutions, was an important prerequisite for vaccine acceptance, but participants also expressed doubts about the rapid vaccine development process. Our findings emphasise the need to move beyond the study of factors driving vaccine hesitancy, and instead to focus on how people personally perceive vaccination in their particular social and political context.

The sudden and dramatic advent of the COVID-19 pandemic led to urgent demands for timely, relevant, yet rigorous research. This paper discusses the origin, design, and execution of the SolPan research commons, a large-scale, international, comparative, qualitative research project that sought to respond to the need for knowledge among researchers and policymakers in times of crisis. The form of organization as a research commons is characterized by an underlying solidaristic attitude of its members and its intrinsic organizational features in which research data and knowledge in the study is shared and jointly owned. As such, the project is peer-governed, rooted in (idealist) social values of academia, and aims at providing tools and benefits for its members. In this paper, we discuss challenges and solutions for qualitative studies that seek to operate as research commons.

Abstract This study investigates the underlying climate processes behind the largest recorded mangrove dieback event along the Gulf of Carpentaria coast in northern Australia in late 2015. Using satellite-derived fractional canopy cover (FCC), variation of the mangrove canopies during recent decades are studied, including a severe dieback during 2015–2016. The relationship between mangrove FCC and climate conditions is examined with a focus on the possible role of the 2015–2016 El Niño in altering favorable conditions sustaining the mangroves. The mangrove FCC is shown to be coherent with the low-frequency component of sea level height (SLH) variation related to the El Niño Southern Oscillation (ENSO) cycle in the equatorial Pacific. The SLH drop associated with the 2015–2016 El Niño is identified to be the crucial factor leading to the dieback event. A stronger SLH drop occurred during austral autumn and winter, when the SLH anomalies were about 12% stronger than the previous very strong El Niño events. The persistent SLH drop occurred in the dry season of the year when SLH was seasonally at its lowest, so potentially exposed the mangroves to unprecedented hostile conditions. The influence of other key climate factors is also discussed, and a multiple linear regression model is developed to understand the combined role of the important climate variables on the mangrove FCC variation.

Introduction Frailty is a strong predictor of adverse postoperative outcomes. Prehabilitation may improve outcomes after surgery for older people with frailty by addressing physical and physiologic deficits. The objective of this trial is to evaluate the efficacy of home-based multimodal prehabilitation in decreasing patient-reported disability and postoperative complications in older people with frailty having major surgery.Methods and analysis We will conduct a multicentre, randomised controlled trial of home-based prehabilitation versus standard care among consenting patients >60 years with frailty (Clinical Frailty Scale>4) having elective inpatient major non-cardiac, non-neurologic or non-orthopaedic surgery. Patients will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of >3 weeks of prehabilitation (exercise (strength, aerobic and stretching) and nutrition (advice and protein supplementation)). The study has two primary outcomes: in-hospital complications and patient-reported disability 30 days after surgery. Secondary outcomes include survival, lower limb function, quality of life and resource utilisation. A sample size of 750 participants (375 per arm) provides >90% power to detect a minimally important absolute difference of 8 on the 100-point patient-reported disability scale and a 25% relative risk reduction in complications, using a two-sided alpha value of 0.025 to account for the two primary outcomes. Analyses will follow intention to treat principles for all randomised participants. All participants will be followed to either death or up to 1 year.Ethics and dissemination Ethical approval has been granted by Clinical Trials Ontario (Project ID: 1785) and our ethics review board (Protocol Approval #20190409-01T). Results will be disseminated through presentation at scientific conferences, through peer-reviewed publication, stakeholder organisations and engagement of social and traditional media.Trial registration number NCT04221295.

