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Background: Patient-reported outcome measures (PROMs) were originally developed as research tools; however, there is increasing interest in using PROMs to inform clinical care. Prior work has shown the benefits of implementing PROMs at the point of care, but a patient's health numeracy (their ability to understand and work with numbers) may affect their ability to interpret PROM results. Materials and Methods: We recruited patients presenting to an outpatient orthopedic clinic. Forty-nine patients completed a survey that included demographic information, the short-form General Health Numeracy Test, and accuracy questions about four PROM displays (bar graph, table, line graph, pictograph) that indicated the same PROM results. Results: Patients with higher health numeracy answered all display accuracy questions correctly (P=.016). Patients who preferred using the table were more likely to answer display accuracy questions incorrectly (odds ratio, 0.013, P=.024). The two most frequently preferred PROM formats were bar graphs and tables, and most patients preferred to learn about their PROM function scores via a combination of displays and verbal discussions. Conclusion: Patient health numeracy is associated with the ability to correctly interpret visual displays of PROMs. Implementation of PROMs at point of care currently does not account for health numeracy. Efforts to account for health numeracy when using PROMs at point of care may improve the efficacy of using PROMs to improve outcomes in orthopedic surgery. [Orthopedics. 2024;47(5):e255–e260.] [ABSTRACT FROM AUTHOR]

Given the importance of climate in shaping species' geographic distributions, climate change poses an existential threat to biodiversity. Climate envelope modeling, the predominant approach used to quantify this threat, presumes that individuals in populations respond to climate variability and change according to species-level responses inferred from spatial occurrence data--such that individuals at the cool edge of a species' distribution should benefit from warming (the "leading edge"), whereas individuals at the warm edge should suffer (the "trailing edge"). Using 1,558 tree-ring time series of an aridland pine (Pinus edulis) collected at 977 locations across the species' distribution, we found that trees everywhere grow less in warmer-than-average and drier-than-average years. Ubiquitous negative temperature sensitivity indicates that individuals across the entire distribution should suffer with warming--the entire distribution is a trailing edge. Species-level responses to spatial climate variation are opposite in sign to individual-scale responses to time-varying climate for approximately half the species' distribution with respect to temperature and the majority of the species' distribution with respect to precipitation. These findings, added to evidence from the literature for scale-dependent climate responses in hundreds of species, suggest that correlative, equilibrium-based range forecasts may fail to accurately represent how individuals in populations will be impacted by changing climate. A scale-dependent view of the impact of climate change on biodiversity highlights the transient risk of extinction hidden inside climate envelope forecasts and the importance of evolution in rescuing species from extinction whenever local climate variability and change exceeds individual-scale climate tolerances. [ABSTRACT FROM AUTHOR]

Simple Summary: Although women 70 years of age and older represent a large percentage of newly diagnosed breast cancer cases, older individuals are drastically underrepresented in clinical trials. Most women diagnosed with breast cancer at 70 years of age and older present with hormone receptor-positive (HR+) breast cancer. Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapy has become the standard of care for metastatic HR+ breast cancer. This study reports that metastatic breast cancer patients ≥70 years of age receiving CDK4/6 inhibitor-based treatment, particularly when combined with an aromatase inhibitor, experience prolonged progression-free survival but display no such prolongation in overall survival and report more frequent adverse effects to treatment. The reported findings can aid in the development of optimized treatments based on age and help older patients weigh treatment options. The largest portion of breast cancer patients diagnosed after 70 years of age present with hormone receptor-positive (HR+) breast cancer subtypes. Cyclin-dependent kinase (CDK) 4/6 inhibitor treatment, in conjunction with endocrine therapy, has become standard-of-care for metastatic HR+ breast cancer. In total, 320 patients with metastatic breast cancer receiving CDK4/6 inhibitor combined with fulvestrant or an aromatase inhibitor were enrolled in an ongoing observational study or were included in an IRB-approved retrospective study. All patients receiving CDK4/6 inhibitor-based therapy that were ≥70 years of age (n = 111) displayed prolonged progression-free survival (27.6 months) as compared to patients <70 years of age (n = 209, 21.1 months, HR = 1.38, p < 0.05). Specifically, patients receiving a CDK4/6 inhibitor with an aromatase inhibitor who were ≥70 years of age (n = 79) displayed exceptionally prolonged progression-free survival (46.0 months) as compared to patients receiving the same treatment who were <70 years of age (n = 161, 21.8 months, HR = 1.71, p < 0.01). However, patients ≥70 years of age also experienced more frequent adverse responses to CDK4/6 inhibitor-based treatment leading to dose reduction, hold, or discontinuation than the younger cohort (69% and 53%, respectively). Treatment strategies that may decrease toxicity without affecting efficacy (such as dose titration) are worth further exploration. [ABSTRACT FROM AUTHOR]

