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We describe a case of a 46-year-old man in Missouri, USA, with newly diagnosed advanced HIV and PCR-confirmed mpox keratitis. The keratitis initially resolved after intravenous tecovirimat and penicillin for suspected ocular syphilis coinfection. Despite a confirmatory negative PCR, he developed relapsed, ipsilateral PCR-positive keratitis and severe ocular mpox requiring corneal transplant.

Abstract Changes in leaf phenology from warming spring and autumn temperatures have lengthened the temperate zone growing “green” season and breeding window for migratory birds in North America. However, the fitness benefits of an extended breeding season will depend, in part, on whether species have sufficient dietary flexibility to accommodate seasonal changes in prey availability. We used fecal DNA metabarcoding to test the hypothesis that seasonal changes in the diets of the insectivorous, migratory black‐throated blue warbler (Setophaga caerulescens) track changes in the availability of arthropod prey at the Hubbard Brook Experimental Forest, New Hampshire, USA. We examined changes across the breeding season and along an elevation gradient encompassing a 2‐week difference in green season length. From 98 fecal samples, we identified 395 taxa from 17 arthropod orders; 242 were identified to species, with Cecrita guttivitta (saddled prominent moth), Theridion frondeum (eastern long‐legged cobweaver), and Philodromus rufus (white‐striped running crab spider) occurring at the highest frequency. We found significant differences in diet composition between survey periods and weak differences among elevation zones. Variance in diet composition was highest late in the season, and diet richness and diversity were highest early in the season. Diet composition was associated with changes in prey availability surveyed over the green season. However, several taxa occurred in diets more or less than expected relative to their frequency of occurrence from survey data, suggesting that prey selection or avoidance sometimes accompanies opportunistic foraging. This study demonstrates that black‐throated blue warblers exhibit diet flexibility and track seasonal changes in prey availability, which has implications for migratory bird responses to climate‐induced changes in insect communities with longer green seasons.

Abstract Immune responses to COVID-19 vaccination are attenuated in adult solid organ transplant recipients (SOTRs) and additional vaccine doses are recommended for this population. However, whether COVID-19 mRNA vaccine responses are limited in pediatric SOTRs (pSOTRs) compared to immunocompetent children is unknown. Due to SARS-CoV-2 evolution and mutations that evade neutralizing antibodies, T cells may provide important defense in SOTRs who mount poor humoral responses. Therefore, we assessed anti-SARS-CoV-2 IgG titers, surrogate neutralization, and spike (S)-specific T-cell responses to COVID-19 mRNA vaccines in pSOTRs and their healthy siblings (pHCs) before and after the bivalent vaccine dose. Despite immunosuppression, pSOTRs demonstrated humoral responses to both ancestral strain and Omicron subvariants following the primary ancestral strain monovalent mRNA COVID-19 series and multiple booster doses. These responses were not significantly different from those observed in pHCs and significantly higher six months after vaccination than responses in adult SOTRs two weeks post-vaccination. However, pSOTRs mounted limited S-specific CD8+ T-cell responses and qualitatively distinct CD4+ T-cell responses, primarily producing IL-2 and TNF with less IFN-γ production compared to pHCs. Bivalent vaccination enhanced humoral responses in some pSOTRs but did not shift the CD4+ T-cell responses toward increased IFN-γ production. Our findings indicate that S-specific CD4+ T cells in pSOTRs have distinct qualities with unknown protective capacity, yet vaccination produces cross-reactive antibodies not significantly different from responses in pHCs. Given altered T-cell responses, additional vaccine doses in pSOTRs to maintain high titer cross-reactive antibodies may be important in ensuring protection against SARS-CoV-2.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients’ physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

This review highlights some established and some more contemporary mechanisms responsible for heart failure (HF)-induced skeletal muscle wasting and weakness. We first describe the effects of HF on the relationship between protein synthesis and degradation rates, which determine muscle mass, the involvement of the satellite cells for continual muscle regeneration, and changes in myofiber calcium homeostasis linked to contractile dysfunction. We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment. Overall, HF causes multiple impairments related to autophagy, anabolic-catabolic signaling, satellite cell proliferation, and calcium homeostasis, which together promote fiber atrophy, contractile dysfunction, and impaired regeneration. Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF, the effects of satellite cell dynamics remain poorly explored.

Abstract Records of beach morphologic change and concurrent hydrodynamic forcing are needed to understand how coastlines in different environments change over time. This submission contains data for the period 2006 to 2021, for two contrasting macrotidal environments in southwest England: (i) cross-shore dominated, dissipative, sandy Perranporth Beach, Cornwall; and (ii) longshore-dominated, reflective gravel beaches within Start Bay, Devon. Data comprise monthly to annual beach profile surveys, annual merged topo-bathymetries, in addition to observed and numerically modelled wave and water levels. These data provide a valuable resource for modelling the behaviour of coastal types not covered by other currently available datasets.

Researchers studying avian space use, dispersal, survival, and migration select tracking tags that optimize tag size (dimensions) and mass relative to the focal species to minimize risk to birds as they move and fly. Here we argue that antenna length and transmitter color are also critical tag design parameters that must be considered. Based on a review of the songbird tracking literature and unpublished cases, we found most cases of entanglement, which can result in bird injuries and death, occurred with longer antennas (>13 cm). However, such cases cannot infer rates of mortality or survival, nor may they be representative of entanglements across antenna lengths and studies using radio tags. Additionally, white or brightly colored transmitters that contrast with plumage, particularly of cryptically colored females and juveniles, may increase visibility to predators and result in higher mortality, or alternatively, cause a female to eject a nestling by mistaking the tag for a fecal sac or foreign object. Consequently, we call on researchers to report and publish cases of antenna entanglement, and for journal editors to encourage and applaud such reports, such that data can be compiled to inform guidelines on tag antenna lengths for different species. Future research is also needed to examine the impacts of tag color on parental behavior and survival of tagged birds. Meanwhile, researchers should strive to ensure that their tag color does not contrast markedly with avian plumages, while also taking care not to alter (i.e., do not color over) areas required for harness attachment, activating and deactivating tags. We hope such efforts will enable researchers and manufacturers to make more informed decisions about tracking tag design, particularly with respect to balancing the benefits of longer antennas, which provide greater power and detection distance, with risks of bird entanglement and mortality.

