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Background: Fever is o common symptom in critically ill patients and may induce complications and increase mortality in intensive care unit (ICU) patients. Therefore, explorations of effective fever management and related cultural factors of influence are important. Purpose: This study explores the cultural context of the ICU-nurse fever management decision-making process. Methods: This qualitative study was undertaken using a grounded theory approach. We developed a semi-structured questionnaire for in-depth interviews conducted with 11 participants from 7 ICUs in 3 hospitals. Constant comparison, theoretical sampling, literature review, member checking and an expert panel were used to ensure research trustworthiness. Results: The "ICU's unit culture of fever management" category that emerged from study data comprised the two subcategories of "stubbornly persist in traditional fever management" and "ICUs have no standardized fever management guidelines." Unit culture was found to affect the fever management process of ICU nurses significantly. This study discovered that a prevent lack of a standardized fever protocol led participants to manage patient fever symptoms using traditional ICU practices that were not based on published evidence. Participants thus expressed feeling uncertain about their treatments, which could negatively impact upon the quality of care given to critically ill patients, Conclusions / Implications for practice: Findings indicate ICU cultural mores are an important factor influencing the fever management process for nurses Thus, we suggest that nursing education and medical institutions consider empirical evidence and unit culture when developing fever management guidelines in order to facilitate effective nurse decision-making. [ABSTRACT FROM AUTHOR]

We examine the performances of several popular Lévy jump models and some of the most sophisticated affine jump-diffusion models in capturing the joint dynamics of stock and option prices. We develop efficient Markov chain Monte Carlo methods for estimating parameters and latent volatility/jump variables of the Lévy jump models using stock and option prices. We show that models with infinite-activity Lévy jumps in returns significantly outperform affine jump-diffusion models with compound Poisson jumps in returns and volatility in capturing both the physical and risk-neutral dynamics of the S&P 500 index. We also find that the variance gamma model of Madan, Carr, and Chang with stochastic volatility has the best performance among all the models we consider. [ABSTRACT FROM AUTHOR]

Lévy processes have been receiving increasing attention in financial modeling. One distinctive feature of such models is that their characteristic functions are readily available. Inference based on characteristic functions is very useful for studying Levy processes. By incorporating the recent advances in nonparametric approaches, empirical likelihood methods based on characteristic functions are developed in this paper for parameter estimation, testing a particular parametric class including the presence of a jump component in the Levy process and testing for symmetry of a distribution. Simulation and case studies confirm the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

There is a growing demand for complementary and alternative medicines (CAMs) among people with cancer. This study aims to describe how nurses’ respond to people with cancer who use CAMs, and the factors which might contribute to these different responses. A grounded theory approach was used. Six semistructured interviews were conducted with nurses who were working in cancer settings. The core category which emerged from this study was ‘nurses’ responses towards patients who use CAMs’. Nurses respond in a variety of ways to patients who use CAMs. They include: open, sceptical and ambivalent responses. A range of factors which influence the way nurses respond were also identified. These include the ambiguous definitions of CAM, nurses’ personal philosophies, life experiences, evidence of the therapy’s effectiveness, impact on patients, the motives of patients who use CAM and organizational culture. Several implications for nursing education and practice are identified from these findings. [ABSTRACT FROM AUTHOR]

Cardiac ATP-sensitive K+ (KATP) channels are formed by Kir6.2 and SUR2A subunits. We produced transgenic mice that express dominant negative Kir6.x pore-forming subunits (Kir6.1-AAA or Kir6.2-AAA) in cardiac myocytes by driving their expression with the α-myosin heavy chain promoter. Weight gain and development after birth of these mice were similar to nontransgenic mice, but an increased mortality was noted after the age of 4–5 too. Transgenic mice lacked cardiac KATP channel activity as assessed with patch clamp techniques. Consistent with a decreased current density observed at positive voltages, the action potential duration was increased in these mice. Some myocytes developed EADs after isoproterenol treatment. Hemodynamic measurements revealed no significant effects on ventricular function (apart from a slightly elevated heart rate), whereas in vivo electrophysiological recordings revealed a prolonged ventricular effective refractory period in transgenic mice. The transgenic mice tolerated stress less well as evident from treadmill stress tests. The proarrhythmogenic features and lack of adaptation to a stress response in transgenic mice suggest that these features are intrinsic to the myocardium and that KATP channels in the myocardium have an important role in protecting the heart from lethal arrhythmias and adaptation to stress situations. [ABSTRACT FROM AUTHOR]

