Effects of photobiomodulation and caffeine treatment on acute kidney injury in a hypoxic ischemic neonatal rat model.

Hypoxic ischemic encephalopathy (HIE) occurs in 2-5/1000 births, with acute kidney injury (AKI) occurring in 40%. AKI increases morbidity and mortality. Caffeine, an adenosine receptor antagonist, and photobiomodulation (PBM), working on cytochrome c oxidase, are potential treatments for AKI. To examine effects of caffeine and PBM on AKI in rats, Day 7 pups underwent a HIE intervention (Modified Rice-Vannucci model) replicating pathology observed in humans. Caffeine was administered for 3 days and/or PBM for 5 days following HIE. Weights and urine for biomarkers (NGAL, albumin, KIM-1, osteopontin) were collected prior to HIE, daily post intervention and at sacrifice. Both treatments reduced kidney injury seen on electron microscopy, but not when combined. HIE elevated urinary NGAL and albumin on Days 1-3 post-HIE, before returning to control levels. This elevation was significantly reduced by PBM or caffeine. KIM-1 was significantly elevated for 7 days post-HIE and was reduced by both treatments. Osteopontin was not altered by HIE or the treatments. Treatments, individually but not in combination, improved HIE-induced reductions in the enzymatic activity of mitochondrial complexes II-III. PBM and caffeine also improved weight gain. PBM and caffeine reduces AKI diagnosed by urinary biomarkers and confirmed by EM findings.

Adaptations of an Effective Evidence-Based Pediatric Weight Management Intervention.

Current childhood obesity treatment programs do not address medically underserved populations or settings where all members of an interdisciplinary team may not exist-either within one organization or within the community. In this paper, we describe the use of a community-academic partnership to iteratively adapt Epstein's Traffic Light Diet (TLD), into Building Healthy Families (BHF), a community-placed evidence-based pediatric weight management intervention (PWMI) and evaluate its effectiveness in reducing BMI z scores. Nine cohorts of families completed BHF. Participants included children aged 6-12 years with obesity (M = 9.46, SD = 1.74). The Framework for Reporting Adaptations and Modifications-Expanded guided our classification of modifications across BHF cohorts. Using the FRAME reporting structure, the changes that were documented were (1) planned and occurred pre-implementation, (2) based on decisions from local stakeholders (e.g., school administrator, members of the implementation team), and (3) specific to changes in content and context-with a focus on implementation and potential for local scale-up. The nature of the adaptations included adding elements (whole of family approach), removing elements (calorie counting), and substituting elements (steps for minutes of physical activity). Across 9 cohorts, 84 families initiated the BHF program, 69 families successfully completed the 12-week program, and 45 families returned for 6-month follow-up assessments. Results indicated that the BMI z score in children was reduced by 0.31 ± 0.17 at 6 months across all cohorts. Reduction in BMI z score ranged from 0.41 in cohort 4 to 0.13 in cohort 5. Iterative adaptations to BHF were completed to improve the fit of BHF to the setting and participants and have contributed to a sustained community PWMI that adheres to the underlying principles and core elements of other evidence-based PWMIs. Monitoring adaptations and related changes to outcomes can play a role in long-term sustainability and effectiveness.

Endocytosed silver nanoparticles degrade in lysosomes to form secondary nanoparticle structures during expression of autophagy genes in osteogenic cells.

Silver nanoparticles (AgNPs) are increasingly used in combination with biomaterials, such as bone grafts, to provide antimicrobial properties. Our research focused on the cytotoxic and intracellular uptake mechanism of AgNPs on osteogenic cells, and the affected gene expression of osteoblasts exposed to AgNPs. Osteoblast cells were found to be relatively resistant to AgNP exposure, compared to osteoclasts, with a higher IC50 and fewer adverse morphological features. AgNPs were endocytosed within lysosomes, which resulted in the secondary internal formation of curved AgO nano-chains assemblies within the cytosol. Furthermore, osteoblasts demonstrated an oxidative stress response, with autophagic cell death mechanisms, as indicated from qRT2-PCR analysis, with sustained upregulation of the protective gene Heme Oxygenase 1 reaching 86-fold by 48 hours (10 µg/mL). The internalization and fate of AgNPs in osteogenic cells, and the resulting impact on gene expression over time provide further understanding of the nanotoxicity mechanism of AgNPs.

