Storylines of family medicine VII: family medicine across the lifespan.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'VII: family medicine across the lifespan', authors address the following themes: 'Family medicine maternity care', 'Seeing children as patients brings joy to work', 'Family medicine and the care of adolescents', 'Reproductive healthcare across the lifespan', 'Men's health', 'Care of older adults', and 'Being with dying'. May readers appreciate the range of family medicine in these essays.

Evaluation of the role of AXL in fusion-positive pediatric rhabdomyosarcoma identifies the small-molecule inhibitor bemcentinib (BGB324) as potent chemosensitizer.

Rhabdomyosarcoma (RMS) is a highly aggressive pediatric cancer with features of skeletal muscle differentiation. Over 80% of the high-risk patients ultimately fail to respond to chemotherapy treatment, leading to limited therapeutic options and dismal prognostic rates. The lack of response - and subsequent tumor recurrence - is driven in part by stem cell-like cells, the tumor subpopulation that is enriched after treatment, and characterized by expression of the AXL receptor tyrosine kinase (AXL). AXL mediates survival, migration and therapy resistance in several cancer types; however, its function in RMS remains unclear. In this study, we investigated the role of AXL in RMS tumorigenesis, migration and chemotherapy response, and whether targeting of AXL with small molecule inhibitors could potentiate the efficacy of chemotherapy. We show that AXL is expressed in a heterogeneous manner in patient-derived xenografts (PDXs), primary cultures and cell line models of RMS, consistent with its stem-cell-state selectivity. By generating a CRISPR/Cas9 AXL knock-out and overexpressing models, we show that AXL contributes to the migratory phenotype of RMS, but not to chemotherapy resistance. Instead, pharmacological blockade with the AXL inhibitors bemcentinib (BGB324), cabozantinib and NPS-1034 rapidly killed RMS cells in an AXL-independent manner, and augmented the efficacy of the chemotherapeutics vincristine and cyclophosphamide. In vivo administration of the combination of bemcentinib and vincristine exerted strong anti-tumoral activity in a rapidly progressing PDX mouse model, significantly reducing tumor bruden compared to single-agent treatment. Collectively, our data identify bemcentinib as a promising drug to improve chemotherapy efficacy in RMS patients.

Greater need but reduced access: a population study of planned and elective surgery rates in adult mental health service users.

AIMS: Timely access to surgery is an essential part of healthcare. People living with mental health (MH) conditions may have higher rates of chronic illness requiring surgical care but also face barriers to care. There is limited evidence about whether unequal surgical access contributes to health inequalities in this group. METHODS: We examined 1.22 million surgical procedures in public and private hospitals in New South Wales (NSW), Australia, in 2019. In a cross-sectional study of 76,320 MH service users aged 18 and over, surgical procedure rates per 1,000 population were compared to rates for 6.23 million other NSW residents after direct standardisation for age, sex and socio-economic disadvantage. Rates were calculated for planned and emergency surgery, for major specialty groups, for the top 10 procedure blocks in each specialty group and for 13 access-sensitive procedures. Subgroup analyses were conducted for hospital and insurance type and for people with severe or persistent MH conditions. RESULTS: MH service users had higher rates of surgical procedures (adjusted incidence rate ratio [aIRR]: 1.53, 95% CI: 1.51-1.56), due to slightly higher planned procedure rates (aIRR: 1.22, 95% CI: 1.19-1.24) and substantially higher emergency procedure rates (aIRR: 3.60, 95% CI: 3.51-3.70). Emergency procedure rates were increased in all block groups with sufficient numbers for standardisation. MH service users had very high rates (aIRR > 4.5) of emergency cardiovascular, skin and plastics and respiratory procedures, higher rates of planned coronary artery bypass grafting, coronary angiography and cholecystectomy but lower rates of planned ophthalmic surgery, cataract repair, shoulder reconstruction, knee replacement and some plastic surgery procedures. CONCLUSIONS: Higher rates of surgery in MH service users may reflect a higher prevalence of conditions requiring surgical care, including cardiac, metabolic, alcohol-related or smoking-related conditions. The striking increase in emergency surgery rates suggests that this need may not be being met, particularly for chronic and disabling conditions which are often treated by planned surgery in private hospital settings in the Australian health system. A higher proportion of emergency surgery may have serious personal and health system consequences.

Molecular Signatures of Normal Pressure Hydrocephalus: A Largescale Proteomic Analysis of Cerebrospinal Fluid.

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer's disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.

