Search

Multiple imputation by chained equations (MICE) has emerged as a popular approach for handling missing data. A central challenge for applying MICE is determining how to incorporate outcome information into covariate imputation models, particularly for complicated outcomes. Often, we have a particular analysis model in mind, and we would like to ensure congeniality between the imputation and analysis models. We propose a novel strategy for directly incorporating the analysis model into the handling of missing data. In our proposed approach, multiple imputations of missing covariates are obtained without using outcome information. We then utilize the strategy of imputation stacking, where multiple imputations are stacked on top of each other to create a large data set. The analysis model is then incorporated through weights. Instead of applying Rubin's combining rules, we obtain parameter estimates by fitting a weighted version of the analysis model on the stacked data set. We propose a novel estimator for obtaining standard errors for this stacked and weighted analysis. Our estimator is based on the observed data information principle in Louis' work and can be applied for analyzing stacked multiple imputations more generally. Our approach for analyzing stacked multiple imputations is the first method that can be easily applied (using R package StackImpute) for a wide variety of standard analysis models and missing data settings.

Over the past two decades, accumulating evidence has indicated that individuals experience challenge and hindrance stressors in qualitatively different ways, with the former being linked to more positive outcomes than the latter. Indeed, challenge stressors are believed to have net positive effects even though they can also lead to a range of strains, eliciting beliefs that managers can enhance performance outcomes by increasing the frequency of challenge stressors experienced in the workplace. The current article questions this conventional wisdom by developing theory that explains how different patterns of challenge stressor exposure influence employee outcomes. Across 2 field studies, our results supported our theory, indicating that when challenge stressors vary across time periods, they have negative indirect effects on employee performance and well-being outcomes. In contrast, when employees experience a stable pattern of challenge stressors across time periods, they have positive indirect effects on employee performance and well-being outcomes. These results, which suggest that the benefits of challenge stressors may not outweigh their costs when challenge stressors fluctuate, have important implications for theory and practice. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

BACKGROUND Anatomical site is strongly associated with head and neck cancer etiology, and etiology and patient sociodemographic characteristics are prognostic factors for survival. It is not known whether the effects of these predictors persist over the postdiagnosis period or are strongest proximal to the time of diagnosis. METHODS Using survival times and causes of death for 180,434 patients with head and neck cancer in the Surveillance, Epidemiology, and End Results cancer registry (1973-2015), the empirical cumulative incidences of cancer-specific death and other-cause death were calculated with a competing risks framework, and the time-dependent effects (hazard ratios) of anatomical tumor site (oropharynx, oral cavity, or hypopharynx/larynx), age, sex, race, and year of diagnosis on cancer-specific death and other-cause death, stratified by tumor stage, were estimated. RESULTS All effects were significantly time-varying (P

Young adults are at high risk for sexual harassment and sexual assault. Although attention has been given to prevention on college campuses, the need for prevention may be at least as high for young adults who do not attend college as for young adults who do. In October 2019, we administered a nationally representative survey of 893 adults to measure sexual harassment and sexual assault victimization during a recall period defined as “during college years” for respondents who had enrolled in college at any time or “ages 18-24” for respondents not in college. Reported rates of sexual harassment (32.7%) and sexual assault (24.6%) during early adulthood were similar for respondents who reported having ever enrolled in college and for respondents who reported never attending college. Women were more likely than men to report both sexual harassment (37.4% vs 22.4%) and sexual assault (36.0% vs 16.0%) during early adulthood. Compared with respondents aged ≥30, respondents aged 18-29 were 105% more likely to report sexual harassment and 65% more likely to report sexual assault. Moreover, sexual harassment experiences predicted sexual assault victimization (adjusted odds ratio = 18.1). This study highlights the importance of attending to sexual harassment and sexual assault risks for young adults through research, policy, and criminal justice structures beyond institutions of higher education. Evidence that sexual harassment is strongly associated with sexual assault victimization of young adults highlights the importance of naming and stemming early behavioral transgressions across the US population.

Objectives Research on life course inequality and successful aging has sought to understand how events and challenges may lead to poor outcomes in later life for some individuals, while others fare well in the face of adversity. Among internalized resources, research suggests psychological resilience is protective in the face of challenges, but little is known about the predictive efficacy of this measure compared to other resources such as mastery. This paper examines connections between psychological resilience and later life health compared to other internalized resources. Method Standardized associations between 4 resources (resilience, mastery, optimism, hopelessness) and 5 health outcomes were tested using short-term health transitions and longer term health trajectories in a structural equation modeling (SEM) framework using the Leave Behind Questionnaire (LBQ) and linked Health and Retirement Study (HRS) between 2006/2008 and 2014/2016 (n = 11,050–12,823). Results Psychological resilience had consistent and robust associations with health transitions and trajectories. Further, the effects of this resource were generally 4–10 times greater than for mastery, optimism, and hopelessness in combined models. Trajectory analyses replicate these findings and suggest the beneficial associations of resilience over time were persistent for some health outcomes, and cumulative for others. Discussion The results suggest that psychological resilience is powerfully associated with health in later life, with substantially greater predictive efficacy than other commonly used resource measures. Future research should establish how this intrapersonal resource works alongside structural and interpersonal resources to promote and protect health and functioning in the face of challenges and adversity.

In the original Bitcoin paper and other research papers since, it is assumed that Bitcoin blocks are mined at the instants of a homogeneous Poisson process. Based on blockchain block arrival data a...

Aim The involvement of pelvic sidewall (PSW) lymph nodes in rectal cancer is a marker of locally advanced disease and poor prognosis. Eastern countries generally advocate lateral lymph node dissection (LLND) over the Western approach of neoadjuvant chemoradiotherapy and more limited surgery. The aim of this study was to evaluate how these advanced cancers were treated in three UK Health Boards. Methodology This was a retrospective review of three colorectal multidisciplinary team meetings from 2008 to 2016. All patients with rectal cancer and suspicious PSW lymph nodes on pretreatment MRI were included. Results There were 153 (6.2%) patients who met the inclusion criteria from a total of 2461 diagnosed rectal cancers. There was significant variability between the three centres with surgical intervention ranging from 59.2% to 84.4%, P = 0.015. There were 81 patients who had neoadjuvant chemoradiotherapy prior to surgery; of these 67 (82.7%) still had positive PSW nodes on the restaging MRI, but only 13 (19.4%) had LLND. There was no difference in local recurrence (15.3% vs 11.8%, P = 0.66), 5-year overall survival (69.2% vs 80.1%, P = 0.16) or 5-year disease-free survival (69.2% vs 79.4%, P = 0.72) between patients having LLND and those receiving standard neoadjuvant treatment followed by total mesorectal excision surgery. Conclusions This study has demonstrated that rectal cancer patients with PSW positive nodal disease have advanced disease, mostly of the lower rectum, and receive a highly heterogeneous spectrum of therapies, even within a relatively small geographical area. Greater accuracy in our preoperative staging is needed to select those patients who will benefit from LLND surgery.

Teaching introductory statistics is a service requirement for many mathematics faculty, and the audience is often anxious about the subject and not always excited about the material. Making class f...