Abstract Skeletal muscle atrophy is a common clinical feature of many acute and chronic conditions. Circular RNAs (circRNAs) are covalently closed RNA transcripts that are involved in various physiological and pathological processes, but their role in muscle atrophy remains unknown. Global circRNA expression profiling indicated that circRNAs are involved in the pathophysiological processes of muscle atrophy. circTmeff1 is identified as a potential circRNA candidate that influences muscle atrophy. It is further identified that circTmeff1 is highly expressed in multiple types of muscle atrophy in vivo and in vitro. Moreover, the overexpression of circTmeff1 triggers muscle atrophy in vitro and in vivo, while the knockdown of circTmeff1 expression rescues muscle atrophy in vitro and in vivo. In particular, the knockdown of circTmeff1 expression partially rescues muscle mass in mice during established atrophic settings. Mechanistically, circTmeff1 directly interacts with TAR DNA‐binding protein 43 (TDP‐43) and promotes aggregation of TDP‐43 in mitochondria, which triggers the release of mitochondrial DNA (mtDNA) into cytosol and activation of the cyclic GMP‐AMP synthase (cGAS)/ stimulator of interferon genes (STING) pathway. Unexpectedly, TMEFF1‐339aa is identified as a novel protein encoded by circTmeff1 that mediates its pro‐atrophic effects. Collectively, the inhibition of circTmeff1 represents a novel therapeutic approach for multiple types of skeletal muscle atrophy.

Black-throated blue warbler ( Setophaga caerulescens ) populations have been declining at the southern edge of the breeding range in North Carolina over the past two decades. Determining the causes of population declines in migratory species requires knowledge of the threats faced throughout the entire annual cycle, necessitating accurate information about the migratory routes and non-breeding areas used by birds. We used light-level geolocators to identify the fall migratory routes and non-breeding distributions of adults breeding at the southern edge of the range in North Carolina ( n = 5), where populations are declining, and at the core of the range in New Hampshire ( n = 8), where populations are stable. The strength of migratory connectivity was moderate (mean = 0.42). New Hampshire birds used non-breeding areas broadly distributed across the Caribbean, whereas North Carolina birds used a restricted non-breeding area largely in the Dominican Republic. Suitable forest cover declined at a higher rate from 2000 to 2019 in the Dominican Republic than in other Caribbean countries (8.4% vs. 2–4% loss), exposing birds from the trailing edge to significantly higher suitable habitat loss on the non-breeding grounds compared with range-core birds. Birds from the two study populations also exhibited differing migratory routes, with North Carolina birds migrating south through Florida and many New Hampshire birds performing an overwater flight from the Carolinas to the Caribbean. Our results suggest the possibility that, at least for this species, forest loss on the island of Hispaniola could be exacerbating population declines at the southern edge of the breeding range in North Carolina.

Abstract Background To understand how suicide management occurs within the primary care setting in terms of follow-up assessments and referral practices. Methods At an initial primary care visit, adolescents (aged 12–20 years old) completed electronic screening. Data were focused on youth who endorsed a suicidal risk item while completing screening at two Midwestern primary care clinics. Data were collected through retrospective chart reviews to analyze actions taken by the primary care physician at the youth’s initial visit and follow-up visit within the next 12 months. Results At initial visits 200 adolescents endorsed a suicidal risk item and 39 (19.5%) were considered to be concerning by their primary care physician. The average age was 14.7 years old (SD ± 2.0). Seventy-two percent (n = 144) were female, and 65% (n = 129) identified as Black. At initial visits, significant differences between suicidal concern groups were found in reporting active suicidal ideation, past suicide attempts, those who were referred to behavioral health counseling, and those who had a diagnosis of depression. Interestingly, only 13% (n = 25) of all patients who endorsed the suicide item were asked whether or not there were weapons in their home and primary care providers asked only 7% (n = 13) of all patients whether they had a safety plan. Conclusions There was inconsistent follow-up for adolescents with a history of suicide concerns. At this time, national guidelines do not exist regarding primary care follow-up of youth with suicide concerns. Guidelines are a necessary precursor for practice improvement. Trial Registration Clinical Trials Registry: NCT02244138 . Registration date, September 1, 2014.

Endoplasmic Reticulum stress induces cell non-autonomous Unfolded Protein Response (UPR) activation. Here the authors show that long-chain ceramides are secreted from muscle cells in extracellular vesicles and induce cell non-autonomous UPR activation in muscle cells in response to lipotoxcity.

Abstract Understanding the ecological consequences of supplemental feeding to both hummingbirds and the plants they pollinate is complicated by logistical challenges associated with assessing relative dietary resource use with commonly applied observational methods. Here, we describe the results of research conducted to assess the relative use of feeder and flower nectar by Broad‐tailed (Selasphorus platycercus) and Rufous hummingbirds (Selasphorus rufus) using two distinct methodological variations to measure the δ13C values of exhaled CO2. Because of the relatively quick time in which both species switch from exogenous to endogenous resources to fuel metabolism, our experiment allowed us to assess resource use at two timescales. Our results suggest variability in the relative contributions of the two dietary sources within and among species and timescales, with most birds employing a mixture of feeder and flower sugars as fuel sources. This diversity in relative resource use may mitigate potential negative effects of supplemental feeding on hummingbirds and their plant symbionts.

Abstract Background Adult-onset leukoencephalopathies are a group of heterogeneous disorders characterized by white matter abnormalities. Leukoencephalopathy is usually encountered in children, but here we report a case with adult-onset leukoencephalopathy. Also, we explore this concept of uncertainty in medicine by discussing the approach to this case that has multiple possible etiologies. Case presentation A 70-year-old Caucasian male presented with a subacute onset of cognitive impairment and mood disturbances associated with behavioral changes. Neuroimaging demonstrated high-intensity lesions involving cerebral white matter. Progressive dementia and cognitive decline followed. Multiple possible etiologies are discussed based on the patient presentation and risk factors. Conclusion Adult-onset leukoencephalopathy can become a diagnostic challenge. Certain approaches need to be developed to explore the uncertainty of such conditions and to improve diagnostic yield.