Women's mobility and transport in the peripheries of three African cities: Reflecting on early impacts of COVID-19.

This paper reflects on the mobility experiences of women in African cities in COVID-19, based on research conducted both prior to and following entry into the COVID-19 'moment'. It draws on material collected during an ongoing action research study aimed at addressing the everyday transport and mobility challenges faced by young women living in poor peripheral communities of three African cities - Abuja, Cape Town and Tunis. The project has the specific objective of supporting young women's improved access to employment opportunities through trialling various mobility/transport-related skills interventions (based on prior in-depth analysis of mobility constraints). With the onset of COVID-19 some readjustments to the research focus and planned interventions became necessary. The research teams, together with an NGO partner, are now working to chart how young women's everyday experiences of mobility and transport - both as transport users and as transport sector workers - are changing as processes of lockdown and their relaxation evolve. The paper covers the period from early 2019 through to March 2021, and offers reflections regarding 'lived experiences' of mobility practice pre-pandemic, during the pandemic, and the potential longer-term mobility-related impacts for women resident in low-income neighbourhoods in a post-COVID-19 era. This leads to consideration of key policy lessons. There is potential for prioritisation of Non-Motorised Transport interventions towards a green restart that would benefit women (for instance through promoting women's cycling), and for growing women's participation as transport operators, even perhaps the usage of drones to aid women's safer pedestrian travel. But such interventions will require far greater representation of women in COVID-19 and wider transport decision-making entities than has hitherto been the case.

Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy-dependent modification of the keratinocyte immunophenotype.

BACKGROUND: Atopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of T helper (Th)1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced our understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict the importance of a specific pathway in AD or cellular responses to different inflammatory stimuli. OBJECTIVES: To understand changes in keratinocyte transcriptomic programmes in human cutaneous disease during development of inflammation and in response to treatment. METHODS: We performed in silico deconvolution of the whole-skin transcriptome. Using co-expression clustering and machine-learning tools, we resolved the gene expression of bulk skin (seven datasets, n = 406 samples), firstly, into keratinocyte phenotypes identified by unsupervised clustering and, secondly, into 19 cutaneous cell signatures of purified populations from publicly available datasets. RESULTS: We identify three unique transcriptomic programmes in keratinocytes - KC1, KC2 and KC17 - characteristic of immune signalling from disease-associated Th cells. We cross-validate those signatures across different skin inflammatory conditions and disease stages and demonstrate that the keratinocyte response during treatment is therapy dependent. Broad-spectrum treatment with ciclosporin ameliorated the KC17 response in AD lesions to a nonlesional immunophenotype, without altering KC2. Conversely, the specific anti-Th2 therapy, dupilumab, reversed the KC2 immunophenotype. CONCLUSIONS: Our analysis of transcriptomic signatures in cutaneous disease biopsies reveals the effect of keratinocyte programming in skin inflammation and suggests that the perturbation of a single axis of immune signal alone may be insufficient to resolve keratinocyte immunophenotype abnormalities.

Anti-biofilm activity of silver nanoparticle-containing glass ionomer cements.

