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Background: National guidelines suggest the use of natriuretic peptides in suspected heart failure but there have been no studies comparing assays in primary care.Aim: To test and compare the diagnostic accuracy and utility of B-type natriuretic peptide (BNP) and N-terminal B-type natriuretic peptide (NT proBNP) in diagnosing heart failure due to left ventricular systolic dysfunction in patients with suspected heart failure referred by GPs to one-stop diagnostic clinics.Design Of Study: Community cohort, prospective, diagnostic accuracy study.Setting: One-stop diagnostic clinics in Darlington Memorial and Bishop Auckland General Hospitals and general practices in South Durham.Subjects: Two hundred and ninety-seven consecutive patients with symptoms and signs suggestive of heart failure referred from general practice.Method: The study measured sensitivity, specificity, positive and negative predictive values (PPV, NPV), and area under receiver operating characteristic curve for BNP (near patient assay) and NT proBNP (laboratory assay) in diagnosis of heart failure due to left ventricular systolic dysfunction. The NPV of both assays was determined as a potential method of reducing the number of referrals for echocardiography.Results: One hundred and fourteen of the 297 patients had left ventricular systolic dysfunction (38%). At the manufacturer's recommended cut-off of 100 pg/ml BNP gave a NPV of 82%. BNP performed better at a cut-off of 40 pg/ml with a NPV of 88%. At a cut-off of 150 pg/ml, NT proBNP gave a NPV of 92%. Using cut-offs of 40 pg/ml and 150 pg/ml for BNP and NT pro-BNP, respectively, could have prevented 24% and 25% of referrals to the clinic, respectively.Conclusions: In this setting, NT pro-BNP performed marginally better than BNP, and would be easier to use practically in primary care. A satisfactory cut-off has been identified, which needs validating in general practice. NT pro-BNP could be used to select referrals to a heart failure clinic or for echocardiography. This process needs testing in real-life general practice. [ABSTRACT FROM AUTHOR]

We have recently described the novel autoantigen plasminogen activator inhibitor (PAI-1) in systemic lupus erythematosus (SLE). The aim of this study was to determine the prevalence and clinical significance of anti-PAI-1 autoantibodiesin patients with SLE. Autoantibodies to recombinant PAI-1 were measured in retrospective sera of 48 lupus patients by immunoassay in order to assess their clinical significance. This showed that 71% of sera from 48 lupus patients had significantly elevated anti-PAI-1 autoantibodiesas compared with normal control subjects (P < 0.0001). There was a weak but significant (P < 0.043) correlation with anti-dsDNA autoantibodies. In longitudinal studies, autoantibodies against PAI-1 correlated with clinical parameters measured by the BILAG disease activity index including global clinical score. Our study demonstrates the high frequency of novel autoantibodies to PAI-1 in patients with lupus. The serial clinical correlations with anti-PAI-1 autoantibodies also support the hypothesis that these autoantibodies may play a pathogenic role in lupus. [ABSTRACT FROM AUTHOR]

We explore the extent of 'responsible purchasing' by employers--the degree to which employers collect and use nonfinancial information in selecting and managing employee health plans. Most firms believe that they have some responsibility for assessing the quality of the health plans they offer. Some pay attention to plan characteristics such as the ability to provide adequate access to providers and services and scores on enrollee satisfaction surveys. A more limited but still notable number of firms take specific actions based on responsible purchasing information. Because of countervailing pressures, however, it is not clear whether or not the firms most involved in responsible purchasing are signaling a developing trend. [ABSTRACT FROM AUTHOR]

