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Additional file 5. Guelph Family Health Study consortium members.

The transport of energy and information in semiconductors is limited by scattering between electronic carriers and lattice phonons, resulting in diffusive and lossy transport that curtails all semiconductor technologies. Using Re6Se8Cl2, a van der Waals (vdW) superatomic semiconductor, we demonstrate the formation of acoustic exciton-polarons, an electronic quasiparticle shielded from phonon scattering. We directly image polaron transport in Re6Se8Cl2 at room temperature and reveal quasi-ballistic, wavelike propagation sustained for nanoseconds and several microns. Shielded polaron transport leads to electronic energy propagation orders of magnitude greater than in other vdW semiconductors, exceeding even silicon over nanoseconds. We propose that, counterintuitively, quasi-flat electronic bands and strong exciton-acoustic phonon coupling are together responsible for the remarkable transport properties of Re6Se8Cl2, establishing a new path to ballistic room-temperature semiconductors.

Additional file 1. Stepwise determination of free sugars from ASA24-Canada-2016 data.

Additional file 4. Snack intake by major and minor snack categories and their contribution to free sugar energy intake among children.

Additional file 2. Categories and subcategories of snacks and beverages (Adapted from Bernstein et al., 2016).

Additional file 3. Participant flow chart.

Additional file1. Appendix A: Embase search strategy for literature mapping exercise. Appendix B: Ovid MEDLINE search strategy for systematic review. Appendix C: Full results from literature mapping exercise. Appendix D: Risk of bias and measurement property appraisal results. Appendix E: Data extraction table of measurement properties.

This thesis investigated free sugar (FS) intake from snacks and beverages among young Canadian children and compared intake with World Health Organization recommendations that FS intake be limited to

A nomogram was recently published by Sun et al. to predict overall survival (OS) and the additional benefit of concurrent chemoradiation (CCRT) vs. radiotherapy (RT) alone, in stage II NPC treated with conventional RT. We aimed to assess the predictors of OS and to externally validate the nomogram in the IMRT era. We analyzed stage II NPC patients treated with definitive RT alone or CCRT between 2001 and 2011 under the territory-wide Hong Kong NPC Study Group 1301 study. Clinical parameters were studied using the Cox proportional hazards model to estimate OS. The nomogram by Sun et al. was applied with 1000 times bootstrap resampling to calculate the concordance index, and we compared the nomogram predicted and observed 5-year OS. There were 482 patients included. The 5-year OS was 89.0%. In the multivariable analysis, an age &gt, 45 years was the only significant predictor of OS (HR, 1.98, 95%CI, 1.15–3.44). Other clinical parameters were insignificant, including the use of CCRT (HR, 0.99, 95%CI, 0.62–1.58). The nomogram yielded a concordance index of 0.55 (95% CI, 0.49–0.62) which lacked clinically meaningful discriminative power. The nomogram proposed by Sun et al. should be interpreted with caution when applied to stage II NPC patients in the IMRT era. The benefit of CCRT remained controversial.

Magnetic semiconductors are a powerful platform for understanding, utilizing and tuning the interplay between magnetic order and electronic transport. Compared to bulk crystals, two-dimensional magnetic semiconductors have greater tunability, as illustrated by the gate modulation of magnetism in exfoliated CrI$_3$ and Cr$_2$Ge$_2$Te$_6$, but their electrically insulating properties limit their utility in devices. Here we report the simultaneous electrostatic and magnetic control of electronic transport in atomically-thin CrSBr, an A-type antiferromagnetic semiconductor. Through magnetotransport measurements, we find that spin-flip scattering from the interlayer antiferromagnetic configuration of multilayer flakes results in giant negative magnetoresistance. Conversely, magnetoresistance of the ferromagnetic monolayer CrSBr vanishes below the Curie temperature. A second transition ascribed to the ferromagnetic ordering of magnetic defects manifests in a large positive magnetoresistance in the monolayer and a sudden increase of the bulk magnetic susceptibility. We demonstrate this magnetoresistance is tunable with an electrostatic gate, revealing that the ferromagnetic coupling of defects is carrier mediated.