Racial Differences in Treatment Intensity at the End of Life Among Older Adults with Heart Failure: Evidence from the Health and Retirement Study.

Background: Black Americans experience the highest prevalence of heart failure (HF) and the worst clinical outcomes of any racial or ethnic group, but little is known about end-of-life care for this population. Objective: Compare treatment intensity between Black and White older adults with HF near the end of life. Design: Negative binomial and logistic regression analyses of pooled, cross-sectional data from the Health and Retirement Study (HRS). Setting/Subjects: A total of 1607 U.S. adults aged 65 years and older with HF who identify as Black or White, and whose proxy informant participated in an HRS exit interview between 2002 and 2016. Measurements: We compared four common measures of treatment intensity at the end of life (number of hospital admissions, receipt of care in an intensive care unit (ICU), utilization of life support, and whether the decedent died in a hospital) between Black and White HF patients, controlling for demographic, social, and health characteristics. Results: Racial identity was not significantly associated with the number of hospital admissions or admission to an ICU in the last 24 months of life. However, Black HF patients were more likely to spend time on life support (odds ratio [OR] = 2.16, confidence interval [CI] = 1.35-3.44, p = 0.00) and more likely to die in a hospital (OR = 1.53, CI = 1.03-2.28, p = 0.04) than White HF patients. Conclusion: Black HF patients were more likely to die in a hospital and to spend time on life support than White HF patients. Thoughtful and consistent engagement with HF patients regarding treatment preferences is an important step in addressing inequities.

The Association between Psychosocial Stressors and Gestational Weight Gain: Analysis of the National Pregnancy Risk Assessment Monitoring System (PRAMS) Results from 2012 to 2015.

OBJECTIVE: Both psychosocial stress and gestational weight gain are independently associated with adverse maternal and fetal outcomes. Studies of the association between psychosocial stress and gestational weight gain (GWG) have yielded mixed results. The objective of this study was to evaluate the association between psychosocial stress and GWG in a large population-based cohort. METHODS: Data from the nationally representative Pregnancy Risk Assessment Monitoring System (PRAMS) Phase 7 questionnaire 2012-2015 was utilized. Maternal psychosocial stress was assessed through response to questions designed to examine four domains of psychosocial stress (i.e., traumatic, financial, emotional, partner-related) three months prior to or during pregnancy. GWG was categorized using pre-pregnancy BMI and total GWG into inadequate, adequate, or excessive according to the Institute of Medicine's GWG guidelines. Multinomial logistic regression was used to evaluate the association between psychosocial stressors and adequacy of GWG. Analyses took into account complex survey design. RESULTS: All respondents who delivered ≥ 37 weeks gestation with GWG information available were included in the analysis (n = 119,183). After adjusting for confounders, patients who reported financial stress were more likely to experience excessive versus adequate GWG (RRR 1.09 [95%CI: 1.02-1.17]). Exposure to any of the stressor groups did not significantly increase the risk of inadequate GWG. CONCLUSIONS: This large, population-based study revealed that among pregnant people in the US, exposure to financial stress is associated with higher risk of excessive GWG. Understanding the role stress plays in GWG will help to inform initiatives targeting this important aspect of prenatal care.

A Secondary Data Analysis of Technology Access as a Determinant of Health and Impediment in Social Needs Screening and Referral Processes.

Introduction: Although health systems increasingly integrate social needs screening and referrals into routine care, the effectiveness of these interventions and for whom they work remains unclear. Methods: Patients (N=4,608) seen in the emergency department were screened for social needs (e.g., transportation, housing, food) and offered an opportunity to receive outreach from community service specialists. Results: Among 453 patients with 1 or more social needs who requested assistance, outreach specialists connected with 95 (21.0%). Patients preferred to be contacted through their telephone (n=21, 60.2%), email (n=126, 28.0%), someone else's telephone (n=30, 6.7%), or first by telephone followed by email (n=23, 5.1%). Preferred contact method varied by patient age; endorsement of unmet transportation, housing, and utility needs; receipt of service outreach; and differences in emergency department utilization from the 6 months before the index visit to the 6 months after. Conclusions: Because limited access to a stable telephone or internet connection may prevent patients from connecting with resource referrals, social needs interventions may not benefit the most underserved populations who are at the highest risk of negative health outcomes. Future research should investigate whether communication preferences are an important indicator of needs and how to adapt social needs screening and referral processes so that they are more accessible to populations who may experience more frequent disruptions in methods utilized for digital communication.