Extreme weather events across coastal environments are expected to increase in frequency under predicted climate change scenarios. These events can impact coastal recreational fisheries and their supporting ecosystems by influencing the productivity of fish stocks or altering behaviours and decision-making among fishers. Using off-site telephone/diary survey data on estuarine and oceanic recreational fishing activity in eastern Australia, we analyse interannual and geographic variability in bream (Acanthopagrus spp) and snapper (Chrysophrys auratus) catch, total effort and total catch per unit effort (CPUE) through a period (2013/2014, 2017/2018 and 2019/2020) that encompassed severe drought, bushfires and flooding. Interacting spatial and temporal differences were detected for bream and may reflect spatial variation in the intensity and extent of some of the extreme weather events. The catch of snapper did not change temporally, providing little evidence that this species' catch may be influenced by the extreme weather events. Independent bioregional and temporal effects on effort were detected, while CPUE only showed significant bioregional differences. Although adverse conditions created by the extreme weather events may have dissuaded fisher participation and impacted effort, we propose that the observed temporal patterns in effort reflect the early influence of socio-economic changes brought on by the COVID-19 pandemic on coastal recreational fishing, over and above the impacts of extreme weather events. This study demonstrates how interrelated ecological, social and economic factors can shape coastal recreational fisheries and facilitates development of management strategies to address future threats to the sector., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Ochwada-Doyle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

For many species, the relationship between space use and diet composition is complex, with individuals adopting varying space use strategies such as territoriality to facilitate resource acquisition. Coyotes ( Canis latrans ) exhibit two disparate types of space use; defending mutually exclusive territories (residents) or moving nomadically across landscapes (transients). Resident coyotes have increased access to familiar food resources, thus improved foraging opportunities to compensate for the energetic costs of defending territories. Conversely, transients do not defend territories and are able to redirect energetic costs of territorial defense towards extensive movements in search of mates and breeding opportunities. These differences in space use attributed to different behavioral strategies likely influence foraging and ultimately diet composition, but these relationships have not been well studied. We investigated diet composition of resident and transient coyotes in the southeastern United States by pairing individual space use patterns with analysis of stable carbon (δ 13 C) and nitrogen (δ 15 N) isotope values to assess diet. During 2016-2017, we monitored 41 coyotes (26 residents, 15 transients) with GPS radio-collars along the Savannah River area in the southeastern United States. We observed a canopy effect on δ 13 C values and little anthropogenic food in coyote diets, suggesting 13 C enrichment is likely more influenced by reduced canopy cover than consumption of human foods. We also observed other land cover effects, such as agricultural cover and road density, on δ 15 N values as well as reduced space used by coyotes, suggesting that cover types and localized, resident-like space use can influence the degree of carnivory in coyotes. Finally, diets and niche space did not differ between resident and transient coyotes despite differences observed in the proportional contribution of potential food sources to their diets. Although our stable isotope mixing models detected differences between the diets of resident and transient coyotes, both relied mostly on mammalian prey (52.8%, SD = 15.9 for residents, 42.0%, SD = 15.6 for transients). Resident coyotes consumed more game birds (21.3%, SD = 11.6 vs 13.7%, SD = 8.8) and less fruit (10.5%, SD = 6.9 vs 21.3%, SD = 10.7) and insects (7.2%, SD = 4.7 vs 14.3%, SD = 8.5) than did transients. Our findings indicate that coyote populations fall on a feeding continuum of omnivory to carnivory in which variability in feeding strategies is influenced by land cover characteristics and space use behaviors., Competing Interests: The authors declare that they have no competing interests., (© 2024 Webster et al.)

Organizations need a better "learning by doing" approach.