Effective diagnosis of disease and its progression can be aided by 19 F magnetic resonance imaging (MRI) techniques. Specifically, the inherent sensitivity of the spin-lattice relaxation time (T1 ) of 19 F nuclei to oxygen partial pressure makes 19 F MRI an attractive non-invasive approach to quantify tissue oxygenation in a spatiotemporal manner. However, there are only few materials with the adequate sensitivity to be used as oxygen-sensitive 19 F MRI agents at clinically relevant field strengths. Motivated by the limitations in current technologies, we report highly fluorinated monomers that provide a platform approach to realize water-soluble, partially fluorinated copolymers as 19 F MRI agents with the required sensitivity to quantify solution oxygenation at clinically relevant magnetic field strengths. The synthesis of a systematic library of partially fluorinated copolymers enabled a comprehensive evaluation of copolymer structure-property relationships relevant to 19 F MRI. The highest-performing material composition demonstrated a signal-to-noise ratio that corresponded to an apparent 19 F density of 220 mm, which surpasses the threshold of 126 mm 19 F required for visualization on a three Tesla clinical MRI. Furthermore, the T1 of these high performing materials demonstrated a linear relationship with solution oxygenation, with oxygen sensitivity reaching 240×10-5 mmHg-1 s-1 . The relationships between material composition and 19 F MRI performance identified herein suggest general structure-property criteria for the further improvement of modular, water-soluble 19 F MRI agents for quantifying oxygenation in environments relevant to medical imaging.

Background Approximately 30,000 people per annum undergo major, emergency abdominal, gastrointestinal surgery, of which 36% (~10,800) are carried out for emergency colorectal pathology. Approximately 14% of all patients requiring emergency surgery undergo laparoscopic surgery. Aims The aims of the LaCeS feasibility trial (Laparoscopic versus Open Colorectal Surgery in the Acute Setting) were to assess the feasibility, safety and acceptability of performing a large-scale definitive phase III randomised controlled trial with a comparison of emergency laparoscopic with open surgery for acute colorectal pathology. Methods LaCeS was designed as a prospective, multicentre, single blind, parallel group, pragmatic, randomised controlled feasibility trial with an integrated qualitative study. Randomisation was performed centrally with patients being randomised on a 1:1 basis between laparoscopic or open surgery. Results A total of 64 patients were recruited across 5 centres. The overall average steady state recruitment rate was 1.2 patients/month. Baseline compliance for clinical and HrQoL data was 99.8% and 93.8% respectively. The conversion rate from laparoscopic to open surgery was 39.4% (95% CI 22.9% – 57.9%). The 30 day post-operative complication rate was 27.3% (95% CI 13.3- 45.5) in the laparoscopic arm and 41.9% (95% CI 24.6 – 60.9) in the open arm. Discussion The LaCeS feasibility trial has demonstrated that it is possible to evaluate laparoscopic surgery in the emergency colorectal setting within the context of a randomised controlled trial. LaCeS has demonstrated that it is possible to recruit to a surgical trial in the emergency setting, with good compliance to trial procedures and processes, and overall acceptability by patients and clinicians. The safety data obtained for laparoscopic emergency colorectal surgery indicate an acceptable safety profile, particularly when considering it to that observed in the open arm. Trial Registration ISRCTN15681041 https://doi.org/10.1186/ISRCTN15681041. Funding body: National Institute of Health Research – Research for Patient Benefit

Pacific walruses (Odobenus rosmarus divergens) play a vital role in Arctic marine ecosystems and the subsistence lifestyle of Alaska Native communities. Museum collections contain numerous archaeological and historic walrus specimens that have proven useful in a variety of studies; however, for many cases, the sex of these specimens is unknown. Sexes of adult (> 5 years determined by tooth aging) Atlantic walruses (Odobenus rosmarus rosmarus) have been accurately determined in previous studies using mandible measurements. We tested the validity of this approach for Pacific walruses, and used full fusion of the mandibular symphysis to define adults. Using high precision digital calipers (± 0.01 mm), four measurements were taken either on the left or right side of 91 walrus mandibles: 80 modern mandibles (70 known-sex specimens; 10 unknown-sex specimens) and 11 archaeological mandibles of unknown sex. We used linear discriminant function analysis (LDFA) to determine what measurements best distinguished Pacific walrus males from females. Minimum mandible thickness had the most predictive power, whereas mandible length, height, and depth, were less predictive. Posterior probabilities indicated that LDFA classified the known-sex Pacific walruses with 100% accuracy, and unknown sex with ≥ 90% probability. The ability to define the sex of unknown individuals accurately could greatly increase the sample size of future projects dealing with skeletal remains, and will improve future research efforts.

Multistate modelling is a strategy for jointly modelling related time-to-event outcomes that can handle complicated outcome relationships, has appealing interpretations, can provide insight into different aspects of disease development and can be useful for making individualized predictions. A challenge with using multistate modelling in practice is the large number of parameters, and variable selection and shrinkage strategies are needed in order for these models to gain wider adoption. Application of existing selection and shrinkage strategies in the multistate modelling setting can be challenging due to complicated patterns of data missingness, inclusion of highly correlated predictors and hierarchical parameter relationships. In this article, we discuss how to modify and implement several existing Bayesian variable selection and shrinkage methods in a general multistate modelling setting. We compare the performance of these methods in terms of parameter estimation and model selection in a multistate cure model of recurrence and death in patients treated for head and neck cancer. We can view this work as a case study of variable selection and shrinkage in a complicated modelling setting with missing data.

The simultaneous quantification of several transcripts via multiplex PCR can accelerate research in fish physiological responses to diet and enable the development of superior aquafeeds for farmed fish. We designed two multiplex PCR panels that included assays for 40 biomarker genes representing key aspects of fish physiology (growth, metabolism, oxidative stress, and inflammation) and 3 normalizer genes. We used both panels to assess the physiological effects of replacing fish meal and fish oil by terrestrial alternatives on Atlantic salmon smolts. In a 14-week trial, we tested three diets based on marine ingredients (MAR), animal by-products and vegetable oil (ABP), and plant protein and vegetable oil (VEG). Dietary treatments affected the expression of genes involved in hepatic glucose and lipid metabolism (e.g., srebp1, elovl2), cell redox status (e.g., txna, prdx1b), and inflammation (e.g., pgds, 5loxa). At the multivariate level, gene expression profiles were more divergent between fish fed the marine and terrestrial diets (MAR vs. ABP/VEG) than between the two terrestrial diets (ABP vs. VEG). Liver ARA was inversely related to glucose metabolism (gck)- and growth (igfbp-5b1, htra1b)-related biomarkers and hepatosomatic index. Liver DHA and EPA levels correlated negatively with elovl2, whereas ARA levels correlated positively with fadsd5. Lower hepatic EPA/ARA in ABP-fed fish correlated with the increased expression of biomarkers related to mitochondrial function (fabp3a), oxidative stress (txna, prdx1b), and inflammation (pgds, 5loxa). The analysis of hepatic biomarker gene expression via multiplex PCR revealed potential physiological impacts and nutrient-gene interactions in Atlantic salmon fed lower levels of marine-sourced nutrients.