e18029 Background: Patients with recurrent or metastatic nasopharyngeal cancer (R/M NPC) who failed platinum-based chemotherapy have poor prognoses. We report the clinical activity and safety of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor (TGF)-βRII receptor fused to a human IgG1 antibody blocking programmed death-ligand 1 (PD-L1), in patients with heavily pretreated R/M NPC. Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Methods: Eligible patients had histologically confirmed NPC that had recurred at distant sites and were not amenable to curative treatment. All patients received at least one prior line of platinum-based chemotherapy for recurrent disease. Patients were treated with bintrafusp alfa (1200mg every 2 weeks) until disease progression. The sample size was estimated to assume a 40% objective response rate (ORR) to bintrafusp alfa compared with 20% for checkpoint inhibitors. Modified Simon two-stage optimal design was used (power, 80%; a = 0.05; P0 = 0.20; P1 = 0.40; n1 = 18; n = 33 with an additional five patients to allow for ineligibility or other reasons). The primary endpoint was ORR and secondary endpoints included survival and toxicity. Expression of PD-L1 in archived tumors, plasma clearance of Epstein-Barr virus (EBV) DNA, plasma clearance of TGF-β, and exosomal PD-L1 were assessed for a potential correlation with ORR. (NCT 04396886). Results: Out of 43 patients screened, 38 patients were enrolled. After a median follow-up of 14.9 months (range: 1.6-23.3 months), the confirmed ORR was 23.7% (95% CI: 12.4-38.8%) (complete response, n = 1; partial response, n = 8). The median treatment duration was 1.8 months (range: 0.5-14.3 months). 8 patients (21.1%) and 2 patients (5.3%) received bintrafusp alfa for > 6 months and > 12 months respectively. The 1-year overall survival (OS) rate was 57.5% (95% CI, 40.2% to 71.5%) and 1-year progression-free survival rate was 23% (95% CI, 10.1% to 39.4%). ORR was higher in patients with a decreasing trend in EBV-DNA at week 4 (40% vs. 6.3%, p = 0.02), whereas high exosomal PD-L1 levels at week 4 were predictive of worse ORR (5.3% vs. 41.7%, p = 0.012). There were no associations between clinical outcome and tissue PD-L1 expression (p = 0.952) or plasma TGF-β clearance (p = 0.28). 16 patients (42.4%) experienced ≥ grade 3 treatment-related adverse events, most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). Conclusions: Bintrafusp alfa has promising activity in heavily pretreated R/M NPC and a favorable 1-year OS rate, though the observed activity was not as high as the study initially aimed. The biomarker results warrant validation in larger cohorts. Clinical trial information: NCT04396886.

Urbanisation and climate change are expected to introduce novel public health, environmental, and sustainability challenges. Epidemiological studies indicate that climate and public health vulnerabilities vary by neighbourhood. However, data at these spatial levels are largely unavailable despite studies demonstrating that geographically aggregated data mask disparities. To address this gap, this dissertation developed and applied high resolution geospatial vulnerability and health indicators across British Columbia (BC), Canada. The first dataset applied principal components analysis to more than 30 measures to map exposures, population sensitivities, adaptive capacities, and overall vulnerabilities of four climate hazards (extreme heat, inland flooding and sea level rise, wildfire smoke, and ground-level ozone) across 4188 dissemination areas in two health regions. A principal components analysis revealed varied opportunities for adaptive capacities across all hazards (16%-47% contribution to variation in overall vulnerability), with the greatest contribution found for flooding (47%). Overall, sensitivity explained the most variance, suggesting strategies targeting age and those with pre-existing health conditions in public health and emergency responses. Building on this result, the second dataset linked mortality data and sociodemographic information in a Bayesian small area model to estimate life expectancy (LE) at birth and 20 causes of mortality over 27 years across 368 Census Tracts (CTs) in Metro Vancouver, BC. The dataset identified spatial LE gaps of more than 10 years that widened in recent years. Absolute inequalities decreased for all diseases except for neoplasms, but relative inequalities increased for all causes. In the final study, difference-in-differences models were applied to the small area mortality data to evaluate relationships with population density and sociodemographic measures to assess optimum density levels, and the effects of density changes over time. At densities above ~9,400 persons per km2, LE began to decrease more rapidly. By cause, densification was linked to decreased mortality for major causes of mortality in the region, such as cardiovascular diseases, neoplasms, and diabetes. Through these three studies, this dissertation provided evidence for the importance of local-level indicators of health, vulnerability, and built environment variables for future and ongoing surveillance of healthy and resilient cities.