Misalignment of social support in the social media posts of young adult cancer caregivers.

BACKGROUND: Compared with older cancer caregivers, young adult cancer caregivers (YACC) experience greater stress and depression during the first 6 months of caregiving. Social support can buffer the negative psychological effects associated with cancer caregiving. However, the misalignment of social support is associated with increased distress and worse emotional well-being. As YACC are more likely to utilize social media (SM) to seek social support compared with older cancer caregivers, they may be at greater risk of experiencing the misalignment of social support and related negative outcomes. OBJECTIVE: The purpose of this study was to identify ways that SM posts containing support for YACC's were potentially misaligned with the social support desired by YACC. METHODS: In this secondary analysis, cancer-related SM posts (N = 760) from 34 YACC's SM accounts were extracted for 6 months following the day of cancer diagnosis and imported into NVivo qualitative analysis software. Open coding of posts from four YACC identified a pattern of SM posts containing responses that may misalign with social support requests, and could be perceived as dismissive of YACC's emotions. Similar posts were grouped together, forming categories which were used to create a codebook and applied in coding all posts from the remaining 30 YACC. RESULTS: Content analysis identified three categories of social support misalignment originating from YACC's SM posts: supplications (n = 251, 33%), prevailing (n = 7, 10.1%), and consolations (n = 16, 2.1%). Supplications involved prayer or trust in god, prevailing posts compared dealing with cancer to a fight and suggested that the person would overcome cancer, and consolations used quotes, song lyrics, and or general reassurances in SM posts. CONCLUSIONS: Findings suggest that when YACC use SM during cancer experiences, they may interpret SM posts as social support or as misalignment of social support requests, which in turn can lead to either improved quality of life or additional distress (respectively). This study adds to the body of knowledge regarding how YACC use social media for social support and may inform future interventions designed to match YACC's desired support with support offered.

Adverse Childhood Experiences Are Associated With Personality Disorder: A Prospective, Longitudinal Study.

There is a lack of studies that have prospectively examined adverse childhood experiences (ACEs) in association with a personality disorder (PD). Data from a sample of 8,199 adolescents first assessed for ACEs were linked with subsequent data from the Norwegian Patient Register in order to obtain diagnoses of a PD in adulthood (after a 14-year follow-up). We used logistic regression analysis. Any type of ACE gave a 3.8-fold higher risk of developing a PD. Abuse, more specifically emotional abuse, came out as one of the strongest predictors. Of the adolescents who developed a PD, approximately 90% had a history of ACE. The results of this study support the importance of assessing ACEs, such as abuse, neglect, and household dysfunction, in the diagnostic procedure and treatment for PD.

Predicting the effect of fouling organisms and climate change on integrated shellfish aquaculture.

Aquaculture industry represents a continuously growing sector playing a fundamental role in pursuing United Nation's goals. Increasing sea-surface temperatures, the growth of encrusting species and current cage cleaning practices proved to affect the productivity of commercial species. Here, through a Dynamic Energy Budget application under two different IPCC scenarios, we investigate the long-term effects of Pennaria disticha fragments' on Mytilus galloprovincialis' functional traits as a result of cage cleaning practices. While Climate-Change did not exert a marked effect on mussels' Life-History traits, the simulated effect of cage cleanings highlighted a positive effect on total weight, fecundity and time to commercial size. West-Mediterranean emerged as the most affected sector, with Malta, Montenegro, Morocco, Syria, Tunisia and Turkey between the top-affected countries. These outcomes confirm the reliability of a DEB-approach in projecting at different spatial and temporal scale eco-physiological results, avoiding the limitation of short-term studies and the difficulties of long-term ones.

Establishing priorities for implementation of large language models in pathology and laboratory medicine.

Artificial intelligence and machine learning have numerous applications in pathology and laboratory medicine. The release of ChatGPT prompted speculation regarding the potentially transformative role of large-language models (LLMs) in academic pathology, laboratory medicine, and pathology education. Because of the potential to improve LLMs over the upcoming years, pathology and laboratory medicine clinicians are encouraged to embrace this technology, identify pathways by which LLMs may support our missions in education, clinical practice, and research, participate in the refinement of AI modalities, and design user-friendly interfaces that integrate these tools into our most important workflows. Challenges regarding the use of LLMs, which have already received considerable attention in a general sense, are also reviewed herein within the context of the pathology field and are important to consider as LLM applications are identified and operationalized.

