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Ecologists have traditionally studied intraspecific variation by sampling species across their geographic ranges. However, whether this classic approach produces samples that accurately represent species' climatic niches is largely unknown. Alternative niche‐based study designs using species' climatic niches to inform sampling locations should more efficiently and completely capture the breadth of the niche, but the magnitude of this difference and how it may vary is unclear. Here we use conifers as a model system to explore these issues and reach specific recommendations for future sampling designs. Using an independent data set of high‐quality species' occurrences, we first show that recent publications examining variation across geographic space do a poor job of capturing the full breadth of species' niches, such that on average, only 22% of species' niche space was sampled. This was also true of a large compiled database, the International Tree‐Ring Data Bank (ITRDB), which yielded average niche coverage of only 45%. Finally, we simulated common sampling designs (i.e. random points, grids and transects) in both geographic and niche‐based sampling frameworks. Using two sampling metrics, niche coverage and niche undersampling, we measured how completely and evenly these simulated studies characterized the niches of 64 North American conifers. Niche‐based sampling better represented species' niches than geographic sampling, with the magnitude of this difference depending on study design and sample size. Niche‐based gridded study designs achieved the most complete sampling at all but the smallest sample sizes, covering ~15–25% more of a species' niche than similar designs implemented geographically. With fewer than 10 samples, however, all study designs performed poorly, and niche‐based transects achieved slightly higher niche coverage. Consequently, when more than a handful of samples are collected, we recommend that studies seeking to characterize variation across a species' niche consider using a gridded study design implemented in a niche‐based sampling framework.

Aim The assumption that the native distributions of species are in equilibrium with climate has been shown to be frequently violated, despite its centrality to many niche model applications. We currently lack a framework that predicts these violations. Here, we examine whether variation in climatic disequilibrium is structured by properties of species’ native distributions and climatic niches. Location Global. Methods We built climatic niche models for 106 pine (Pinus L.) species, including 25 that have naturalized outside their native range. We measured the extent of climate space occupied exclusively by naturalized populations and considered what fraction of this space was available within the native continent and near the native range. We examined the consequences of disequilibrium for estimates of potential range filling and sister species niche conservatism. Results Most species (23 of 25) have naturalized in climate conditions outside the native niche, leading to increases in the total known suitable climate space. Increases in niche size were negatively related to native niche size. Increases were often large; one species expanded its niche by almost 10% of the global climate space. These increases were associated primarily with cooler, wetter and less seasonal climates. Increases in known niche size lowered potential range filling estimates within species’ native continent and ecoregion. Naturalized data did not strengthen support for niche conservatism among sister species. Main conclusions Among pines, climatic disequilibrium is the norm and not the exception. The magnitude of this disequilibrium can be vast, such that the native range greatly under‐represents the true climatic tolerances of some species. Fortunately, this disequilibrium can be predicted largely by the size of a species’ native niche. Accounting for this disequilibrium can improve our ability to characterize ecological phenomena, including potential range filling. This is an essential step towards improving the conservation value of ecological niche models.

Anthropogenic climate change is predicted to cause many extinctions worldwide1. Although species endemic to islands or archipelagos have high conservation value and are vulnerable to human impacts2,3, there has been no global analysis of climate-driven extinction risk focused on island endemics. Here, we use conifers as a model system to assess extinction risk among island endemics under climate projections for 2070. We employ the emerging technique of combining native and non-native occurrence data to model climatic conditions under which each species can sustain a population4–7 and also incorporate horticultural data to model the broader range of conditions that allow short-term survival. Our projections indicate that some species will retain suitable climatic conditions, some will experience conditions completely precluding survival and others will experience intermediate-risk conditions that lead to population decline and eventual extinction. Based on different climate change models, we report island size thresholds of 400 to 20,000 km2, below which extinction risks increase. These patterns are driven by correlations among island area and the breadth of species’ realized, fundamental and tolerance niches. Notably, realized and fundamental niche breadth are positively correlated. Our results highlight management interventions needed to protect species from climate-driven extinction across islands of different sizes.