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Artificial neural networks (ANNs) are popular machine learning techniques used to model autonomous agents. Spiking neural networks (SNNs) provide the ability to reproduce spatio-temporal dynamics by transmitting information through action potentials or spikes. Given their more biologically realistic characteristic, they are particularly attractive for modelling biological systems, including the analysis and understanding of biological self organisation. As with many neural models, the difficulty in achieving the desired performance is finding the appropriate parameters settings. A commonly used autonomous approach is given by genetic algorithms (GAs), which provide an evolution-based search technique inspired by natural adaptation processes. The performance of these meta-heuristic search techniques depends on the settings of its hyperparameters, which present a challenging task on their own.In this work, a multi-agent simulation model embedded in NetLogo is investigated. It simulates an artificial ant navigating through a virtual maze with many obstacles in search of food. Through this process the ant is controlled by an SNN, whose parameter optimisation is examined and optimised in this thesis using GAs of two different tools (L2L and BehaviorSearch). Afterwards, a deeper investigation on the optimized SNNs is covered to understand and explain the observed behavior in the simulation.

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Older adults are faced with an increased risk of comorbid chronic disease such as diabetes. While multiple health behavior change interventions (MHCIs) are known to improve clinical outcomes more than targeted interventions, less is known whether such effects persist in older populations. The objective of the study was to examine the effects of multiple chronic condition (CC) remote monitoring program enrollment and mental health program enrollment on glucose and blood pressure reduction, adjusting for self-monitoring behaviors. In a sample of 594 older adults (age 55+, 14% 65+ years, 46.8% female) evaluated over a 12-month period, statistical models showed that older adults with uncontrolled diabetes (A1c >= 7.0%) had a 7.9 pt. reduction in blood glucose for each additional program enrolled and a 22.7 pt. reduction in blood glucose when enrolled in mental health compared to those not enrolled. Similarly, older adults with uncontrolled hypertension (BP >= 130/80) had a 4.8 pt. reduction in systolic blood pressure for each additional program enrolled and a 7.2 pt. reduction in systolic blood pressure when enrolled in mental health compared to those not enrolled. The findings indicate the potential for multiprogram digital health interventions that incorporate mental health to further improve clinical outcomes in older adults suffering from multiple chronic diseases, namely diabetes and hypertension.

Additional file 3. Informed Consent Form.

Additional file 1. SPIRIT checklist.

Additional file 2. WHO Trial Registration Data Set - Structured Summary.

A summary document highlighting the results of a vulnerability assessment of climate-related health hazards in the Vancouver Coastal Health and Fraser Health regions. This vulnerability assessment of climate-related health hazards was developed with the financial support of Vancouver Coastal Health.

Additional file 4. Surveys and DASH Questionnaire.

Objective. To characterize educational attainment and experiences of current US pharmacy school deans and chairs. Methods. A cross-sectional study using a publicly available listing of accredited schools and information. Results. Among 134 deans and 301 chairs, 79.9% and 65.5% held a professional degree (BSPharm and/or PharmD), 33.6% and 26.2% completed PGY-1 residencies, 12.7% and 15.6% completed post-PharmD fellowships, 23.1% and 33.9% completed post-doctoral fellowships, and 13.4% and 18.3% held BPS certification, respectively. Fewer than 1 in 5 were employed at an alma mater. Ninety (20.7%) deans and chairs completed AACP's Academic Leadership Fellows Program. Average current tenure was 5.7 and 5.1 years for deans and chairs, respectively. Conclusion. The majority of deans and chairs held a pharmacy professional degree and the prevalence of post-graduate educational and leadership training is increasing. Future research should apply mixed methods to investigate educational attainment and employment experience of deans and chairs, institutional hiring trends, and how these characteristics compare between newer and established programs.