OBJECTIVE: To develop a silver nanoparticle (AgNP) formulation for incorporation into glass ionomer cements (GICs) which minimises biofilm growth on restoration surfaces. METHODS: GICs, Fuji IX, Ketac Molar, and Riva Selfcure were modified with 6, 10 and 24 µg per GIC capsule of α-lipoic acid-capped AgNPs. Monoculture biofilms of Streptococcus mutans were cultured (72 h) on GIC specimens (n = 3) and biofilm accumulation was quantified using a viability stain with confocal laser scanning microscopy. Compression strength and flexural strength (CS & FS) were measured according to ISO 9917-1:2007 (n = 8, n = 25). GIC colour was measured at 0, 1, and 14 days following AgNP incorporation using a digital spectrophotometer. Silver release from AgNP-modified GIC specimens was monitored at 1, 3, 7 and 14 days using inductively coupled plasma-mass spectrometry. RESULTS: AgNP-modified Fuji IX demonstrated the greatest reduction in biofilm accumulation, with 10 µg Ag/capsule inhibiting biofilm formation by 99%. Ketac Molar and Riva Selfcure required 24 µg Ag/capsule to achieve 78% biofilm reduction. AgNP-modified GICs demonstrated significantly higher CS and FS than sintered silver-containing GICs, and possessed equivalent or higher strength values when compared to unmodified GICs. The colour shades of AgNP-modified GICs were more comparable to VITA shades of non-modified GICs than were sintered silver-containing GICs. The silver (≥99.6%) remained within the GIC for at least two weeks following incorporation. SIGNIFICANCE: AgNP-modified GICs exhibited significant antibiofilm activity and retained mechanical properties equivalent or superior to non-modified GICs. AgNP-modified GICs could reduce bacterial colonisation on and around restorations thereby reducing restoration failure caused by secondary caries.

Cross-Canada differences in early-stage breast cancer treatment and acute-care use.

Background: Chemotherapy has improved outcomes in early-stage breast cancer, but treatment practices vary, and use of acute care is common. We conducted a pan-Canadian study to describe treatment differences and the incidence of emergency department visits (edvs), edvs leading to hospitalization (edvhs), and direct hospitalizations (hs) during adjuvant chemotherapy. Methods: The cohort consisted of women diagnosed with early-stage breast cancer (stages i-iii) during 2007-2012 in British Columbia, Manitoba, Ontario, or Nova Scotia who underwent curative surgery. Parallel provincial analyses were undertaken using linked clinical, registry, and administrative databases. The incidences of edvs, edvhs, and hs in the 6 months after treatment initiation were examined for patients treated with adjuvant chemotherapy. Results: The cohort consisted of 50,224 patients. The proportion of patients who received chemotherapy varied by province, with Ontario having the highest proportion (46.4%), and Nova Scotia, the lowest proportion (38.0%). Age, stage, receptor status, comorbidities, and geographic location were associated with receipt of chemotherapy in all provinces. Ontario had the highest proportion of patients experiencing an edv (36.1%), but the lowest proportion experiencing h (6.4%). Conversely, British Columbia had the lowest proportion of patients experiencing an edv (16.0%), but the highest proportion experiencing h (26.7%). The proportion of patients having an edvh was similar across provinces (13.9%-16.8%). Geographic location was associated with edvs, edvhs, and hs in all provinces. Conclusions: Intra- and inter-provincial differences in the use of chemotherapy and acute care were observed. Understanding variations in care can help to identify gaps and opportunities for improvement and shared learnings.

Clinical development of targeted and immune based anti-cancer therapies.

Cancer is currently the second leading cause of death globally and is expected to be responsible for approximately 9.6 million deaths in 2018. With an unprecedented understanding of the molecular pathways that drive the development and progression of human cancers, novel targeted therapies have become an exciting new development for anti-cancer medicine. These targeted therapies, also known as biologic therapies, have become a major modality of medical treatment, by acting to block the growth of cancer cells by specifically targeting molecules required for cell growth and tumorigenesis. Due to their specificity, these new therapies are expected to have better efficacy and limited adverse side effects when compared with other treatment options, including hormonal and cytotoxic therapies. In this review, we explore the clinical development, successes and challenges facing targeted anti-cancer therapies, including both small molecule inhibitors and antibody targeted therapies. Herein, we introduce targeted therapies to epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), anaplastic lymphoma kinase (ALK), BRAF, and the inhibitors of the T-cell mediated immune response, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein-1 (PD-1)/ PD-1 ligand (PD-1 L).