The role of Neutrophil extracellular traps (NETs) in the immunopathogenesis of Diabetic Kidney Disease (DKD) remains elusive. We used a machine learning approach to identify differentially expressed genes (DEGs) associated with NETs in human DKD kidney biopsy datasets and validated the results using single-nucleus RNA sequencing datasets. The expressions of these candidate genes and related cytokines were verified in blood obtained from DKD patients. Three NETs-associated genes (ITGAM, ITGB2 and TLR7) were identified, which all showed significant upregulation in both glomerular and tubulointerstitial compartments in human DKD kidneys. DKD patients showed significantly higher number of activated neutrophils with increased ITGAM and ITGB2 expression, higher serum IL-6 but lower IL-10, compared to healthy controls (p all <0.01). This study suggests that dysregulation of NETs-associated genes ITGAM and ITGB2 are related to the pathogenesis of DKD, and may serve as novel diagnostic markers and therapeutic targets in DKD. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Social prescribing (SP) is a holistic and collaborative approach to help individuals access community-based supports and services for their nonmedical social needs. The aim of this study was to assess the needs and priorities of Canadian older adults (aged 55 years and older), with a focus on optimizing SP programs for those who are systemically disadvantaged and socially marginalized., Methods: Semistructured focus groups (N = 10 groups, 43 participants) were conducted online via Zoom with participants from across Canada. Data transcription and thematic analysis were completed in NVivo. Analyses were informed by self-determination theory., Results: Our results suggest that older adults desire SP programs that respect their ability to maintain their autonomy and independence, aid and facilitate the development of connectedness and belonging, are built on a foundation of trust and relationship-building in interactions with providers and link workers, and prioritize the person and thus personalize SP to the unique needs of each individual., Conclusion: SP programs should be informed by the values of older adults. As work is currently underway to formalize and scale SP in Canada, personalizing these programs to the unique circumstances, needs and priorities of participants should be a top priority., Competing Interests: The authors declare there are no conflicts of interest.

Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment-length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify cancer-specific methylation (CSM) and fragment-length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab., Significance: Analysis of methylation and fragment length in plasma using cfMeDIP-seq provides a tumor-naive approach to measure ctDNA with results comparable with a tumor-informed bespoke ctDNA. Early kinetics within the first weeks of treatment in methylation and fragment quantity can predict outcomes with pembrolizumab in patients with various advanced solid tumors. This article is featured in Selected Articles from This Issue, p. 897., (©2024 The Authors; Published by the American Association for Cancer Research.)

Long-term environmental monitoring surveys are designed to achieve a desired precision (measured by variance) of resource conditions based on natural variability information. Over time, increases in resource variability and in data use to address issues focused on small areas with limited sample sizes require bolstering of attainable precision. It is often prohibitive to do this by increasing sampling effort. In cases with spatially overlapping monitoring surveys, composite estimation offers a statistical way to obtain a precision-weighted combination of survey estimates to provide improved population estimates (more accurate) with improved precisions (lower variances). We present a composite estimator for overlapping surveys, a summary of compositing procedures, and a case study to illustrate the procedures and benefits of composite estimation. The study uses the two terrestrial monitoring surveys administered by the Bureau of Land Management (BLM) that entirely overlap. Using 2015-18 data and 13 land-health indicators, we obtained and compared survey and composite indicator estimates of percent area meeting land-health standards for sagebrush communities in Wyoming's Greater Sage-Grouse (Centrocercus urophasianus) Core and NonCore conservation areas on BLM-managed lands. We statistically assessed differences in indicator estimates between the conservation areas using composite estimates and estimates of the two surveys individually. We found composite variance to be about six to 24 units lower than 37% of the survey variances and composite estimates to differ by about six to 10 percentage points from six survey estimates. The composite improvements resulted in finding 11 indicators to statistically differ (p <0.05) between the conservation areas compared to only six and seven indicators for the individual surveys. Overall, we found composite estimation to be an efficient and useful option for improving environmental monitoring information where two surveys entirely overlap and suggest how this estimation method could be beneficial where environmental surveys partially overlap and in small area applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objectives This is the protocol for an evidence and gap map. The objectives are as follows: The aim of this evidence and gap map is to map the available evidence on the effectiveness of social prescribing interventions addressing a non-medical, health-related social need for older adults in any setting. Specific objectives are as follows: 1.To identify existing evidence from primary studies and systematic reviews on the effects of community-based interventions that address non-medical, health-related social needs of older adults to improve their health and wellbeing.2.To identify research evidence gaps for new high-quality primary studies and systematic reviews.3.To highlight evidence of health equity considerations from included primary studies and systematic reviews., (© 2024 The Authors. Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Obesity is a state of metabolic dysfunction that can lead to dyslipidemia and impaired glucose homeostasis. Apple polyphenols have been shown to ameliorate dyslipidemia/metabolic dysfunction in humans. The influence of apple (poly)phenols on energy metabolism in high-fat (HF) diet-induced obese mice remains controversial. This study examined the effect of dietary supplementation of (poly)phenol-rich 'Daux Belan' apple (DB; 6.2 mg gallic acid equivalence (GAE)/mouse/day; 0.15% (poly)phenol) in the form of freeze-dried powder on glucose and lipid metabolism in male HF-fed C57BL/6NCrl mice, in comparison to low-(poly)phenol-containing 'Zestar' apple (Z; 0.4 mg GAE/mouse/day). Obesity, glucose intolerance, hypertriglyceridemia, and hepatic lipid vacuolation were induced by HF feeding while circulating cholesterol levels remained unchanged. DB apple supplementation did not protect against HF-induced body weight gain, hyperglycemia, hepatic triglyceride level elevation, and hepatic lipid vacuolation at the tested dosage. Future studies should be conducted with increased DB dosage and employ apple (poly)phenols supplemented in the form of extracts or sugar-free powder., (© 2023. Springer Nature Limited.)