Addressing the widespread problem of sexual assault in college environments requires both prevention programming and policies addressing sexual misconduct in institutions of higher education. Through the Campus Sexual Assault Policy and Prevention Initiative, nine programs funded by the Office on Women’s Health approached this problem within a network of eight to 13 campuses apiece, supported by national organizations and local task forces. Near the close of the 3-year project period (June 2016–June 2019), key informant interviews were conducted with project directors and campus representatives. Contextual factors elucidating the project approaches, challenges, and successes were investigated through 31 interviews (nine grantee interviews and 22 campus representative interviews). Analyses across all interview content contributed to the development of several key themes related to staffing efforts to strengthen campus policies and prevention programs, working within institutions of varying structural characteristics, infusing efforts with trauma-informed perspectives, attending to cultural differences across campuses, and seeking to follow recommended guidelines in the context of campus-specific factors. Overall, the interviewees reported specific progress toward the program goals.

Despite substantial theoretical and empirical work examining the relation between attention-deficit/hyperactivity disorder (ADHD) and cortisol response, mixed results across studies suggest there are potential moderators in this link that have been previously unexplored. Emotion dysregulation (ED) and sluggish cognitive tempo (SCT) commonly co-occur with ADHD, with one another, and have yet to be included together in investigations exploring this relation. The current study examined the moderating effects of ED and SCT on the relation between symptoms of ADHD and cortisol response. Salivary cortisol response after participation in a novel social group was examined in 102 children (Mage = 8.75 years, 69.6% male), approximately half with ADHD. A significant three-way interaction of ADHD, ED, and SCT on cortisol response (p = .014) indicated the strongest association between ADHD and cortisol response when ED and SCT were low (p = .047), with children low in ADHD showing greater cortisol response in the presence of elevated ED (p = .033) or SCT (p = .021). These findings point to a pattern of cortisol responding that is specific to ADHD symptomatology, possibly indicating attenuated hypothalamic-pituitary-adrenal axis activity, and demonstrate the effect of ED and SCT on social functioning. Other clinical implications based on the findings across different levels of ADHD, ED, and SCT symptoms are discussed. Future research should seek to explore the mechanisms underlying the different patterns of responding.

In 2015, Guglielmi and Badia discussed optimal strategies in a particular type of service system with two strategic servers. In their setup, each server can be either active or inactive and an active server can be requested to transmit a sequence of packets. The servers have varying probabilities of successfully transmitting when they are active, and both servers receive a unit reward if the sequence of packets is transmitted successfully. Guglielmi and Badia provided an analysis of optimal strategies in four scenarios: where each server does not know the other’s successful transmission probability; one of the two servers is always inactive; each server knows the other’s successful transmission probability and they are willing to cooperate. Unfortunately, the analysis by Guglielmi and Badia contained some errors. In this paper we correct these errors. We discuss three cases where both servers (I) communicate and cooperate; (II) neither communicate nor cooperate; (III) communicate but do not cooperate. In particular, we obtain the unique Nash equilibrium strategy in Case II through a Bayesian game formulation, and demonstrate that there is a region in the parameter space where there are multiple Nash equilibria in Case III. We also quantify the value of communication or cooperation by comparing the social welfare in the three cases, and propose possible regulations to make the Nash equilibrium strategy the socially optimal strategy for both Cases II and III. doi:10.1017/S1446181120000048

This paper presents the synthesis and structural characterization of 6,6′-bis[(1R,2S,5R)-isomenthoxy]-2,2′-bipyridine obtained by homocoupling of chiral pyridyl-ether 2-bromo-6-[(1R,2S,5R)-isomenthoxy]-pyridine. The two-step synthetic procedure afforded chiral bipyridine in a good yield and the structure of the compound is determined by X-ray diffraction. It crystallizes in a non-centrosymmetric chiral crystal structure type (P2, a = 10.7543(8) A, b = 8.4488(6) A, c = 15.8964(10) A, β = 104.035(7)°, V = 1401.24(17) A3, Z = 2). Moreover, the compound is characterized by FTIR, high resolution mass spectrometry and its complexation capacity to transition metals is studied by UV-Vis spectroscopy.

In the US, mortality in sickle cell disease (SCD) increases after age 18–20 years. Biomarkers of mortality risk can identify patients who need intensive follow-up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3–20 years into an observational study in 2006–2010 and followed 497 patients for a median of 88 months (range 1–105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality. Estimated survival to 18 years was 99% and to 25 years, 94%. Causes of death were known in seven of 10 patients: stroke in four (hemorrhagic two, infarctive one, unspecified one), multiorgan failure one, parvovirus B19 infection one, sudden death one. Baseline TRV ≥2.7 m/second (>2 SD above the mean in age-matched and gender-matched non-SCD controls) was observed in 20.0% of patients who died vs 4.6% of those who survived (P = .012 by the log rank test for equality of survival). The baseline variable most strongly associated with an elevated TRV was a high hemolytic rate. Additional biomarkers associated with mortality were ferritin ≥2000 μg/L (observed in 60% of patients who died vs 7.8% of survivors, P < .001), forced expiratory volume in 1 minute to forced vital capacity ratio (FEV1/FVC)

Dipole moment (μ) is a critical parameter for molecules and nanomaterials as it affects many properties. In metal–thiolate (SR) nanoclusters (NCs), μ is commonly low (0–5 D) compared to quantum dot...

© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Adolescent dating and relationship violence is associated with health harms and is an important topic for sex education. School-based interventions addressing this have been effective in the USA, but schools in England confront pressures that might hinder implementation. We assessed the feasibility of, and contextual enablers/barriers to implementing Project Respect, a whole-school intervention. We conducted a pilot trial with process evaluation in six English secondary schools. Intervention comprised: training; policy-review; mapping and patrolling ‘hotspots’; parent information; help-seeking app; and a curriculum (including student-led campaigns) targeting dating violence. Process evaluation included assessments of fidelity and interviews with the trainer and school staff. Schools delivered training and lessons partially or completely and made parent and app information available. Two schools conducted policy reviews; none patrolled hotspots or implemented campaigns. Implementation was strengthened where staff saw dating violence as a priority. Delivery was undermined where staff were insufficiently involved, lacked time for planning or struggled to timetable lessons, and where new school challenges undermined engagement. School-based health interventions must work to build staff buy-in and ensure they do not overburden schools. Dating and relationship violence might best be addressed in this context as a broader aspect of sex education.

We prove a counterintuitive result concerning the expected hitting/absorption time for a class of Markov chains. The “paradox” already shows itself in the following elementary example that is suita...

The optimal dietary requirement of omega-3 long-chain polyunsaturated fatty acids (ω3 LC-PUFA), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), for Atlantic salmon that promotes growth and health warrants careful investigation. We used 44K microarrays to study the influence of increasing levels of dietary DHA + EPA (0, 1.0, and 1.4% of the diet, as formulated) in the presence of high linoleic acid (LA) on Atlantic salmon growth and liver transcriptome. After a 14-week feeding trial, Atlantic salmon fed diet ω3LC0 (i.e. 0% of DHA + EPA) showed significantly lower final weight and weight gain, and higher feed conversion ratio compared with ω3LC1.0 and ω3LC1.4 diet groups. The microarray experiment identified 55 and 77 differentially expressed probes (Rank Products analyses; PFP

This study investigates the effects of narcissism, envy and self-promotion on travellers’ sharing of travel-related photographs of themselves (“selfies”) through social media, based upon social com...