Type 1 fimbriae are filamentous structures on Escherichia coli. These structures are important adherence factors. Because binding to the host cells is the first step of infection, type 1 fimbria is an important virulence factor of pathogenic E. coli. Expression of type 1 fimbria is regulated by a phase variation in which each individual bacterium can alternate between fimbriated (phase-ON) and nonfimbriated (phase-OFF) states. The phase variation is regulated by the flipping of the 314-bp fimS fragment, which contains the promoter driving the expression of the genes required for the synthesis of type 1 fimbria. Thus, the bacterial proteins able to interact with fimS are likely to be involved in regulating the expression of type 1 fimbria. To identify novel type 1 fimbria-regulating factors, we used an E. coli K12 proteome chip to screen for the bacterial factors able to interact with a 602-bp DNA fragment containing fimS and its adjacent regions. The Spr protein was identified by the proteome chip-based screening and further confirmed to be able to interact with fimS by electrophoretic mobility shift assay. Deletion of spr in the neonatal meningitis E. coli strain RS218 significantly increased the ratio of the bacterial colonies that contained the type 1 fimbria phase-ON cells on agar plates. In addition, Spr interfered with the interactions of fimS with the site-specific recombinases, FimB and FimE, which are responsible for mediating the flipping of fimS. These results suggest that Spr is involved in the regulation of type 1 fimbria expression through direct interaction with the invertible element fimS. These findings facilitate our understanding of the regulation of type 1 fimbria.

Type 2 diabetes mellitus (T2DM) is a chronic and progressive medical condition that has reached pandemic levels, currently affecting 368 million people worldwide. With previous research demonstrating that T2DM is largely irreversible, the focus is now on developing and disseminating structured diabetes self-management education and support (DSME) programs to help patients live as healthfully as possible without exacerbating their illness. In recent years, several DSME interventions have demonstrated clinically meaningful changes in T2DM patients; however, there appears to be little translation of these programs from research into real world settings because these settings often lack clear blueprints for how to create or implement DSME programs that best fit their organizational needs and structure. Thus, the current study aimed to address this research-practice gap through the development of a brief, theoretically-driven, and behaviorally-focused group-based DSME curriculum for use in real world settings. Phase 1 of the study entailed concentrated efforts to join behavioral health researchers, community health leaders, and T2DM experts in combining the Common Sense Model of Self-Regulation (a prominent health behavior theory), cognitive behavioral principles, and current guidelines from the American Diabetes Association into a novel DSME curriculum. Phase 2 of the study then focused on implementing the resulting four-session curriculum, An Active Approach to Diabetes Self-Management, in local community centers and examining its early acceptability, feasibility, and effectiveness in producing clinical and psychosocial outcomes of interest. A total of 22 adults with T2DM, ranging in age from 35 to 87 years, were recruited from four community organizations and entered into four separate groups. Results indicate statistically significant improvements in participants' glycemic control, diabetes knowledge, and diabetes self-efficacy over the course of the study. In addition, results indicate that both participants and community liaisons were highly satisfied with the intervention. These findings contribute to the field's growing knowledge of how best to capitalize on clinical, research, and real world expertise to design thoughtful and practical DSME programs.