Objective: The growing trend to use wearable devices to track activity and health data has the potential to positively impact the patient experience with their health care at home and with their care team. As part of a pilot program, the U.S. Department of Veterans Affairs (VA) distributed Fitbits to Veterans through four VA medical centers. Our objective was to assess the program from both Veterans' and clinicians' viewpoints. Specifically, we aimed to understand barriers to Fitbit setup and use for Veterans, including syncing devices with a VA mobile application (app) to share data, and assess the perceived value of the device functions and ability to share information from the Fitbit with their care team. In addition, we explored the clinicians' perspective, including how they expected to use the patient-generated health data (PGHD)., Methods: We performed semi-structured interviews with 26 Veterans and 16 VA clinicians to assess the program. Responses to each question were summarized in order of frequency of occurrence across participants and audited by an independent analyst for accuracy., Results: Our findings reveal that despite setup challenges, there is support for the use of Fitbits to engage Veterans and help manage their health. Clinicians believed there were benefits for having Veterans use the Fitbits and expected to use the PGHD in a variety of ways as part of the Veterans' care plans, including monitoring progress toward health behavior goals. Veterans were overwhelmingly enthusiastic about using the Fitbits; this enthusiasm seems to extend beyond the 3 month "novelty period.", Conclusion: The pilot program for distributing Fitbits to Veterans appears to be successful from both Veterans' and clinicians' perspectives and suggests that expanded use of wearable devices should be considered. Future studies will need to carefully consider how to incorporate the PGHD into the electronic health record and clinical workflow., Competing Interests: None declared., (Thieme. All rights reserved.)

Genome integrity must be tightly preserved to ensure cellular survival and to deter the genesis of disease. Endogenous and exogenous stressors that impose threats to genomic stability through DNA damage are counteracted by a tightly regulated DNA damage response (DDR). RNA binding proteins (RBPs) are emerging as regulators and mediators of diverse biological processes. Specifically, RBPs that bind to adenine uridine (AU)-rich elements (AREs) in the 3' untranslated region (UTR) of mRNAs (AU-RBPs) have emerged as key players in regulating the DDR and preserving genome integrity. Here we review eight established AU-RBPs (AUF1, HuR, KHSRP, TIA-1, TIAR, ZFP36, ZFP36L1, ZFP36L2) and their ability to maintain genome integrity through various interactions. We have reviewed canonical roles of AU-RBPs in regulating the fate of mRNA transcripts encoding DDR genes at multiple post-transcriptional levels. We have also attempted to shed light on non-canonical roles of AU-RBPs exploring their post-translational modifications (PTMs) and sub-cellular localization in response to genotoxic stresses by various factors involved in DDR and genome maintenance. Dysfunctional AU-RBPs have been increasingly found to be associated with many human cancers. Further understanding of the roles of AU-RBP S in maintaining genomic integrity may uncover novel therapeutic strategies for cancer.

We partnered with Alaska's Pick.Click.Give. programme to implement a statewide natural field experiment with 540,000 Alaskans designed to examine two of the main motivations for charitable giving: concerns for the benefits to self (impure altruism or 'warm glow') or concerns for the benefits to others (pure altruism). Our empirical results highlight the relative importance of appeals to self: individuals who received such an appeal were 6.6% more likely to give and gave 23% more than counterparts in the control group. Yet, a message that instead appealed to recipient benefits (motivated by altruism) had no statistically significant effect on average donations relative to the control group. We also find evidence of long-run effects of warm-glow appeals in the subsequent year. Our results have import for theoreticians and empiricists interested in modelling charitable giving as well as practitioners and policymakers., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Physical activity (PA) promotion is a complex challenge, with the Global Action Plan on Physical Activity (GAPPA) endorsing a systems approach and recommending countries assess existing areas of progress which can be strengthened. This paper reports a process facilitating a systems approach for identifying current good practice and gaps for promoting PA in Ireland. Elements of participatory action research were enabled through 3 stages: (1) aligning examples of actions from Irish policy documents (n = 3) to the GAPPA, (2) workshop with stakeholders across multiple sectors, and (3) review of outputs. Data collected through the workshop were analyzed using a deductive thematic analysis guided by the GAPPA. The policy context in Ireland aligns closely to the GAPPA with the creation of Active Systems the most common strategic objective across policy documents. Forty participants (50% male) took part in the systems approach workshop, which after revision resulted in 80 examples of good practice and 121 actions for greater impact. A pragmatic and replicable process facilitating a systems approach was adopted and showed current Irish policy and practices align with the GAPPA "good practices." The process provides existing areas of progress which can be strengthened, as well as the policy opportunities and practice gaps.