Abstract Background Salivary detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proposed as an alternative to nasopharyngeal or oropharyngeal swab testing. Our group previously published a study demonstrating that both testing methods identified SARS-CoV-2 using polymerase chain reaction (PCR)-based detection methodology. We therefore conducted a follow-up study using antibody testing to evaluate the accuracy of saliva versus swabs for COVID-19 detection and the durability of antibody response. Methods Venous blood samples were collected from consenting participants and the presence of serum antibodies for SARS-CoV-2 was evaluated on a large, automated immunoassay platform by the Roche anti-SARS-CoV-2 qualitative assay (Roche Diagnostics, Laval Quebec). Individuals with a serum antibody cut-off index (COI) ≥ 1.0 were considered positive. Results In asymptomatic and mildly symptomatic patients with a previously positive standard swab and/or saliva SARS-CoV-2 PCR-test, 42 demonstrated antibodies with 13 patients positive by swab alone, and 8 patients positive by saliva alone. Conclusions Despite their status as ‘current standard’ for COVID-19 testing, these findings highlight limitations of PCR-based tests.

Pharyngeal abscesses require urgent management as they have the propensity to cause severe and life-threatening complications. The introduction of antibiotics has led to a dramatic decline in the incidence of these infections. Regardless, abscess formation continues to be observed in the peritonsillar, parapharyngeal, and retropharyngeal spaces. Oropharyngeal and hypopharyngeal abscesses that cause airway obstruction are scarcely reported and tend to be secondary to other processes. Herein, we describe the case of an 83-year-old man presenting with an idiopathic, obstructive, oropharyngeal wall abscess, extending from the infratonsillar region to the hypopharynx, which recurred after initial surgical management 12 years prior for the same process. He required reintervention during both episodes for rapid reaccumulation. A detailed electronic literature search of PubMed and MedLine was performed for studies reporting on recurrent pharyngeal abscesses and their management. Results were limited to articles published in English from inception to August 2021. The timely management of pharyngeal infections acutely obstructing the airway is crucial. Physicians should adopt close and frequent monitoring and have a low threshold for reimaging should symptoms worsen or fail to improve after the initial surgical intervention.

Fecal contamination of surface water has been associated with multiple enteric disease outbreaks and food recalls. Thus, it is important to understand factors associated with fecal contamination of agricultural water sources. Since fecal indicator bacteria (FIB) were used to monitor surface water for potential fecal contamination, the purpose of the present study was to characterize associations between environmental factors, and (i) FIB (E. coli, Enterococcus, and coliform) levels, and (ii) host-specific fecal marker detection. This study used data collected from 224 sites along 3 waterways, which spanned an urban-rural gradient around Syracuse, New York. Between 2008 and 2017, 2,816 water samples were collected, and E. coli, Enterococcus, and/or coliform concentrations were enumerated. Thirty-one samples were also tested for human and ruminant microbial source-tracking markers. Water quality (e.g., turbidity, nitrate) and weather data were also collected for each site. Univariable Bayesian regression was used to characterize the relationship between each microbial target and land use, water quality, and weather factor. For each model, probability of direction and region of practical equivalence overlap (ROPE) were calculated to characterize the association's direction and strength, respectively. While levels of different FIB were not correlated with each other, FIB levels were associated with environmental conditions. Specifically, FIB levels were also positively associated with temperature, nutrient and sediment levels. Log10 E. coli levels increased by 0.20 (CI = 0.11, 0.31) and log10 Enterococcus levels increased by 0.68 (CI = 0.08, 1.24) for each log10 increase in salinity and nitrate, respectively. These findings may indicate that similar processes drove microbial, sediment, and nutrient contamination of the sampled watersheds. While fecal contamination was strongly associated with land use, the direction of association varied between FIBs and the buffer distance used to calculate land use metrics. E. coli levels and human marker detection were positively associated with percent pasture cover within 122, 366, and 1,098 m of the sampling site, while Enterococcus and coliform levels were only associated with pasture cover within 1,098 m (not 122 or 366 m). Ruminant markers were positively associated with pasture cover within 122 m, but not 366 or 1,098 m. These findings highlight the importance of considering (i) adjacent land use (and associated non-point sources of contamination) when developing strategies for managing fecal hazards associated in agricultural and recreational water, and (ii) spatial scale (e.g., 122 vs. 1,098 m) when developing these strategies.