Employment can provide numerous benefits to quality of life, mental health, and social inclusion, which can be particularly important for people with disabilities. In a pilot study, the feasibility of Conversing with Others, a direct skills teaching (DST) group intervention to teach individuals with disabilities a work‐related soft skill focused on conversational skills, was assessed. This mixed methods study delivered the Conversing with Others curriculum in‐person or via telehealth to 119 participants. The intervention was based on the DST method of teaching skills through smaller, digestible, structured lessons. Both modalities showed improvement in participants' perceptions of their conversational skills. A non‐inferiority test indicated that the telehealth and in‐person group interventions were comparable. Overall, the study supported the feasibility of in‐person and telehealth interventions for teaching workplace conversational skills. [ABSTRACT FROM AUTHOR]

Background and Purpose: Since the COVID-19 pandemic, the use and implementation of telehealth has expanded, with implementation moving ahead of best practice recommendations due to necessity. Telehealth has improved access and care coordination for patients with various neurologic conditions; however, information regarding therapeutic intensity, safety, and appropriateness is lacking. In 2021, the Academy of Neurologic Physical Therapy formed a Telehealth Taskforce to provide clinical and educational resources for its members and the neurologic physical therapy (PT) community. The purpose of this special interest article is to provide consensus-driven best practice resources developed by the Taskforce and describe the process of creating these resources to assist with telehealth implementation in neurologic PT practice, advocate for continued utilization, and shine light on opportunities for future research. Summary of Key Points: In this special interest article, we describe the process, challenges, and opportunities of developing and disseminating resources to educate, train, and support telehealth implementation in neurologic clinical practice. Four key strategies to facilitate telehealth implementation emerged: (1) increase knowledge of resources related to telehealth and mobile applications; (2) develop and disseminate evidence-based and consensus-based best practice recommendations for telehealth in neurologic PT; (3) provide future recommendations for integrating telehealth in PT, education, research, and clinical practice; and (4) encourage advocacy for inclusion of telehealth within the PT community. We explain the need to continue research and provide recommendations to expand telehealth research in neurologic clinical practice. Recommendations for Clinical Practice: This article highlights the potential and future of telehealth in neurologic PT practice. Our recommendations provide current clinical tools and resources for telehealth implementation following a knowledge-to-action framework and suggest areas for future research. [ABSTRACT FROM AUTHOR]

Purpose: Exclusive breastfeeding promotes gut microbial compositions associated with lower rates of metabolic and autoimmune diseases. Its cessation is implicated in increased microbiome-metabolome discordance, suggesting a vulnerability to dietary changes. Formula supplementation is common within our low-income, ethnic-minority community. We studied exclusively breastfed (EBF) neonates' early microbiome-metabolome coupling in efforts to build foundational knowledge needed to target this inequality. Methods: Maternal surveys and stool samples from seven EBF neonates at first transitional stool (0-24 hours), discharge (30-48 hours), and at first appointment (days 3-5) were collected. Survey included demographics, feeding method, medications, medical history and tobacco and alcohol use. Stool samples were processed for 16S rRNA gene sequencing and lipid analysis by gas chromatography-mass spectrometry. Alpha and beta diversity analyses and Procrustes randomization for associations were carried out. Results: Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria were the most abundant taxa. Variation in microbiome composition was greater between individuals than within (p=0.001). Palmitic, oleic, stearic, and linoleic acids were the most abundant lipids. Variation in lipid composition was greater between individuals than within (p=0.040). Multivariate composition of the metabolome, but not microbiome, correlated with time ( p=0.030). Total lipids, saturated lipids, and unsaturated lipids concentrations increased over time (p=0.012, p=0.008, p=0.023). Alpha diversity did not correlate with time (p=0.403). Microbiome composition was not associated with each samples' metabolome (p=0.450). Conclusion: Neonate gut microbiomes were unique to each neonate; respective metabolome profiles demonstrated generalizable temporal developments. The overall variability suggests potential interplay between influences including maternal breastmilk composition, amount consumed and living environment. [ABSTRACT FROM AUTHOR]

