Radiation-grafted anion-exchange membranes (AEM) containing pendent benzyltrimethylammonium, 1-benzyl-3-methylimidazolium and 1-benzyl-2,3-dimethylimidazolium functional head-groups were synthesised ...with ion-exchange capacities in the range 1.7-1.9 meq g super(-1). The ionic conductivities of the AEMs were also comparable (24.5 plus or minus 1.8 mS cm super(-1) at 50 degree C). The alkali stability (in aqueous potassium hydroxide (1 mol dm super(-3)) at 60 degree C) of the 1-benzyl-2,3-dimethylimidazolium head-groups was superior to the 1-benzyl-3-methylimidazolium but inferior to the benzyltrimethylammonium benchmark head-groups. Radiation-grafted AEMs containing pendent 1-benzyl-2,3-dimethylimidazolium head-groups are not suitable for application in electrochemical devices containing highly alkaline environments.
•Role of psychosocial interventions in OUD treatment is equivocal.•We comprehensively described evidence in this area.•Extant research has generally ignored rehabilitative effects of psychosocial ...interventions.
Mapped the sources and types of evidence available on psychosocial interventions in the treatment of opioid use disorder (OUD), with and without pharmacotherapies.
Six electronic databases were searched for research published until July 1, 2019. Included studies were coded on publication characteristics, evidence sources, treatment settings and modalities, study populations and patient characteristics, intervention(s) offered to patients, research questions addressed in experimental studies, and outcomes investigated.
We identified 305 empirical studies of 54,607 patients. Most studies (64 %; n = 194) compared psychosocial interventions to alternative treatment(s) (183 RCTs and 11 quasi-experiments) while 28 % (n = 86) used observational designs, and 8% (n = 25) used qualitative methods. Trials infrequently investigated effects of stand-alone psychosocial interventions without pharmacotherapies (20% of all RCTs). Regardless of research question or study design, program retention and illicit drug use were the most common outcomes investigated (> 81% of all studies and RCTs), typically among longstanding male heroin users attending specialty outpatient addiction services. Studies rarely examined (a) OUD treatment in general health care or prescription OUD (each < 6 % of all studies and RCTs), (b) effects of social assistance (employment, education, social support) and harm reduction (each < 6 % of studies; < 7 % of RCTs), and (c) health-related quality of life and satisfaction with care (each < 10 % and < 15 % of all studies and RCTs, respectively).
Scant evidence is available on the putative rehabilitative effects of psychosocial interventions, either as stand-alone treatments or in an adjunct role to pharmacotherapies.
The Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on the Mars Reconnaissance Orbiter (MRO) collected hyperspectral images of the Martian surface and atmosphere from September 27, 2006, ...through May 7, 2022. Over that time, nearly twenty scientific investigations were completed, most of which arose as a result of the findings from previous investigations. Two review papers published in 2009 (Murchie et al., 2009a, b) described the initial two-year investigation during MRO's Primary Science Phase, its key findings, and the CRISM data products that were developed and released to the community through that time. Here we describe the conduct and evolution of the CRISM investigation since then, which includes MRO's Extended Science Phase and first five Extended Missions. We document the physical changes in the instrument as it aged, including capabilities that were lost as well as new modes of operation not initially envisioned; the new science questions that were investigated and their key findings; anatomy of the extensive collection of data products that have been released to the Planetary Data System; the “final” radiometric calibration; high-order derived products produced from high-resolution targeted observations and global mapping campaigns; and data processing and analysis tools which have been developed and released by the CRISM team.
•CRISM acquired Mars orbital measurement from Sep. 2007 through May 2022.•The orbital science investigations and constituent observation types are described.•Final radiometric calibration is described.•Characteristics and processing of derived data products is described.
Objective:
The current study investigated driver vigilance in partially automated vehicles to determine whether increased task demands reduce a driver’s ability to monitor for automation failures and ...whether the vigilance decrement associated with hazard detections is due to driver overload.
