► Older driver’s behaviour were studied in a framework of hierarchical models. ► Older drivers reported improvement of higher level and decline of lowest level skills. ► Inner states or adverse ...conditions were associated with stress and avoidance. ► Driving-related stress is connected to self-regulation of driving. ► Women are more likely to respond to driving-related stress by regulating the driving.
Previous research on older drivers has indicated connections between self-rated driving ability, confidence in their own driving, driving-related stress, and self-regulatory behaviour. However, more systematic associations between older drivers’ perceptions on their own driving and self-regulation or driver stress and self-regulation behaviour, and possible gender differences in these, have not been obtained in previous studies. The aim of the present study was to gain a better understanding of older drivers’ self-regulatory driving and the motivators behind this behaviour, by placing this behaviour in the modern traffic psychological framework of the driving task. 888 drivers aged 75 or older completed a structured phone interview about their perceived changes in driving skills, driving-related discomfort, and avoidance of driving situations. The results showed that when reporting change, the participants were more likely to report improvement of higher level skills and decline of the lowest level skills. Women were less likely to report improvement and more likely to report decline of skills. Driving situations related to inner states or adverse conditions were more often associated with discomfort and avoidance than situations related to infrastructure, and women were more likely to report discomfort and avoidance of driving situations. The results suggest that older drivers generally show good self-judgement of changes in their driving skills and acknowledge the different types of skills comprised in the driving task. The results also provide a better understanding of older drivers’ self-regulation of driving and gender differences in this, thus providing a better understanding in particular of women drivers’ self-regulation and increased risk of premature driving cessation. These findings may be valuable when encouraging older drivers, especially women, to prolong their driving.
This study is the first to develop a questionnaire to measure employees’ perceptions of the use of the action strategies selection, optimisation, and compensation (SOC) beyond the individual level, ...which has so far been lacking in research and practice. The study thus contributes an important tool for research into the role of SOC strategies at the leadership, group, and individual levels for long and healthy working lives. It may also be used by practitioners as a tool to provide input when developing targeted interventions to support long and healthy working lives. The development of the questionnaire was based on SOC theory, qualitative and cognitive interviews, and existing SOC questionnaires. The validity and reliability of the questionnaire were tested on data from a cross-sectional survey with responses from 785 nurses and 244 dairy workers. Results from confirmatory factor analyses supported the theoretically expected nine-factor structure of the questionnaire in both study populations (nurses and dairy workers). Furthermore, the results largely supported the criterion validity and internal reliability of the scales in the questionnaire. Nevertheless, further validation across additional occupational groups is needed.
Background: Individual use of selection, optimisation, and compensation (SOC) is positively associated with work ability; however, this association has never been explored at the group or leadership ...levels.Aim: The aim of this study is to explore the strength of associations between employee-rated use of SOC at the individual, group, and leadership levels and self-rated work ability among nurses. Method: A random sample of 2000 nurses were invited to participate in a questionnaire survey, among whom 785 responded.Results: Employee-rated use of SOC at the individual and group levels was positively associated with self-rated work ability when controlling for psychosocial working environment factors and health. The association was strongest at the group level.Conclusion: Efforts to enhance the collective use of SOC may prove beneficial to maintain the work ability of nurses and retain them in the profession.
Most European countries are gradually increasing the state pension age, but this may run counter to the capabilities and wishes of older workers. The objective of this study is to identify ...opportunities in the workplace for supporting a prolonged working life in different groups in the labour market. A representative sample of 11,200 employed workers ≥ 50 years responded to 15 questions in random order about opportunities at their workplace for supporting a prolonged working life. Respondents were stratified based on the Danish version of the International Standard Classification of Occupations (ISCO). Using frequency and logistic regression procedures combined with model-assisted weights based on national registers, results showed that the most common opportunities at the workplace were possibilities for more vacation, reduction of working hours, flexible working hours, access to treatment, further education and physical exercise. However, ISCO groups 5-9 (mainly physical work and shorter education) had in general poorer access to these opportunities than ISCO groups 1-4 (mainly seated work and longer education). Women had poorer access than men, and workers with reduced work ability had poorer access than those with full work ability. Thus, in contrast with actual needs, opportunities at the workplace were lower in occupations characterized by physical work and shorter education, among women and among workers with reduced work ability. This inequality poses a threat to prolonging working life in vulnerable groups in the labour market.
