Abstract Purpose The present article investigated individual and aggregated effects of cannabis-related perceptions and other cannabis-related indicators on 12-month cannabis use prevalence and ...frequency among 15–16 year olds using multilevel analysis across 32 European countries. Methods Data on cannabis use, perceptions of availability, risks and friends’ use as well as socio-demographic characteristics were taken from the 2007 European School Survey Project on Alcohol and Other Drugs. At the country level, aggregated measures of the perceptions were used. Data on cannabis price and 12-month cannabis use prevalence in the total population were taken from the World Drug Report. The analytical sample comprised 86,107 students (82.5% of the overall 2007 international database). Results Strong and persistent individual-level effects were identified for perceived availability, perceived harm, and the number of cannabis using friends. The effects on cannabis use prevalence and frequency were more pronounced than country-level effects. At the country level, aggregated perceived peer consumption and population prevalence were significant predictors, whereas price was not found to be related to both outcome variables. The association between perceived friends’ use and cannabis use was moderated by aggregated perceived availability. Conclusions Proximal influences related to the immediate social situation seem to be more strongly associated with cannabis use than do distal influences related to social contexts, emphasizing the importance of personal attitudes and perceptions in substance use behavior. Prevention programs may focus on informing adolescents about the potential risks of cannabis and on correcting misperceptions of social norms. Policy measures may target on reducing visibility of drug use.
This paper presents the new and now open-source version
2.1 of the REgional Model of INvestments and Development (REMIND). REMIND,
as an integrated assessment model (IAM), provides an integrated view ...of the
global energy–economy–emissions system and explores self-consistent
transformation pathways. It describes a broad range of possible futures and
their relation to technical and socio-economic developments as well as
policy choices. REMIND is a multiregional model incorporating the economy
and a detailed representation of the energy sector implemented in the
General Algebraic Modeling System (GAMS). It uses non-linear optimization to
derive welfare-optimal regional transformation pathways of the
energy-economic system subject to climate and sustainability constraints for
the time horizon from 2005 to 2100. The resulting solution corresponds to the
decentralized market outcome under the assumptions of perfect foresight of
agents and internalization of external effects. REMIND enables the analyses of
technology options and policy approaches for climate change mitigation with
particular strength in representing the scale-up of new technologies,
including renewables and their integration in power markets. The REMIND code
is organized into modules that gather code relevant for specific topics.
Interaction between different modules is made explicit via clearly defined
sets of input and output variables. Each module can be represented by different
realizations, enabling flexible configuration and extension. The spatial
resolution of REMIND is flexible and depends on the resolution of the input
data. Thus, the framework can be used for a variety of applications in a
customized form, balancing requirements for detail and overall runtime and
complexity.
In Paris, France, December 2015, the Conference of the Parties (COP) to the United Nations Framework Convention on Climate Change (UNFCCC) invited the Intergovernmental Panel on Climate Change (IPCC) ...to provide a special report in 2018 on the impacts of global warming of 1.5 °C above pre-industrial levels and related global greenhouse gas emission pathways. In Nairobi, Kenya, April 2016, the IPCC panel accepted the invitation. Here we describe the response devised within the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) to provide tailored, cross-sectorally consistent impact projections to broaden the scientific basis for the report. The simulation protocol is designed to allow for (1) separation of the impacts of historical warming starting from pre-industrial conditions from impacts of other drivers such as historical land-use changes (based on pre-industrial and historical impact model simulations); (2) quantification of the impacts of additional warming up to 1.5 °C, including a potential overshoot and long-term impacts up to 2299, and comparison to higher levels of global mean temperature change (based on the low-emissions Representative Concentration Pathway RCP2.6 and a no-mitigation pathway RCP6.0) with socio-economic conditions fixed at 2005 levels; and (3) assessment of the climate effects based on the same climate scenarios while accounting for simultaneous changes in socio-economic conditions following the middle-of-the-road Shared Socioeconomic Pathway (SSP2, Fricko et al., 2016) and in particular differential bioenergy requirements associated with the transformation of the energy system to comply with RCP2.6 compared to RCP6.0. With the aim of providing the scientific basis for an aggregation of impacts across sectors and analysis of cross-sectoral interactions that may dampen or amplify sectoral impacts, the protocol is designed to facilitate consistent impact projections from a range of impact models across different sectors (global and regional hydrology, lakes, global crops, global vegetation, regional forests, global and regional marine ecosystems and fisheries, global and regional coastal infrastructure, energy supply and demand, temperature-related mortality, and global terrestrial biodiversity).
DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a ...frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3-72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8-not reached NR); median progression-free survival was 5.7 months (2.2-9.7); median overall survival was not reached (8.7 months-NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination 75%), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.
AIM To investigate the association between hepatic steatosis and change in left ventricular mass index(LVMI) over five years, and examine whether systolic and diastolic blood pressures are mediators ...of the association between hepatic steatosis and LVMI using a general population sample.METHODS We analyzed data from the Study of Health in Pomerania. The study population comprised 1298individuals aged 45 to 81 years. Hepatic steatosis was defined as the presence of a hyperechogenic pattern of the liver together with elevated serum alanine transferase levels. Left ventricular mass was determined echocardiographically and indexed to height2.7. Path analyses were conducted to differentiate direct and indirect paths from hepatic steatosis to LVMI encompassing systolic and diastolic blood pressure as potential mediating variables.RESULTS Hepatic steatosis was a significant predictor for all measured echocardiographic characteristics at baseline. Path analyses revealed that the association of hepatic steatosis with LVMI change after five years was negligibly small(β =-0.12, s.e. = 0.21, P = 0.55). Systolic blood pressure at baseline was inversely associated with LVMI change(β =-0.09, s.e. = 0.03, P < 0.01), while no association between diastolic blood pressure at baseline and LVMI change was evident(β = 0.03, s.e. = 0.05, P = 0.56). The effect of the indirect path from hepatic steatosis to LVMI via systolic baseline blood pressure was small(β =-0.20, s.e. = 0.10, P = 0.07). No indirect effect was observed for the path via diastolic baseline blood pressure(β = 0.03, s.e. = 0.06, P = 0.60). Similar associations were observed in the subgroup of individuals not receiving beta-blockers, calcium channel blockers, or drugs acting on the reninangiotensin system.CONCLUSION Baseline associations between hepatic steatosis and LVMI do not extend to associations with LVMI change after five years. More studies are needed to study the longitudinal effects of hepatic steatosis on LVMI.
Sealing of the paracellular cleft by tight junctions is of central importance for epithelia and endothelia to function as efficient barriers between the extracellular space and the inner milieu. ...Occludin and claudins represent the major tight junction components involved in establishing this barrier function. A special situation emerges at sites where three cells join together. Tricellulin, a recently identified tetraspan protein concentrated at tricellular contacts, was reported to organize tricellular as well as bicellular tight junctions. Here we show that in MDCK cells, the tricellulin C-terminus is important for the basolateral translocation of tricellulin, whereas the N-terminal domain appears to be involved in directing tricellulin to tricellular contacts. In this respect, identification of homomeric tricellulin-tricellulin and of heteromeric tricellulin-occludin complexes extends a previously published model and suggests that tricellulin and occludin are transported together to the edges of elongating bicellular junctions and get separated when tricellular contacts are formed.
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