Recent research suggests that over 75% of resources extracted globally now go toward creating, maintaining, or operating material stocks (MS) to provide societal services like housing, transport,... Show moreRecent research suggests that over 75% of resources extracted globally now go toward creating, maintaining, or operating material stocks (MS) to provide societal services like housing, transport, education, and health. However, the integrity of current and future built environments, and the capacity of the system to continue providing services, are threatened by extreme events and sea-level rise (SLR). This is especially significant for the most disaster-prone countries in the world: Small Island Developing States. In the aftermath of disasters, complex rebuilding efforts require substantial material and economic resources, oftentimes incurring massive debt. Understanding the composition and dynamics of MS and environmental threats is essential for current and future sustainable development. Drawing on open-source OpenStreetMap (OSM) data, we conducted a spatially explicit material stock analysis (MSA) for The Bahamas for 2021, where we included buildings and transport MS, and SLR exposure scenarios. Total MS was estimated at 76 million tonnes (Mt) or 191 tonnes per capita (t/cap) of which transport comprises 43%. These MS are likely to increase by 36 Mt in the future. Simulations show that under 1-, 2-, or 3-m SLR scenarios, around 4, 6, and 9 Mt of current MS will be exposed, with transport MS at greatest risk, with over 80% of total exposure in each scenario. Our findings highlight the critical role that key MS play in sustainability and resilience, contributing to the emphasis on effective development planning and climate change adaptation strategies, and to the exploration of the use of OSM data for studying these objectives. Show less
Martin del Campo, F.; Singh, S.J.; Fishman, T.; Thomas, A.; Noll, D.; Drescher, M. 2023
Resource-use patterns may entail systemic risks and cascade effects, which consequently inhibit the ability to deliver socioeconomic services. Identifying resource-use patterns exhibiting systemic... Show moreResource-use patterns may entail systemic risks and cascade effects, which consequently inhibit the ability to deliver socioeconomic services. Identifying resource-use patterns exhibiting systemic risks and reshaping their combinations is a potential lever in realizing the transition to a sustainable, resilient, and resource-secure system. Using an island context to assess the quantity and composition of resource throughput enables a more comprehensive analysis of these risks. This article presents the first mass-balance account of socio-metabolic flows for The Bahamas in 2018, to identify socio-metabolic risks and cascading effects. Socio-metabolic risks are systemic risks related to critical resource availability, material circulation integrity, and (in)equities in cost and benefit distributions. We utilize the economy-wide material flow accounting framework to map the material flow patterns across the economy. In 2018, annual direct material input was estimated at 9.4 t/cap/yr, of which 60% were imports. High masses of waste (1.4 t/cap/yr) remained unrecovered due to the lack of recycling. Total domestic extraction (DE) were dominated by non-metallic minerals with more than 80%, while marine biomass makes up barely 1% of total DE. Due to its linear, undiversified metabolism, and heavy imports dependency, the system is susceptible to socio-metabolic risks and cascading effects including low levels of self-sufficiency, high vulnerability to shocks, commodity price fluctuations, threats to sensitive ecosystems, health impacts, and economic losses, among others. A holistic resource management strategy and nature-based solutions that consider the trade-offs and synergies between different resource-use patterns are critical when exploring potential plans for metabolic risk reduction. Show less
Li, H.Y.; Engel, C.; Hoya, M. de la; Peterlongo, P.; Yannoukakos, D.; Livraghi, L.; ... ; CIMBA Consortium 2022
Purpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense... Show morePurpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense pathogenic variants (PVs) with those associated with protein truncating (PTC) variants.Methods: We collected 582 informative pedigrees segregating 1 of 28 missense PVs in BRCA1 and 153 pedigrees segregating 1 of 12 missense PVs in BRCA2. We analyzed 324 pedigrees with PTC variants in BRCA1 and 214 pedigrees with PTC variants in BRCA2. Cancer risks were estimated using modified segregation analysis.Results: Estimated breast cancer risks were markedly lower for women aged >50 years carrying BRCA1 missense PVs than for the women carrying BRCA1 PTC variants (hazard ratio [HR] = 3.9 [2.4-6.2] for PVs vs 12.8 [5.7-28.7] for PTC variants; P =.01), particularly for missense PVs in the BRCA1 C-terminal domain (HR = 2.8 [1.4-5.6]; P =.005). In case of BRCA2, for women aged >50 years, the HR was 3.9 (2.0-7.2) for those heterozygous for missense PVs compared with 7.0 (3.3-14.7) for those harboring PTC variants. BRCA1 p.[Cys64Arg] and BRCA2 p.[Trp2626Cys] were associated with particularly low risks of breast cancer compared with other PVs.Conclusion: These results have important implications for the counseling of at-risk women who harbor missense PVs in the BRCA1/2 genes. (C) 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved. Show less
CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short... Show moreCSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures. Show less
Recent evidence shows that climate change is leading to irreversible and existential impacts on vulnerable communities and countries across the globe. Among other effects, this has given rise to... Show moreRecent evidence shows that climate change is leading to irreversible and existential impacts on vulnerable communities and countries across the globe. Among other effects, this has given rise to public debate and engagement around notions of climate crisis and emergency. The Loss and Damage (L&D) policy debate has emphasized these aspects over the last three decades. Yet, despite institutionalization through an article on L&D by the United Nations Framework Convention on Climate Change (UNFCCC) in the Paris Agreement, the debate has remained vague, particularly with reference to its remit and relationship to adaptation policy and practice. Research has recently made important strides forward in terms of develop- ing a science perspective on L&D. This article reviews insights derived from recent publications by the Intergovernmental Panel on Climate Change (IPCC) and others, and presents the implications for science and policy. Emerging evidence on hard and soft adaptation limits in certain systems, sectors and regions holds the potential to further build momentum for climate policy to live up to the Paris ambition of stringent emission reductions and to increase efforts to support the most vulnerable. L&D policy may want to consider actions to extend soft adaptation limits and spur transformational, that is, non- standard risk management and adaptation, so that limits are not breached. Financial, technical, and legal support would be appropriate for instances where hard limits are transgressed. Research is well positioned to further develop robust evidence on critical and relevant risks at scale in the most vulnerable countries and communities, as well as options to reduce barriers and limits to adaptation. Show less
Versteeg, M.; Hendriks, R.A.; Thomas, A.; Ommering, B.W.C.; Steendijk, P. 2020
Objectives To investigate the definitions and applications of 'spaced learning' and to propose future directions for advancing its study and practice in health professions education. Method The... Show moreObjectives To investigate the definitions and applications of 'spaced learning' and to propose future directions for advancing its study and practice in health professions education. Method The authors searched five online databases for articles published on spaced learning in health professions education prior to February 2018. Two researchers independently screened articles for eligibility with set inclusion criteria. They extracted and analysed key data using both quantitative and qualitative methods. Results Of the 2972 records retrieved, 120 articles were included in the review. More than 90% of these articles were published in the last 10 years. The definition of spaced learning varied widely and was often not theoretically grounded. Spaced learning was applied in distinct contexts, including online learning, simulation training and classroom settings. There was a large variety of spacing formats, ranging from dispersion of information or practice on a single day, to intervals lasting several months. Generally, spaced learning was implemented in practice or testing phases and rarely during teaching. Conclusions Spaced learning is infrequently and poorly defined in the health professions education literature. We propose a comprehensive definition of spaced learning and emphasise that detailed descriptions of spacing formats are needed in future research to facilitate the operationalisation of spaced learning research and practice in health professions education. Show less