Towards a sustainable fisher-dolphin coexistence: Understanding depredation, assessing economic damage and evaluating management options.

Finding solutions for a sustainable coexistence between wildlife and humans is considered among the most challenging environmental management issues for scientists, conservationists, managers, and stockholders world-wide. Depredation by the common bottlenose dolphin (Tursiops truncatus) on small scale fisheries has increased in the recent years, leading to a growing conflict in many areas of the Mediterranean Sea and pressing for urgent management solutions. This study aims at developing a management framework for a sustainable coexistence between fishers and dolphins in Sardinia (Mediterranean Sea). Relying on the combination of different approaches (field study, literature review and Multi Criteria Decision Analysis), the scientific evidence necessary for understanding dolphin depredation were updated and improved, the related economic damage was calculated, and different management options were identified and evaluated by several stakeholder groups to support the decision-making process. Averaging for all investigated net types (gillnet and trammel net), a depredation frequency of 53% was found, the highest values ever found in both Sardinia and many other Mediterranean sites. Depredation probability was influenced by different factors, such as net type, fishing operation duration, depth of the fishing site and period. The estimated economic damage due to depredation ranges on average between 6492 and 11,925 euro per year and depends on the type of fishing net. The results from the field study, the literature review and the stakeholder involvement allowed us to define the most plausible and shared management options, identifying a framework for assessing and managing the conflict between fishers and dolphins for the creation of a more sustainable vision for the future.

Prenatal phthalate exposure and fetal penile length and width.

BACKGROUND: Phthalates are endocrine-disrupting chemicals with anti-androgenic qualities and studies reported associations between prenatal phthalate exposure and infant genitalia. This study investigated whether increased prenatal phthalate exposure is associated with decreased fetal penile measures. METHODS: Data was from the New York University Children's Health and Environment Study (2016-2019). Maternal urinary concentrations of 16 phthalate metabolites were quantified at <18 weeks gestation as a proxy for fetal exposure (n = 334 male pregnancies). We retrospectively measured penile length and width using ultrasounds conducted 18-24 weeks gestation (n = 173 fetuses). Associations of maternal urinary levels of phthalates with fetal penile length and width were determined using linear regression models. RESULTS: 57.2% of women were Hispanic, 31.8% Non-Hispanic White, 6.4% Asian, 2.3% Non-Hispanic Black, and 2.3% multiple races. Mean maternal age was 32 years (standard deviation [SD] = 5.7). Mean penile length was 7.13 mm (SD = 1.47) and width was 6.16 mm (SD = 0.87). An inverse relationship was observed between maternal levels of mono-ethyl phthalate and fetal penile length, and mono-(7-carboxy-n-heptyl) phthalate and penile width, though estimates were small and not significant when considering correction for multiple comparisons. CONCLUSIONS: In our cohort we found no clinically meaningful associations between early pregnancy phthalate exposure and fetal penile length or width. IMPACT: First-trimester phthalate metabolites were assessed in pregnant women in New York City. Penile length and width were retrospectively measured on clinically assessed ultrasounds conducted ≥18 weeks and <24 weeks of gestation. In this cohort, no clinically meaningful associations were observed between first-trimester prenatal phthalate exposure and fetal penile length. This study contributes to the limited but growing research on the impact of prenatal phthalate exposure on male fetal genital development. The results emphasize that there may not be a clear association between prenatal phthalate exposure and fetal penile length and width, and further research on this topic may be required.

Prevalence of Neuropathic Pain in Patients with Osteoarthritis.

Objective The aim of this study was to determine the prevalence of neuropathic pain and characterize the quality of life of patients with osteoarthritis who consulted a pain clinic in Southwestern Colombia. Methods A cross-sectional study was conducted via telephone survey. Participants ≥18 years of age with a diagnosis of osteoarthritis were included. The LANSS questionnaire was used to evaluate symptoms and signs of neuropathic pain, and the Short Form-8 was used to evaluate quality of life. Results Response rate was 54.1% (46/85). The male-to-female ratio was 5:1, with an average age of 72 ± 10 years. Most participants (91.3%) had severe pain. The prevalence of neuropathic pain was 28.3% (95%CI = 15.99-43.46), and the prevalence of neuropathic pain amongst women was 84.6% (95%CI = 54.55-98.01). Dysesthesias and paroxysmal pain were present in 92.3% of individuals with neuropathic pain. Regarding quality of life, limitations in physical activity were the most significant, as 63% of individuals reported such limitations. Conclusion Neuropathic pain was found to be prevalent and had a negative impact on physical function, highlighting the need for therapeutic strategies targeted to specific neuropathic pain pathways in patients with osteoarthritis.