BackgroundDifferences between early-onset and late-onset adult asthma have not been comprehensively described using prospective data.AimsTo characterise the differences between early-onset and late-onset asthma in a longitudinal cohort study.MethodsThe Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort. Respiratory histories and spirometry were first performed in 1968 when participants were aged 7 (n=8583). The cohort was traced and resurveyed from 2002 to 2005 (n=5729 responses) and a sample, enriched for asthma and bronchitis participated in a clinical study when aged 44 (n=1389).ResultsOf the entire TAHS cohort, 7.7% (95% CI 6.6% to 9.0%) had early-onset and 7.8% (95% CI 6.4% to 9.4%) late-onset asthma. Atopy and family history were more common in early-onset asthma while female gender, current smoking and low socioeconomic status were more common in late-onset asthma. The impact on lung function of early-onset asthma was significantly greater than for late-onset asthma (mean difference prebronchodilator (BD) FEV1/FVC −2.8% predicted (−5.3 to −0.3); post-BD FEV1FVC −2.6% predicted (−5.0 to −0.1)). However, asthma severity and asthma score did not significantly differ between groups. An interaction between asthma and smoking was identified and found to be associated with greater fixed airflow obstruction in adults with late-onset asthma. This interaction was not evident in adults with early-onset disease.ConclusionsEarly-onset and late-onset adult asthma are equally prevalent in the middle-aged population. Major phenotypic differences occur with asthma age-of-onset; while both share similar clinical manifestations, the impact on adult lung function of early-onset asthma is greater than for late-onset asthma.

Traumatic spinal cord injury (SCI) may result in tetraplegia (motor and/or sensory nervous system impairment of the arms, trunk and legs) or paraplegia (motor and/or sensory impairment of the trunk and/or legs only). The adverse effects of SCI on health, fitness and functioning are frequently compounded by profoundly sedentary behaviour. People with paraplegia (PP) and tetraplegia (TP) have reduced exercise capacity due to paralysis/paresis and reduced exercising stroke volume. TP often further reduces exercise capacity due to lower maximum heart-rate and respiratory function. There is strong, consistent evidence that exercise can improve cardiorespiratory fitness and muscular strength in people with SCI. There is emerging evidence for a range of other exercise benefits, including reduced risk of cardio-metabolic disease, depression and shoulder pain, as well as improved respiratory function, quality-of-life and functional independence. Exercise recommendations for people with SCI are: ≥30min of moderate aerobic exercise on ≥5d/week or ≥20min of vigorous aerobic ≥3d/week; strength training on ≥2d/week, including scapula stabilisers and posterior shoulder girdle; and ≥2d/week flexibility training, including shoulder internal and external rotators. These recommendations may be aspirational for profoundly inactive clients and stratification into “beginning”, “intermediate” and “advanced” will assist application of the recommendations in clinical practice. Flexibility exercise is recommended to preserve upper limb function but may not prevent contracture. For people with TP, Rating of Perceived Exertion may provide a more valid indication of exercise intensity than heart rate. The safety and effectiveness of exercise interventions can be enhanced by initial screening for autonomic dysreflexia, orthostatic hypotension, exercise-induced hypotension, thermoregulatory dysfunction, pressure sores, spasticity and pain.

BackgroundClassifying individuals at high chronic obstructive pulmonary disease (COPD)-risk creates opportunities for early COPD detection and active intervention.ObjectiveTo develop and validate a statistical model to predict 10-year probabilities of COPD defined by post-bronchodilator airflow obstruction (post-BD-AO; forced expiratory volume in 1 s/forced vital capacity<5th percentile).SettingGeneral Caucasian populations from Australia and Europe, 10 and 27 centres, respectively.ParticipantsFor the development cohort, questionnaire data on respiratory symptoms, smoking, asthma, occupation and participant sex were from the Tasmanian Longitudinal Health Study (TAHS) participants at age 41–45 years (n=5729) who did not have self-reported COPD/emphysema at baseline but had post-BD spirometry and smoking status at age 51–55 years (n=2407). The validation cohort comprised participants from the European Community Respiratory Health Survey (ECRHS) II and III (n=5970), restricted to those of age 40–49 and 50–59 with complete questionnaire and spirometry/smoking data, respectively (n=1407).Statistical methodRisk-prediction models were developed using randomForest then externally validated.ResultsArea under the receiver operating characteristic curve (AUCROC) of the final model was 80.8% (95% CI 80.0% to 81.6%), sensitivity 80.3% (77.7% to 82.9%), specificity 69.1% (68.7% to 69.5%), positive predictive value (PPV) 11.1% (10.3% to 11.9%) and negative predictive value (NPV) 98.7% (98.5% to 98.9%). The external validation was fair (AUCROC 75.6%), with the PPV increasing to 17.9% and NPV still 97.5% for adults aged 40–49 years with ≥1 respiratory symptom. To illustrate the model output using hypothetical case scenarios, a 43-year-old female unskilled worker who smoked 20 cigarettes/day for 30 years had a 27% predicted probability for post-BD-AO at age 53 if she continued to smoke. The predicted risk was 42% if she had coexistent active asthma, but only 4.5% if she had quit after age 43.ConclusionThis novel and validated risk-prediction model could identify adults aged in their 40s at high 10-year COPD-risk in the general population with potential to facilitate active monitoring/intervention in predicted ‘COPD cases’ at a much earlier age.

