Changes in Registered Nurse Employment Plans and Workplace Assessments.

Importance: The US registered nurse (RN) workforce is in flux, with high rates of burnout, intention to leave, and vacancies. Rapid, repeated assessments of the nursing workforce can help hospital executives and policymakers enact effective recruitment and retention strategies. Objective: To identify changes in practicing RNs' employment plans and workplace assessments between the 2022 and 2023 surveys. Design, Setting, and Participants: This survey study compared data collected from the Michigan Nurses' Study at 2 time points: February 22 to March 1, 2022, and May 17 to June 1, 2023. Practicing RNs with an active, unrestricted license in Michigan and a valid individual email address were included. Main Outcome and Measures: The primary outcome was nurses' intention to leave their current position within 1 year. In the 2023 survey, nurses who planned to leave were queried on their next career step and the primary reason for their planned departure. Workplace assessments included questions about abusive or violent workplace events, emotional exhaustion, job satisfaction, the practice environment's delivery of high-quality care, and the clinical setting's safety rating. Regression analysis was used to examine workplace assessments and personal factors associated with planned departures. Results: This study obtained data on 9150 nurses (6495 females [71.0%]) and 7059 nurses (5134 females [72.7%]) responding to the 2022 (response rate, 8.3%) and 2023 (response rate, 7.4%) surveys, respectively. In the 2023 survey, 32.0% (2259) of nurses planned to leave their position, compared with 39.1% (3576) in the 2022 survey. Of these nurses, 957 (41.8%) planned to leave their current employer but remain in nursing, with workloads as the most frequently cited reason (29.4% [672]). Compared with the 2022 cohort, nurses in the 2023 sample reported less workplace abuse or violence (4591 [50.2%] vs 3063 [43.4%]; P < .001), fewer understaffed shifts (4407 [48.2%] vs 2898 [41.0%]; P < .001), and less frequent use of mandatory overtime (1709 [18.7%] vs 824 [11.7%]; P < .001). Factors associated with increased likelihood for planned departures included workplace abuse or violence (odds ratio [OR], 1.39; 95% CI, 1.05-1.82) and higher emotional exhaustion scores (OR, 3.05; 95% CI, 2.38-3.91). Favorable practice environments (OR, 0.37; 95% CI, 0.22-0.62) and excellent clinical setting safety ratings (OR, 0.28; 95% CI, 0.14-0.56) were associated with lower likelihood of planned departure. Conclusions and Relevance: Results of this study showed that nurses reported improved workplace conditions in the 2023 vs the 2022 survey; however, planned departure rates, abusive or violent events, and unsafe conditions remained high, and understaffing remained a primary concern for most nurses. Health system leaders and policymakers should prioritize initiatives that support nurse retention and reduce potential workforce instability.

The phase behavior of skin-barrier lipids: a combined approach of experiments and simulations.

Skin barrier function is localized in its outermost layer, the stratum corneum (SC), which is comprised of corneocyte cells embedded in an extracellular lipid matrix containing ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs). The unique structure and composition of this lipid matrix are important for skin barrier function. In this study, experiments and molecular dynamics simulation were combined to investigate the structural properties and phase behavior of mixtures containing nonhydroxy sphingosine CER (CER NS), CHOL, and FFA. X-ray scattering for mixtures with varying CHOL levels revealed the presence of the 5.4 nm short-periodicity phase in the presence of CHOL. Bilayers in coarse-grained multilayer simulations of the same compositions contained domains with thicknesses of approximately 5.3 nm and 5.8 nm that are associated with elevated levels respectively of CER sphingosine chains with CHOL, and CER acyl chains with FFA chains. The prevalence of the thicker domain increased with decreasing CHOL content. This might correspond to a phase with ∼5.8 nm spacing observed by X-rays (other details unknown) in mixtures with lower CHOL content. Scissoring and stretching frequencies from Fourier transform infrared spectroscopy (FTIR) also indicate interaction between FFA and CER acyl chains and little interaction between CER acyl and CER sphingosine chains, which requires CER to adopt predominantly an extended conformation. In the simulated systems, neighbor preferences of extended CER chains align more closely with the FTIR observations than those of CERs with hairpin ceramide chains. Both FTIR and simulations of reverse-mapped atomistic multilayer membranes detect a hexagonal to fluid phase transition between 65 and 80 ºC. These results demonstrate the utility of a collaborative experimental and simulation effort in gaining a more comprehensive understanding of SC lipid membranes.