Abstract Active surveillance (AS) in the management of small, low risk papillary thyroid cancer (PTC) as an alternative option to thyroidectomy, is an area of active research. A national Canadian study is proposed to evaluate the long-term outcomes of patients with small, low risk PTC who choose AS or surgery. This letter describes the proceedings of a national investigator meeting to plan the study. Graphical abstract

Abstract Background Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. Methods This is a multicenter phase II study randomizing one hundred and forty patients with T1–2 N0–2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50–60 Gy based on risk factors). Patients will be stratified based on smoking status (

BackgroundSaliva sampling is a promising alternative to nasopharyngeal swabs for SARS-CoV-2 testing, but acceptability data is lacking. We characterize the acceptability of saliva sampling and nasopharyngeal swabs for primary decision makers and their children after experiencing both testing modalities.MethodsWe administered a cross-sectional survey to participants aged 6-to-17 years and their primary decision makers at an Ottawa community COVID-19 testing centre in March 2021. Included were participants meeting local guidelines for testing. Excluded were those identified prior to participation as having inability to complete the consent, sampling, or survey process. Acceptability in multiple hypothetical scenarios was rated using a 5-point Likert scale. Pain was measured using the Faces Pain Scale-Revised (FPS-R). Preference for testing was assessed with direct binary questions.Results48 participants and 48 primary decision makers completed the survey. Nasopharyngeal swab acceptability differed between scenarios, ranging 79% [95%CI: 66, 88] to 100% [95%CI: 95, 100]; saliva sampling acceptability was similar across scenarios, ranging 92% [95%CI: 82, 97] to 98% [95%CI: 89, 99]. 58% of youth described significant pain with nasopharyngeal swabbing, versus none with saliva sampling. 90% of children prefer saliva sampling. 66% of primary decision makers would prefer nasopharyngeal swabbing if it were 10% more sensitive.ConclusionThough youth prefer saliva sampling over nasopharyngeal swabs, primary decision makers present for testing remain highly accepting of both. Acceptance of nasopharyngeal swabs, however, varies with the testing indication and is influenced by perceived test accuracy. Understanding factors that influence sampling acceptance will inform more successful testing strategies.

Listeria monocytogenes is a Gram-positive, intracellular pathogen responsible for the highly fatal foodborne illness listeriosis. Establishing intracellular infections requires the coordinated expressions of a variety of virulence factors, such as the pore-forming toxin listeriolysin O (LLO), in response to various intra- and extracellular signals. For example, we previously reported that L. monocytogenes differentially modulated LLO production in response to exogenous propionate, a short chain fatty acid either used in salt form as a human food ingredient or produced endogenously by gut microbial fermentation. Therefore, propionate is likely a continuously present signal throughout the L. monocytogenes transmission and infection process. However, little is known about the role of propionate in modulating L. monocytogenes-host interactions. Here we investigated the impact of propionate treatment on L. monocytogenes intracellular infections using cell culture infection models. Propionate treatment was performed separately on L. monocytogenes or host cells before or during infections to better distinguish pathogen-versus-host responses to propionate. Intracellular CFU in RAW264.7 macrophages and plaque diameters in L-fibroblasts were measured as proxy for intracellular infection outcomes. Nitrite levels and cellular morphology were also measured to assess host responses to propionate. We found that propionate pretreatment of anaerobic, but not aerobic, L. monocytogenes significantly enhanced subsequent intracellular infections in both cell types and nitrite production by infected macrophages. Propionate treatment of uninfected macrophages significantly altered cell morphology, seen by longer cells and greater migration, and reduced nitrite concentration in activated macrophages. Treatment of macrophages with propionate prior to or during infections significantly inhibited intracellular growth of L. monocytogenes, including those pre-treated with propionate. These results showcased an opposing effect of propionate on L. monocytogenes intracellular infections and strongly support propionate as an important signaling molecule for both the pathogen and the host cell that can potentially alter the outcome of L. monocytogenes-host interactions.

