Analysis of data on the certificate of advanced graduate specialization program as collected by means of questionnaire

Thesis (Ed.M.)--Boston Universit

Multifunctional enzyme engineering by computational design for lignocellulosic valorization

Biomass- acting enzymes are vital components of biorefinery processes that aim to convert complex, lignocellulosic biomass into fuels, chemicals and materials and therefore, much effort has focused on the improvement of their characteristics (activity, stability, cost of production, etc) as well as on the discovery and development of novel enzymes. Metagenomic approaches revealed that in the Bacteroidetes phylum functionally related genes are often organized in characteristic clusters, known as Polysaccharide Utilization Loci (PUL) reflecting that biomass- acting enzymes act in synergy and that enzyme proximity is important to target complex substrates. In this study we designed a tailored made multifunctional enzyme, combining enzymes isolated from a xylan PUL (1). Computational simulations were performed to define and optimize engineered versions of a multi-domain GH10 endo- xylanase by replacing carbohydrate binding module (CBM) and grafting two new catalytic domains: either a GH43 xylosidase or a CE1 carbohydrate-esterase activities also present in the same PUL. The multifunctional enzymes were then experimentally assessed, demonstrating that chimeric GH10-GH43 had both activities and thus represents a powerful biological tool for hemicellulose deconstruction. Bastien, G., et al. (2013). Mining for hemicellulases in the fungus-growing termite Pseudacanthotermes militaris using functional metagenomics. Biotechnology for biofuels 6(1): 7

Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO)

INTRODUCTION: Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians' concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid-base abnormalities in children following kidney transplantation compared with current practice.The aim of the Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO) trial was to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte 148 compared with intravenous fluid currently administered. METHODS AND ANALYSIS: PLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of <135 mmol/L. Secondary outcomes include symptoms of acute hyponatraemia, other electrolyte and acid-base imbalances and transplant kidney function.The primary outcome will be analysed using a logistic regression model adjusting for donor type (living vs deceased donor), patient weight (<20 kg vs ≥20 kg pretransplant) and transplant centre as a random effect. ETHICS AND DISSEMINATION: The trial received Health Research Authority approval on 20 January 2020. Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain

Adapting and Implementing Appreciative Advising Framework to Train Orientation Leaders

Expanding upon the work of Hendley (2010) who introduced the concept of adapting the six phase Appreciative Advising framework (Bloom, Hutson, & He, 2008) to orientation leader training, this article demonstrates how to construct and implement an effective training program for orientation leaders. It provides practical application of each phase of Appreciative Advising for bother orientation training facilitators and orientation leaders. In doing so, this article demonstrates how the six phases of Appreciative Advising offer a framework that incorporates and emphasizes the development of the informational, conceptual, and relational skill sets desired from orientation leaders. This development begins during training and transcends to leaders' interaction with incoming students. Appreciative approach to training has the power to positively impact the orientation leaders as well as the new students

Effectiveness of a peer-refugee delivered psychological intervention to reduce psychological distress among adult Syrian refugees in the Netherlands: study protocol

Background: Syrian refugees face multiple hardships and adversities which put them at risk for the development of mental health problems. However, access to adequate mental health care in host countries is limited. The WHO has developed Problem Management Plus (PM+), a brief, scalable psychological intervention, delivered by non-specialist helpers, that addresses common mental disorders in people affected by adversity. This study is part of the STRENGTHS project, that aims to evaluate peer-refugee delivered psychological interventions for Syrian refugees in Europe and the Middle East. Objective: To evaluate the effectiveness and cost-effectiveness of the peer-refugee delivered PM+ intervention among Syrian refugees with elevated levels of psychological distress in the Netherlands. Methods: PM+ will be tested in a randomized controlled trial (RCT) among Arabic-speaking Syrian refugees in the Netherlands aged 18 years and above with self-reported psychological distress (Kessler Psychological Distress Scale; K10 >15) and impaired daily functioning (WHO Disability Assessment Schedule; WHODAS 2.0 >16). Participants (N = 380) will be randomized into care as usual with PM+ (CAU/PM+, n = 190) or CAU only (CAU, n = 190). Baseline, 1-week post-intervention, and 3-month and 12-month follow-up assessments will be conducted. Primary outcomes are symptoms of depression and anxiety. Secondary outcomes are functional impairment, posttraumatic stress disorder symptoms, self-identified problems, anger, health and productivity costs, and hair cortisol concentrations. A process evaluation will be carried out to evaluate treatment dose, protocol fidelity and stakeholder views on barriers and facilitators to implementing PM+. Results and Conclusions: PM+ has proved effectiveness in other populations and settings. After positive evaluation, the adapted manual and training materials for individual PM+ will be made available through the WHO to encourage further replication and scaling up. Trial registration: Trial registration Dutch Trial Registry, NL7552, registered prospectively on March 1, 2019. Medical Ethics Review Committee VU Medical Center Protocol ID 2017.320, 7 September 2017

Disrupting Bordetella Immunosuppression Reveals a Role for Eosinophils in Coordinating the Adaptive Immune Response in the Respiratory Tract.

Recent findings revealed pivotal roles for eosinophils in protection against parasitic and viral infections, as well as modulation of adaptive immune responses in the gastric mucosa. However, the known effects of eosinophils within the respiratory tract remain predominantly pathological, associated with allergy and asthma. Simulating natural respiratory infections in mice, we examined how efficient and well-adapted pathogens can block eosinophil functions that contribute to the immune response. Bordetella bronchiseptica, a natural pathogen of the mouse, uses the sigma factor btrS to regulate expression of mechanisms that interfere with eosinophil recruitment and function. When btrS is disrupted, immunomodulators are dysregulated, and eosinophils are recruited to the lungs, suggesting they may contribute to much more efficient generation of adaptive immunity induced by this mutant. Eosinophil-deficient mice failed to produce pro-inflammatory cytokines, to recruit lymphocytes, to organize lymphoid aggregates that resemble Bronchus Associated Lymphoid Tissue (BALT), to generate an effective antibody response, and to clear bacterial infection from the respiratory tract. Importantly, the failure of eosinophil-deficient mice to produce these lymphoid aggregates indicates that eosinophils can mediate the generation of an effective lymphoid response in the lungs. These data demonstrate that efficient respiratory pathogens can block eosinophil recruitment, to inhibit the generation of robust adaptive immune responses. They also suggest that some post-infection sequelae involving eosinophils, such as allergy and asthma, might be a consequence of bacterial mechanisms that manipulate their accumulation and/or function within the respiratory tract

Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH)

The UK-REACH cohort was established to understand why ethnic minority healthcare workers (HCWs) are at risk of poorer outcomes from COVID-19 when compared with their White ethnic counterparts in the UK. Through study design, it contains a uniquely high percentage of participants from ethnic minority backgrounds about whom a wide range of qualitative and quantitative data have been collected. A total of 17 891 HCWs aged 16–89 years (mean age: 44) have been recruited from across the UK via all major healthcare regulators, individual National Health Service hospital trusts and UK HCW membership bodies who advertised the study to their registrants/staff to encourage participation in the study. Data available include linked healthcare records for 25 years from the date of consent and consent to obtain genomic sequencing data collected via saliva. Online questionnaires include information on demographics, COVID-19 exposures at work and home, redeployment in the workforce due to COVID-19, mental health measures, workforce attrition and opinions on COVID-19 vaccines, with baseline (n = 15 119), 6 (n = 5632) and 12-month follow-up (n = 6535) data captured. Request data access and collaborations by following documentation found at https://www.uk-reach.org/main/data_sharing

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast

Purpose: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. Materials and methods: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. Results: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p