BACKGROUND: The World Bank report warns that the poor living in informal settlements and slum conditions are the most likely to be killed or harmed by extreme weather. They are morevulnerable to disasters often due to clogged drains, land subsidence, heat waves, and increased health risks. Disaster management (DM) in slums is part of a larger development problem in developing countries. However, analytical literature on the exact link and nature of problemsfaced by slum dwellers due to climate change and disasters is scarce. More research is needed to address the gap in literature between increasing urbanisation and the implications for the urban poor in disaster management plans (DMPs). METHODOLOGY: This research was granted approval by the Hamilton Health Sciences ResearchEthics Board on May 28, 2014. In June 2014, semi-structured interviews and focus groups were conducted, including 24 interviews and 9 focus groups with community members (CMs), 12 interviews with key informants from organisations in the civil society (CSOs), and 3 interviews with Government officials (GOs). The interviews and focus groups were transcribed verbatim (to the extent possible) and imported into NVivo 10 (QSR International) for qualitative content analysis. RESULTS: Five key points were made by participants in the focus groups and interviews: 1.) Some physical and non-physical infrastructure needs were not considered by GOs and CSOs for slum upgrading, such as the repair of shelter roofs and the creation of self-formed slum groups, 2.) Bottom-up participation and citizen engagement needed to be improved during the design and implementation of DMPs, 3.) Communication was pertinent during all phases of the DM cycle, including multisectorial involvement from all three stakeholder groups, 4.) Different barrierswere raised, including urbanization and planning, which affected the required participation and communication in DM, and 5.) Even substantial levels of water in the home at 3-4 inches high were described as waterlogging rather than flooding, suggesting that disasters were being normalised. DISCUSSION AND CONCLUSION: By describing different measures and approaches that are used for and by the urban poor, new DM strategies are suggested (such as scaling up and including new components in Slum Upgrading Programs). Several recommendations were made to improve DM planning, including the need to overcome several barriers and the potential of formulating contextual DMPs (such as an Earthquake Action Plan). A novel finding was the apparent normalisation of disasters. This raises important questions about how disasters are framed in Ahmedabad and the policy solutions that result from it. Climate change was seldom noted, even though it is expected to increase the frequency and intensity of future disasters. These findings can be considered for policy makers in megacities around the world and in the post-2015 Millennium Development Goals and Hyogo Framework of Action. Thesis Master of Science (MSc)

Approximately one-third of children and teenagers between the ages of 2 and 19 living in the United States today are considered overweight or obese. Previous research suggests that parents may play a complex role in the development of childhood overweight and obesity, and that parental over-control of child eating and feeding may put a child at particular risk for increased weight. Interventions to reduce parental over-control of eating have been developed, yet a research-practice gap exists in which recruitment of parents for such interventions has proven challenging. Using a previously studied intervention (5 Keys for Happy, Healthy Family Eating) to reduce parental control over child eating as a model obesity prevention program, the current study was comprised of two inter-related sub-studies. The goal of the first was to help bridge the research-practice gap by building community-research partnerships, identifying key recruitment strategies, and interviewing parents and community stakeholders to help elucidate barriers to parent participation in prevention interventions. The goal of the second was to examine the effectiveness of 5 Keys in reducing parental over-control of eating in the sample of participants successfully recruited for the study. In the first study, 11 collaborations were built, 6 sites were particularly active in participant recruitment for 5 Keys, and 30 parents, participants, and community stakeholders were interviewed to identify key themes in parents’ hesitation to engage in prevention initiatives like 5 Keys. The following themes were identified: lack of time; parents’ desire for a “convenient” program; parents’ desire for family-based interventions; and parents’ desire for “short and sweet” solutions. In the second study, 10 overweight parents completed the 5 Keys intervention. By the end of five sessions, four of 10 demonstrated clinically meaningful reductions in parental pressure on child to eat and six of 10 demonstrated clinically meaningful reductions in parental restriction of child eating. Recommendations are made for how to engage with both community partners and parents to further refine 5 Keys and similar obesity prevention interventions and test their effectiveness and acceptability by parents and community members.

The need for the research project is driven by the Crossrail project in London for which new 7 m diameter tunnels are to be constructed close to numerous existing operational tunnels of the London Underground (LU) network. The main aim of this research is to investigate the impact of new tunnel excavations on existing tunnels. This research component is based on field instrumentation and experimental work conducted on half-scale grey cast iron (GCI) tunnel lining segments with chemical composition similar to the Victorian age GCI segments in the LU network. Currently, there is great uncertainty about the behaviour of segmental linings. General belief is that the behaviour of the lining is influenced by the behaviour of the joints, but there has been little experimental work to investigate this relationship. The laboratory experiments aim to find out the deformation behaviour of the bolted segmental lining and the influence of parameters such as overburden pressure, bolt preload and presence of grommets at small distortions. The measured behaviour of the segmental lining is compared against the theoretical behaviour of a continuous lining based on the assumption of linear elasticity. The laboratory results are used to assess the validity of the tunnel assessment methods used by the industry. The results from the parametric tests will form the basis for future experimental investigations taking the half-scale test ring to large deformations and ultimately to failure. The field component involved taking measurements of existing bolted segmental grey cast iron tunnels. Small sections of tunnels constructed at the LU Acton Depot, at Tottenham Court Road Station and in the Central Line running tunnel were monitored to gain an understanding of the deformation of tunnels from construction and self-weight, from ground loading and finally from the influence of adjacent tunnelling works. The thesis proposes recommendations for future in-tunnel monitoring based on the findings obtained in this research. Open Access