The interaction of the azetidine thiazole side chain with the active site loop (ASL) 3 drives the evolution of IMP metallo-ß-lactamase against tebipenem.

Imipenemase (IMP) metallo-ß-lactamases (MBLs) hydrolyze almost all available ß-lactams including carbapenems and are not inhibited by any commercially available ß-lactamase inhibitor. Tebipenem (TP) pivoxil is the first orally available carbapenem and possesses a unique bicyclic azetidine thiazole moiety located at the R2 position. TP has potent in vitro activity against Enterobacterales producing extended-spectrum and/or AmpC ß-lactamases. Thus far, the activity of TP against IMP-producing strains is understudied. To address this knowledge gap, we explored the structure activity relationships of IMP MBLs by investigating whether IMP-6, IMP-10, IMP-25, and IMP-78 [MBLs with expanded hydrolytic activity against meropenem (MEM)] would demonstrate enhanced activity against TP. Most of the Escherichia coli DH10B strains expressing IMP-1 variants displayed a ≥twofold MIC difference between TP and MEM, while those expressing VIM or NDM variants demonstrated comparable MICs. Catalytic efficiency (kcat/KM) values for the TP hydrolysis by IMP-1, IMP-6, IMP-10, IMP-25, and IMP-78 were significantly lower than those obtained for MEM. Molecular dynamic simulations reveal that V67F and S262G substitutions (found in IMP-78) reposition active site loop 3, ASL-3, to better accommodate the bicyclic azetidine thiazole side chain, allowing microbiological/catalytic activity to approach that of comparison MBLs used in this study. These findings suggest that modifying the R2 side chain of carbapenems can significantly impact hydrolytic stability. Furthermore, changes in conformational dynamics due to single amino acid substitutions should be used to inform drug design of novel carbapenems.

Contribution of Electrostatic CH3-π Interactions to Recognition of Histone Asymmetric Dimethylarginine by the SPIN1 Triple Tudor Domain.

Methylation of arginine (Arg) residues on histones creates a new binding epitope, enabling recognition by aromatic cage binding pockets in Tudor domains; these protein-protein interactions (PPIs) govern gene expression. Despite their biological importance, the molecular details of methylated Arg recognition are poorly understood. While the desolvation, hydrogen bonding, and guanidinium stacking of methylated Arg have been explored in model systems and proposed to contribute to binding, direct interactions between the methyl groups and the aromatic residues in the binding pocket have not previously been investigated. Herein, we mechanistically study the CH3-π interactions between the SPIN1 triple Tudor domain and histone asymmetric dimethylarginine. We find that these CH3-π interactions are electrostatically tunable, exhibiting cation-π character, albeit attenuated relative to cation-π interactions with quaternary ammonium ions, offering key insight into how methylation of Arg alters its binding epitope to enable new PPIs.

Quantifying error in effect size estimates in attention, executive function, and implicit learning.

Accurate quantification of effect sizes has the power to motivate theory and reduce misinvestment of scientific resources by informing power calculations during study planning. However, a combination of publication bias and small sample sizes (∼N = 25) hampers certainty in current effect size estimates. We sought to determine the extent to which sample sizes may produce errors in effect size estimates for four commonly used paradigms assessing attention, executive function, and implicit learning (attentional blink, multitasking, contextual cueing, and serial response task). We combined a large data set with a bootstrapping approach to simulate 1,000 experiments across a range of N (13-313). Beyond quantifying the effect size and statistical power that can be anticipated for each study design, we demonstrate that experiments with lower N may double or triple information loss. We also show that basing power calculations on effect sizes from similar studies yields a problematically imprecise estimate between 40% and 67% of the time, given commonly used sample sizes. Last, we show that skewness of intersubject behavioral effects may serve as a predictor of an erroneous estimate. We conclude with practical recommendations for researchers and demonstrate how our simulation approach can yield theoretical insights that are not readily achieved by other methods such as identifying the information gained from rejecting the null hypothesis and quantifying the contribution of individual variation to error in effect size estimates. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Top 10 Signs and Symptoms of Psychotropic Adverse Drug Events to Monitor in Residents of Long-Term Care Facilities.