Abstract Cigarette smoke (CS) is the major risk factor for COPD and is linked to cardiopulmonary dysfunction. Exercise training as part of pulmonary rehabilitation is recommended for all COPD patients. It has several physiological benefits, but the mechanisms involved remain poorly defined. Here, we employed transcriptomic profiling and examined lung endothelium to investigate novel interactions between exercise and CS on cardiopulmonary alterations. Mice were exposed to 20 weeks of CS, CS + 6 weeks of high‐intensity interval training on a treadmill, or control. Lung and cardiac (left and right ventricle) tissue were harvested and RNA‐sequencing was performed and validated with RT‐qPCR. Immunohistochemistry assessed pulmonary arteriolar changes. Transcriptome analysis between groups revealed 37 significantly regulated genes in the lung, 21 genes in the left ventricle, and 43 genes in the right ventricle (likelihood‐ratio test). Validated genes that showed interaction between exercise and CS included angiotensinogen (p = 0.002) and resistin‐like alpha (p = 0.019) in left ventricle, with prostacyclin synthetase different in pulmonary arterioles (p = 0.004). Transcriptomic profiling revealed changes in pulmonary and cardiac tissue following exposure to CS, with exercise training exerting rescue effects. Exercise‐regulated genes included angiotensinogen and resistin‐like alpha, however, it remains unclear if these represent potential candidate genes or biomarkers that could play a role during pulmonary rehabilitation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitor have become widely used in patients with diabetes, heart failure, and kidney disease to improve clinical outcomes and diminish hospitalizations. They have also been associated with increased serum magnesium levels in patients with type 2 diabetes. The use of SGLT2 inhibitors resulted in improved magnesium homeostasis in a series of patients with refractory hypomagnesemia with urinary magnesium wasting. However, the role of SLGT2 inhibitors in patients with hypomagnesemia without urinary magnesium wasting remains unexplored. We report 2 cases with refractory hypomagnesemia without significant urinary magnesium wasting and dramatically improved serum magnesium levels after the initiation of SGLT2 inhibitors. Case 1 achieved independence from weekly intravenous magnesium infusions and reached sustainably greater serum magnesium levels with decreased oral magnesium supplementation and increased urinary fractional excretion of magnesium. Case 2 demonstrated improved serum magnesium levels with reduced oral magnesium supplementation without significant reduction in urinary fractional excretion of magnesium. These findings not only expand the use of SGLT2 inhibitors but also open the door for further studies to better understand the pathophysiology of how magnesium homeostasis is altered with inhibition of SGLT2.

Gabapentin (Neurontin) is an anti-epileptic drug that has had wide off-label prescription use since market release due to presumed negligible abuse potential. However, trends in drug misuse have demonstrated that gabapentin misuse is occurring, particularly in those with a history of opioid misuse. This is concerning, because although gabapentin has no direct ligand activity at opioid receptors, it does potentiate the analgesic effect of opioids, and concurrent use of gabapentin and opioids may increase the risk of respiratory depressive effects of opioids. This study investigates the incidence of gabapentin detected in urine samples collected for clinical drug screening purposes in a local hospital emergency department and in postmortem samples submitted by medical examiners in the St. Louis metropolitan area. The prevalence of gabapentin and co-detected drugs in both populations is contrasted, compared, and discussed. This study found that 30% of urine samples collected from patients with suspected drug intoxication presenting to SSM Health Saint Louis University Hospital, a quaternary care medical center, were positive for gabapentin, and nearly two thirds of those were also positive for oxycodone. Over a 6-month period, the incidence of gabapentin positive postmortem cases increased from 18% to 20%. Nearly all gabapentin positive postmortem cases were also positive for an opioid, the most significant being fentanyl, suggesting that gabapentin misuse may be due to its potentiating effect of opioid drug action. This study also highlights the limited utility of immunoassay-based urine drug screens.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces inflammatory response, cytokine storm, venous thromboembolism, coagulopathy, and multiple organ damage. Resting endothelial cells prevent coagulation, control blood flow, and inhibit inflammation. However, it remains unknown how SARS-CoV-2 induces strong molecular signals in distant cells for immunopathogenesis. In this study, we examined the consequence of human endothelial cells, microvascular endothelial cells (HMEC-1), and liver endothelial cells (TMNK-1) to exosomes isolated from plasma of mild or severe COVID-19 patients. We observed a significant induction of NLRP3, caspase-1, and interleukin-1β (IL-1β) mRNA expression in endothelial cells following exposure to exosomes from severe COVID-19 patients compared with that from patients with mild disease or healthy donors. Activation of caspase-1 was noted in the endothelial cell culture medium following exposure to the COVID-19 exosomes. Furthermore, COVID-19 exosomes significantly induced mature IL-1β secretion in both HMEC-1 and TMNK-1 endothelial cell culture medium. Thus, our results demonstrated for the first time that exosomes from COVID-19 plasma trigger NLRP3 inflammasome in endothelial cells of distant organs resulting in IL-1β secretion and inflammatory response. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health problem. Although the vaccine controls infection, understanding the molecular mechanism of pathogenesis will help in developing future therapies. Furthermore, several investigators predicted the involvement of endothelial cell-related inflammation in SARS-CoV-2 infection and using extracellular vesicles as a cargo to carry a drug or vaccine for combating SARS-CoV-2 infection. However, the mechanism by which endothelial cells are inflamed remains unknown. Our present study highlights that exosomes from severe COVID-19 patients can enhance inflammasome activity in distant endothelial cells for augmentation of immunopathogenesis and opens an avenue for developing therapies.

Abstract One major cause of traumatic injury is firearm-related wounds (i.e., ballistic trauma), common in both civilian and military populations, which is increasing in prevalence and has serious long-term health and socioeconomic consequences worldwide. Common primary injuries of ballistic trauma include soft-tissue damage and loss, haemorrhage, bone fracture, and pain. The majority of injuries are of musculoskeletal origin and located in the extremities, such that skeletal muscle offers a major therapeutic target to aid recovery and return to normal daily activities. However, the underlying pathophysiology of skeletal muscle ballistic trauma remains poorly understood, with limited evidence-based treatment options. As such, this review will address the topic of firearm-related skeletal muscle injury and regeneration. We first introduce trauma ballistics and the immediate injury of skeletal muscle, followed by detailed coverage of the underlying biological mechanisms involved in regulating skeletal muscle dysfunction following injury, with a specific focus on the processes of muscle regeneration, muscle wasting and vascular impairments. Finally, we evaluate novel approaches for minimising muscle damage and enhancing muscle regeneration after ballistic trauma, which may have important relevance for primary care in victims of violence.