BackgroundThe traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.MethodsThis is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient’s choice. Our primary objective is to determine the rate of ‘failure’ of disease management in respective AS and surgical arms as defined by: i) AS arm – surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.DiscussionThe results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.Registration detailsThis prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery.

Objective Patient-centered decision making is increasingly identified as a desirable component of medical care. To manage indeterminate thyroid nodules, patients are offered the options of surveillance, diagnostic hemithyroidectomy, or molecular testing. Our objective was to identify factors associated with decision making in this population. Study Design This is a retrospective cross-sectional study of patients with Bethesda III and IV thyroid nodules. Setting Multi-institutional. Methods Factors of interest included age, sex, socioeconomic status (SES), nodule size, institution, attending surgeon, surgeon payment model, and hospital type. Our outcome of interest was the initial management decision made by patients. Results A total of 956 patients were included. The majority of patients had Bethesda III nodules (n = 738, 77%). A total of 538 (56%) patients chose surgery, 413 (43%) chose surveillance, and 5 (1%) chose molecular testing. There was a significant variation in management decision based on attending surgeon (proportion of patients choosing surgery: 15%-83%; P ≤.0001). Fee-for-service surgeon payment models (odds ratio [OR], 1.657; 95% CI, 1.263-2.175; P < .001) and community hospital settings (OR, 1.529; 95% CI, 1.145-2.042; P < .001) were associated with the decision for surgery. Larger nodule size, younger patients, and Bethesda IV nodules were also associated with surgery. Conclusion While it seems appropriate that larger nodules, younger age, and higher Bethesda class were associated with decision for surgery, we also identified attending surgeon, surgeon payment model, and hospital type as important factors. Given this, standardizing management discussions may improve patient-centered shared decision making.

Abstract Background Central giant cell granulomas are benign tumours of the mandible, presenting in children and young adults. Divided into non- and aggressive subtypes, the aggressive subtype is relatively rare and can occasionally progress rapidly, resulting in significant morbidity. Case presentation We present a case of an aggressive central giant cell granuloma (CGCG) in a six year-old female. The lesion originated in the right mandibular ramus and progressed rapidly to involve the condyle. Diagnosis was made using a combination of imaging and pathology. A timely en bloc resection of the hemi-mandible was performed with placement of a reconstructive titanium plate and condylar prosthesis. Conclusion Our case demonstrates the importance of considering CGCG in the differential diagnosis of rapidly progressive mandibular lesions in the pediatric population. Prompt diagnosis and management can greatly improve long-term outcomes.

Abstract Background Tobacco smoking is the leading cause of cancer, preventable death, and disability. Smoking cessation can increase life expectancy by nearly a decade if achieved in the third or fourth decades of life. Various stop smoking interventions are available including pharmacotherapies, electronic cigarettes, behavioural support, and alternative therapies. This protocol outlines an evidence review which will evaluate the benefits and harms of stop smoking interventions in adults. Methods The evidence review will consist of two stages. First, an overview of systematic reviews evaluating the benefits and harms of various stop smoking interventions delivered in or referred from the primary care setting will be conducted. The second stage will involve updating a systematic review on electronic cigarettes identified in the overview; randomized controlled trials will be considered for outcomes relating to benefits while randomized controlled trials, non-randomized controlled trials, and comparative observational studies will be considered for evaluating harms. Search strategies will be developed and peer-reviewed by medical information specialists. The search strategy for the updated review on e-cigarettes will be developed using that of the candidate systematic review. The MEDLINE®, PsycINFO, Embase, and the Cochrane Library electronic databases will be searched as of 2008 for the overview of reviews and from the last search date of the selected review for the updated review. Organizational websites and trial registries will be searched for unpublished or ongoing reviews/studies. Two reviewers will independently screen the title and abstracts of citations using the liberal accelerated method. Full-text screening will be performed independently by two reviewers. Extracted data will be verified by a second reviewer. Disagreements regarding full-text screening and data extraction will be resolved by consensus or third-party adjudication. The methodological quality of systematic reviews, risk of bias of randomized and non-randomized trials, and methodological quality of cohort studies will be evaluated using AMSTAR 2, the Cochrane risk of bias tool, and a modified version of the Scottish Intercollegiate Guidelines Network critical appraisal tool, respectively. The GRADE framework will be used to assess the quality of the evidence for outcomes. Discussion The evidence review will evaluate the benefits and harms of various stop smoking interventions for adults. Findings will be used to inform a national tobacco cessation guideline by the Canadian Task Force on Preventive Health Care. Systematic review registration PROSPERO (CRD42018099691, CRD42018099692)