The metastasis suppressor, NDRG1, differentially modulates the endoplasmic reticulum stress response.

The metastasis suppressor, N-myc downstream regulated gene-1 (NDRG1), is a stress response protein that is involved in the inhibition of multiple oncogenic signaling pathways. Initial studies have linked NDRG1 and the endoplasmic reticulum (ER) stress response. Considering this, we extensively examined the mechanism by which NDRG1 regulates the ER stress response in pancreatic and colon cancer cells. We also examined the anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), which induces NDRG1 expression and causes ER stress. The expression of NDRG1 was demonstrated to regulate the three main arms of the ER stress response by: (1) increasing the expression of three major ER chaperones, binding immunoglobulin protein (BiP), calreticulin, and calnexin; (2) suppressing the protein kinase, RNA-activated (PKR)-like ER kinase (PERK); (3) inhibiting the inositol-requiring kinase 1α (IRE1α) arm; and (4) increasing the cleavage of activating transcription factor 6 (ATF6). An important finding was that NDRG1 enhances the anti-proliferative and anti-migratory activity of Dp44mT. This increased efficacy could be related to the following effects in the presence of Dp44mT and NDRG1, namely: markedly increased activation of the PERK target, eukaryotic translation initiation factor 2α (eIF2α); the maintenance of activating transcription factor 4 (ATF4) expression; high cytosolic Ca+2 that increases the sensitivity of cells to apoptosis via activation of the calmodulin-dependent kinase II (CaMKII) signaling cascade; and increased pro-apoptotic C/EBP-homologous protein (CHOP) expression. Collectively, this investigation dissects the molecular mechanisms through which NDRG1 manipulates the ER stress response and its ability to potentiate the activity of the potent anti-cancer agent, Dp44mT.

ORE identifies extreme expression effects enriched for rare variants.

MOTIVATION: Non-coding rare variants (RVs) may contribute to Mendelian disorders but have been challenging to study due to small sample sizes, genetic heterogeneity and uncertainty about relevant non-coding features. Previous studies identified RVs associated with expression outliers, but varying outlier definitions were employed and no comprehensive open-source software was developed. RESULTS: We developed Outlier-RV Enrichment (ORE) to identify biologically-meaningful non-coding RVs. We implemented ORE combining whole-genome sequencing and cardiac RNAseq from congenital heart defect patients from the Pediatric Cardiac Genomics Consortium and deceased adults from Genotype-Tissue Expression. Use of rank-based outliers maximized sensitivity while a most extreme outlier approach maximized specificity. Rarer variants had stronger associations, suggesting they are under negative selective pressure and providing a basis for investigating their contribution to Mendelian disorders. AVAILABILITY AND IMPLEMENTATION: ORE, source code, and documentation are available at https://pypi.python.org/pypi/ore under the MIT license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The role of scientific evidence in decisions to adopt complex innovations in cancer care settings: a multiple case study in Nova Scotia, Canada.

BACKGROUND: Health care delivery and outcomes can be improved by using innovations (i.e., new ideas, technologies, and practices) supported by scientific evidence. However, scientific evidence may not be the foremost factor in adoption decisions and is rarely sufficient. The objective of this study was to examine the role of scientific evidence in decisions to adopt complex innovations in cancer care. METHODS: Using an explanatory, multiple case study design, we examined the adoption of complex innovations in five purposively sampled cases in Nova Scotia, Canada. Data were collected via documents and key informant interviews. Data analysis involved an in-depth analysis of each case, followed by a cross-case analysis to develop theoretically informed, generalizable knowledge on the role of scientific evidence in innovation adoption that may be applied to similar settings and contexts. RESULTS: The analyses identified key concepts alongside important caveats and considerations. Key concepts were (1) scientific evidence underpinned the adoption process, (2) evidence from multiple sources informed decision-making, (3) decision-makers considered three key issues when making decisions, and (4) champions were essential to eventual adoption. Caveats and considerations related to the presence of urgent problems and short-term financial pressures and minimizing risk. CONCLUSIONS: The findings revealed the different types of issues decision-makers consider while making these decisions and why different sources of evidence are needed in these processes. Future research should examine how different types of evidence are legitimized and why some types are prioritized over others.