As migratory species move through the stages of their annual cycle, individuals often display variation in the degree to which they remain in proximity to one another, a phenomenon called migratory connectivity. We show scale dependence in the strength of migratory connectivity in Painted Buntings (Passerina ciris), a North American passerine with disjunct eastern and interior breeding populations. Based on light-level geolocator data from 112 individuals at 11 breeding sites, migratory connectivity between breeding and wintering grounds was strong at the range-wide scale, with interior and eastern Painted Buntings remaining separated throughout the annual cycle. Conversely, migratory connectivity within the eastern and interior populations was weak, with individuals from different breeding areas mixing extensively on winter quarters. We found weak migratory connectivity within populations as birds moved from the breeding grounds to the wintering grounds (breeding-to-winter), with individuals from different regions of each population mixing extensively on the wintering grounds. The interior population, however, displayed strong migratory connectivity as birds moved from the breeding grounds to the intermediate molting grounds (breeding-to-molting), with birds from different breeding sites showing contrasting migratory strategies during the molting period. Our results suggest that spatial scale dependence of migratory connectivity is likely to be a pervasive phenomenon, given that migratory routes and the likelihood of molt migration often differ among populations. When possible, researchers should be deliberate about the spatial design of tracking studies to reduce potential biases that can result from spatial scale-dependent migratory connectivity.

Piezo1 forms mechanically activated nonselective cation channels that contribute to endothelial response to fluid flow. Here we reveal an important role in the control of capillary density. Conditional endothelial cell–specific deletion of Piezo1 in adult mice depressed physical performance. Muscle microvascular endothelial cell apoptosis and capillary rarefaction were evident and sufficient to account for the effect on performance. There was selective upregulation of thrombospondin-2 (TSP2), an inducer of endothelial cell apoptosis, with no effect on TSP1, a related important player in muscle physiology. TSP2 was poorly expressed in muscle endothelial cells but robustly expressed in muscle pericytes, in which nitric oxide (NO) repressed the Tsp2 gene without an effect on Tsp1. In endothelial cells, Piezo1 was required for normal expression of endothelial NO synthase. The data suggest an endothelial cell–pericyte partnership of muscle in which endothelial Piezo1 senses blood flow to sustain capillary density and thereby maintain physical capability.

Abstract Background Suicide risk among individuals with schizophrenia (SZ) is intractably high, with over 40% of individuals attempting to take their own lives during their lifetime and an estimated 5–10% completing suicide. At present, available pharmacological and psychotherapeutic treatments offer limited risk reduction benefits, and thus, there remains an urgent need to explore novel interventions that will ameliorate this risk. Aerobic exercise (AE) has been shown to improve a number of predictors of suicide risk (e.g., depressed mood, sleeping difficulties). As individuals with SZ display a highly sedentary lifestyle, AE may reduce suicide risk. Methods Employing a multi-site, single-blind, randomized clinical trial design, we will examine the impact of AE on risk for suicide and related variables in individuals with SZ. Participants will be randomized to one of two 12-week exercise interventions: AE or a stretching and toning (ST) control intervention. Primary outcome measures will include suicide risk (Columbia Suicide Severity Rating Scale, C-SSRS) and aerobic fitness (VO2max), along with additional measures of suicide risk, mood, emotion regulation, sleep, cognition, and physical activity, with assessments completed at baseline and after 6 and 12 weeks of interventions. Discussion It is hypothesized that AE will reduce suicide risk among individuals with SZ. This study may offer support for a more efficacious treatment method for this population in addition to the pre-existing pharmacological and psychotherapeutic treatment regimens. Trial registration Clinicaltrials.gov, NCT03270098 . Registered on September 1, 2017.

Abstract Background Pulmonary hypertension leads to right ventricular heart failure and ultimately to cardiac cachexia. Cardiac cachexia induces skeletal muscles atrophy and contractile dysfunction. MAFbx and MuRF1 are two key proteins that have been implicated in chronic muscle atrophy of several wasting states. Methods Monocrotaline (MCT) was injected over eight weeks into mice to establish pulmonary hypertension as a murine model for cardiac cachexia. The effects on skeletal muscle atrophy, myofiber force, and selected muscle proteins were evaluated in wild-type (WT), MuRF1, and MuRF2-KO mice by determining muscle weights, in vitro muscle force and enzyme activities in soleus and tibialis anterior (TA) muscle. Results In WT, MCT treatment induced wasting of soleus and TA mass, loss of myofiber force, and depletion of citrate synthase (CS), creatine kinase (CK), and malate dehydrogenase (MDH) (all key metabolic enzymes). This suggests that the murine MCT model is useful to mimic peripheral myopathies as found in human cardiac cachexia. In MuRF1 and MuRF2-KO mice, soleus and TA muscles were protected from atrophy, contractile dysfunction, while metabolic enzymes were not lowered in MuRF1 or MuRF2-KO mice. Furthermore, MuRF2 expression was lower in MuRF1KO mice when compared to C57BL/6 mice. Conclusions In addition to MuRF1, inactivation of MuRF2 also provides a potent protection from peripheral myopathy in cardiac cachexia. The protection of metabolic enzymes in both MuRF1KO and MuRF2KO mice as well as the dependence of MuRF2 expression on MuRF1 suggests intimate relationships between MuRF1 and MuRF2 during muscle atrophy signaling.

Abstract Background Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D‐HF). Methods In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age‐matched controls (n = 25), DM (n = 10), CHF (n = 52), and D‐HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole‐body exercise capacity. Results Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D‐HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D‐HF patients only (P < 0.05), which strongly correlated to exercise capacity (R2 = 0.64; P < 0.001). Mitochondrial impairments in D‐HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti‐oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D‐HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05). Conclusions Patients with D‐HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D‐HF.

Abstract Background Previous studies in heart failure with reduced ejection fraction (HFrEF) suggest that skeletal muscle mitochondrial impairments are associated with exercise intolerance in men. However, the nature of this relationship in female patients remains to be elucidated. This study aimed to determine the relationship between skeletal muscle mitochondrial impairments and exercise intolerance in male and female patients with HFrEF. Methods Mitochondrial respiration, enzyme activity, and gene expression were examined in pectoralis major biopsies from age‐matched male (n = 45) and female (n = 11) patients with HFrEF and healthy‐matched male (n = 24) and female (n = 11) controls. Mitochondrial variables were compared between sex and related to peak exercise capacity. Results Compared with sex‐matched controls, complex I mitochondrial oxygen flux was 17% (P = 0.030) and 29% (P = 0.013) lower in male and female patients with HFrEF, respectively, which correlated to exercise capacity (r = 0.71; P > 0.0001). Female HFrEF patients had a 32% (P = 0.023) lower mitochondrial content compared with controls. However, after adjusting for mitochondrial content, male patients demonstrated lower complex I function by 15% (P = 0.030). Expression of key mitochondrial genes regulating organelle dynamics and maintenance (i.e. optic atrophy 1, peroxisome proliferator‐activated receptor γ coactivator‐1α, NADH:ubiquinone oxidoreductase core subunit S1/S3, and superoxide dismutase 2) were selectively lower in female HFrEF patients. Conclusions These data provide novel evidence that HFrEF induces divergent sex‐specific mitochondrial phenotypes in skeletal muscle that predispose towards exercise intolerance, impacting mitochondrial ‘quantity' in female patients and mitochondrial ‘quality' in male patients. Therapeutic strategies to improve exercise tolerance in HFrEF should consider targeting sex‐specific mitochondrial abnormalities in skeletal muscle.