Background: This study investigates the association between the implementation of new technology in the workplace and the subsequent loss of paid employment among older workers. Methods: We estimated ...the prospective risk of loss of paid employment (register-based) from questions on new technology among 10,320 older workers (≥50 years). To investigate potential differences between work types, analyses were stratified by job function: (1) work with symbols (office, administration, analysis, IT), (2) work with people (people, service, care), (3) work in the field of production (processing, producing or moving things). Results: The introduction of new technology at the workplace reduced the risk of losing paid employment among older workers working with symbols (risk ratio RR 0.74, 95% CI 0.72–0.76) and in the field of production (RR 0.83, 95% CI 0.80–0.85), whereas new technology increased this risk among those working with people (RR 1.22, 95% CI 1.19–1.26). Being involved in the introduction of new technology and receiving adequate training in its use decreased the risk of loss of paid employment. Conclusions: Depending on the context, the introduction of new technology at work associates positively as well as negatively with future labour market participation among older workers. Worker involvement and adequate training in the use of new technology seem to be important for retaining workers in the labour market.
Awake craniotomy is currently a useful surgical approach to help identify and preserve functional areas during cortical and subcortical tumor resections. Methodologies have evolved over time to ...maximize patient safety and minimize morbidity using this technique. The goal of this study is to analyze a single surgeon's experience and the evolving methodology of awake language and sensorimotor mapping for glioma surgery.
The authors retrospectively studied patients undergoing awake brain tumor surgery between 1986 and 2014. Operations for the initial 248 patients (1986-1997) were completed at the University of Washington, and the subsequent surgeries in 611 patients (1997-2014) were completed at the University of California, San Francisco. Perioperative risk factors and complications were assessed using the latter 611 cases.
The median patient age was 42 years (range 13-84 years). Sixty percent of patients had Karnofsky Performance Status (KPS) scores of 90-100, and 40% had KPS scores less than 80. Fifty-five percent of patients underwent surgery for high-grade gliomas, 42% for low-grade gliomas, 1% for metastatic lesions, and 2% for other lesions (cortical dysplasia, encephalitis, necrosis, abscess, and hemangioma). The majority of patients were in American Society of Anesthesiologists (ASA) Class 1 or 2 (mild systemic disease); however, patients with severe systemic disease were not excluded from awake brain tumor surgery and represented 15% of study participants. Laryngeal mask airway was used in 8 patients (1%) and was most commonly used for large vascular tumors with more than 2 cm of mass effect. The most common sedation regimen was propofol plus remifentanil (54%); however, 42% of patients required an adjustment to the initial sedation regimen before skin incision due to patient intolerance. Mannitol was used in 54% of cases. Twelve percent of patients were active smokers at the time of surgery, which did not impact completion of the intraoperative mapping procedure. Stimulation-induced seizures occurred in 3% of patients and were rapidly terminated with ice-cold Ringer's solution. Preoperative seizure history and tumor location were associated with an increased incidence of stimulation-induced seizures. Mapping was aborted in 3 cases (0.5%) due to intraoperative seizures (2 cases) and patient emotional intolerance (1 case). The overall perioperative complication rate was 10%.
Based on the current best practice described here and developed from multiple regimens used over a 27-year period, it is concluded that awake brain tumor surgery can be safely performed with extremely low complication and failure rates regardless of ASA classification; body mass index; smoking status; psychiatric or emotional history; seizure frequency and duration; and tumor site, size, and pathology.
Phosphorylation of the MLKL pseudokinase by the RIPK3 kinase leads to MLKL oligomerization, translocation to, and permeabilization of, the plasma membrane to induce necroptotic cell death. The ...precise choreography of MLKL activation remains incompletely understood. Here, we report Monobodies, synthetic binding proteins, that bind the pseudokinase domain of MLKL within human cells and their crystal structures in complex with the human MLKL pseudokinase domain. While Monobody-32 constitutively binds the MLKL hinge region, Monobody-27 binds MLKL via an epitope that overlaps the RIPK3 binding site and is only exposed after phosphorylated MLKL disengages from RIPK3 following necroptotic stimulation. The crystal structures identified two distinct conformations of the MLKL pseudokinase domain, supporting the idea that a conformational transition accompanies MLKL disengagement from RIPK3. These studies provide further evidence that MLKL undergoes a large conformational change upon activation, and identify MLKL disengagement from RIPK3 as a key regulatory step in the necroptosis pathway.
