Issue 11: Scaling Canada’s Local Immigration Partnerships (LIPs) Model for Proactive Refugee Resettlement

In this issue of Policy Points we provide a vision for scaling up Canada’s Local Immigration Partnership (LIP) model for refugee resettlement abroad. Global refugee resettlement is an issue that needs a coordinated and collaborative approach that includes communities as partners. Canada presents a proactive and responsive solution to this problem. First introduced in Ontario in 2008, LIPs are a community-based collaborative model for newcomer resettlement and integration that has proven successful in many local communities across Canada. Most importantly, LIPs played an important role in the resettlement of Syrian refugees in several communities across Canada in 2015-2016. The recommendation in this brief aims to offer details to scale up LIPs, a Canadian model of local community involvement in refugee resettlement for the international community

Targeting of glut5 for transporter-mediated drug-delivery is contingent upon substrate hydrophilicity

Specific link between high fructose uptake and cancer development and progression highlighted fructose transporters as potential means to achieve GLUT-mediated discrimination between normal and cancer cells. The gained expression of fructose-specific transporter GLUT5 in various cancers offers a possibility for developing cancer-specific imaging and bioactive agents. Herein, we explore the feasibility of delivering a bioactive agent through cancer-relevant fructose-specific transporter GLUT5. We employed specific targeting of GLUT5 by 2,5-anhydro-D-mannitol and investigated several drug conjugates for their ability to induce cancer-specific cytotoxicity. The proof-of-concept analysis was carried out for conjugates of chlorambucil (CLB) in GLUT5-positive breast cancer cells and normal breast cells. The cytotoxicity of conjugates was assessed over 24 h and 48 h, and significant dependence between cancer-selectivity and conjugate size was observed. The differences were found to relate to the loss of GLUT5-mediated uptake upon increased conjugate size and hydrophobicity. The findings provide information on the substrate tolerance of GLUT5 and highlight the importance of maintaining appropriate hydrophilicity for GLUT-mediated delivery

Quadratic quantum speedup in evaluating bilinear risk functions

Computing nonlinear functions over multilinear forms is a general problem with applications in risk analysis. For instance in the domain of energy economics, accurate and timely risk management demands for efficient simulation of millions of scenarios, largely benefiting from computational speedups. We develop a novel hybrid quantum-classical algorithm based on polynomial approximation of nonlinear functions and compare different implementation variants. We prove a quadratic quantum speedup, up to polylogarithmic factors, when forms are bilinear and approximating polynomials have second degree, if efficient loading unitaries are available for the input data sets. We also enhance the bidirectional encoding, that allows tuning the balance between circuit depth and width, proposing an improved version that can be exploited for the calculation of inner products. Lastly, we exploit the dynamic circuit capabilities, recently introduced on IBM Quantum devices, to reduce the average depth of the Quantum Hadamard Product circuit. A proof of principle is implemented and validated on IBM Quantum systems

QPO emission from moving hot spots on the surface of neutron stars: a model

We present recent results of 3D magnetohydrodynamic simulations of neutron stars with small misalignment angles, as regards the features in lightcurves produced by regular movements of the hot spots during accretion onto the star. In particular, we show that the variation of position of the hot spot created by the infalling matter, as observed in 3D simulations, can produce high frequency Quasi Periodic Oscillations with frequencies associated with the inner zone of the disk. Previously reported simulations showed that the usual assumption of a fixed hot spot near the polar region is valid only for misalignment angles relatively large. Otherwise, two phenomena challenge the assumption: one is the presence of Rayleigh-Taylor instabilities at the disk-magnetospheric boundary, which produce tongues of accreting matter that can reach the star almost anywhere between the equator and the polar region; the other one is the motion of the hot spot around the magnetic pole during stable accretion. In this paper we start by showing that both phenomena are capable of producing short-term oscillations in the lightcurves. We then use Monte Carlo techniques to produce model lightcurves based on the features of the movements observed, and we show that the main features of kHz QPOs can be reproduced. Finally, we show the behavior of the frequencies of the moving spots as the mass accretion rate changes, and propose a mechanism for the production of double QPO peaks.Comment: MNRAS accepted on 2009 December 11, 14 pages, 12 figure

Gender and Racial Disparity Among Liver Transplantation Professionals: Report of a Global Survey.

Equality, diversity, and inclusion (EDI) are fundamental principles. Little is known about the pattern of practice and perceptions of EDI among liver transplant (LT) providers. International Liver Transplant Society (ILTS) EDI Committee survey around topics related to discrimination, mentorship, and gender. Answers were collected and analyzed anonymously. Worldwide female leadership was also queried via publicly available data. The survey was e-mailed to 1312 ILTS members, 199 responses (40.7% female) were collected from 38 countries (15.2% response rate). Almost half were surgeons (45.7%), 27.6% hepatologists and 26.6% anesthetists. Among 856 LT programs worldwide, 8.2% of leadership positions were held by females, and 22% of division chiefs were female across all specialties. Sixty-eight of respondents (34.7%) reported some form of discrimination during training or at their current position, presumably related to gender/sexual orientation (20.6%), race/country of origin (25.2%) and others (7.1%). Less than half (43.7%) received mentorship when discrimination occurred. An association between female responses and discrimination, differences in compensation, and job promotion was observed. This survey reveals alarmingly high rate of experience with racial and gender disparity, lack of mentorship, and very low rates of female leadership in the LT field and calls to action to equity and inclusion