Long-term datasets of integrated environmental variables, co-located together, are relatively rare. The UK Environmental Change Network (ECN) was launched in 1992 and provides the UK with its only long-term integrated environmental monitoring and research network for the assessment of the causes and consequences of environmental change. Measurements, covering a wide range of physical, chemical, and biological “driver” and “response” variables are made in close proximity at ECN terrestrial sites using protocols incorporating standard quality control procedures. This paper describes the datasets (there are 19 published ECN datasets) for these co-located measurements, containing over 20 years of data (1993–2015). The data and supporting documentation are freely available from the NERC Environmental Information Data Centre under the terms of the Open Government Licence using the following DOIs. Meteorology Meteorology: https://doi.org/10.5285/fc9bcd1c-e3fc-4c5a-b569-2fe62d40f2f5 (Rennie et al., 2017a) Biogeochemistry Atmospheric nitrogen chemistry: https://doi.org/10.5285/baf51776-c2d0-4e57-9cd3-30cd6336d9cf (Rennie et al., 2017b) Precipitation chemistry: https://doi.org/10.5285/18b7c387-037d-4949-98bc-e8db5ef4264c (Rennie et al., 2017c) Soil solution chemistry: https://doi.org/10.5285/b330d395-68f2-47f1-8d59-3291dc02923b (Rennie et al., 2017d) Stream water chemistry: https://doi.org/10.5285/fd7ca5ef-460a-463c-ad2b-5ad48bb4e22e (Rennie et al., 2017e) Stream water discharge: https://doi.org/10.5285/8b58c86b-0c2a-4d48-b25a-7a0141859004 (Rennie et al., 2017f) Invertebrates Moths: https://doi.org/10.5285/a2a49f47-49b3-46da-a434-bb22e524c5d2 (Rennie et al., 2017g) Butterflies: https://doi.org/10.5285/5aeda581-b4f2-4e51-b1a6-890b6b3403a3 (Rennie et al., 2017h) Carabid beetle: https://doi.org/10.5285/8385f864-dd41-410f-b248-028f923cb281 (Rennie et al., 2017i) Spittle bugs: https://doi.org/10.5285/aff433be-0869-4393-b765-9e6faad2a12b (Rennie et al., 2018) Vegetation Baseline: https://doi.org/10.5285/a7b49ac1-24f5-406e-ac8f-3d05fb583e3b (Rennie et al., 2016a) Coarse grain: https://doi.org/10.5285/d349babc-329a-4d6e-9eca-92e630e1be3f (Rennie et al., 2016b) Woodland: https://doi.org/10.5285/94aef007-634e-42db-bc52-9aae86adbd33 (Rennie et al., 2017j) Fine grain: https://doi.org/10.5285/b98efec8-6de0-4e0c-85dc-fe4cdf01f086 (Rennie et al., 2017k) Vertebrates Frogs: https://doi.org/10.5285/4d8c7dd9-8248-46ca-b988-c1fc38e51581 (Rennie et al., 2017l) Birds (Breeding bird survey): https://doi.org/10.5285/5886c3ba-1fa5-49c0-8da8-40e69a10d2b5 (Rennie et al., 2017m) Birds (Common bird census): https://doi.org/10.5285/8582a02c-b28c-45d2-afa1-c1e85fba023d (Rennie et al., 2017n) Bats: https://doi.org/10.5285/2588ee91-6cbd-4888-86fc-81858d1bf085 (Rennie et al., 2017o) Rabbits and deer: https://doi.org/10.5285/0be0aed3-f205-4f1f-a65d-84f8cfd8d50f (Rennie et al., 2017p)

Bronfenbrenner's Ecological Framework was utilized to examine the complexity of the teacher turnover problem in regard to structural inequalities within education that need to be dismantled to create equitable outcomes for all students. Hierarchical cluster analysis was implemented to investigate school report card data of elementary schools in a rural school district (n = 18) and an urban school district (n = 41) in geographical proximity in the southeastern United States. Clusters were formed using school level variables including the breakdown of student race/ethnicity, percentage of economically disadvantaged students, teacher turnover rates, years of teaching experience, and a school performance measure. Four clusters emerged from the analysis. Across all variables there were significant differences found between clusters (p <0.001) in the school performance measure, teacher turnover rates, student race/ethnicity, and percentage of students receiving free/reduced price lunch. The percentage of teachers with between 4 and 10 years of experience was statistically equivalent across all cluster groups, differences were found in the number of initially licensed teachers (a low of 9.9% in Cluster 2 to a high of 27.0% in Cluster 4) and teachers with 10 or more years experience (ranging from 46.5% in Cluster 4 to 62.2% in Cluster 2).

Abstract Background Chronic heart failure (CHF) leads to diaphragm myopathy that significantly impairs quality of life and worsens prognosis. In this study, we aimed to assess the efficacy of a recently discovered small‐molecule inhibitor of MuRF1 in treating CHF‐induced diaphragm myopathy and loss of contractile function. Methods Myocardial infarction was induced in mice by ligation of the left anterior descending coronary artery. Sham‐operated animals (sham) served as controls. One week post‐left anterior descending coronary artery ligation animals were randomized into two groups—one group was fed control rodent chow, whereas the other group was fed a diet containing 0.1% of the compound ID#704946—a recently described MuRF1‐interfering small molecule. Echocardiography confirmed development of CHF after 10 weeks. Functional and molecular analysis of the diaphragm was subsequently performed. Results Chronic heart failure induced diaphragm fibre atrophy and contractile dysfunction by ~20%, as well as decreased activity of enzymes involved in mitochondrial energy production (P