OBJECTIVE: The dyslipidemia of type 2 diabetes mellitus has multiple etiologies and impairs lipoprotein functionality, thereby increasing risk for cardiovascular disease. High-density lipoproteins ... Show moreOBJECTIVE: The dyslipidemia of type 2 diabetes mellitus has multiple etiologies and impairs lipoprotein functionality, thereby increasing risk for cardiovascular disease. High-density lipoproteins (HDLs) have several beneficial effects, notably protecting the heart from myocardial ischemia. We hypothesized that glycation of HDL could compromise this cardioprotective effect.APPROACH AND RESULTS: We used in vitro (cardiomyocytes) and ex vivo (whole heart) models subjected to oxidative stress together with HDL isolated from diabetic patients and nondiabetic HDL glycated in vitro (methylglyoxal). Diabetic and in vitro glycated HDL were less effective (P<0.05) than control HDL in protecting from oxidative stress. Protection was significantly, inversely correlated with the degree of in vitro glycation (P<0.001) and the levels of hemoglobin A1c in diabetic patients (P<0.007). The ability to activate protective, intracellular survival pathways involving Akt, Stat3, and Erk1/2 was significantly reduced (P<0.05) using glycated HDL. Glycation reduced the sphingosine-1-phosphate (S1P) content of HDL, whereas the S1P concentrations of diabetic HDL were inversely correlated with hemoglobin A1c (P<0.005). The S1P contents of in vitro glycated and diabetic HDL were significantly, positively correlated (both <0.01) with cardiomyocyte survival during oxidative stress. Adding S1P to diabetic HDL increased its S1P content and restored its cardioprotective function.CONCLUSIONS: Our data demonstrate that glycation can reduce the S1P content of HDL, leading to increased cardiomyocyte cell death because of less effective activation of intracellular survival pathways. It has important implications for the functionality of HDL in diabetes mellitus because HDL-S1P has several beneficial effects on the vasculature. Show less
Thomas, A.; Belaidi, E.; Aron-Wisnewsky, J.; Zon, G.C. van der; Levy, P.; Clement, K.; ... ; Guigas, B. 2016
Reversed phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) is the gold standard technique in bioanalysis. However, hydrophilic interaction chromatography (HILIC) could represent... Show moreReversed phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) is the gold standard technique in bioanalysis. However, hydrophilic interaction chromatography (HILIC) could represent a viable alternative to RPLC for the analysis of polar and/or ionizable compounds, as it often provides higher MS sensitivity and alternative selectivity. Nevertheless, this technique can be also prone to matrix effects (ME). ME are one of the major issues in quantitative LC-MS bioanalysis. To ensure acceptable method performance (i.e., trueness and precision), a careful evaluation and minimization of ME is required. In the present study, the incidence of ME in HILIC-MS/MS and RPLC-MS/MS was compared for plasma and urine samples using two representative sets of 38 pharmaceutical compounds and 40 doping agents, respectively. The optimal generic chromatographic conditions in terms of selectivity with respect to interfering compounds were established in both chromatographic modes by testing three different stationary phases in each mode with different mobile phase pH. A second step involved the assessment of ME in RPLC and HILIC under the best generic conditions, using the post-extraction addition method. Biological samples were prepared using two different sample pre-treatments, i.e., a non-selective sample clean-up procedure (protein precipitation and simple dilution for plasma and urine samples, respectively) and a selective sample preparation, i.e., solid phase extraction for both matrices. The non-selective pretreatments led to significantly less ME in RPLC vs. HILIC conditions regardless of the matrix. On the contrary, HILIC appeared as a valuable alternative to RPLC for plasma and urine samples treated by a selective sample preparation. Indeed, in the case of selective sample preparation, the compounds influenced by ME were different in HILIC and RPLC, and lower and similar ME occurrence was generally observed in RPLC vs. HILIC for urine and plasma samples, respectively. The complementary of both chromatographic modes was also demonstrated, as ME was observed only scarcely for urine and plasma samples when selecting the most appropriate chromatographic mode. Show less