Nickel catalysis allied with cyclodiphosphazane or VAPOL-derived phosphoramidite ligands provides selective access to monoprotected vicinal diols by reductive coupling of dienol ethers and aldehydes. The observed regioselectivity is unprecedented, in that the diene reacts at the least nucleophilic and most hindered C atom that is attached to the oxygen substituent rather than at the terminal position. Notably, both syn and anti diastereomers of the products can be accessed depending on the configuration of the diene partner with usually excellent diastereo- and enantioselectivity.

This study explores whether an oath to honesty can reduce both shirking and lying among crowd-sourced internet workers. Using a classic coin-flip experiment, we first confirm that a substantial majority of Mechanical Turk workers both shirk and lie when reporting the number of heads flipped. We then demonstrate that lying can be reduced by first asking each worker to swear voluntarily on his or her honor to tell the truth in subsequent economic decisions. Even in this online, purely anonymous environment, the oath significantly reduced the percent of subjects telling "big" lies (by roughly 27%), but did not affect shirking. We also explore whether a truth-telling oath can be used as a screening device if implemented after decisions have been made. Conditional on flipping response, MTurk shirkers and workers who lied were significantly less likely to agree to an ex-post honesty oath. Our results suggest oaths may help elicit more truthful behavior, even in online crowd-sourced environments., Competing Interests: The authors have declared that no competing interests exist.

Although infants with meconium ileus usually present with apparent symptoms shortly after birth, the diagnosis of meconium ileus and cystic fibrosis (CF) may be delayed, awaiting newborn screening (NBS) results. We present the case of an 11-day-old term girl with delayed passage of meconium at 48 hours who had 2 subsequent small meconium stools over the following week. There was a normal feeding history and no signs of abdominal distension or distress. She then presented with an acute abdomen, decompensated shock, bowel perforation, and peritonitis, requiring multiple intestinal surgeries. Her NBS for CF was positive, and CF was ultimately confirmed with mutation analysis. Her course was complicated by prolonged parenteral feedings and mechanical ventilation via tracheostomy. The infant was managed with soy oil, medium chain triglycerides, olive oil, fish oil lipids and experienced only transaminitis without cholestasis and no chronic liver sequelae, with subsequent normalization of her transaminases without treatment. Because her only symptom was decreased stool output and NBS results were unavailable, the CF diagnosis was delayed until she presented in extremis. Delayed meconium passage and decreased stool output during the first week of life should lead to suspicion and additional evaluation for CF while awaiting NBS results. Careful monitoring is indicated to prevent serious, life-threatening complications. The use of soy oil, medium chain triglycerides, olive oil, fish oil lipids for infants requiring prolonged parenteral nutrition may also be considered proactively to prevent cholestasis, particularly for high risk groups., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

The US Department of Veterans Affairs (VA) is using an automated short message service application named "Annie" as part of its coronavirus disease 2019 (COVID-19) response with a protocol for coronavirus precautions, which can help the veteran monitor symptoms and can advise the veteran when to contact his or her VA care team or a nurse triage line. We surveyed 1134 veterans on their use of the Annie application and coronavirus precautions protocol. Survey results support what is likely a substantial resource savings for the VA, as well as non-VA community healthcare. Moreover, the majority of veterans reported at least 1 positive sentiment (felt more connected to VA, confident, or educated and/or felt less anxious) by receiving the protocol messages. The findings from this study have implications for other healthcare systems to help manage a patient population during the coronavirus pandemic., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2020. This work is written by US Government employees and is in the public domain in the US.)