The two primary causes of surf zone injuries (SZIs) worldwide, including fatal drowning and severe spinal injuries, are rip currents (rips) and shore-break waves. SZIs also result from surfing and bodyboarding activity. In this paper we address the primary environmental controls on SZIs along the high-energy meso–macro-tidal surf beach coast of southwestern France. A total of 2523 SZIs recorded by lifeguards over 186 sample days during the summers of 2007, 2009 and 2015 were combined with measured and/or hindcast weather, wave, tide, and beach morphology data. All SZIs occurred disproportionately on warm sunny days with low wind, likely because of increased beachgoer numbers and hazard exposure. Relationships were strongest for shore-break- and rip-related SZIs and weakest for surfing-related SZIs, the latter being also unaffected by tidal stage or range. Therefore, the analysis focused on bathers. More shore-break-related SZIs occur during shore-normal incident waves with average to below-average wave height (significant wave height, Hs = 0.75–1.5 m) and around higher water levels and large tide ranges when waves break on the steepest section of the beach. In contrast, more rip-related drownings occur near neap low tide, coinciding with maximised channel rip flow activity, under shore-normal incident waves with Hs >1.25 m and mean wave periods longer than 5 s. Additional drowning incidents occurred at spring high tide, presumably due to small-scale swash rips. The composite wave and tide parameters proposed by Scott et al. (2014) are key controlling factors determining SZI occurrence, although the risk ranges are not necessarily transferable to all sites. Summer beach and surf zone morphology is interannually highly variable, which is critical to SZI patterns. The upper beach slope can vary from 0.06 to 0.18 between summers, resulting in low and high shore-break-related SZIs, respectively. Summers with coast-wide highly (weakly) developed rip channels also result in widespread (scarce) rip-related drowning incidents. With life risk defined in terms of the number of people exposed to life threatening hazards at a beach, the ability of morphodynamic models to simulate primary beach morphology characteristics a few weeks or months in advance is therefore of paramount importance for predicting the primary surf zone life risks along this coast.

Abstract Improved understanding of how our coasts will evolve over a range of time scales (years‐decades) is critical for effective and sustainable management of coastal infrastructure. A robust knowledge of the spatial, directional and temporal variability of the inshore wave climate is required to predict future coastal evolution and hence vulnerability. However, the variability of the inshore directional wave climate has received little attention, and an improved understanding could drive development of skillful seasonal or decadal forecasts of coastal response. We examine inshore wave climate at 63 locations throughout the United Kingdom and Ireland (1980–2017) and show that 73% are directionally bimodal. We find that winter‐averaged expressions of six leading atmospheric indices are strongly correlated (r = 0.60–0.87) with both total and directional winter wave power (peak spectral wave direction) at all studied sites. Regional inshore wave climate classification through hierarchical cluster analysis and stepwise multi‐linear regression of directional wave correlations with atmospheric indices defined four spatially coherent regions. We show that combinations of indices have significant skill in predicting directional wave climates (R2 = 0.45–0.8; p

Paenibacillus larvae is the causative agent of American Foulbrood (AFB), the most destructive bacterial infection in honeybees. Even antibiotic-sensitive strains of P. larvae can produce recurrent AFB months to weeks post-antibiotic treatment due to the survival of bacterial spores. Recently, phages that infect P. larvae have been shown to effectively combat AFB in the field. Here, we present evidence that phages not only bind to vegetative P. larvae but also bind to P. larvae spores. Spore binding was observed in the results of three specific experiments: (1) bacteria counted by flow cytometry generated quantitative data of FITC-labeled phages that were bound to vegetative bacteria as well as those bound to spores, (2) electron microscopy captured images of phages bound to the surface of spores in both horizontal and vertical positions, and (3) phages incubated with P. larvae spores bound to the spores and created plaques in vegetative bacteria under conditions not conducive to spore activation, indicating that binding to spores is reversible and that the phages are still active. Identification of phages with reversible spore-binding capability for use in phage therapy may improve treatment of sporulating bacterial infections.

It is critical to understand nutrient dynamics within different plant parts to correctly fine-tune agronomic advices, and to update breeding programs for increasing nutrient use efficiencies and yields. Farmer’s field-based research was conducted to assess the effects of nitrogen (N), phosphorus (P), and potassium (K) levels on dry matter and nutrient accumulation, partitioning, and remobilization dynamics in three popular maize (Zea mays L.) hybrids (P3522, P3396, and Rajkumar) over two years in an alluvial soil of West Bengal, India. Experimental results revealed that NPK rates as well as different cultivars significantly (p ≤ 0.05) influenced the dry matter accumulation (DMA) in different plant parts of maize at both silking and physiological maturity. The post-silking dry matter accumulation (PSDMA) and post-silking N, P, and K accumulations (PSNA, PSPA, PSKA) were highest in cultivar P3396. However, cultivar P3522 recorded the highest nutrient remobilizations and contributions to grain nutrient content. Total P and K accumulation were highest with 125% of the recommended dose of fertilizer (RDF) while total N accumulation increased even after 150% RDF (100% RDF is 200 kg N, 60 kg P2O5, and 60 kg K2O ha–1 for the study region). Application of 125% RDF was optimum for PSDMA. The PSNA continued to increase up to 150% RDF while 125% RDF was optimum for PSPA. Cultivar differences significantly affected both remobilization efficiency (RE) and contribution to grain nutrient content for all tested macronutrients (N, P, and K). In general, RE as well as contribution to grain nutrient content was highest at 125% RDF for N and K, and at 100% RDF for P (either significantly or at par with other rates) for plots receiving nutrients. For all tested cultivars, nutrient remobilization and contribution to grain nutrient content was highest under nutrient-omission plots and absolute control plots. Both year and cultivar effects were non-significant for both grain and stover yields of maize. Application of 75% RDF was sufficient to achieve the attainable yield at the study location. The cultivar P3522 showed higher yield over both P3396 and Rajkumar, irrespective of fertilizer doses, although, the differences were not statistically significant (p ≥ 0.05). The study underscores the importance of maize adaptive responses in terms of nutrients accumulation and remobilization at different levels of nutrient availability for stabilizing yield.

Background People with chronic heart failure (CHF) experience severe skeletal muscle dysfunction, characterized by mitochondrial abnormalities, which exacerbates the primary symptom of exercise intolerance. However, the molecular triggers and characteristics underlying mitochondrial abnormalities caused by CHF remain poorly understood. Methods and Results We recruited 28 patients with CHF caused by reduced ejection fraction and 9 controls. We simultaneously biopsied skeletal muscle from the pectoralis major in the upper limb and from the vastus lateralis in the lower limb. We phenotyped mitochondrial function in permeabilized myofibers from both sites and followed this by complete RNA sequencing to identify novel molecular abnormalities in CHF skeletal muscle. Patients with CHF presented with upper and lower limb skeletal muscle impairments to mitochondrial function that were of a similar deficit and indicative of a myopathy. Mitochondrial abnormalities were strongly correlated to symptoms. Further RNA sequencing revealed a unique transcriptome signature in CHF skeletal muscle characterized by a novel triad of differentially expressed genes related to deficits in energy metabolism including adenosine monophosphate deaminase 3, pyridine nucleotide‐disulphide oxidoreductase domain 2, and lactate dehydrogenase C. Conclusions Our data suggest an upper and lower limb metabolic myopathy that is characterized by a unique transcriptome signature in skeletal muscle of humans with CHF.

