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with a means to reliably assess the operational performance and readily calculate optimal capacity requirements.We examined whether the association between emotionally demanding work and risk of register-based long-term sickness absence (LTSA, ≥6 weeks) was buffered by high leadership quality among 25 416 Danish employees during 52-week follow-up. Emotional demands were measured at the job group level, whereas leadership quality was measured by workers rating their closest manager. Emotionally demanding work was associated with a higher risk of LTSA, regardless if leadership quality was high or low, with neither multiplicative nor additive interaction. We conclude that we found no evidence for high leadership quality buffering the effect of emotionally demanding work on risk of LTSA.Mass media campaigns are an effective population-level intervention for preventing tobacco use. However, little evidence exists for whether these campaigns similarly influence demographic subgroups. This study examined the effects of the truth® campaign to reduce tobacco use among demographic subgroups. We used data from a national, continuous, cross-sectional tracking survey of 15-24-year-olds (n = 32 331). We used a measure of weekly aggregated campaign exposure to assess whether cigarette smoking intentions and current cigarette use varied by race/ethnicity, financial situation and population density subgroups, controlling for factors known to be associated with tobacco use. Examining estimates across subgroup categories in light of the overall model estimates revealed that the effects of week-level campaign exposure on cigarette smoking intentions and current cigarette use were similar across subgroups. Wald tests of equality across estimates in each subgroup suggested that the estimates did not differ from one another in any given instance. The truth campaign does not differ significantly in its capacity to prompt declines in tobacco use across a broad spectrum of US youth and young adults. Mass media tobacco prevention campaigns can be an effective and critical component of a comprehensive tobacco control program, particularly with respect to reducing tobacco-related disparities among demographic subgroups.

To study the dynamics, mechanisms and fitness cost of resistance selection to cefepime, zidebactam and cefepime/zidebactam in Pseudomonas aeruginosa.

WT P. aeruginosa PAO1 and its ΔmutS derivative (PAOMS) were exposed to stepwise increasing concentrations of cefepime, zidebactam and cefepime/zidebactam. Selected mutants were characterized for change in susceptibility profiles, acquired mutations, fitness, virulence and in vivo susceptibility to cefepime/zidebactam. Mutations were identified through WGS. In vitro fitness was assessed by measuring growth in minimal medium and human serum-supplemented Mueller-Hinton broth. Virulence was determined in Caenorhabditis elegans and neutropenic mice lung infection models. In vivo susceptibility to a human-simulated regimen (HSR) of cefepime/zidebactam was studied in neutropenic mice lung infection.

Resistance development was lower for the cefepime/zidebactam combination than for the individual components and high-level resistance was only achieved for PAOMS. find more Cefepime resistance development was associated with mutations leading to the hyperexpression of AmpC or MexXY-OprM, combined with PBP3 mutations and/or large chromosomal deletions involving galU. Zidebactam resistance was mainly associated with mutations in PBP2. On the other hand, resistance to cefepime/zidebactam required multiple mutations in genes encoding MexAB-OprM and its regulators, as well as PBP2 and PBP3. Cumulatively, these mutations inflicted significant fitness cost and cefepime/zidebactam-resistant mutants (MIC = 16-64 mg/L) remained susceptible in vivo to the HSR.

Development of cefepime/zidebactam resistance in P. aeruginosa required multiple simultaneous mutations that were associated with a significant impairment of fitness and virulence.

Development of cefepime/zidebactam resistance in P. aeruginosa required multiple simultaneous mutations that were associated with a significant impairment of fitness and virulence.

Malnutrition affects approximately 20% of older adult populations in Europe, yet their views on the condition are rarely explored. This qualitative study aimed to explore the experiences of older adults living with malnutrition and prescribed oral nutritional supplements in the community setting.

Semi-structured individual interviews were used to collect data from 13 community-dwelling individuals aged ≥60 years with a current or previous prescription for oral nutritional supplements. Self-perceived health status was measured using the EuroQol EQ-5D-5L, a short questionnaire and visual analogue scale. Interviews were audio-recorded and transcribed verbatim. Interview data were organized using NVivo 12 and analyzed using inductive thematic analysis.