Background A study was initiated at Roswell Park Comprehensive Cancer Center to capture the real-world experience related to the use of CDK4/6 inhibitors (Ciclibs) for the treatment of metastatic hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-). Patients and Methods A total of 222 patients were evaluated who received CDK4/6 inhibitors in the period from 2015 to 2021. Detailed clinical and demographic information was obtained on each patient and used to define clinical and demographic features associated with progression-free survival on CDK4/6 inhibitor-based therapies. Results In this real-world analysis, the majority of patients received palbociclib as the CDK4/6 inhibitor with letrozole or fulvestrant as the predominant endocrine therapies. The median progression-free survival (PFS) in the letrozole (27.6 months) and fulvestrant (17.2 months) groups were comparable to that observed in clinical trials. As expected, age at start of the treatment and menopausal status influenced endocrine therapy utilization but were not associated with PFS. Patients with recurrent disease had shorter PFS (P =.0024) than those presenting with de novo metastasis. The presence of visceral metastasis trended toward shorter PFS (P =.051). Similarly, prior endocrine therapy (P =.003) or chemotherapy (P =.036) was associated with shorter PFS. Body mass index was not associated with PFS or with dose interruption and/or modification. While the number of minorities in this analysis is limited (n = 26), these patients as a group had statistically shorter PFS on treatment (P =.002). Conclusions The real-world progression-free survival with CDK4/6 inhibitors mimics that observed in the clinical trial. A number of clinical and demographic features were associated with PFS on CDK4/6 inhibitor-based therapy. Further studies are ongoing to validate these findings incorporating additional cancer centers. [ABSTRACT FROM AUTHOR]

A second-order constant-coefficient nonhomogeneous difference equation is presented as a template for deriving a model form to predict above breast height tree stem profiles. Comparative analysis of the precision and bias of the model with several commonly used polynomial models on a white oak (Quercus alba L.) tree profile data set indicates that the difference approach produces profile equations equivalent in precision and bias to the traditional methods for constructing profile equations. Because the fitted equations can be forced easily through two upper stem diameters, the model has the distinct advantage over other modeling methods by allowing the model to be adjustable for differing form classes and points. Also, because the solution of the difference equation is always path invariant, no matter which stem profile diameters the equation is forced through, the same tree profile is generated. As the method does not require a total height, it is adaptable to situations where profile measurements are only taken to an indefinite merchantable height. Resume: Une equation a differences non homogenes et a coefficient constant de second ordre est presentee comme gabarit pour deriver une forme de modele de prediction du defilement du tronc des arbres au-dessus de la hauteur de poitrine. Une analyse comparative de la precision et du biais du modele avec plusieurs modeles polynomiaux couramment utilises a ete effectuee sur un ensemble de donnees de defilement du chene blanc (Quercus alba L.). Les resultats indiquent que l'approche aux differences produit des equations de defilement equivalentes, en termes de precision et de biais, aux methodes traditionnelles de prediction du defilement. Comme on peut facilement forcer les equations ajustees a passer par deux diametres superieurs du tronc, le modele a un net avantage sur d'autres methodes de modelisation en etant ajustable pour differents points et differentes classes de forme. En outre, comme la solution de l'equation a differences est toujours a parcours invariable, le meme defilement est genere peu importe les diametres du tronc a travers lesquels l'equation est forcee de passer. Comme la methode ne necessite pas la mesure de la hauteur totale, elle peut s'adapter aux situations ou des mesures du defilement sont prises seulement a une hauteur indeterminee dans la partie marchande du tronc. [Traduit par la Redaction], Introduction The traditional approach to stem profile equation development is to fit the dependent variable of the ratio of stem diameter to diameter at breast height (DBH) to a function [...]