Background:
Drivers of partially automated vehicles are expected to monitor for signs of automation failure. Previous research has shown that a driver’s ability to perform this duty declines over time. One possible explanation for this vigilance decrement is that the extreme demands of vigilance causes overload and leads to depletion of limited attentional resources required for vigilance.
Method:
Participants completed a 40-min drive in a simulated partially automated vehicle and were tasked with monitoring for hazards that represented potential automation failures. Two factors were manipulated to test the impact of monitoring demands on performance: Spatial uncertainty and event rate.
Results:
As predicted, hazard detection performance was poorer when monitoring demands were increased, and performance declined as a function of time on task. Subjective reports also indicated high workload and task-induced stress.
Conclusion:
Drivers of partially automated vehicles are impaired by the vigilance decrement and elevated task demands, meaning that safe operation becomes less likely when the demands associated with monitoring automation increase and as a drive extends in duration. This study also supports the notion that vigilance performance in partially automated vehicles is likely due to driver overload.
Application:
Developers of automation technologies should consider countermeasures that attenuate a driver’s cognitive load when tasked with monitoring automation.
Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been ...relatively small, and knowledge about these risks is limited.
Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided.
During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea BCNU, etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of ≥5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of ≥6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided.
Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points.
RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study the role of RAC1P29S in melanoma development and reveal that RAC1P29S ...activates PAK, AKT, and a gene expression program initiated by the SRF/MRTF transcriptional pathway, which results in a melanocytic to mesenchymal phenotypic switch. Mice with ubiquitous expression of RAC1P29S from the endogenous locus develop lymphoma. When expressed only in melanocytes, RAC1P29S cooperates with oncogenic BRAF or with NF1-loss to promote tumorigenesis. RAC1P29S also drives resistance to BRAF inhibitors, which is reversed by SRF/MRTF inhibitors. These findings establish RAC1P29S as a promoter of melanoma initiation and mediator of therapy resistance, while identifying SRF/MRTF as a potential therapeutic target.
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•RAC1P29S activates PAK, AKT, and the SRF/MRTF transcription program in melanocytes•RAC1P29S induces a melanocytic to mesenchymal transition through SRF/MRTF and PAK•RAC1P29S cooperates with BRAF mutation or NF1 deletion to promote melanomagenesis•RAC1P29S induces resistance to BRAF inhibitors through SRF/MRTF
RAC1P29S is a common mutation in human cutaneous melanoma. Lionarons et al. show that RAC1P29S induces a melanocytic to mesenchymal switch via an SRF/MRTF-mediated gene expression program, cooperates with BRAF in melanomagenesis, and drives BRAF inhibitor resistance, which is reversed by SRF/MRTF inhibition.
Partial T cell depletion is used in solid organ transplantation as a valuable strategy of peritransplant induction immunosuppression. Using a murine cardiac allograft model, we recently demonstrated ...that this led to lymphopenia-induced (homeostatic) proliferation among the residual nondepleted lymphocytes. Rather than promoting tolerance, peritransplant T cell-depleting Abs actually resulted in resistance to tolerance induction by costimulatory blockade. In this study we show that memory T cells predominate shortly after subtotal lymphodepletion due to two distinct mechanisms: relative resistance to depletion and enhanced homeostatic proliferation. In contrast, regulatory cells (CD4+ CD25+ Foxp3+) are depleted as efficiently as nonregulatory cells and exhibit reduced homeostatic expansion compared with memory cells. The resistance to tolerance induction seen with subtotal T cell depletion can be overcome in two different ways: first, by the adoptive transfer of additional unprimed regulatory cells at the time of transplant, and second, by the adjunctive use of nondepleting anti-CD4 and anti-CD8 mAbs, which effectively block homeostatic expansion. We conclude that the resistance to tolerance induction seen after subtotal lymphocyte depletion can be attributed to alterations in the balance of naive, memory, and regulatory T cells. These data have clinically relevant implications related to the development of novel strategies to overcome resistance to tolerance.
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