Small nanoparticles, a.k.a. nanoclusters, of transition metals have been studied extensively for a wide range of applications due to their highly tunable properties dependent on size, structure, and composition. For these small particles, there has been considerable effort towards theoretically predicting what is the most energetically favorable arrangement of atoms when forming a nanocluster. In this work, we develop a computational framework that couples density-functional theory calculations with mathematical optimization modeling to identify highly stable, mono-metallic transition metal nanoclusters of various sizes. This is accomplished by devising and solving a rigorous mathematical optimization model that maximizes a general cohesive energy function to obtain nanocluster structures of provably maximal cohesiveness. We then utilize density-functional theory calculations and error term regression to identify model corrections that are necessary to account with better accuracy for different transition metals. This allows us to encode metal-specific, analytical functions for cohesive energy into a mathematical optimization-based framework that can accurately predict which nanocluster geometries will be most cohesive according to density-functional theory calculations. We employ our framework in the context of Ag, Au, Cu, Pd and Pt, and we present sequences of highly cohesive nanoclusters for sizes up to 100 atoms, yielding insights into structures that might be experimentally accessible and/or structures that could be used as model nanoclusters for further study.

Objective: Cauda Equina Syndrome (CES) is a challenging condition to diagnose due to such variability in clinical features and poor correlation with MRI findings. It requires surgery within hours to avoid damage to the bowel, bladder, sexual organs and lower limbs. There are empirical studies exploring patients’ perspectives of having CES, however, there is no literature to review NHS staff perceptions of managing this neurosurgical emergency. The aim is to explore perceptions of senior clinical staff who commonly manage patients with suspected CES in secondary care within the Emergency Department (ED) and Trauma and Orthopaedics (T&O) to improve the management of CES. The main objective is to identify barriers to successful management and possible solutions to improve care. Methods: A self-administered non-validated questionnaire was designed to identify barriers experienced and potential solutions. In addition, a Nominal Group Technique (NGT) was used to gain a greater insight. The qualitative data obtained was analysed by thematic analysis. Results: The questionnaire generated a 73% response rate. Six senior clinicians attended the NGT with representation from the three clinical specialities; ED, T&O and Advanced Physiotherapy Practitioner (APP). The challenges and potential solutions were categorised into themes and subthemes. The barriers highlighted included; staff confidence in clinical diagnosis; fear of litigation and inter-professional relations; patient psychosocial factors, expectations and comorbidities; lack of agreed local pathway. The solutions raised include; staff training; standardising local/national pathway; access to daily Magnetic Resonance Imaging (MRI) slots. Conclusion: Patient safety and accurate diagnosis of CES is at the forefront of decision-making despite organisation barriers and limitations of existing pathways. A shift away from admission to expedite an urgent MRI requires a change to traditional clinical practice and expectations. In times of rising pressures and financial constraints, collaborative working is essential to implement and sustain the required changes highlighted in this study.

Background Blood loss during adult spinal deformity surgery is multifactorial. Anesthetic-related factors, such as mode of mechanical ventilation, may contribute to intraoperative blood loss. The aim of this study was to determine the influence of ventilator mode and ventilator parameters on intraoperative blood loss and transfusion requirements in patients undergoing prone position spine surgery. Methods This single-center retrospective study examined electronic medical records of patients ≥18 years of age who underwent elective prone position spine surgery between May 2015 and June 2016. Associations between ventilator mode and ventilator parameters with intraoperative estimated blood loss (EBL), packed red blood cells (PRBCs), fresh-frozen plasma (FFP), cryoprecipitate and platelet transfusions, and subfascial drain output were examined using multiple linear regression models controlling for age, sex, American Society of Anesthesiologist (ASA) physical status score, body mass index (BMI), preoperative blood coagulation parameters and laboratory values, operative levels, cage constructs, osteotomies, transforaminal lumbar interbody fusions, laminectomies, reoperation, spine surgery invasiveness index, and operative time. In a secondary analysis, EBL, blood product transfusions, and postoperative drain output were compared between pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV) propensity score-matched cohorts. Results Nine hundred forty-six records were reviewed, and 822 were included in the analysis. After adjusting for confounding, no statistically significant associations were observed between mode of ventilation and intraoperative EBL (estimate, -2; 95% confidence interval [CI], -248 to 245; P = .99) or blood product transfusions (PRBC: estimate, -9; 95% CI, -154 to 135; P = .90; FFP: estimate, -3; 95% CI, -59 to 54; P = .93; cryoprecipitate: estimate, -14; 95% CI, -70 to 43; P = .63; platelets: -7; 95% CI, -39 to 24; P = .64). After propensity score matching (n = 27 per group), no significant differences were observed in EBL (mean difference, 525 mL; 95% CI, -15 to 1065; P = .056) or blood transfusions (PRBC: mean difference, 208 mL; 95% CI, -23 to 439; P = .077; FFP (mean difference, 34 mL; 95% CI, -17 to 84; P = .19); cryoprecipitate (mean difference, 55 mL; 95% CI, -24 to 133; P = .17); or platelets (mean difference, 26 mL; 95% CI, -12 to 64; P = .18) between PCV and VCV groups. Conclusions In prone position spine surgery, neither mode of mechanical ventilation nor airway pressure is associated with intraoperative blood loss or need for allogeneic transfusion. Use of modern ventilation strategies using lung protective techniques may mitigate differences in blood loss previously observed between PCV and VCV modes.

Gill damage represents a significant challenge in the teleost fish aquaculture industry globally, due to the gill’s involvement in several vital functions and direct contact with the surrounding environment. To examine the local and systemic effects accompanying gill damage (which is likely to negatively affect gill function) of Atlantic salmon, we performed a field sampling to collect gill and liver tissue after several environmental insults (e.g., harmful algal blooms). Before sampling, gills were visually inspected and gill damage was scored; gill scores were assigned from pristine [gill score 0 (GS0)] to severely damaged gills (GS3). Using a 44K salmonid microarray platform, we aimed to compare the transcriptomes of pristine and moderately damaged (i.e., GS2) gill tissue. Rank Products analysis (5% percentage of false-positives) identified 254 and 34 upregulated and downregulated probes, respectively, in GS2 compared with GS0. Differentially expressed probes represented genes associated with functions including gill remodeling, wound healing, and stress and immune responses. We performed gill and liver qPCR for all four gill damage scores using microarray-identified and other damage-associated biomarker genes. Transcripts related to wound healing (e.g., neb and klhl41b) were significantly upregulated in GS2 compared with GS0 in the gills. Also, transcripts associated with immune and stress-relevant pathways were dysregulated (e.g., downregulation of snaclec 1-like and upregulation of igkv3) in GS2 compared with GS0 gills. The livers of salmon with moderate gill damage (i.e., GS2) showed significant upregulation of transcripts related to wound healing (i.e., chtop), apoptosis (e.g., bnip3l), blood coagulation (e.g., f2 and serpind1b), transcription regulation (i.e., pparg), and stress-responses (e.g., cyp3a27) compared with livers of GS0 fish. We performed principal component analysis (PCA) using transcript levels for gill and liver separately. The gill PCA showed that PC1 significantly separated GS2 from all other gill scores. The genes contributing most to this separation were pgam2, des, neb, tnnt2, and myom1. The liver PCA showed that PC1 significantly separated GS2 from GS0; levels of hsp70, cyp3a27, pparg, chtop, and serpind1b were the highest contributors to this separation. Also, hepatic acute phase biomarkers (e.g., serpind1b and f2) were positively correlated to each other and to gill damage. Gill damage-responsive biomarker genes and associated qPCR assays arising from this study will be valuable in future research aimed at developing therapeutic diets to improve farmed salmon welfare.