The clinical features and impact of SARS-CoV-2/COVID-19 infection in children with Cystic Fibrosis (CF): A Qatari experience.

BACKGROUND: SARS-CoV-2 in children with cystic fibrosis (CF) has been reported to cause mild illness without pre-existing severe lung disease. This review described the clinical presentation and course of COVID-19 infection in children with CF in Qatar. METHODS: The pediatric CF registry of 51 patients in Qatar was reviewed for COVID-19 cases from February 2020 to February 2022. Demographics, vaccination status, symptoms, and course were reviewed. Data were expressed as median, range, frequencies, and percentages. RESULTS: The study included eight patients with CF below 18 years of age infected with COVID-19. The incidence of COVID-19 in children with CF was 15.7%. The median age was 11 (2-18) years. Half of the cohort were males. Seven patients were pancreatic sufficient (I1234V mutation), and one was pancreatic insufficient (3129del4 mutation). The median baseline FEV1 was 91 (78-107%) predicted. None had received CFTR modulators or undergone a lung transplant. Three patients were vaccinated before their infections. Two of them were asymptomatic. Six patients (75%) had a cough and flu-like symptoms. Three patients had a fever. Two patients were hospitalized due to pulmonary exacerbation; both had mild CF-lung disease. None required respiratory support. CONCLUSION: We report a favorable outcome of COVID-19 infection in children with CF, similar to published international studies. Our findings are attributable to the community-dominant milder CFTR mutation, precautionary measures, and causative COVID-19 strain. More longitudinal data are needed to study these factors as potential protective mechanisms.

Factors associated with functional decline in COVID-19 elderly survivors hospitalized in a tertiary care center.

BACKGROUND: The information on functional decline after hospitalization for COVID-19 is limited in older adults (OAs). OBJECTIVE: To determine the association of inflammation (ferritin) and coagulation markers (D-dimer) and clinical factors with the functional status of OAs who suffered from COVID-19 six months after hospital discharge in Mexico. MATERIAL AND METHODS: Ambispective cohort study of 158 patients older than 65 years hospitalized for moderate-severe COVID-19 with complete electronic records that would allow to collect information and to contact them six months after discharge. Functional impairment was defined as a decrease ≥ 10 points on the Barthel index. Using logistic regression analysis, the risk of association of biochemical and clinical factors with functional deterioration during follow-up was determined. RESULTS: 46.2% of participants exhibited functional decline. Associated factors included age ≥ 73 years (OR = 2.53), chronic kidney disease (OR = 4.57), an ABC-Goals score ≥ 8 (OR = 2.4), ferritin ≥ 605 ng/mL (OR = 3.94) and D-dimer ≥ 930 ng/mL (OR = 17.56). CONCLUSION: COVID-19 infection did not only represent a disease with a high risk of mortality during the acute phase, but is also associated with a high risk of functional impairment after hospital discharge.

ANTECEDENTES: La información acerca del deterioro funcional después de una hospitalización por COVID-19 es limitada en personas mayores (PM). OBJETIVO: Determinar la asociación entre marcadores de inflamación (ferritina), coagulación (dímero D), factores clínicos y el estado funcional de PM que padecieron COVID-19 a seis meses del alta hospitalaria en México. MATERIAL Y MÉTODOS: Estudio de cohorte ambispectiva de 158 pacientes mayores de 65 años hospitalizados por COVID-19 moderado-grave con expediente electrónico completo que permitiera recolectar información y contactarlos a los seis meses del alta. Se definió deterioro funcional como disminución ≥ 10 puntos del índice de Barthel. Mediante regresión logística se determinó el riesgo de asociación entre factores bioquímicos y clínicos y deterioro funcional en el tiempo de seguimiento. RESULTADOS: 46.2 % de los participantes presentó pérdida funcional. Los factores asociados fueron edad ≥ 73 años (RM = 2.53), enfermedad renal crónica (RM = 4.57), puntuación ABC-Goals ≥ 8 (RM = 2.4), ferritina ≥ 605 ng/mL (RM = 3.94) y dímero-D ≥ 930 ng/mL FEU (RM = 17.56). CONCLUSIÓN: La infección por COVID-19 no solo representa una enfermedad con alto riesgo de mortalidad durante la fase aguda, sino que también se asocia a un alto riesgo de deterioro funcional posterior al egreso hospitalario.