The dogs shit on the roof and then, every two weeks or so, the man in Apartment 311 climbs out the window with a plastic shovel and scoops the shit [...]

Simple Summary: In search of genetic factors that affect cancer risks in BRCA carriers, we carried out the first whole-genome sequencing study in a unique registry of familial ovarian cancer, selected to enrich with BRCA1/2 carriers. We are the first to survey rare variants, particularly the non-coding variants for BRCA modifier genes and identified PPARGC1A, a master regulator of mitochondrial biogenesis, as a novel putative BRCA modifier. This finding can help improve cancer risk prediction and provide personalized preventive care for BRCA carriers. While BRCA1 and BRCA2 mutations are known to confer the largest risk of breast cancer and ovarian cancer, the incomplete penetrance of the mutations and the substantial variability in age at cancer onset among carriers suggest additional factors modifying the risk of cancer in BRCA1/2 mutation carriers. To identify genetic modifiers of BRCA1/2, we carried out a whole-genome sequencing study of 66 ovarian cancer patients that were enriched with BRCA carriers, followed by validation using data from the Pan-Cancer Analysis of Whole Genomes Consortium. We found PPARGC1A, a master regulator of mitochondrial biogenesis and function, to be highly mutated in BRCA carriers, and patients with both PPARGC1A and BRCA1/2 mutations were diagnosed with breast or ovarian cancer at significantly younger ages, while the mutation status of each gene alone did not significantly associate with age of onset. Our study suggests PPARGC1A as a possible BRCA modifier gene. Upon further validation, this finding can help improve cancer risk prediction and provide personalized preventive care for BRCA carriers. [ABSTRACT FROM AUTHOR]

Estimates of the percentage of species "committed to extinction" by climate change range from 15% to 37%. The question is whether factors other than climate need to be included in models predicting species' range change. We created demographic range models that include climate vs. climate‐plus‐competition, evaluating their influence on the geographic distribution of Pinus edulis, a pine endemic to the semiarid southwestern U.S. Analyses of data on 23,426 trees in 1941 forest inventory plots support the inclusion of competition in range models. However, climate and competition together only partially explain this species' distribution. Instead, the evidence suggests that climate affects other range‐limiting processes, including landscape‐scale, spatial processes such as disturbances and antagonistic biotic interactions. Complex effects of climate on species distributions—through indirect effects, interactions, and feedbacks—are likely to cause sudden changes in abundance and distribution that are not predictable from a climate‐only perspective. [ABSTRACT FROM AUTHOR]

Summary Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome‐wide association study (GWAS) and a transcriptome‐wide association study (TWAS) in 260 patients of European‐descent from the DFCI 05–001 ALL trial, with validation in 101 patients of European‐descent from the DFCI 11–001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05–001 trial (p = 1.7 × 10−8). In DFCI 11–001 trial, we observed a consistent trend of this variant with fracture. The variant was an eQTL for two nearby genes, CD93 and THBD. In TWAS, genetically predicted ACAD9 expression was associated with an increased risk of bone toxicities, which was confirmed by meta‐analysis of the two cohorts (meta‐p = 2.4 × 10−6). In addition, a polygenic risk score of heel quantitative ultrasound speed of sound was associated with fracture risk in both cohorts (meta‐p = 2.3 × 10−3). Our findings highlight the genetic influence on treatment‐related bone toxicities in this patient population. The genes we identified in our study provide new biological insights into the development of bone adverse events related to ALL treatment. [ABSTRACT FROM AUTHOR]