Abstract Background We sought to expand upon preliminary data suggesting that metformin confers a survival benefit to patients with head and neck squamous cell carcinoma (HNSCC). Methods A large-scale retrospective cohort study of all patients in Ontario diagnosed with squamous cancer of the larynx, hypopharynx, and nasopharynx between Dec 1st 2007 to Dec 1st 2012 was undertaken. The Institute for Clinical and Evaluative Sciences was accessed to obtain patient demographic, treatment and outcome information. We included patients on metformin at the time of diagnosis. Kaplan Meier methods and Cox Regression models were used. Results Patients taking metformin at the time of diagnosis had a higher comorbid status but were otherwise similar to patients without metformin usage. Using multivariate analysis, neither overall survival nor disease specific survival was improved in patients on metformin (OS: HR 1.123, p = .338; DSS: HR 1.048, p = .792). Conclusions No survival advantage was observed in patients with HNSCC taking metformin at the time of diagnosis.

Background: Going forward, the routine implementation of genomic surveillance activities and outbreak investigation is to be expected. We sought to systematically identify the emerging ethical challenges; and to systematically assess the gaps in ethical frameworks or thinking and identify where further work is needed to solve practical challenges. Methods: We systematically searched indexed academic literature from PubMed, Google Scholar, and Web of Science from 2000 to April 2019 for peer-reviewed articles that substantively engaged in discussion of ethical issues in the use of pathogen genome sequencing technologies for diagnostic, surveillance and outbreak investigation. Results: 28 articles were identified; nine United States, five United Kingdom, five The Netherlands, three Canada, two Switzerland, one Australia, two South Africa, and one Italy. Eight articles were specifically about the use of sequencing in HIV. Eleven were not specific to a particular disease. Results were organized into four themes: tensions between public and private interests; difficulties with translation from research to clinical and public health practice; the importance of community trust and support; equity and global partnerships; and the importance of context. Conclusion: While pathogen sequencing has the potential to be transformative for public health, there are a number of key ethical issues that must be addressed, particularly around the conditions of use for pathogen sequence data. Ethical standards should be informed by public values, and further empirical work investigating stakeholders’ views are required. Development in the field should also be under-pinned by a strong commitment to values of justice, in particular global health equity.

This study focused on three female superintendents from poverty and how they elevated out of poverty to become successful superintendents in their school districts and help students living in poverty.

Abstract Background Human papillomavirus (HPV) is an important cause of head and neck squamous cell carcinoma (HNSCC), especially in young people. These tumours overexpress p16 and respond well to treatment. The rapid detection of HPV in patients with HNSCC may expedite treatment when p16 status is not immediately available. Methods Saliva-based DNA collection kits and nested polymerase chain reaction (PCR) were used to determine the HPV status of 62 individuals with biopsy-proven HNSCC. Immunohistochemistry was used to determine tumour p16 status. Results A total of 62 patients were included in the study. Twenty-nine samples (47%) were positive for HPV DNA, the majority of which were high risk (HR) subtypes (79%). Patients who tested positive for HR HPV were more likely to have a tumour arising in the oropharynx compared to a non-oropharyngeal site (74 vs 26%; p = 0.003). A positive HR HPV saliva assay was 100% specific (95% CI 59–100%) and had a 100% positive predictive value (95% CI 75–100%) for a p16 positive tumour arising in the oropharynx. In contrast, a negative HR HPV assay had a 96% negative predictive value (95% CI 80–100%) for tumours arising in a non-oropharyngeal site. Independent of site, the saliva assay had a sensitivity of 77% (95% CI 54–91%) and a specificity of 94% (95% CI 77–99%), respectively, for a p16 positive tumour. Conclusion We show that a saliva based assay is an effective method for detecting HPV in patients with HNSCC and that a positive HR HPV test is highly specific for p16 positive tumours arising in the oropharynx. This simple and rapid test could be used in cases where a biopsy of the primary tumour is not readily available.