Due to the fine-grained nature of shale, organic matter particles are generally micro- and nano-scale in size. Functional groups differ between different organic matter types and as such provide unique chemical information for organic matter. Micro-FTIR can provide direct measurement to characterize sample features at the micrometer scale. However, optical diffraction limits its application at the nanometer scale. As a non-destructive high-resolution scanning probe technique, atomic force microscopy (AFM) is very powerful in nanoscale research and has been widely used in the fields of polymers, semiconductors, electrochemistry and biology. To provide a better combination of AFM’s unique advantages with nanoscale chemical analysis, the AFM-IR technique has been developed in recent years and also attracted the attention of geologists to explore the application in geological materials.In this research, AFM-IR which is a quite new technique in geological research was used to investigate the in-situ geochemical characteristics of organic matter in shale. Nanoscale molecular composition of individual organic particles was captured nondestructively, and the distribution of typical functional groups was displayed via 2D IR mapping. In our samples, both alginite and inertinite display chemical homogeneity. The former is dominated by oxygenated and aliphatic contents which indicates a higher hydrocarbon generation potential, whereas the latter is dominated by aromatic carbon. In contrast, migrated solid bitumen particles show compositional heterogeneities at the nanometer scale as some are aromatic-rich and others are aliphatic-rich. Finally, linking this advanced nanochemical technique to potential applications in subsurface energy was explored. This research demonstrates that AFM-IR is a powerful tool to examine the in-situ nanoscale geochemical characteristics of different organic matter types, which can also provide implications for energy applications.

Lepeophtheirus salmonis (sea lice) and bacterial co-infection threatens wild and farmed Atlantic salmon performance and welfare. In the present study, pre-adult L. salmonis-infected and non-infected salmon were intraperitoneally injected with either formalin-killed Aeromonas salmonicida bacterin (ASAL) or phosphate-buffered saline (PBS). Dorsal skin samples from each injection/infection group (PBS/no lice, PBS/lice, ASAL/no lice, and ASAL/lice) were collected at 24 h post-injection and used for transcriptome profiling using a 44K salmonid microarray platform. Microarray results showed no clear inflammation gene expression signatures and revealed extensive gene repression effects by pre-adult lice (2,189 down and 345 up-regulated probes) in the PBS-injected salmon (PBS/lice vs. PBS/no lice), which involved basic cellular (e.g., RNA and protein metabolism) processes. Lice repressive effects were not observed within the group of ASAL-injected salmon (ASAL/lice vs. ASAL/no lice); on the contrary, the observed skin transcriptome changes –albeit of lesser magnitude (82 up and 1 down-regulated probes)– suggested the activation in key immune and wound healing processes (e.g., neutrophil degranulation, keratinocyte differentiation). The molecular skin response to ASAL was more intense in the lice-infected (ASAL/lice vs. PBS/lice; 272 up and 11 down-regulated probes) than in the non-infected fish (ASAL/no lice vs. PBS/no lice; 27 up-regulated probes). Regardless of lice infection, the skin’s response to ASAL was characterized by the putative activation of both antibacterial and wound healing pathways. The transcriptomic changes prompted by ASAL+lice co-stimulation (ASAL/lice vs. PBS/no lice; 1878 up and 3120 down-regulated probes) confirmed partial mitigation of lice repressive effects on fundamental cellular processes and the activation of pathways involved in innate (e.g., neutrophil degranulation) and adaptive immunity (e.g., antibody formation), as well as endothelial cell migration. The qPCR analyses evidenced immune-relevant genes co-stimulated by ASAL and lice in an additive (e.g., mbl2b, bcl6) and synergistic (e.g., hampa, il4r) manner. These results provided insight on the physiological response of the skin of L. salmonis-infected salmon 24 h after ASAL stimulation, which revealed immunostimulatory properties by the bacterin with potential applications in anti-lice treatments for aquaculture. As a simulated co-infection model, the present study also serves as a source of candidate gene biomarkers for sea lice and bacterial co-infection.

Objectives. Assessment of erectile dysfunction (ED) burden could improve health outcomes associated with underlying cardiometabolic and psychological causes of ED. This study provided updated real-world evidence (RWE) on ED epidemiology and quantified healthcare resource utilization (HCRU) and health-related quality of life (HRQoL) burden among men with ED in the UK. Methods. This cross-sectional, prospective real-world evidence study was conducted via a self-reported Internet survey in 2018 in the UK general population. Prevalence of ED was estimated; HCRU and HRQoL were compared between men with ED versus without ED via bivariate analysis. Results. Of 12,490 men included, 41.5% reported ED; 7.5% of men reported severe ED; ED was most prevalent in Wales (44.3%). Men with ED were older (54.1 ± 14.5 vs. 46.8 ± 14.1 years) and often reported modifiable lifestyle risk factors, including smoking (32.8% vs. 26.3%), drinking alcohol (76.1% vs. 71.0%), not exercising (21.7% vs. 19.4%), and being overweight or obese (64.9% vs. 54.6%). Additionally, men with ED more often reported ≥1 comorbid chronic conditions (73.7% vs. 47.7%), including hypertension (31.8% vs. 16.3%), hyperlipidemia (27.6% vs. 14.0%), depression (24.3% vs. 14.6%), anxiety (23.3% vs. 16.6%), and diabetes (15.9% vs. 6.1%) versus men without ED (all,p p

Deterministic epidemic models that allow for replenishment of susceptibles typically display damped oscillatory behaviour. If the population is initially fully susceptible, once an epidemic takes off a distinct trough will exist between the first and second waves of infection. Epidemic dynamics are, however, influenced by stochastic effects, particularly when the prevalence is low. At the beginning of an epidemic, stochastic die-out is possible and well characterised through use of a branching process approximation. Conditional on an epidemic taking off, stochastic extinction is highly unlikely during the first epidemic wave, but the probability of extinction increases again as the wave declines. Extinction during this period, prior to a potential second wave of infection, is defined as 'epidemic fade-out'. We consider a set of observed epidemics, each distinct and having evolved independently, in which some display fade-out and some do not. While fade-out is necessarily a stochastic phenomenon, the probability of fade-out will depend on the model parameters associated with each epidemic. Accordingly, we ask whether time-series data for the epidemics contain sufficient information to identify the key driver(s) of different outcomes-fade-out or otherwise-across the sub-populations supporting each epidemic. We apply a Bayesian hierarchical modelling framework to synthetic data from an SIRS model of epidemic dynamics and demonstrate that we can (1) identify when the sub-population specific model parameters supporting each epidemic have significant variability and (2) estimate the probability of epidemic fade-out for each sub-population. We demonstrate that a hierarchical analysis can provide precise estimates of the probability of fade-out than is possible if considering each epidemic in isolation. Our methods may be applied to both epidemiological and other biological data to identify where differences in outcome-fade-out or recurrent infection/waves are purely due to chance or driven by underlying changes in the parameters driving the dynamics.