PAX3-FOXO1 uses its activation domain to recruit CBP/P300 and shape RNA Pol2 cluster distribution.

Activation of oncogenic gene expression from long-range enhancers is initiated by the assembly of DNA-binding transcription factors (TF), leading to recruitment of co-activators such as CBP/p300 to modify the local genomic context and facilitate RNA-Polymerase 2 (Pol2) binding. Yet, most TF-to-coactivator recruitment relationships remain unmapped. Here, studying the oncogenic fusion TF PAX3-FOXO1 (P3F) from alveolar rhabdomyosarcoma (aRMS), we show that a single cysteine in the activation domain (AD) of P3F is important for a small alpha helical coil that recruits CBP/p300 to chromatin. P3F driven transcription requires both this single cysteine and CBP/p300. Mutants of the cysteine reduce aRMS cell proliferation and induce cellular differentiation. Furthermore, we discover a profound dependence on CBP/p300 for clustering of Pol2 loops that connect P3F to its target genes. In the absence of CBP/p300, Pol2 long range enhancer loops collapse, Pol2 accumulates in CpG islands and fails to exit the gene body. These results reveal a potential novel axis for therapeutic interference with P3F in aRMS and clarify the molecular relationship of P3F and CBP/p300 in sustaining active Pol2 clusters essential for oncogenic transcription.

Paleoenvironmental inferences on the Late Miocene hominoid-bearing site of Can Llobateres (NE Iberian Peninsula): An ecometric approach based on functional dental traits.

Hispanopithecus laietanus from the Late Miocene (9.8 Ma) of Can Llobateres 1 (CLL1; Vallès-Penedès Basin, NE Iberian Peninsula) represents one of the latest occurrences of fossil apes in Western mainland Europe, where they are last recorded at ∼9.5 Ma. The paleoenvironment of CLL1 is thus relevant for understanding the extinction of European hominoids. To refine paleoenvironmental inferences for CLL1, we apply ecometric models based on functional crown type (FCT) variables-a scoring scheme devised to capture macroscopic functional traits of occlusal shape and wear surfaces of herbivorous large mammal molars. Paleotemperature and paleoprecipitation estimates for CLL1 are provided based on published regional regression models linking average FCT of large herbivorous mammal communities to climatic conditions. A mapping to Whittaker's present-day biome classification is also attempted based on these estimates, as well as a case-based reasoning via canonical variate analysis of FCT variables from five relevant biomes. Estimates of mean annual temperature (25 °C) and mean annual precipitation (881 mm) classify CLL1 as a tropical seasonal forest/savanna, only in partial agreement with the canonical variate analysis results, which classify CLL1 as a tropical rainforest with a higher probability. The former biome agrees better with previous inferences derived from fossil plants and mammals, as well as preliminary isotopic data. The misclassification of CLL1 as a tropical forest is attributed to the mixture of forest-adapted taxa with others adapted to more open environments, given that faunal and plant composition indicates the presence of a dense wetland/riparian forest with more open woodlands nearby. The tested FCT ecometric approaches do not provide unambiguous biome classification for CLL1. Nevertheless, our results are consistent with those from other approaches, thus suggesting that FCT variables are potentially useful to investigate paleoenvironmental changes through time and space-including those that led to the extinction of European Miocene apes.

Large Language Models and Medical Education: Preparing for a Rapid Transformation in How Trainees Will Learn to Be Doctors.

Artificial intelligence has the potential to revolutionize health care but has yet to be widely implemented. In part, this may be because, to date, we have focused on easily predicted rather than easily actionable problems. Large language models (LLMs) represent a paradigm shift in our approach to artificial intelligence because they are easily accessible and already being tested by frontline clinicians, who are rapidly identifying possible use cases. LLMs in health care have the potential to reduce clerical work, bridge gaps in patient education, and more. As we enter this era of healthcare delivery, LLMs will present both opportunities and challenges in medical education. Future models should be developed to support trainees to develop skills in clinical reasoning, encourage evidence-based medicine, and offer case-based training opportunities. LLMs may also change what we continue teaching trainees with regard to clinical documentation. Finally, trainees can help us train and develop the LLMs of the future as we consider the best ways to incorporate LLMs into medical education. Ready or not, LLMs will soon be integrated into various aspects of clinical practice, and we must work closely with students and educators to make sure these models are also built with trainees in mind to responsibly chaperone medical education into the next era.