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants. DESIGN: A 3-round Delphi study. SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries. METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms. RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth. CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

Evaluating ChatGPT's moral competence in health care-related ethical problems.

Objectives: Artificial intelligence tools such as Chat Generative Pre-trained Transformer (ChatGPT) have been used for many health care-related applications; however, there is a lack of research on their capabilities for evaluating morally and/or ethically complex medical decisions. The objective of this study was to assess the moral competence of ChatGPT. Materials and methods: This cross-sectional study was performed between May 2023 and July 2023 using scenarios from the Moral Competence Test (MCT). Numerical responses were collected from ChatGPT 3.5 and 4.0 to assess individual and overall stage scores, including C-index and overall moral stage preference. Descriptive analysis and 2-sided Student's t-test were used for all continuous data. Results: A total of 100 iterations of the MCT were performed and moral preference was found to be higher in the latter Kohlberg-derived arguments. ChatGPT 4.0 was found to have a higher overall moral stage preference (2.325 versus 1.755) when compared to ChatGPT 3.5. ChatGPT 4.0 was also found to have a statistically higher C-index score in comparison to ChatGPT 3.5 (29.03 ± 11.10 versus 19.32 ± 10.95, P =.0000275). Discussion: ChatGPT 3.5 and 4.0 trended towards higher moral preference for the latter stages of Kohlberg's theory for both dilemmas with C-indices suggesting medium moral competence. However, both models showed moderate variation in C-index scores indicating inconsistency and further training is recommended. Conclusion: ChatGPT demonstrates medium moral competence and can evaluate arguments based on Kohlberg's theory of moral development. These findings suggest that future revisions of ChatGPT and other large language models could assist physicians in the decision-making process when encountering complex ethical scenarios.

Quality improvement in the era of boarding and burnout: A postpandemic blueprint.

The COVID-19 pandemic led to unprecedented challenges to healthcare quality in the emergency department, including directly impacting quality metrics and worsening barriers to the quality improvement process such as burnout, staff turnover, and boarding. We aimed to develop a blueprint for postpandemic quality improvement to address these specific barriers, focused on prioritizing frontline staff engagement from idea generation to implementation and assessment. Drawing from teamwork literature, we constructed a process that emphasized egalitarian conversations, psychological safety, and creating an environment where staff could feel heard at every step of the process. We applied this blueprint to improving rates of patients who leave without being seen and achieved a four percentage point reduction (9% vs. 5%, p < 0.001), with high rates of staff satisfaction with the process. We conclude that while postpandemic quality improvement presents significant challenges, we can rise to meet those challenges by adapting existing quality improvement processes to increase frontline staff engagement.

Deletion of miR-146a enhances therapeutic protein restoration in model of dystrophin exon skipping.

Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by the absence of dystrophin protein. One current DMD therapeutic strategy, exon skipping, produces a truncated dystrophin isoform using phosphorodiamidate morpholino oligomers (PMOs). However, the potential of exon skipping therapeutics has not been fully realized as increases in dystrophin protein have been minimal in clinical trials. Here, we investigate how miR-146a-5p, which is highly elevated in dystrophic muscle, impacts dystrophin protein levels. We find inflammation strongly induces miR-146a in dystrophic, but not wild-type myotubes. Bioinformatics analysis reveals that the dystrophin 3' UTR harbors a miR-146a binding site, and subsequent luciferase assays demonstrate miR-146a binding inhibits dystrophin translation. In dystrophin-null mdx52 mice, co-injection of miR-146a reduces dystrophin restoration by an exon 51 skipping PMO. To directly investigate how miR-146a impacts therapeutic dystrophin rescue, we generated mdx52 with body-wide miR-146a deletion (146aX). Administration of an exon skipping PMO via intramuscular or intravenous injection markedly increases dystrophin protein levels in 146aX vs. mdx52 muscles while skipped dystrophin transcript levels are unchanged supporting a post-transcriptional mechanism of action. Together, these data show that miR-146a expression opposes therapeutic dystrophin restoration, suggesting miR-146a inhibition warrants further research as a potential DMD exon skipping co-therapy.