The composition and characteristics of organic matter within shales can reveal important information on hydrocarbon generation, migration and accumulation processes during catagenesis. It may also impact upon the chemical properties and mechanical behavior of shales acting as hydrocarbon reservoirs or caprocks/seals for carbon and subsurface energy storage. Here we apply advanced atomic force microscopy-based infrared spectroscopy (AFM-IR) to capture the in-situ chemical structure of nanoscale molecular composition of individual organic particles and map the distribution of typical functional groups nondestructively; something that cannot be achieved via conventional analysis since some methods damage the sample, some only collect bulk measurements and some do not achieve nano-scale resolution. The nanoscale geochemical characteristics of organic matter in thermally mature samples of a Baltic Basin shale, from Lithuania and the Bowland Shale, from the UK, obtained from AFM-IR, are compared in this study. Significant chemical heterogeneity can be observed in migrated solid bitumen. In contrast, graptolite, alginite and inertinite generally display homogeneous molecular composition. The potential role of laminae as barriers to the vertical migration of hydrocarbons is also apparent. This research provides insights into nanoscale geochemical information on different organic matter types in thermally-mature shales to enhance the understanding of molecular structure transformation of organic matter during hydrocarbon expulsion and migration processes, and also sheds light on implications of nanogeochemistry for enhanced gas recovery, carbon sequestration and underground hydrogen storage-related energy applications. We also characterised specific materials which have not been reported in other geological studies using AFM-IR. Some of them display similar characteristics to other organic matter particles in the samples, but the possibilities of unknown organic contaminants introduced to the sample during sample storage or preparation stages cannot be ruled out. A comprehensive analysis on this undefined organic material is provided. Standardized approaches during sample preparation and storage are required for future research to dislodge potential surface-attached contaminants.

BACKGROUND Although playgrounds are designed to promote outdoor play, children with disabilities may be unable to engage in these spaces due to intrinsic and extrinsic factors. Previous research has examined inclusive/accessible playground design when developing new playgrounds; however, it is unclear if there is a best-practice tool for evaluating the inclusivity of existing playground structures. OBJECTIVE A scoping review of both peer-reviewed and grey literature will be employed to explore evaluation tools for playground inclusivity, to enable the participation of children with disabilities. METHODS The conduct of this study will adhere to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. A search for peer-reviewed research studies will be conducted in the following electronic databases: MEDLINE, Scopus, CINAHL, and Embase. Grey literature will be examined via a three-step process: (1) a search in the Canadian Health Research Collection Database; (2) a targeted Google search; and (3) reference list searching. Titles, abstracts, keywords, and full texts of identified studies will be independently screened for inclusion by two reviewers. A synthesis of included articles will describe the publication and auditing tool details. A summary of the findings will highlight the types of playgrounds measured, types of disability considered, measures of inclusion used, and psychometric properties. RESULTS Database searches for peer-reviewed articles were completed in December 2021. A total of 1471 unique records were returned after the removal of 559 duplicate records. Full texts of 167 studies meeting eligibility criteria will be reviewed. The peer-reviewed research search will guide the grey literature search. The scoping review is planned for completion in 2022. CONCLUSIONS A rigorous search of the literature will determine the availability of tools for evaluating existing playground structures for the inclusivity of children with disabilities. The results will inform recommendations on tool applications, and applicable knowledge translation activities. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/37312

BackgroundInflammatory activation has been associated with the severity and progression of chronic heart failure (CHF). Although cardiac rehabilitation is an important therapy, acute bouts of exercise may lead to increases in pro-inflammatory cytokines with exercise intensity mediating these changes.ObjectiveTo evaluate the acute inflammatory response in patients living with CHF during a randomized trial following Steady State (SS) or High Intensity Interval (HIIT) training.MethodsPatients living with CHF (n = 14) were stratified (for body mass and aerobic power) and randomized into SS and HIIT cycle exercise. The HIIT exercise training involved 2 min work:recovery phases at 90:40% heart rate reserve. The SS exercise training involved continuous exercise at 65% of heart rate reserve (matched total work). Acute inflammatory markers were evaluated (via ELISA) at baseline, immediately following the bout, and at 6, 24, and 48 h post-exercise.ResultsThere was limited differences in the changes in inflammatory biomarkers across time between the HIIT and SS groups. Both groups experienced a significant (p < 0.05) change in Interleukin-6 immediately post-exercise.ConclusionsA single bout of HIIT or SS does not result in excessive inflammatory activation in CHF patients. Acute HIIT and SS result in similar changes in inflammatory markers. These findings have important implications for exercise training and rehabilitation programs in persons living with CHF.

Publisher Copyright: © 2022 British Ecological Society. An increasing number of species are facing unprecedented levels of threat to their long-term survival due to the direct and indirect impacts of climate change. Key opportunities for science to inform wildlife management are linked to increasing our understanding of how changes in climatic conditions will impact species, as well as whether, and how, managers may facilitate species' ability to adapt to change. However, information on species' climate change vulnerability and the effectiveness of potential conservation actions are not yet strategically collected or collated; this disconnect between threat level, ecological research and conservation practice is reducing the opportunities to guide decision-making, ultimately hindering conservation outcomes. To demonstrate this point, we explore how existing knowledge can be brought together in a pressure-state-response framework that connects climate change ecology, conservation evidence assessments and management. Seabirds in Western Europe are used as a case study, as they are well-researched and vulnerable to climate change. Using a combination of literature reviews and surveys, we identify the main threats posed to seabirds in the region by climate change, as well as existing conservation actions that could be applied to lessen the impacts of each of these threats. Our results show that 29% of the types of actions considered for reducing the impacts of climate change on seabirds are either associated with conflicting evidence or lack sufficient information to make robust conclusions about their effectiveness: actions aiming at restoring or creating habitat, encouraging relocation, treating or preventing disease, and reducing inter-species competition all have limited or mixed evidence to support their use. Moreover, several threats identified by conservation practitioners as being of high priority to address, such as changes in prey abundance and eutrophication, have few or no viable identified actions to reduce their impact on seabirds. Synthesis and applications. We suggest that existing knowledge on species vulnerability to climate change and evidence of conservation action effectiveness should be more commonly brought together in tailored pressure-state-response frameworks. Such an approach provides an easily transferable platform for identifying missing information and areas where connections between research and management need to be tightened to improve conservation outcomes.