Abstract Predicting the drivers of incursion and expansion of vector‐borne diseases as part of early‐warning strategies (EWS) is a major challenge for geographically extensive diseases where spread is mediated by spatial heterogeneity in climate and other environmental drivers. Geospatial data on these environmental drivers are increasingly available affording opportunities for application to a predictive disease ecology paradigm provided the data can be synthesized and harmonized with fine‐scale, highly resolved data on vector and host responses to their environment. Here, we apply a multi‐scale big data–model integration approach using human‐guided machine learning to objectively evaluate the importance of a large suite of spatially distributed environmental variables (>400) to develop EWS for vesicular stomatitis (VS), a common viral vector‐borne vesicular disease affecting livestock throughout the Americas. Two temporally and phylogenetically distinct events were used to develop disease occurrence–environment relationships in incursion (2004) and expansion years (2005), and then to test those relationships (2014, 2015) at two scales: (1) local and (2) landscape to regional. Our results show that VS occurrence at a local scale of individual landowners was related to conditions that can be monitored (rainfall, temperatures, streamflow) or modified (vegetation). On‐site green vegetation during the month of occurrence and higher rainfall four months prior combined with either cool daytime (expansion) or nighttime (incursion) temperatures one month prior were indicators of VS occurrence. Distance to running water (incursion) and host density based on neighboring ranches (expansion) with infected animals were also important in individual years. At landscape‐to‐regional scales, conditions that favor specific VSV biological vectors were indicated, either black flies in incursion years or biting midges in expansion years. Changes in viral genetic lineage were less important to patterns in VS occurrence than factors affecting the host–vector–environment interactions. In combination with our onset map based on latitude, elevation, and long‐term annual precipitation, this year‐ and scale‐specific information can be used to develop strategies to minimize effects of future VS events. This big data approach coupled with expert knowledge and machine learning can be applied to other emerging diseases for improvement in understanding, prediction, and management of vector‐borne diseases.

Importance Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer antipsychotics as augmentation treatment for depression. Objective This study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression. Design Population-based new-user/active comparator cohort study. Setting National healthcare claims data from the US Medicaid program from 2001–2010 linked to the National Death Index. Participants Non-elderly adults (25–64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer antipsychotic or with a second antidepressant. Patients with alternative indications for antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded. Exposure Augmentation treatment for depression with a newer antipsychotic or with a second antidepressant. Main outcome All-cause mortality during study follow-up ascertained from the National Death Index. Results The analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses. Conclusion Augmentation with newer antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer antipsychotic augmentation.

A cross-sectional survey design was used to assess Arkansas parents’/guardians’ intentions to vaccinate their child against COVID-19. Parents/guardians whose oldest child was age 0–11 years (n = 171) or 12–17 years (n = 198) were recruited between 12 July and 30 July 2021 through random digit dialing. Among parents/guardians with an age-eligible child, age 12–17, 19% reported their child had been vaccinated, and 34% reported they would have their child vaccinated right away. Among parents/guardians with a child aged 0–11, 33% of parents/guardians reported they would have their child vaccinated right away. Twenty-eight percent (28%) of parents/guardians whose oldest child was 12–17 and 26% of parents/guardians whose oldest child was 0–11 reported they would only have their child vaccinated if their school required it; otherwise, they would definitely not vaccinate them. For both groups, parents’/guardians’ education, COVID-19 vaccination status, and COVID-19 vaccine hesitancy were significantly associated with intentions to vaccinate their child. More than a third of parents/guardians whose child was eligible for vaccination at the time of the survey reported they intended to have them vaccinated right away; however, they had not vaccinated their child more than two months after approval. This finding raises questions about the remaining barriers constraining some parents/guardians from vaccinating their child.

Maureen Donnelly’s (2016) relative positionalism correctly handles any fixed arity relation with any symmetry such a relation can have, yielding the intuitively correct way(s) in which that relation can apply. And it supplies an explanation of what is going on in the world that makes this the case. But it has at least one potential shortcoming — one that its opponents are likely to seize upon: it can only handle relations with 'fixed' arities. It is unable to handle relations with 'variable' arities. I argue that, all else being equal, relative positionalism ought nonetheless to be preferred to its closest competitors — at least to the extent that the explanation it supplies of relational application is plausible — even though those competitors can handle variable arity relations in addition to fixed arity relations.

Background: Dipeptidyl peptidase-4 (DPP-4) may be a suitable biomarker to identify people with severe asthma who have greater activation of the interleukin-13 (IL-13) pathway and may therefore benefit from IL-13-targeted treatments. We report the analytical performance of an Investigational Use Only immunoassay and provide data on the biological range of DPP-4 concentrations. Methods: We assessed assay performance, utilising analyses of precision, linearity and sensitivity; interference from common endogenous assay interferents, and from asthma and anti-diabetic medications, were also assessed. The assay was used to measure the range of serum DPP-4 concentrations in healthy volunteers and subjects with diabetes and severe, uncontrolled asthma. Results: The total precision of DPP-4 concentration measurement (determined using percentage coefficient of variation) was ≤5% over 20 days. Dilution analysis yielded linear results from 30 to 1305 ng/mL; the limit of quantitation was 19.2 ng/mL. No notable endogenous or drug interferences were observed at the expected therapeutic concentration. Median DPP-4 concentrations in healthy volunteers and subjects with asthma or Type 1 diabetes were assessed, with concentrations remaining similar in subjects with diabetes and asthma across different demographics. Conclusion: These analyses indicate that the ARCHITECT DPP-4 Immunoassay is a reliable and robust method for measuring serum DPP-4 concentration. Keywords: Asthma, Automated immunoassay, Biomarker, Dipeptidyl peptidase-4, IL-13

As librarians are generally advocates of open access and data sharing, it is a bit surprising that peer-reviewed journals in the field of librarianship have been slow to adopt data sharing policies. Starting October 1, 2019, the Journal of the Medical Library Association (JMLA) is taking a step forward and implementing a firm data sharing policy to increase the rigor and reproducibility of published research, enable data reuse, and promote open science. This editorial explains the data sharing policy, describes how compliance with the policy will fit into the journal’s workflow, and provides further guidance for preparing for data sharing.