Risky effort.

Decision-making involves weighing up the outcome likelihood, potential rewards, and effort needed. Previous research has focused on the trade-offs between risk and reward or between effort and reward. Here we bridge this gap and examine how risk in effort levels influences choice. We focus on how two key properties of choice influence risk preferences for effort: changes in magnitude and probability. Two experiments assessed people's risk attitudes for effort, and an additional experiment provided a control condition using monetary gambles. The extent to which people valued effort was related to their pattern of risk preferences. Unlike with monetary outcomes, however, there was substantial heterogeneity in effort-based risk preferences: People who responded to effort as costly exhibited a "flipped" interaction pattern of risk preferences. The direction of the pattern depended on whether people treated effort as a loss of resources. Most, but not all, people treat effort as a loss and are more willing to take risks to avoid potentially high levels of effort.

Evaluation of a safety-engineered peripherally inserted intravenous catheter with multiple access blood control: clinician acceptability and ease of use.

AIM: Acceptability of a new safety-engineered peripherally inserted intravenous catheter (PIVC) with multiple access blood control (MBC) was evaluated in this observational study by experienced volunteer clinicians on healthy volunteers. METHODS: Clinicians and healthy volunteers were recruited for this study. Observers documented study procedures, including if there was any blood leakage from the catheter hub at various times during hub connections and disconnections and how many attempts it took a clinician to get a successful stick. Clinicians responded to yes-or-no and Likert-scale questionnaires describing their experiences with PIVC with MBC after each procedure. Questionnaire data were summarized by frequency and percent of responses; analyses were conducted using binomial statistics. RESULTS: Overall, clinicians considered PIVC with MBC to be acceptable (93.6% agreement). Clinicians were able to easily remove the catheter protective cap, insert the catheter, visualize primary and secondary flashbacks, easily remove the needle from the catheter hub and determine if the safety clip was activated after withdrawing the needle. In addition, they were able to connect or disconnect and flush extension sets. Clinicians did not have to change their insertion technique, found the catheter easy to insert, and believed the catheter would protect them from blood exposure during insertion of the catheter and subsequent hub accesses (agreement ranged from 82.3% to 98.9%). CONCLUSIONS: No blood leakage was observed from the catheter hub at any time during the procedures. Overall, clinicians found the new PIVC with MBC to be acceptable, easy to use, and functioned properly. HIGHLIGHTS: Acceptability, usability, and ease of use of a new safety-engineered PIVC with MBC was evaluated. PIVC with MBC was >93% acceptable: prevented blood exposure after multiple insertions/removals. Most clinicians (96%) achieved first stick success when using their product. PIVC with MBC was easy to use, worked properly and allowed clinicians to keep their PIVC technique.

Vitamin D Maintains Growth and Bone Mineral Density against a Background of Severe Vitamin A Deficiency and Moderate Toxicity in a Swine Model.

Excessive vitamin A (VA) negatively impacts bone. Interactions between VA and vitamin D (VD) in bone health are not well-understood. This study used a traditional two-by-two factorial design. Pigs were weaned and randomized to four treatments (n = 13/group): -A-D, -A+D, +A-D, and +A+D for 3 and 5 wk. Serum, liver, kidney, adrenal glands, spleen, and lung were analyzed by ultra-performance LC. Growth was evaluated by weight measured weekly and BMD by DXA. Weights were higher in -A+D (18.1 ± 1.0 kg) and +A+D (18.2 ± 2.3 kg) at 5 wk than in -A-D (15.5 ± 2.1 kg) and +A-D (15.8 ± 1.5 kg). Serum retinol concentrations were 0.25 ± 0.023, 0.22 ± 0.10, 0.77 ± 0.12, and 0.84 ± 0.28 µmol/L; and liver VA concentrations were 0.016 ± 0.015, 0.0065 ± 0.0035, 2.97 ± 0.43, 3.05 ± 0.68 µmol/g in -A-D, -A+D, +A-D, and +A+D, respectively. Serum 25(OH)D3 concentrations were 1.5 ± 1.11, 1.8 ± 0.43, 27.7 ± 8.91, and 23.9 ± 6.67 ng/mL in -A-D, +A-D, -A+D, +A+D, respectively, indicating a deficiency in -D and adequacy in +D. BMD was highest in +D (p < 0.001). VA and the interaction had no effect on BMD. Dietary VD influenced weight gain, BMD, and health despite VA status.