We developed a sensitive, simple, inexpensive and rapid bead-based immunoassay platform, composed of liposomal nanovesicle amplification system, Gentamycin sulfate beads and 96-well filtration plates. In the beginning of the assay, Gentamycin sulfate beads, Gentamycin sulfate and Gentamycin specific antibody were incubated in a bottom-sealed 96-well filtration plate. After incubation, washing was done by running washing buffer through the unsealed filtration plate with only gravity and the antibody-Gentamycin bead complexes were retained in the plate. Fluorescent dye-loaded protein G-liposomal nanovesicles were then added to specifically bind to antibodies on the retained beads. After washing unbound nanovesicles, millions of fluorescent dye molecules were released by adding a detergent solution to lyse liposomal nanovesicles. The limit of detection (LOD) of this novel detection platform in TBS and in skim milk were 52.65 ng/mL and 14.16 ng/mL, which are both sufficient for detecting the 200 ng/mL Codex maximum residual level (MRL). The dynamic ranges were both from each of their LODs to 100 μg/mL. The 50% inhibition concentrations (IC50) in TBS and skim milk were 199.66 ng/mL and 360.81 ng/mL, respectively. We also demonstrated the good specificity of this platform by comparing detection results between pure Gentamycin solution and a mixture solution of 6 different antibiotics including Gentamycin in skim milk. The entire assay with 60 samples was conducted within 2h. In sum, this novel biosensing platform not only fulfilled most benefits of magnetic bead-based assays, but also was inexpensive and convenient by replacing the magnetic separation with filtration plate separation.

Background: South Africa’s mineral resources have produced, and continue to produce, enormous economic wealth; yet decades of colonialism, apartheid, capital flight, and challenges in the neoliberal post-apartheid era have resulted in high rates of occupational lung disease and low rates of compensation for ex-miners and their families. Given growing advocacy and activism of current and former mine workers, initiatives were launched by the South African government in 2012 to begin to address the legacy of injustice. This study aimed to assess developments over the last 5 years in providing compensation, quantify shortfalls and explore underlying challenges. Methods: Using the database with compensable disease claims from over 200,000 miners, the medical assessment database of 400,000 health records and the employment database with 1.6 million miners, we calculated rates of claims, unpaid claims and shortfall in claim filing for each of the southern African countries with at least 25,000 miners who worked in South African mines, by disease type and gender. We also conducted interviews in Johannesburg, Eastern Cape, Lesotho and a local service unit near a mine site, supplemented by document review and auto-reflection, adopting the lens of a critical rights-based approach. Results: By the end of 2017, 111,166 miners had received compensation (of which 55,864 were for permanent lung impairment, and another 52,473 for tuberculosis), however 107,714 compensable claims remained unpaid. Many (28.4%) compensable claims are from Mozambique, Lesotho, Swaziland, Botswana and elsewhere in southern Africa, a large proportion of which have been longstanding. A myriad of diverse systemic barriers persist, especially for workers and their families outside South Africa. Calculating predicted burden of occupational lung disease compared to compensable claims paid suggests a major shortfall in filing claims in addition to the large burden of still unpaid claims. Conclusion: Despite progress made, our analysis reveals ongoing complex barriers and illustrates that the considerable underfunding of the systems required for sustained prevention and social protection (including compensation) needs urgent attention. With class action suits in the process of settlement, the globalized mining sector is now beginning to be held accountable. A critical rights-based approach underlines the importance of ongoing concerted action by all.