Association of skeletal muscle and serum metabolites with maximum power output gains in response to continuous endurance or high-intensity interval training programs: The TIMES study - A randomized controlled trial

Recent studies have begun to identify the molecular determinants of inter-individual variability of cardiorespiratory fitness (CRF) in response to exercise training programs. However, we still have an incomplete picture of the molecular mechanisms underlying trainability in response to exercise training. Objective We investigated baseline serum and skeletal muscle metabolomics profile and its associations with maximal power output (MPO) gains in response to 8-week of continuous endurance training (ET) and high-intensity interval training (HIIT) programs matched for total units of exercise performed (the TIMES study). Methods Eighty healthy sedentary young adult males were randomized to one of three groups and 70 were defined as completers (> 90% of sessions): ET (n = 30), HIIT (n = 30) and control (CO, n = 10). For the CO, participants were asked to not exercise for 8 weeks. Serum and skeletal muscle samples were analyzed by 1H-NMR spectroscopy. The targeted screens yielded 43 serum and 70 muscle reproducible metabolites (intraclass > 0.75; coefficient of variation < 25%). Associations of baseline metabolites with MPO trainability were explored within each training program via three analytical strategies: (1) correlations with gains in MPO; (2) differences between high and low responders to ET and HIIT; and (3) metabolites contributions to the most significant pathways related to gains in MPO. The significance level was set at P < 0.01 or false discovery rate of 0.1. Results The exercise programs generated similar gains in MPO (ET = 21.4 +/- 8.0%; HIIT = 24.3 +/- 8.5%). MPO associated baseline metabolites supported by all three levels of evidence were: serum glycerol, muscle alanine, proline, threonine, creatinine, AMP and pyruvate for ET, and serum lysine, phenylalanine, creatine, and muscle glycolate for HIIT. The most common pathways suggested by the metabolite profiles were aminoacyl-tRNA biosynthesis, and carbohydrate and amino acid metabolism. Conclusion We suggest that MPO gains in both programs are potentially associated with metabolites indicative of baseline amino acid and translation processes with additional evidence for carbohydrate metabolism in ET142CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP149201/2015-0; 140302/2018-288881.135219/2016-012018/24108-9; 2016/057417Sao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/24108-9, 2016/057417]; Support Fund for Teaching, Research and Extension (FAEPEX) [2021/16]; National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development (CNPq) [149201/2015-0, 140302/2018-2]; Coordination for the Improvement of Higher Education Personnel (PDSE-CAPES) [88881.135219/2016-01]; COBRE center grant from the U.S.A. National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIH8 1P30GM118430-02]; NIH-funded COBRE grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIH 8P30GM118430-01]; National Institute of General Medical Sciences of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [2 U54 GM104940

Addressing the Burden and Management Strategies for Disparities and Inequities Among Liver Transplant Professionals: The ILTS Experience.

Medical professional environments are becoming increasingly multicultural, international, and diverse in terms of its specialists. Many transplant professionals face challenges related to gender, sexual orientation or racial background in their work environment or experience inequities involving access to leadership positions, professional promotion, and compensation. These circumstances not infrequently become a major source of work-related stress and burnout for these disadvantaged, under-represented transplant professionals. In this review, we aim to 1) discuss the current perceptions regarding disparities among liver transplant providers 2) outline the burden and impact of disparities and inequities in the liver transplant workforce 3) propose potential solutions and role of professional societies to mitigate inequities and maximize inclusion within the transplant community

Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: A snapshot of 1144 patients in the JUMP trial

JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate- or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis – a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib’s mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a ≥50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov

Are the outflows in FU Orionis systems driven by the stellar magnetic field?

FU Orionis (FUOR) outbursts are major optical brightening episodes in low-mass protostars that correspond to rapid mass-accretion events in the innermost region of a protostellar disc. The outbursts are accompanied by strong outflows, with the inferred mass outflow rates reaching ~10% of the mass inflow rates. Shu et al. proposed that the outflows represent accreted disc material that is driven centrifugally from the spun-up surface layers of the protostar by the stellar magnetic field. This model was critiqued by Calvet et al., who argued that it cannot reproduce the photospheric absorption-line shifts observed in the prototype object FU Ori. Calvet et al. proposed that the wind is launched, instead, from the surface of the disc on scales of a few stellar radii by a non-stellar magnetic field. In this paper we present results from numerical simulations of disc accretion on to a slowly rotating star with an aligned magnetic dipole moment that gives rise to a kilogauss-strength surface field. We demonstrate that, for parameters appropriate to FU Ori, such a system can develop a strong, collimated disc outflow of the type previously identified by Romanova et al. in simulations of protostars with low and moderate accretion rates. At the high accretion rate that characterizes FUOR outbursts, the radius at which the disc is truncated by the stellar magnetic field moves much closer to the stellar surface, but the basic properties of the outflow, which is launched from the vicinity of the truncation radius along opened-up stellar magnetic field lines, remain the same, and are distinct from those of the mechanism proposed by Shu et al. We show that the simulated outflow can in principle account for the main observed characteristics of FUOR winds, including the photospheric line shifts measured in FU Ori.Comment: 11 pages, 4 figures, 1 table, to appear in MNRA