Diet therapy for diabetes involves controlling carbohydrate intake in order to manage blood glucose concentrations. Simple carbohydrates, like sucrose, quickly and potently raise blood glucose when ingested, and are typically perceived as sweet. Sweetness is innately pleasurable and contributes to the positive hedonic evaluation of foods and beverages. There is some evidence to suggest that individuals with diabetes mellitus may be less able to detect sweetness, which could result in increased intake and, thus, more difficulty managing blood glucose. A systematic review that included PubMed, PsycInfo, and Embase databases was conducted. Inclusion criteria included observational studies that investigated the sweet taste function of adults with and without diabetes mellitus (Prospero CRD42021225058). The quality of the final included studies was assessed using the Academy of Nutrition and Dietetics' Evidence Analysis Library Quality Criteria Checklist: Primary Research tool. Eighteen studies that compared sweet taste thresholds, intensity ratings, or hedonic responses in adults both with and without diabetes were included. Differences in sweet taste thresholds, both detection and recognition, indicated that individuals with diabetes were less sensitive than healthy controls. The same findings were observed for intensity ratings. Only two studies examined hedonic responses; results were inconclusive.

Joint replacements are among the most common orthopedic procedures performed in the U.S. and will continue to increase with the aging population. It is therefore necessary to account for these and other confounding factors, such as breast implants, when performing dual-energy X-ray absorptiometry (DXA) measurements. Whole-body DXA scans were performed in 771 participants (men ≥50 yr and women ≥55 yr) to assess bone mineral density (BMD) and body composition (fat and lean mass). In the DXA scan analyses of participants with internal metal, these affected regions of interest were replaced with measures from the unaffected, contralateral side, consistent with recommendations of the International Society for Clinical Densitometry. T-scores and Z-scores were recalculated using default sex and ethnicity-matched databases. We also explored effects of breast implants on bone density and body composition analyses. Approximately 13.1% of participants had internal metal artifacts at baseline. Replacing metal artifacts with the unaffected, contralateral side decreased the whole-body BMD by an average of 8.1% (SEM 0.84%; n = 67). In participants with unilateral hip (n = 17) and knee replacements (n = 20), BMD was decreased by an average of 14.1% (SEM 1.7%) and 11.2% (SEM 1.1%), respectively. Fat and lean mass were not significantly affected by metal artifacts, as differences between values with and without metal were within 1%. Two participants had bilateral breast implants, and in a separate trial, one participant had a unilateral breast implant. Bone mineral content (BMC) in the region with the breast implant was 5.8 times higher than the contralateral side, and whole-body BMC was increased by 4.7%. Metal artifacts and breast implants can confound DXA whole-body bone but not fat and lean results. It is therefore important in clinical studies to account for these factors to detect physiologically relevant differences in bone measures., (Copyright © 2021. Published by Elsevier Inc.)