Contributions of biogenic material to the atmospheric ice-nucleating particle population in North Western Europe.

A minute fraction of atmospheric particles exert a disproportionate effect on the phase of mixed-phase clouds by acting as ice-nucleating particles (INPs). To understand the effects of these particles on weather and climate, both now and into the future, we must first develop a quantitative understanding of the major INP sources worldwide. Previous work has demonstrated that aerosols such as desert dusts are globally important INPs, but the role of biogenic INPs is unclear, with conflicting evidence for their importance. Here, we show that at a temperate site all INPs active above -18 °C at concentrations >0.1 L-1 are destroyed on heating, consistent with these INPs being of biological origin. Furthermore, we show that a global model of desert dust INPs dramatically underestimates the measured INP concentrations, but is consistent with the thermally-stable component. Notably, the heat sensitive INPs are active at temperatures where shallow cloud layers in Northern Europe are frequently observed to glaciate. Hence, we suggest that biogenic material is important for primary ice production in this region. The prevalence of heat sensitive, most likely biogenic, INPs in this region highlights that, as a community, we need to quantify the sources and transport of these particles as well as determine their atmospheric abundance across the globe and at cloud altitudes.

E×B Flux Driven Detachment Bifurcation in the DIII-D Tokamak.

A bifurcative step transition from low-density, high-temperature, attached divertor conditions to high-density, low-temperature, detached divertor conditions is experimentally observed in DIII-D tokamak plasmas as density is increased. The step transition is only observed in the high confinement mode and only when the B×∇B drift is directed towards the divertor. This work reports for the first time a theoretical explanation and numerical simulations that qualitatively reproduce this bifurcation and its dependence on the toroidal field direction. According to the model, the bifurcation is primarily driven by the interdependence of the E×B-drift fluxes, divertor electric potential structure, and divertor conditions. In the attached conditions, strong potential gradients in the low field side (LFS) divertor drive E×B-drift flux towards the high field side divertor, reinforcing low density, high temperature conditions in the LFS divertor leg. At the onset of detachment, reduction in the potential gradients in the LFS divertor leg reduce the E×B-drift flux as well, such that the divertor plasma evolves nonlinearly to high density, strongly detached conditions. Experimental estimates of the E×B-drift fluxes, based on divertor Thomson scattering measurements, and their dependence on the divertor conditions are qualitatively consistent with the numerical predictions. The implications for divertor power exhaust and detachment control in the next step fusion devices are discussed.

Eastern Canadian Colorectal Cancer Consensus Conference 2017.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

Patterns of cancer centre follow-up care for survivors of breast, colorectal, gynecologic, and prostate cancer.