The second messenger hydrogen peroxide is required for optimal activation of numerous signal transduction pathways, particularly those mediated by protein tyrosine kinases. One mechanism by which ...hydrogen peroxide regulates cellular processes is the transient inhibition of protein tyrosine phosphatases through the reversible oxidization of their catalytic cysteine, which suppresses protein dephosphorylation. Here we describe a structural analysis of the redox-dependent regulation of protein tyrosine phosphatase 1B (PTP1B), which is reversibly inhibited by oxidation after cells are stimulated with insulin and epidermal growth factor. The sulphenic acid intermediate produced in response to PTP1B oxidation is rapidly converted into a previously unknown sulphenyl-amide species, in which the sulphur atom of the catalytic cysteine is covalently linked to the main chain nitrogen of an adjacent residue. Oxidation of PTP1B to the sulphenyl-amide form is accompanied by large conformational changes in the catalytic site that inhibit substrate binding. We propose that this unusual protein modification both protects the active-site cysteine residue of PTP1B from irreversible oxidation to sulphonic acid and permits redox regulation of the enzyme by promoting its reversible reduction by thiols.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The endogenous production of long-chain polyunsaturated fatty acids (LC-PUFA) in carnivorous teleost species inhabiting freshwater environments is poorly understood. Although a predatory lifestyle ...could potentially supply sufficient LC-PUFA to satisfy the requirements of these species, the nutrient-poor characteristics of the freshwater food web could impede this advantage. In this study, we report the cloning and functional characterisation of an elongase enzyme in the LC-PUFA biosynthesis pathway from striped snakehead (Channa striata), which is a strict freshwater piscivore that shows high deposition of LC-PUFA in its flesh. We also functionally characterised a previously isolated fatty acyl desaturase cDNA from this species. Results showed that the striped snakehead desaturase is capable of Δ4 and Δ5 desaturation activities, while the elongase showed the characteristics of Elovl5 elongases. Collectively, these findings reveal that striped snakehead exhibits the genetic resources to synthesise docosahexaenoic acid (DHA; 22:6n-3) from eicosapentaenoic acid (EPA; 20:5n-3). Both genes are expressed at considerable levels in the brain and the liver. In liver, both genes were up-regulated by dietary C18 PUFA, although this increase did not correspond to a significant rise in the deposition of muscle LC-PUFA. Brain tissue of fish fed with plant oil diets showed higher expression of fads2 gene compared to fish fed with fish oil-based diet, which could ensure DHA levels remain constant under limited dietary DHA intake. This suggests the importance of DHA production from EPA via the ∆4 desaturation step in order to maintain an optimal reserve of DHA in the neuronal tissues of carnivores.
•LC-PUFA biosynthesis genes of striped snakehead fish was functionally characterised.•A Δ4 Fads2 desaturase and Elovl5 elongase were discovered.•Limited LC-PUFA intake revealed elevated fads2 gene expression in liver and brain.•Brain DHA content remained consistent despite limited dietary LC-PUFA intake.
Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a ...clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcriptome sequencing of pre-treatment tumors. We found that tumor mutational burden as a predictor of response was confounded by melanoma subtype, whereas multiple novel genomic and transcriptomic features predicted selective response, including features associated with MHC-I and MHC-II antigen presentation. Furthermore, previous anti-CTLA4 ICB exposure was associated with different predictors of response compared to tumors that were naive to ICB, suggesting selective immune effects of previous exposure to anti-CTLA4 ICB. Finally, we developed parsimonious models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 ICB in individual tumors, with validation in smaller independent cohorts limited by the availability of comprehensive data. Broadly, we present a framework to discover predictive features and build models of ICB therapeutic response.
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