Current algorithms to evaluate gestational age (GA) during pregnancy rely on hospital coding at delivery and are not applicable to non-live births. We developed an algorithm using fertility procedures and fertility tests, without relying on delivery coding, to develop a novel GA algorithm in live-births and stillbirths.Three pregnancy cohorts were identified from 16 health-plans in the Sentinel System: 1) hospital admissions for live-birth, 2) hospital admissions for stillbirth, and 3) medical chart-confirmed stillbirths. Fertility procedures and prenatal tests, recommended within specific GA windows were evaluated for inclusion in our GA algorithm. Our GA algorithm was developed against a validated delivery-based GA algorithm in live-births, implemented within a sample of chart-confirmed stillbirths, and compared to national estimates of GA at stillbirth.Our algorithm, including fertility procedures and 11 prenatal tests, assigned a GA at delivery to 97.9% of live-births and 92.6% of stillbirths. For live-births (n = 4 701 207), it estimated GA within 2 weeks of a reference delivery-based GA algorithm in 82.5% of pregnancies, with a mean difference of 3.7 days. In chart-confirmed stillbirths (n = 49), it estimated GA within 2 weeks of the clinically recorded GA at delivery for 80% of pregnancies, with a mean difference of 11.1 days. Implementation of the algorithm in a cohort of stillbirths (n = 40 484) had an increased percentage of deliveries after 36 weeks compared to national estimates.In a population of primarily commercially-insured pregnant women, fertility procedures and prenatal tests can estimate GA with sufficient sensitivity and accuracy for utility in pregnancy studies.

Survival modeling with time-varying coefficients has proven useful in analyzing time-to-event data with one or more distinct failure types. When studying the cause-specific etiology of breast and prostate cancers using the large-scale data from the Surveillance, Epidemiology, and End Results (SEER) Program, we encountered two major challenges that existing methods for estimating time-varying coefficients cannot tackle. First, these methods, dependent on expanding the original data in a repeated measurement format, result in formidable time and memory consumption as the sample size escalates to over one million. In this case, even a well-configured workstation cannot accommodate their implementations. Second, when the large-scale data under analysis include binary predictors with near-zero variance (e.g., only 0.6% of patients in our SEER prostate cancer data had tumors regional to the lymph nodes), existing methods suffer from numerical instability due to ill-conditioned second-order information. The estimation accuracy deteriorates further with multiple competing risks. To address these issues, we propose a proximal Newton algorithm with a shared-memory parallelization scheme and tests of significance and nonproportionality for the time-varying effects. A simulation study shows that our scalable approach reduces the time and memory costs by orders of magnitude and enjoys improved estimation accuracy compared with alternative approaches. Applications to the SEER cancer data demonstrate the real-world performance of the proximal Newton algorithm.

Infants with inborn errors of immunity (IEI), born in countries where Bacillus-Calmette-Guerin (BCG) vaccination is recommended at birth, are at risk of developing infectious complications following vaccination. A prompt diagnosis of disseminated BCG infection in these infants is essential, as many will require stem cell transplantation (SCT) for the immunologic cure. In patients with IEI, the mortality risk from disseminated mycobacterial infection is high, both before and following SCT.A 7-month-old Qatari infant with an IEI, homozygous IKBKB gene mutation, was evaluated at our institution for SCT. He had a history of recurrent pneumonias, but pretransplant evaluation revealed negative cultures from bronchoalveolar fluid, blood and urine. At 8 months of age, the infant developed skin nodules of unclear etiology, prompting additional evaluation.Given his profound immunosuppression and receipt of broad-spectrum antimicrobials, plasma metagenomic next-generation sequencing (mNGS) was obtained and identified Mycobacterium tuberculosis complex within 72 hours. A skin biopsy was performed, and antimycobacterial therapy was initiated. Mycobacterium bovis-BCG was confirmed from cultures 3 weeks later. Treatment was complicated by elevated serum liver transaminases and aminoglycoside-associated high-frequency hearing loss. The infant completed 14 months of treatment from engraftment. Evaluation for active BCG infection after SCT was negative.In an infant with a unique IEI, plasma mNGS provided the first diagnosis of disseminated BCG infection. We believe that early initiation of antimycobacterial treatment improved the infant's clinical outcome. Plasma mNGS testing should be considered as a noninvasive screen for infectious pathogens in children with IEIs before SCT.

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value

Water resources management is a critical issue in Africa where many regions are subjected to sequential droughts and floods. The objective of our work was to assess spatiotemporal variability in water storage and related controls (climate, human intervention) in major African aquifers and consider approaches toward more sustainable development. Different approaches were used to track water storage, including GRACE/GRACE Follow On satellites for Total Water Storage (TWS); satellite altimetry for reservoir storage, MODIS satellites for vegetation indices, and limited ground-based monitoring. Results show that declining trends in TWS (60–73 km3 over the 18 yr GRACE record) were restricted to aquifers in northern Africa, controlled primarily by irrigation water use in the Nubian and NW Saharan aquifers. Rising TWS trends were found in aquifers in western Africa (23–49 km3), attributed to increased recharge from land use change and cropland expansion. Interannual variability dominated TWS variability in eastern and southern Africa, controlled primarily by climate extremes. Climate teleconnections, particularly El Nino Southern Oscillation and Indian Ocean Dipole, strongly controlled droughts and floods in eastern and southern Africa. Huge aquifer storage in northern Africa suggests that the recent decadal storage declines should not impact the regional aquifers but may affect local conditions. Increasing groundwater levels in western Africa will need to be managed because of locally rising groundwater flooding. More climate resilient water management can be accomplished in eastern and southern Africa by storing water from wet to dry climate cycles. Accessing the natural water storage provided by aquifers in Africa is the obvious way to manage the variability between droughts and floods.

We report statistically significant detections of non-radial nongravitational accelerations based on astrometric data in the photometrically inactive objects 1998 KY$_{26}$, 2005 VL$_1$, 2016 NJ$_{33}$, 2010 VL$_{65}$, 2016 RH$_{120}$, and 2010 RF$_{12}$. The magnitudes of the nongravitational accelerations are greater than those typically induced by the Yarkovsky effect and there is no radiation-based, non-radial effect that can be so large. Therefore, we hypothesize that the accelerations are driven by outgassing, and calculate implied H$_2$O production rates for each object. We attempt to reconcile outgassing induced acceleration with the lack of visible comae or photometric activity via the absence of surface dust and low levels of gas production. Although these objects are small and some are rapidly rotating, surface cohesive forces are stronger than the rotational forces and rapid rotation alone cannot explain the lack of surface debris. It is possible that surface dust was removed previously, perhaps via outgassing activity that increased the rotation rates to their present day value. We calculate dust production rates of order $\sim10^{-4}$ g s$^{-1}$ in each object assuming that the nuclei are bare, within the upper limits of dust production from a sample stacked image of 1998 KY$_{26}$ of $\dot{M}_{\rm Dust}, 21 pages, 9 figures, 3 tables, accepted for publication in the Planetary Science Journal