Ocular mpox, caused by monkeypox virus (MPXV), can threaten eyesight and requires prompt ophthalmologic consultation. Understanding of the disease course, treatments, and treatment durations is limited. We describe a case [...]

This article considers the reauthorization of the Elementary and Secondary Education Act (ESEA) in light of current educational inequities and the impact of the pandemic. The reauthorization presents an opportunity to center equity and justice and revitalize the civil rights aspects of the law. The authors review recent studies about the myriad ways the COVID-19 pandemic affected students, teachers and school systems and situates the reauthorization within the broader political context, including federal aid to states and districts during the pandemic. The authors present overarching policy recommendations: (1) a restructuring of the law's titles to focus on students, teachers, and systems (i.e. schools and districts); (2) a focus on the principles of racial equity, an ecosystem approach to serve students' needs across policy silos (i.e., housing and health), and a focus on research evidence; (3) policy targets for students; (4) policy targets for educators, including professional renewal and retention; (5) policy targets for the education system as a whole, including a focus on fiscal equity and facilitating regional approaches to cross-sector collaborations. The article presents a coherent conceptual framework for a redesign of ESEA with an emphasis on equity, evidence use, and ecosystems that is argued would directly address the needs of students, teachers, and systems.

The late-season extreme fire activity in Southcentral Alaska during 2019 was highly unusual and consequential. Firefighting operations had to be extended by a month in 2019 due to the extreme conditions of hot summer temperature and prolonged drought. The ongoing fires created poor air quality in the region containing most of Alaska’s population, leading to substantial impacts to public health. Suppression costs totaled over $70 million for Southcentral Alaska. This study’s main goals are to place the 2019 season into historical context, provide an attribution analysis, and assess future changes in wildfire risk in the region. The primary tools are meteorological observations and climate model simulations from the NCAR CESM Large Ensemble (LENS). The 2019 fire season in Southcentral Alaska included the hottest and driest June–August season over the 1979–2019 period. The LENS simulation analysis suggests that the anthropogenic signal of increased fire risk had not yet emerged in 2019 because of the CESM’s internal variability, but that the anthropogenic signal will emerge by the 2040–2080 period. The effect of warming temperatures dominates the effect of enhanced precipitation in the trend towards increased fire risk.

The quantification of CO2 emissions from cities using atmospheric measurements requires accurate knowledge of the atmospheric transport. Complex urban terrains significantly modify surface roughness, augment surface energy budgets, and create heat islands, all of which lead to lower horizontal winds and enhanced convection over urban areas. The question remains whether these processes should be included in atmospheric transport models that are used for city scale CO2 inversion, and whether they need to be tailored on a city basis. In this study, we use the WRF model over Paris to address the following research question: does WRF runs at a 3 km resolution, including urban effects and the assimilation of local weather data, perform better than ECMWF forecasts that give fields at 16 km resolution? The analysis of model performances focuses on three variables: air temperature, wind and the planetary boundary layer (PBL) height. The results show that the use of objective analysis and nudging tools are required to obtain good agreements between WRF simulated fields with observations. Surface temperature is well reproduced by both WRF and ECMWF forecasts, with correlation coefficients with hourly observations larger than 0.92 and MBEs within 1°C over one month. Wind speed correlations with hourly observations are similar for WRF (range 0.76~0.85 across stations) and ECMWF (0.79~0.84), but the associated RMSEs and MBEs are better for ECMWF. Conversely, WRF outperforms ECMWF forecasts for its description of wind direction, horizontal and vertical gradients. Sensitivity tests with different WRF physics schemes show that the wind speed and the PBL height are strongly influenced by PBL schemes. The marginal advantage of WRF over ECMWF for the desired application is sufficient to motive additional testing with prescribed CO2 flux maps for comparing modeled CO2 concentrations with available observations in an urban environment.

None at this time.

Providing access to the data underlying research results in published literature allows others to reproduce those results or analyze the data in new ways. Health sciences librarians and information professionals have long been advocates of data sharing. It is time for us to practice what we preach and share the data associated with our published research. This editorial describes the activity of a working group charged with developing a research data sharing policy for the Journal of the Medical Library Association.

BackgroundPeak ratios of pulmonary gas‐exchange to ventilation during exercise (V˙O2/V˙E and V˙CO2/V˙E, termed “circulatory equivalents”) are sensitive to heart failure (HF) severity, likely reflecting low and/or poorly distributed pulmonary perfusion. We tested whether peak V˙O2/V˙E and V˙CO2/V˙E would: (1) distinguish HF patients from controls; (2) be independent of incremental exercise protocol; and (3) correlate with lactate threshold (LT) and ventilatory compensation point (VCP), respectively. Methods and ResultsTwenty‐four HF patients (61±11 years) with reduced ejection fraction (31±8%) and 11 controls (63±7 years) performed ramp‐incremental cycle ergometry. Eighteen HF patients also performed slow (5±1 W/min), medium (9±4 W/min), and fast (19±6 W/min) ramps. Peak V˙O2/V˙E and V˙CO2/V˙E from X‐Y plot, and LT and VCP from 9‐panel plot, were determined by 2 independent, blinded, assessors. Peak V˙O2/V˙E (31.2±4.4 versus 41.8±4.8 mL/L; P

Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC) to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI), and hepatic alanine aminotransferase (ALT), and aspartate aminotransferase (AST), it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.

BackgroundRespiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)—a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in HFpEF by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt HFpEF could reverse impairments. Methods and ResultsObese ZSF1 rats (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3 additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of either sedentary behavior (n=13), high‐intensity interval training (n=11), or moderate‐continuous training (n=11). Obese rats developed an obvious HFpEF phenotype at 20 and 28 weeks. In the diaphragm at 20 weeks, HFpEF induced a shift towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower protein expression in MuRF1 and MuRF2, yet mitochondrial and contractile functional impairments were observed. At 28 weeks, neither the exercise training regimen of high‐intensity interval training or moderate‐continuous training reversed any of the diaphragm alterations induced by HFpEF. ConclusionsThis study, using a well‐characterized rat model of HFpEF underpinned by multiple comorbidities and exercise intolerance (ie, one that closely resembles the patient phenotype), provides evidence that diaphragm alterations and dysfunction induced in overt HFpEF are not reversed following 8 weeks of aerobic exercise training. As such, whether alternative therapeutic interventions are required to treat respiratory muscle weakness in HFpEF warrants further investigation.