The marine macrolide chagosensine is supposedly distinguished by a ( Z,Z )-configured 1,3-chlorodiene contained within a highly strained 16-membered lactone ring, which also incorporates two trans -2,5-disubstituted tetrahydrofuran (THF) rings; this array is unique. After our initial synthesis campaign had shown that the originally proposed structure is incorrect, the published data set was critically revisited to identify potential mis-assignments. The "northern" THF ring and the anti -configured diol in the "southern" sector both seemed to be sites of concern, thus making it plausible that a panel of eight diastereomeric chagosensine-like compounds would allow the puzzle to be solved. To meet the challenge, the preparation of the required building blocks was optimized, and a convergent strategy for their assembly was developed. A key role was played by the cobalt-catalyzed oxidative cyclization of alken-5-ol derivatives ("Mukaiyama cyclization"), which is shown to be exquisitely chemoselective for terminal alkenes, leaving even terminal alkynes (and other sites of unsaturation) untouched. Likewise, a palladium-catalyzed alkyne alkoxycarbonylation reaction with formation of an α-methylene-γ-lactone proved instrumental, which had not found application in natural product synthesis before. Further enabling steps were a nickel-catalyzed "Tamaru-type" homocrotylation, stereodivergent aldehyde homologations, radical hydroindation, and palladium-catalyzed alkyne-1,2-bis-stannation. The different building blocks were assembled in a serial fashion to give the idiosyncratic chlorodienes by an unprecedented site-selective Stille coupling followed by copper-mediated tin/chlorine exchange. The macrolactones were closed under forcing Yamaguchi conditions, and the resulting products were elaborated into the targeted compound library. Yet, only one of the eight diastereomers turned out to be stable in the solvent mixture that had been used to analyze the natural product; all other isomers were prone to ring opening and/or ring expansion. In addition to this stability issue, our self-consistent data set suggests that chagosensine has almost certainly little to do with the structure originally proposed by the isolation team.

Increasing population levels of physical activity (PA) can assist in achieving the United Nations sustainable development goals, benefiting multiple sectors and contributing to global prosperity. Practices and policies to increase PA levels exist at the subnational, national, and international levels. In 2018, the World Health Organization launched the first Global Action Plan on Physical Activity (GAPPA). The GAPPA provides guidance through a framework of effective and feasible policy actions for increasing PA, and requires engagement and advocacy from a wide spectrum of stakeholders for successful implementation of the proposed actions. Early career professionals, including researchers, practitioners, and policymakers, can play a major role with helping "all people being regularly active" by contributing to 4 overarching areas: (1) generation-of evidence, (2) dissemination-of key messages and evidence, (3) implementation-of the evidence-based actions proposed in the GAPPA, and (4) contributing to advocacy for robust national action plans on PA. The contribution of early career professionals can be achieved through 5 pathways: (1) research, (2) workplace/practice, (3) business, (4) policy, and (5) professional and public opinion. Recommendations of how early career professionals can contribute to the generation, dissemination, and implementation of the evidence and actions proposed by the GAPPA are provided.

Prostate cancer (PC) is a leading cause of death in men. Inflammation is one of the initiating processes whereby cells are trafficked into the tumor microenvironment by specific cytokines termed chemokines. This recruitment is complex and involves diverse leukocyte subsets with procancer and anticancer functions. Chemokines promote/abrogate proliferation of cancerous cells, block/aid apoptosis, and are instrumental/detrimental in cancer cell migration required for metastasis. Chemokines guide the release/transport of immune cells that serve as chaperones at sites of inflammation, and after subsequent activation, they lead to an immune response. The variety of immune cells recruited at the site of tumor initiation possess unique functions, and the plethora of chemokines released by each cell derived from a progenitor cell activated under a defined set of conditions dictates its specific role in cancer progression/regression. Geographic consequences that govern the climate and endemic diseases, along with the associated evolutionary effects that at times protect populations from one disease, could lead to genetic variations that determine a role for ethnicity and race in PC risk and susceptibility. Dysregulated expression or an imbalance in the homeostatic mechanisms associated with chemokines is implicated in PC. This review discusses the role of inflammation and chemokines in PC., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)