While it is often suggested that individuals’ pro-environmental behaviors may be linked with their subjective wellbeing, the strength and direction (e.g. positive or negative) of this relation is unclear. Because pro-environmental behaviors impact peoples’ everyday lives, understanding this relation is critical for promoting long-term environmental solutions. Using a series of meta-analyses, we systematically reviewed the literature on the association between individuals’ pro-environmental behaviors and their subjective wellbeing. We hypothesized that the relation between pro-environmental behavior and subjective wellbeing would be positive and strongest among types of behaviors (e.g. sustainable purchase decisions) and indicators of subjective wellbeing which more clearly reflect personal meaning (e.g. warm glow). We sourced studies via PsychINFO, PsychARTICLES, GreenFile, SocINDEX, Web of Science, and Scopus, as well as professional email lists, direct contact with authors who publish in this domain, data from the authorship team, and the European Social Survey (2016). We included studies with quantitative data on the relation between individuals’ pro-environmental behavior and their subjective wellbeing, ultimately identifying 78 studies (73 published, 5 unpublished) for synthesis. Across multiple indicators of pro-environmental behaviors and subjective wellbeing, we found a significant, positive relation (overall r = .243), and this relation did not meaningfully differ across study characteristics (e.g. sample, design). As predicted, the relation was particularly strong for indicators of pro-environmental behavior and subjective wellbeing which clearly reflect meaning, such as sustainable purchase decisions ( r = .291) and for warm glow ( r = .408). We found a robust, positive relation between people’s pro-environmental behaviors and subjective wellbeing, and initial evidence that this relation may be stronger the more clearly behaviors and indicators of subjective wellbeing reflect meaning. Our results indicate that program and policy-makers can seek opportunities to design ‘win-win’ sustainability programs which could positively impact both people and the environment.

Fecal contamination of waterbodies due to poorly managed human and animal waste is a pervasive problem that can be particularly costly to address, especially if mitigation strategies are ineffective at sufficiently reducing the level of contamination. Identifying the most worrisome sources of contamination is particularly difficult in periurban streams with multiple land uses and requires the distinction of municipal, agricultural, domestic pet, and natural (i.e., wildlife) wastes. Microbial source-tracking (MST) methods that target host-specific members of the bacterial order Bacteroidales and others have been used worldwide to identify the origins of fecal contamination. We conducted a dry-weather study of Onondaga Creek, NY, where reducing fecal contamination has been approached mainly by mitigating combined sewer overflow events (CSOs). Over three sampling dates, we measured in-stream concentrations of fecal indicator bacteria; MST markers targeting human, ruminant, and canine sources; and various physical−chemical parameters to identify contaminants not attributable to CSOs or stormwater runoff. We observed that despite significant ruminant inputs upstream, these contaminants eventually decayed and/or were diluted out and that high levels of urban bacterial contamination are most likely due to failing infrastructure and/or illicit discharges independent of rain events. Similar dynamics may control other streams that transition from agricultural to urban areas with failing infrastructure.

Following publication of the original article [1], the authors reported an error in one of the author names. In this Correction the incorrect and correct author names are listed.