Median age was 80.0 (interquartile range 19.5) years, seven were male and six were female. Median health score was 60.0 (interquartile range 35.0) out of 100. Almost one-third reported severe or extreme problems with usual activities, and pain or discomfort. o improve the health status of older adults with malnutrition.The COVID-19 pandemic has emphasised the need to develop effective treatments to combat emerging viruses. Model systems that poorly represent a virus' cellular environment, however, may impede research and waste resources. Collaborations between cell biologists and virologists have led to the rapid development of representative organoid model systems to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that lung organoids, in particular, have advanced our understanding of SARS-CoV-2 pathogenesis, and have laid a foundation to study future pandemic viruses and develop effective treatments.Magnetic confinement nuclear fusion is an important way to realize controllable nuclear fusion. Due to the large current and complicated coil arrangement, there is a complicated electromagnetic environment around the fusion device. In this paper, the B-dot sensor is used to measure the magnetic field, the D-dot sensor is used to measure the electric field, the MAXWELL electromagnetic simulation software is used to simulate the electromagnetic field strength; the simulation and measurement of the spherical Tokamak SUNIST device and the measurement of MARX generator are carried out, then we give corresponding electromagnetic protection suggestions.RNA-binding proteins (RBPs) and their RNA ligands play many critical roles in gene regulation and RNA processing in cells. They are also useful for various applications in cell biology and synthetic biology. However, re-engineering novel and orthogonal RNA-RBP pairs from natural components remains challenging while such synthetic RNA-RBP pairs could significantly expand the RNA-RBP toolbox for various applications. Here, we report a novel library-vs-library in vitro selection strategy based on Phage Display coupled with Systematic Evolution of Ligands by EXponential enrichment (PD-SELEX). Starting with pools of 1.1 × 1012 unique RNA sequences and 4.0 × 108 unique phage-displayed L7Ae-scaffold (LS) proteins, we selected RNA-RBP complexes through a two-step affinity purification process. After six rounds of library-vs-library selection, the selected RNAs and LS proteins were analyzed by next-generation sequencing (NGS). Further deconvolution of the enriched RNA and LS protein sequences revealed two synthetic and orthogonal RNA-RBP pairs that exhibit picomolar affinity and >4000-fold selectivity.In the polarized debates about abortion and voluntary euthanasia, disability advocates, who normally align with left-wing social forces, have tended to side with conservative and religious voices in expressing concerns about the impact of technological and sociopolitical developments on disabled futures. This paper draws on the social model of disability and the virtue ethics tradition to explain the alignment between the religious and disability perspectives, and the theory of transformative choice to highlight the limits and biases of the pro-choice logic. Yet, it also recognizes the inherent contradiction of disabled advocates taking a paternalistic position against the personal agency of women and people facing terminal illnesses. A disability perspective serves the discussion of abortion and euthanasia as an encouragement to work together for the building of a society that enables people with diverse disabilities to exist and flourish, and helps pregnant women, people facing disabling and terminal illnesses, and politicians and social influencers to make informed choices.It is sometimes proposed that killing or harming abortion providers is the only logically consistent position available to opponents of abortion. Since lethal violence against morally responsible attackers is normally viewed as justified in order to defend innocent parties, pro-lifers should also think so in the case of the abortion doctor and so they should act to defend the unborn. In our paper, we defend the mainstream pro-life view against killing abortion doctors. We argue that the pro-life view can, in various ways, reject the assumption that defensive violence to save innocent individuals is always permissible. Now even if that assumption is accepted, we contend that defensive violence against abortion doctors still is not justified. Drawing on Frances Kamm's work, we contend that there are structural similarities between abortion and letting someone die who needs your help to stay alive; and we argue that it is impermissible to kill those who kill in order to avoid giving life-saving aid.

To investigate the physiological effects of rotational shift work on measures of cardio-metabolic function.

Sedentary, healthy men (n = 87; age 37 ± 9 years; body mass index 30.7 ± 5.1 kg m2) were recruited and categorized via occupation. SHIFT group currently employed in rotational shift work defined by 8-12 h morning, afternoon, and night rotations; or NSHIFT working fixed daytime hours. Testing procedures included baseline objective sleep assessment and laboratory testing, conducted between 0600 and 0900 h to assess body composition, cardiorespiratory fitness (VO2peak), inflammatory status [C-reactive protein, interleukin (IL)-6, and tumour necrosis factor-alpha (TNF-α)], glucose metabolism, heart rate variability (HRV), and self-reported leisure time physical activity (PA).

SHIFT reported significantly less leisure time PA (P = 0.019), reduced VO2peak (P = 0.007), higher body fat percentage (BF%) (P = 0.021), increase response time to oral glucose tolerance test (P = 0.016), and higher IL-6 values (d as potential pathogenic mechanisms.Reduced systolic function is central to the pathophysiology and clinical sequelae of acute decompensated heart failure (ADHF) with reduced ejection fraction and cardiogenic shock. These clinical entities are the final common pathway for marked deterioration of right or left ventricular function and can occur in multiple clinical presentations including severe ADHF, myocardial infarction, post-cardiac surgery, severe pulmonary hypertension, and advanced or end-stage chronic heart failure. Inotropic therapies improve ventricular systolic function and may be divided into three classes on the basis of their mechanism of action (calcitropes, mitotropes, and myotropes). Most currently available therapies for cardiogenic shock are calcitropes which can provide critical haemodynamic support, but also may increase myocardial oxygen demand, ischaemia, arrhythmia, and mortality. Emerging therapies to improve cardiac function such as mitotropes (e.g. perhexiline, SGLT2i) or myotropes (e.g. omecamtiv mecarbil) may provide useful alternatives in the future.

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