BACKGROUND: Rising demand on cancer system resources, alongside mounting evidence that demonstrates the safety and acceptability of primary care-led follow-up care, has resulted in some cancer centres discharging patients back to primary care after treatment. At the same time, the ways in which routine cancer follow-up care is provided across Canada continue to vary widely. The objectives of the present study were to investigate patterns of routine follow-up care at a cancer centre for breast, colorectal, gynecologic, and prostate cancer survivors; factors associated with receipt of follow-up care at a cancer centre; and changes in follow-up care at a cancer centre over time. METHODS: We identified all people diagnosed in Nova Scotia with an invasive breast, colorectal, gynecologic, or prostate cancer between 1 January 2006 and 31 December 2013. We linked the resulting population-based dataset, at the patient level, to cancer centre or clinic data and to census data. We identified a nonmetastatic survivor cohort (n = 12,267) and developed decision rules to differentiate routine from non-routine visits during the follow-up care period (commencing 1 year after diagnosis). Descriptive statistics were computed to describe the patterns of routine follow-up care at a cancer centre. Negative binomial regression was used to examine factors associated with visits made and changes over time. RESULTS: Nearly half the survivors (48.4%) had at least 1 follow-up visit to the cancer centre, with variation by disease site (range: 30.2%-62.4%). Disease site and stage at diagnosis were associated with receipt of follow-up care at a cancer centre. For instance, compared with breast cancer survivors, survivors of gynecologic cancer had more visits [incidence rate ratio (irr): 1.48; 95% confidence interval (ci): 1.34 to 1.64], and survivors of colorectal cancer had fewer visits (irr: 0.45; 95% ci: 0.40 to 0.51). Year of diagnosis was associated with follow-up at a cancer centre, with each successive calendar year being associated with an 8% increase in visits made (irr: 1.08; 95% ci: 1.07 to 1.10). CONCLUSIONS: Despite evidence that follow-up care can be effectively and safely delivered in primary care, and despite intensifying demands on oncology services, many survivors continue to receive routine follow-up care at a cancer centre.

Use of physician services during the survivorship phase: a multi-province study of women diagnosed with breast cancer.

INTRODUCTION: Oncologists have traditionally been responsible for providing routine follow-up care for cancer survivors; in recent years, however, primary care providers (pcps) are taking a greater role in care during the follow-up period. In the present study, we used a longitudinal multi-province retrospective cohort study to examine how primary care and specialist care intersect in the delivery of breast cancer follow-up care. METHODS: Various databases (registry, clinical, and administrative) were linked in each of four provinces: British Columbia, Manitoba, Ontario, and Nova Scotia. Population-based cohorts of breast cancer survivors were identified in each province. Physician visits were identified using billings or claims data and were classified as visits to primary care (total, breast cancer-specific, and other), oncology (medical oncology, radiation oncology, and surgery), and other specialties. The mean numbers of visits by physician type and specialty, or by combinations thereof, were examined. The mean numbers of visits for each follow-up year were also examined by physician type. RESULTS: The results showed that many women (>64%) in each province received care from both primary care and oncology providers during the follow-up period. The mean number of breast cancer-specific visits to primary care and visits to oncology declined with each follow-up year. Interprovincial variations were observed, with greater surgeon follow-up in Nova Scotia and greater primary care follow-up in British Columbia. Provincial differences could reflect variations in policies and recommendations, relevant initiatives, and resources or infrastructure to support pcp-led follow-up care. CONCLUSIONS: Optimizing the role of pcps in breast cancer follow-up care might require strategies to change attitudes about pcp-led follow-up and to better support pcps in providing survivorship care.

Replacing sedentary time with sleep, light, or moderate-to-vigorous physical activity: effects on self-regulation and executive functioning.

Recent attention has highlighted the importance of reducing sedentary time for maintaining health and quality of life. However, it is unclear how changing sedentary behavior may influence executive functions and self-regulatory strategy use, which are vital for the long-term maintenance of a health behavior regimen. The purpose of this cross-sectional study is to examine the estimated self-regulatory and executive functioning effects of substituting 30 min of sedentary behavior with 30 min of light activity, moderate-to-vigorous physical activity (MVPA), or sleep in a sample of older adults. This study reports baseline data collected from low-active healthy older adults (N = 247, mean age 65.4 ± 4.6 years) recruited to participate in a 6 month randomized controlled exercise trial examining the effects of various modes of exercise on brain health and function. Each participant completed assessments of physical activity self-regulatory strategy use (i.e., self-monitoring, goal-setting, social support, reinforcement, time management, and relapse prevention) and executive functioning. Physical activity and sedentary behaviors were measured using accelerometers during waking hours for seven consecutive days at each time point. Isotemporal substitution analyses were conducted to examine the effect on self-regulation and executive functioning should an individual substitute sedentary time with light activity, MVPA, or sleep. The substitution of sedentary time with both sleep and MVPA influenced both self-regulatory strategy use and executive functioning. Sleep was associated with greater self-monitoring (B = .23, p = .02), goal-setting (B = .32, p < .01), and social support (B = .18, p = .01) behaviors. Substitution of sedentary time with MVPA was associated with higher accuracy on 2-item (B = .03, p = .01) and 3-item (B = .02, p = .04) spatial working memory tasks, and with faster reaction times on single (B = -23.12, p = .03) and mixed-repeated task-switching blocks (B = -27.06, p = .04). Substitution of sedentary time with sleep was associated with marginally faster reaction time on mixed-repeated task-switching blocks (B = -12.20, p = .07) and faster reaction time on mixed-switch blocks (B = 17.21, p = .05), as well as reduced global reaction time switch cost (B = -16.86, p = .01). Substitution for light intensity physical activity did not produce significant effects. By replacing sedentary time with sleep and MVPA, individuals may bolster several important domains of self-regulatory behavior and executive functioning. This has important implications for the design of long-lasting health behavior interventions. Trial Registration clinicaltrials.gov identifier NCT00438347.