Importance Little is known about the risk factors for, and the risk of, developing post–COVID-19 conditions (PCCs) among children. Objectives To estimate the proportion of SARS-CoV-2–positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2–negative children, and to assess factors associated with PCCs. Design, Setting, and Participants This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2–positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2–negative controls. Exposure SARS-CoV-2 detected via nucleic acid testing. Main Outcomes and Measures Post–COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. Results Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2–positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2–positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2–positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). Conclusions and Relevance In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

Sclerosing epithelioid fibrosarcoma (SEF) was originally described as a peculiar variant of fibrosarcoma in 1995. Subsequent studies showed that conventional SEF was associated with both immunohistochemical expression of MUC4 and EWSR1 / FUS gene rearrangements with CREB3L1 as the predominant fusion partner. Since then, a distinct group of fibrous tumors characterized by YAP1 :: KMT2A and KMT2A :: YAP1 gene rearrangements and SEF-like morphology has been described. These YAP1 :: KMT2A -rearranged sarcomas were further shown to lack both immunohistochemical expression of MUC4 and canonical EWSR1 / FUS gene rearrangements. To better understand whether the YAP1 :: KMT2A -rearranged sarcomas represent a subset of MUC4-negative SEF or a distinct entity, we studied 22 cases of YAP1 :: KMT2A -rearranged sarcomas, the largest series to date, and performed a literature review of all previously reported next-generation sequencing (NGS)-confirmed cases. These sarcomas often arose in young adults with a median age of 38 years and a male to female (M:F) ratio of 1.4:1. They predominantly involved somatic soft tissue; however, we report the first case of a tumor that primarily developed inside bone. Immunohistochemical studies showed that the tumors often demonstrated expression of YAP1 and EMA, while all tested cases were negative for MUC4. NGS confirmed the presence of YAP1 :: KMT2A gene fusions in all cases, some of which initially had false negative results with targeted FISH and solid tumor panel testing. Clinical follow-up information was available in 14 patients with a median follow-up of 25 months (range 1 to 170 months). Local recurrence occurred in three patients (21%) and metastasis developed in seven patients (50%). DNA methylation analysis further showed that YAP1 :: KMT2A -rearranged sarcomas formed a distinct cluster, which was clearly separate from both conventional SEF and low-grade fibromyxoid sarcoma (LGFMS). These results suggest that YAP1 :: KMT2A -rearranged sarcomas likely represent a unique sarcoma subtype with propensity for aggressive behavior.

The biodegradability of porous sol–gel silica microparticles in physiological buffers has been investigated using a USP4 flow-through dissolution tester. In the open configuration, which most closely models in-vivo conditions, the particles dissolved rapidly at pH 7.4, with a rate dependent on the surface area and media flow rate. In the closed configuration, the fastest dissolving 4 mg silica sample was almost completely dissolved in 100 mL of buffer after 36 h. The initial dissolution rates appeared relatively linear but dropped off as dissolved SiO 2 concentrations approached 20–25 ppm. Addition of serum proteins acted to slow dissolution by 20–30%, suggesting a slower degradation in vivo. Silica microparticles administered for controlled release drug delivery would therefore be expected to be eliminated relatively rapidly from the body, depending on the sample size and local fluid flow conditions.