Recent advances in cannabidiol (CBD) use in canines and felines for anxiety management, pain management, and anti-inflammatory effects were reviewed using a literature search conducted with the following keywords: CBD, anxiety, inflammation, pain, dogs, cats, and companion animals. For decades, research on CBD has been hindered due to the status of cannabis (C. sativa L.) as an illicit drug. Limited safety data show that CBD is well-tolerated in dogs, with insufficient information on the safety profile of CBD in cats. Upon oral supplementation of CBD, elevation in liver enzymes was observed for both dogs and cats, and pharmacokinetics of CBD are different in the two species. There is a significant gap in the literature on the therapeutic use of CBD in cats, with no feline data on anxiety, pain, and inflammation management. There is evidence that chronic osteoarthritic pain in dogs can be reduced by supplementation with CBD. Furthermore, experiments are required to better understand whether CBD has an influence on noise-induced fear and anxiolytic response. Preliminary evidence exists to support the analgesic properties of CBD in treating chronic canine osteoarthritis; however, there are inter- and intra-species differences in pharmacokinetics, tolerance, dosage, and safety of CBD. Therefore, to validate the anxiety management, pain management, and anti-inflammatory efficacy of CBD, it is essential to conduct systematic, randomized, and controlled trials. Further, the safety and efficacious dose of CBD in companion animals warrants investigation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Frequent emergency department (ED) visits occur after esophagectomy. We aimed to identify the incidence of and risk factors for conversion from ED visit to inpatient admission., Methods: A retrospective cohort study was performed of consecutive esophagectomies at a tertiary Canadian center (1999 to 2014). Multivariable regression analyses identified factors associated with conversion from ED visit to admission., Results: There were 520 esophagectomies with 6% inhospital mortality (n = 31). Of those discharged, 29.7% (n = 145) had one or more emergency visit and 43.4% (n = 63) of these patients were readmitted to the hospital. First-time ED visits resulted in inpatient conversion 23.4% of the time (n = 34); successive ED visits resulted in increasing conversion. On multivariable analysis, anastomotic leak (adjusted odds ratio 2.45; 95% confidence interval, 1 to 6.01; P = .05) was independently associated with higher odds of conversion to admission. Sensitivity analysis using Poisson regression to model conversion as a rate identified that living in regions further away was associated with lower conversion rate to admission (risk ratio 0.35; 95% confidence interval, 0.13 to 0.94; P = .04)., Conclusions: Although postesophagectomy ED utilization is high, the majority of visits do not convert to admission. With each increasing ED visit, likelihood of converting to admission increases. Anastomotic leakage was associated with higher odds of conversion to admission, possibly related to development of strictures. Access to urgent outpatient endoscopy may help reduce the incidence of ED visits and admission. Although living in regions further away is associated with lower conversion rates to admission at the index hospital, that may be due to patients utilizing closer local hospitals., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The RB1 tumor suppressor gene is mutated in highly aggressive tumors including small-cell lung cancer (SCLC), where its loss, along with TP53 , is required and sufficient for tumorigenesis. While RB1 -mutant cells fail to arrest at G 1 -S in response to cell-cycle restriction point signals, this information has not led to effective strategies to treat RB1 -deficient tumors, as it is challenging to develop targeted drugs for tumors that are driven by the loss of gene function. Our group previously identified Skp2, a substrate recruiting subunit of the SCF-Skp2 E3 ubiquitin ligase, as an early repression target of pRb whose knockout blocked tumorigenesis in Rb1-deficient prostate and pituitary tumors. Here we used genetic mouse models to demonstrate that deletion of Skp2 completely blocked the formation of SCLC in Rb1/Trp53 -knockout mice (RP mice). Skp2 KO caused an increased accumulation of the Skp2-degradation target p27, a cyclin-dependent kinase inhibitor, which was confirmed as the mechanism of protection by using knock-in of a mutant p27 that was unable to bind to Skp2. Building on the observed synthetic lethality between Rb1 and Skp2, we found that small molecules that bind/inhibit Skp2 have in vivo antitumor activity in mouse tumors and human patient-derived xenograft models of SCLC. Using genetic and pharmacologic approaches, antitumor activity was seen with Skp2 loss or inhibition in established SCLC primary lung tumors, in liver metastases, and in chemotherapy-resistant tumors. Our data highlight a downstream actionable target in RB1 -deficient cancers, for which there are currently no targeted therapies available. SIGNIFICANCE: There are no effective therapies for SCLC. The identification of an actionable target downstream of RB1 , inactivated in SCLC and other advanced tumors, could have a broad impact on its treatment., (©2020 American Association for Cancer Research.)