Mapping multimorbidity progression among 190 diseases.

BACKGROUND: Current clustering of multimorbidity based on the frequency of common disease combinations is inadequate. We estimated the causal relationships among prevalent diseases and mapped out the clusters of multimorbidity progression among them. METHODS: In this cohort study, we examined the progression of multimorbidity among 190 diseases among over 500,000 UK Biobank participants over 12.7 years of follow-up. Using a machine learning method for causal inference, we analyzed patterns of how diseases influenced and were influenced by others in females and males. We used clustering analysis and visualization algorithms to identify multimorbidity progress constellations. RESULTS: We show the top influential and influenced diseases largely overlap between sexes in chronic diseases, with sex-specific ones tending to be acute diseases. Patterns of diseases that influence and are influenced by other diseases also emerged (clustering significance Pau > 0.87), with the top influential diseases affecting many clusters and the top influenced diseases concentrating on a few, suggesting that complex mechanisms are at play for the diseases that increase the development of other diseases while share underlying causes exist among the diseases whose development are increased by others. Bi-directional multimorbidity progress presents substantial clustering tendencies both within and across International Classification Disease chapters, compared to uni-directional ones, which can inform future studies for developing cross-specialty strategies for multimorbidity. Finally, we identify 10 multimorbidity progress constellations for females and 9 for males (clustering stability, adjusted Rand index >0.75), showing interesting differences between sexes. CONCLUSION: Our findings could inform the future development of targeted interventions and provide an essential foundation for future studies seeking to improve the prevention and management of multimorbidity.

Mapping out clusters of diseases is crucial to addressing the rising challenge of co-occurrence of multiple diseases, known as multimorbidity. However, the current way of grouping diseases based on their associations isn't enough to understand how they develop over time. We've come up with a new approach to map out how groups of diseases progress together based on the strength of their causal relationships. By looking at how each disease affects the development of others, we can get a better understanding of how they form clusters. Our research goes beyond just showing which diseases occur together, and it's a step toward improving how we prevent and manage multiple health conditions in the future.

Challenges and advances in device-related thrombus in left atrial appendage occlusion.

Oral anticoagulation therapy (OAC) is a mainstay for mitigating stroke and other embolic events in patients with atrial fibrillation (AF). Despite the demonstrated efficacy of OAC in reducing events, many patients are unable to tolerate OAC due to bleeding risks. Left atrial appendage occlusion (LAAO) devices were developed as implantable technologies to moderate stroke risk in patients with intolerance to OAC. Despite clinical data supporting near-comparable protection against thromboembolic events with OAC, device-related thrombus formation has emerged as a critical complication following LAAO that remains a potential limitation to the safety and efficacy of LAAO. Improved biocompatibility of LAAO devices with fluoropolymers, a well-established stent-coating technology used to reduce thrombus formation and promote endothelialization, may optimize outcomes after LAAO.

[Box: see text].

Parkinsonian Tremor as Unstable Feedback in a Physiologically Consistent Control Framework.

Parkinson's disease (PD) is characterized by decreased dopamine in the basal ganglia that causes excessive tonic inhibition of the thalamus. This excessive inhibition seems to explain inhibitory motor symptoms in PD, but the source of tremor remains unclear. This paper investigates how neural inhibition may change the closed-loop characteristics of the human motor control system to determine how this established pathophysiology could produce tremor. The rate-coding model of neural signals suggests increased inhibition decreases signal amplitude, which could create a mismatch between the closed-loop dynamics and the internal models that overcome proprioceptive feedback delays. This paper aims to identify a candidate model structure with decreased-amplitude-induced tremor in PD that also agrees with previously recorded movements of healthy and cerebellar patients. The optimal feedback control theory of human motor control forms the basis of the model. Key additional elements include gating of undesired movements via the basal ganglia-thalamus-motor cortex circuit and the treatment of the efferent copy of the control input as a measurement in the state estimator. Simulations confirm the model's ability to capture tremor in PD and also demonstrate how disease progression could affect tremor and other motor symptoms, providing insight into the existence of tremor and non-tremor phenotypes. Altogether, the physiological underpinnings of the model structure and the agreement of model predictions with clinical observations provides support for the hypothesis that unstable feedback produces parkinsonian tremor. Consequently, these results also support the associated framework for the neuroanatomy of human motor control.