Christopher L Edwards1, Renee Dunn Raynor1, Miriam Feliu1, Camela McDougald1, Stephanie Johnson2, Donald Schmechel3, Mary Wood1, Gary G Bennett4, Patrick Saurona5, Melanie Bonner1, Chante’ Wellington1, Laura M DeCastro6, Elaine Whitworth6, Mary Abrams6, Patrick Logue1, Lekisha Edwards1, Salutario Martinez7, Keith E Whitfield81Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; 2American Psychological Association, Science Directorate, Washington, DC, USA; 3Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC, USA; 4Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA, USA; 5Taub Institute For Research on Alzheimer’s Disease and The Aging Brain, Columbia University, New York, NY, USA; 6Department of Medicine, Division of Hematology, Duke University Medical Center, Durham, NC, USA; 7Department of Radiology, Duke University Medical Center, Durham, NC, USA; 8Duke University, Durham, NC, USAAbstract: Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.Keywords: cerebral vascular event, neuropsychological assessment, sickle cell disease, neuroimaging

Large-scale DNA deformation is ubiquitous in transcriptional regulation in prokaryotes and eukaryotes alike. Though much is known about how transcription factors and constellations of binding sites dictate where and how gene regulation will occur, less is known about the role played by the intervening DNA. In this work we explore the effect of sequence flexibility on transcription factor-mediated DNA looping, by drawing on sequences identified in nucleosome formation and ligase-mediated cyclization assays as being especially favorable for or resistant to large deformations. We examine a poly(dA:dT)-rich, nucleosome-repelling sequence that is often thought to belong to a class of highly inflexible DNAs; two strong nucleosome positioning sequences that share a set of particular sequence features common to nucleosome-preferring DNAs; and a CG-rich sequence representative of high G+C-content genomic regions that correlate with high nucleosome occupancy in vivo. To measure the flexibility of these sequences in the context of DNA looping, we combine the in vitro single-molecule tethered particle motion assay, a canonical looping protein, and a statistical mechanical model that allows us to quantitatively relate the looping probability to the looping free energy. We show that, in contrast to the case of nucleosome occupancy, G+C content does not positively correlate with looping probability, and that despite sharing sequence features that are thought to determine nucleosome affinity, the two strong nucleosome positioning sequences behave markedly dissimilarly in the context of looping. Most surprisingly, the poly(dA:dT)-rich DNA that is often characterized as highly inflexible in fact exhibits one of the highest propensities for looping that we have measured. These results argue for a need to revisit our understanding of the mechanical properties of DNA in a way that will provide a basis for understanding DNA deformation over the entire range of biologically relevant scenarios that are impacted by DNA deformability.

Prevalence of Alzheimer’s disease (AD) will reach epidemic proportions in the United States and worldwide in the coming decades, and with substantially higher rates in African Americans (AAs) than in Whites. Older age, family history, low levels of education, and ɛ4 allele of the apolipoprotein E (APOE) gene are recognized risk factors for the neurodegeneration in AD and related disorders. In AAs, the contributions of APOE gene to AD risk continue to engender a considerable debate. In addition to the established role of cardiovascular disease (CVD) risk in vascular dementia, it is now believed that CVD risk and its endophenotype may directly comediate AD phenotype. Given the pleiotropic effects of APOE on CVD and AD risks, the higher rates of CVD risks in AAs than in Whites, it is likely that CVD risks contribute to the disproportionately higher rates of AD in AAs. Though the advantageous effects of aerobic exercise on cognition is increasingly recognized, this evidence is hardly definitive, and data on AAs is lacking. In this paper, we will discuss the roles of CVD risk factors in the development of AD and related dementias, the susceptibility of these risk factors to physiologic adaptation, and fitness-related improvements in cognitive function. Its relevance to AD prevention in AAs is emphasized.

This paper aims to determine whether the benefits of the combined treatment of solution focused counselling and yoga are more effective than counselling treatment alone in the management of major depression within the university student population. A pilot study with a group having counselling on its own and then the same group having a combination of yoga and counselling treatment two months later. It needs to be noted that there is no control/comparison group in this study.

Best stand establishment depends on both warm and cool germination rates of seed as well as temperatures during five days following planting.