Purpose This first-in-human study evaluated SGN-CD70A, an antibody-drug conjugate (ADC) directed against the integral plasma membrane protein CD70 and linked to a pyrrolobenzodiazepine (PBD) dimer, in patients with relapsed or refractory (R/R) CD70-positive non-Hodgkin lymphoma (NHL) including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Grade 3b follicular lymphoma (FL3b). Methods SGN-CD70A was administered intravenously on Day 1 of 3-week cycles beginning at 8 mcg/kg with planned dose escalation to 200 mcg/kg. Due to observations of prolonged thrombocytopenia, the study was amended to dose every 6 weeks (q6wk). Results Twenty patients were enrolled and treated with SGN-CD70A. The maximum tolerated dose of SGN-CD70A was 30 mcg/kg q6wk. The most common adverse events (AEs) reported were thrombocytopenia (75%), nausea (55%), anemia (50%), and fatigue (50%). The onset for treatment-related thrombocytopenia typically occurred during Cycle 1. Most of the treatment-related events of thrombocytopenia were ≥ Grade 3. Antitumor activity in patients included 1 complete remission (CR) and 3 partial remissions (PRs), 2 of which were ongoing for at least 42.9 weeks. SGN-CD70A exposures were approximately dose proportional, with a mean terminal half-life of 3 to 5 days. Conclusions While modest single-agent activity was observed in heavily pretreated NHL patients, the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term response with limited drug exposure.

Objectives: Esophagectomy is a complex operation with potential for prolonged recovery. We aimed to identify the incidence of and risk factors for any and frequent emergency department visits within 1 year of esophagectomy., Methods: A retrospective cohort study was performed looking at consecutive esophagectomies at a tertiary Canadian center (1999-2014). Multivariable analyses identified factors associated with any emergency department visits and frequent emergency department use (≥3 visits) within 1 year postesophagectomy., Results: There were 520 esophagectomies with in-hospital mortality of 6% (n = 31). Of those discharged, 29.7% (n = 145) had ≥ 1 emergency department visit. Most common causes were feeding tube problems (39.3%; n = 57) and dysphagia/stricture (13.1%; n = 19). Higher income (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.04-1.42 per $10,000) and use of hybrid/minimally invasive esophagectomy (aOR, 3.24; 95% CI, 1.71-6.11) were independently associated with having emergency department visits. Patients with hybrid/minimally invasive esophagectomy were discharged earlier than others (P < .0001). Living outside of our metropolitan area (aOR, 0.36; 95% CI, 0.27-0.49) and having surgery in the later years of the study period (aOR, 0.91; 95% CI, 0.86-0.97; P = .006) were both independently associated with lower odds of emergency department visits. Forty-three patients (8.8%) were frequent emergency department users, with the most common causes of repeat emergency visits being feeding tube problems. Living outside of our metropolitan area was associated with lower odds of frequent emergency visits (aOR, 0.25; 95% CI, 0.14-0.45)., Conclusions: There is high emergency department use within 1 year postesophagectomy. Patients living farther away from our hospital had a lower rate of emergency department use. It is possible that they are utilizing emergency departments nearer to home; this needs further study. Feeding tube problems are the biggest culprits and are potentially modifiable., (Copyright © 2018. Published by Elsevier Inc.)

Background: Although commonly reserved as a last line of defense, experienced centers have reported excellent results with pulmonary embolectomy for massive and submassive pulmonary embolism (PE). We present a contemporary surgical series for PE that demonstrates the utility of peripheral extracorporeal membrane oxygenation (pECMO) for high-risk surgical candidates., Methods: Between June 2005 and April 2011, 29 patients were treated for massive or submassive pulmonary embolism, with surgical embolectomy performed in 26. Four high-risk patients were placed on pECMO, established by percutaneously cannulating the right atrium through a femoral vein and perfusing by a Dacron graft anastomosed to the axillary artery. A small, extracorporeal, rotary assist device was used, interposing a compact oxygenator in the circuit, and maintaining anticoagulation with heparin., Results: Extracorporeal membrane oxygenation was weaned in 3 of 4 patients after 5.3 days (5, 5, and 6), with normalization of right ventricular dysfunction and pulmonary artery pressure (44.0 ± 2.0 to 24.5 ± 5.5 mm Hg) by ECHO. Follow-up computed tomographies showed several peripheral, nearly resorbed emboli in 1 case and complete resolution in 2 others. The fourth patient, not improving after 10 days, underwent surgery where an embolic liposarcoma was extracted. For all 29 cases, hospital and 30-day mortality was 0% and all patients were discharged, with average postoperative length of stay of 15 days for embolectomy and 17 days for pECMO., Conclusions: Heparin therapy with pECMO support is a rapid, effective option for patients who might benefit from pulmonary embolectomy but are at high risk for surgery., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).