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, los autores pertenecientes a la UAM y el nombre del grupo de colaboración, si lo hubiere, This is a pre-copyedited, author-produced PDF of an article accepted for publication in Monthly Notices of the Royal Astronomical Society following peer review. The version of record Monthly Notices of the Royal Astronomical Society 520.2 (2023): 2009-2023 is available online at: https://academic.oup.com/mnras/article-abstract/520/2/2009/6988199?redirectedFrom=fulltext#no-access-message, Reverberation mapping measurements have been used to constrain the relationship between the size of the broad-line region and luminosity of active galactic nuclei (AGN). This R-L relation is used to estimate single-epoch virial black hole masses, and has been proposed to use to standardize AGN to determine cosmological distances. We present reverberation measurements made with Hβ from the 6-yr Australian Dark Energy Survey (OzDES) Reverberation Mapping Program. We successfully recover reverberation lags for eight AGN at 0.12 < z < 0.71, probing higher redshifts than the bulk of Hβ measurements made to date. Our fit to the R-L relation has a slope of α = 0.41 ± 0.03 and an intrinsic scatter of σ = 0.23 ± 0.02 dex. The results from our multi-object spectroscopic survey are consistent with previous measurements made by dedicated source-by-source campaigns, and with the observed dependence on accretion rate. Future surveys, including LSST, TiDES, and SDSS-V, which will be revisiting some of our observed fields, will be able to build on the results of our first-generation multi-object reverberation mapping survey, The DES participants from Spanish institutions are partially supported by MICINN under grants ESP2017-89838, PGC2018-094773, PGC2018-102021, SEV-2016-0588, SEV-2016-0597, and MDM-2015-0509, some of which include ERDF funds from the European Union. IFAE is partially funded by the CERCA program of the Generalitat de Catalunya. Research leading to these re-sults has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013) including ERC grant agreements 240672, 291329, and 306478. We acknowledge support from the Brazilian Instituto Nacional de Ciên-cia e Tecnologia (INCT) do e-Universo (CNPq grant 465376/2014-2). This manuscript has been authored by Fermi Research Alliance, LLC under Contract No. DE-AC02-07CH11359 with the U.S. De-partment of Energy, Office of Science, Office of High Energy Physics.

Mineral authigenesis in mudstones responds differently across the compositional spectrum of fine-grained rocks, resulting in a complex array of possible rock fabrics that affect the mechanical capacity of mudstones. Within carbonate-rich mudstones, geochemical controls on silicate and carbonate mineral reactions are variable and poorly understood. Here we analyse the diagenetic minerals of the carbonate-rich Hodder Mudstone from the Carboniferous Bowland Basin, UK, using SEM petrography combined with X-ray-based inorganic geochemical data. Our findings show that up to 90% of quartz cements in the samples are diagenetic, originating mainly from biogenic silica dissolution and clay mineral reactions. It is also evident that due to the varying diagenetic silica-yielding reactions, authigenic silica overgrowths and isolated authigenic quartz crystals are localized in argillaceous samples, while calcareous samples are characterized by silica replacement textures and quartz/calcite intergrowths. Moreover, euhedral dolomite crystals are concentrated within argillaceous units, whereas calcareous units are characterized by anhedral dolomite precipitation and replacement textures. These finding presents a case for facies-selective cementation, as both early and burial diagenetic alterations were observed to be controlled by primary depositional components of biogenic debris and extrabasinal silicate detritus that resulted in complex and variable precipitation of authigenic minerals.

IMPORTANCE: Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM). OBJECTIVE: To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM. DESIGN, SETTING, AND PARTICIPANTS: A population of patients with late-onset DCM who had undergone genetic testing in 7 international tertiary referral centers worldwide were enrolled from March 1990 to August 2020. A positive genotype was defined as the presence of pathogenic or likely pathogenic (P/LP) variants. MAIN OUTCOMES AND MEASURES: The study outcome was all-cause mortality. RESULTS: A total of 184 patients older than 60 years (103 female [56%]; mean [SD] age, 67 [6] years; mean [SD] left ventricular ejection fraction, 32% [10%]) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin-truncating variants were the most prevalent (present in 46 [25%] of the total population and accounting for 46 [69%] of all genotype-positive patients). During a median (interquartile range) follow-up of 42 (10-115) months, 23 patients (13%) died; 17 (25%) of these were carriers of P/LP variants, while 6 patients (5.1%) were genotype-negative. CONCLUSIONS AND RELEVANCE: Late-onset DCM might represent a distinct subgroup characterized by and a high genetic variation burden, largely due to titin-truncating variants. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in older patients.

In this paper, we present an open source software ($\texttt{SAMUS}$) which simulates constant-density, constant-viscosity liquid bodies subject to tidal forces for a range of assumed viscosites and sizes. This software solves the Navier-Stokes equations on a finite-element mesh, incorporating the centrifugal, Coriolis, self-gravitational, and tidal forces. The primary functionality is to simulate the deformation of minor bodies under the influence of tidal forces. It may therefore be used to constrain the composition and physical structure of bodies experiencing significant tidal forces, such as 99942 Apophis and 1I/`Oumuamua. We demonstrate that $\texttt{SAMUS}$ will be useful to constrain the material properties of Apophis during its near-Earth flyby in 2029. Depending on the material properties, Apophis may experience an area change of up to 0.5\%, with similar effects on the photometric brightness. We also apply $\texttt{SAMUS}$ to constrain the material dynamic viscosity of 1I/`Oumuamua, the first interstellar object discovered traversing the inner Solar System. `Oumuamua experienced a close approach to the Sun at perihelion ($q\simeq 0.25$ au) during which there were significant tidal forces that may have caused deformation of the body. This deformation could have lead to observable changes in the photometric light curve based on the material properties. The application of $\texttt{SAMUS}$ to produce synthetic observations which incorporate tidal deformation effects demonstrate that no deformation -- an infinite dynamic viscosity -- best reproduces the photometric data. While these results indicate that `Oumuamua did not experience significant tidal deformation, a sophisticated model incorporating non-principal axis rotation is necessary to conclusively analyze both `Oumuamua and Apophis., Comment: 26 pages, 15 figures, 5 tables. Accepted by AAS Planetary Science Journal. Split into two papers based on reviewer and editor suggestions. Comments welcome. Publicly available software at https://github.com/astertaylor/Oumuamua

Given the clinical effect of progeria syndrome, understanding the cell mechanical behavior of this pathology could benefit the patient's treatment. Progeria patients show a point mutation in the lamin A/C gene (LMNA), which could change the cell's biomechanical properties. This paper reports a mechano-dynamic analysis of a progeria mutation (c.1824 C > T, p.Gly608Gly) in neonatal rat ventricular myocytes (NRVMs) using cell indentation by atomic force microscopy to measure alterations in beating force, frequency, and contractile amplitude of selected cells within cell clusters. Furthermore, we examined the beating rate variability using a time-domain method that produces a Poincaré plot because beat-to-beat changes can shed light on the causes of arrhythmias. Our data have been further related to our cell phenotype findings, using immunofluorescence and calcium transient analysis, showing that mutant NRVMs display changes in both beating force and frequency. These changes were associated with a decreased gap junction localization (Connexin 43) in the mutant NRVMs even in the presence of a stable cytoskeletal structure (microtubules and actin filaments) when compared with controls (wild type and non-treated cells). These data emphasize the kindred between nucleoskeleton (LMNA), cytoskeleton, and the sarcolemmal structures in NRVM with the progeria Gly608Gly mutation, prompting future mechanistic and therapeutic investigations.