Tumour assessment and staging: United Kingdom National Multidisciplinary Guidelines.

In general, the first decision to be made in a patient with a confirmed head and neck cancer is whether or not to treat the patient before deciding what form of management strategy is appropriate. There is no more important an aspect of head and neck cancer care than the initial evaluation of the patient and the patient's tumour. The practice requires specific expertise and judgement. The current tumour-node-metastasis system relies on morphology of the tumour (anatomical site and extent of disease) but the final decision on treatment hinges on a full assessment of the patient including physiological age and general condition. The aim of this paper is primarily to describe why and how we appraise a patient and their tumour. It addresses the general principles applicable to the topic of evaluation, classification and staging. In addition, the limitations and pitfalls of this process are described. Recommendations • All patients with head and neck cancer (HNC) should undergo tumour classification and staging prior to treatment. (R) • Pre-therapeutic clinical staging of HNCs should be based on at least a C2 factor (evidence obtained by special diagnostic means, e.g. radiographic imaging (e.g. computed tomography, magnetic resonance imaging or ultrasound scan), endoscopy, biopsy and cytology). (R) • Imaging to evaluate the primary site should be performed prior to biopsy to avoid the effect of upstaging from the oedema caused by biopsy trauma. (G) • Panendoscopy is only recommended for symptomatic patients or patients with primary tumours known to have a significant risk of a second (synchronous) primary tumour. (G).

Effects of a DVD-delivered exercise program on patterns of sedentary behavior in older adults: a randomized controlled trial.

INTRODUCTION: In the present study, we examined the influence of a home-based, DVD-delivered exercise intervention on daily sedentary time and breaks in sedentary time in older adults. METHODS: Between 2010 and 2012, older adults (i.e., aged 65 or older) residing in Illinois (N = 307) were randomized into a 6-month home-based, DVD-delivered exercise program (i.e., FlexToBa; FTB) or a waitlist control. Participants completed measurements prior to the first week (baseline), following the intervention period (month 6), and after a 6 month no-contact follow-up (month 12). Sedentary behavior was measured objectively using accelerometers for 7 consecutive days at each time point. Differences in daily sedentary time and breaks between groups and across the three time points were examined using mixed-factor analysis of variance (mixed ANOVA) and analysis of covariance (ANCOVA). RESULTS: Mixed ANOVA models revealed that daily minutes of sedentary time did not differ by group or time. The FTB condition, however, demonstrated a greater number of daily breaks in sedentary time relative to the control condition (p = .02). ANCOVA models revealed a non-significant effect favoring FTB at month 6, and a significant difference between groups at month 12 (p = .02). CONCLUSIONS: While overall sedentary time did not differ between groups, the DVD-delivered exercise intervention was effective for maintaining a greater number of breaks when compared with the control condition. Given the accumulating evidence emphasizing the importance of breaking up sedentary time, these findings have important implications for the design of future health behavior interventions.