Multidimensional fluorescence spectroscopy of wine using synchronous excitation/emission matrices and time-resolved fluorescence interferometric detection.

Wines are complex mixtures of chemical compounds with broad and overlapping absorption and emission spectral features in the UV and visible spectral regions, making them challenging to study with conventional optical spectroscopic techniques. Multidimensional fluorescence spectroscopies correlate fluorescence spectra with other degrees of freedom, and have proven useful for studying complex molecular systems, offering a pathway for the analysis of wines utilising their inherent fluorescence. Here we employ steady-state excitation-emission matrix (EEM) and time-resolved fluorescence spectral measurements to investigate representative commercial white and red wine samples and a fluorescent 'model' wine base. Combining these multidimensional measurement methods provides information on the emission characteristics of the components that wines contain. This investigation illustrates the potential for multidimensional fluorescence techniques as diagnostic tools for the wine industry.

Single gene analysis in yeast suggests nonequilibrium regulatory dynamics for transcription.

Fluctuations in the initiation rate of transcription, the first step in gene expression, ensue from the stochastic behavior of the molecular process that controls transcription. In steady state, the regulatory process is often assumed to operate reversibly, i.e., in equilibrium. However, reversibility imposes fundamental limits to information processing. For instance, the assumption of equilibrium is difficult to square with the precision with which the regulatory process executes its task in eukaryotes. Here we provide evidence - from microscopic analyses of the transcription dynamics at a single gene copy of yeast - that the regulatory process for transcription is cyclic and irreversible (out of equilibrium). The necessary coupling to reservoirs of free energy occurs via sequence-specific transcriptional activators and the recruitment, in part, of ATP-dependent chromatin remodelers. Our findings may help explain how eukaryotic cells reconcile the dual but opposing requirements for fast regulatory kinetics and high regulatory specificity.

Social vulnerability and surgery outcomes: a cross-sectional analysis.

BACKGROUND: Post-operative complications present a challenge to the healthcare system due to the high unpredictability of their incidence. Socioeconomic conditions have been established as social determinants of health. However, their contribution relating to postoperative complications is still unclear as it can be heterogeneous based on community, type of surgical services, and sex and gender. Uncovering these relations can enable improved public health policy to reduce such complications. METHODS: In this study, we conducted a large population cross-sectional analysis of social vulnerability and the odds of various post-surgical complications. We collected electronic health records data from over 50,000 surgeries that happened between 2012 and 2018 at a quaternary health center in St. Louis, Missouri, United States and the corresponding zip code of the patients. We built statistical logistic regression models of postsurgical complications with the social vulnerability index of the tract consisting of the zip codes of the patient as the independent variable along with sex and race interaction. RESULTS: Our sample from the St. Louis area exhibited high variance in social vulnerability with notable rapid increase in vulnerability from the south west to the north of the Mississippi river indicating high levels of inequality. Our sample had more females than males, and females had slightly higher social vulnerability index. Postoperative complication incidence ranged from 0.75% to 41% with lower incidence rate among females. We found that social vulnerability was associated with abnormal heart rhythm with socioeconomic status and housing status being the main association factors. We also found associations of the interaction of social vulnerability and female sex with an increase in odds of heart attack and surgical wound infection. Those associations disappeared when controlling for general health and comorbidities. CONCLUSIONS: Our results indicate that social vulnerability measures such as socioeconomic status and housing conditions could affect postsurgical outcomes through preoperative health. This suggests that the domains of preventive medicine and public health should place social vulnerability as a priority to achieve better health outcomes of surgical interventions.