Faculty Bibliography

Recent research demonstrates that large language models can predict neural activity recorded via electrocorticography during natural language processing. To predict word-by-word neural activity, most prior work evaluates encoding models within individual electrodes and participants, limiting generalizability. Here we analyze electrocorticography data from eight participants listening to the same 30-min podcast. Using a shared response model, we estimate a common information space across participants. This shared space substantially enhances large language model-based encoding performance and enables denoising of individual brain responses by projecting back into participant-specific electrode spaces-yielding a 37% average improvement in encoding accuracy (from r = 0.188 to r = 0.257). The greatest gains occur in brain areas specialized for language comprehension, particularly the superior temporal gyrus and inferior frontal gyrus. Our findings highlight that estimating a shared space allows us to construct encoding models that better generalize across individuals.

Surgical repair of extracapsular hip fractures is associated with a higher rate of successful healing compared to intracapsular fractures; however, a small subset of patients may still experience complications or treatment failure. Potential modes of failure include nonunion, peri-implant fracture, malalignment, cortical impingement or perforation and hardware failure with or without lag screw cutout. Factors determining salvage method include physiologic age, functionality, bone quality, and fracture stability. In this review, potential complications of extracapsular hip fracture repair are described with proposed solutions and supporting literature, when available.

STUDY QUESTION/OBJECTIVE:Is there an association between infertility diagnosis and long-term adult-onset psychiatric conditions in women? SUMMARY ANSWER/CONCLUSIONS:Infertility diagnosis in women is linked to higher risks of mood disorders, anxiety- and stress-related disorders, and behavioral syndromes with physical components, but not schizophrenia or other psychotic disorders, particularly notable from 9 years after the first infertility diagnosis. WHAT IS KNOWN ALREADY/BACKGROUND:Infertility, especially in women, is associated with major mental health challenges around the time of diagnosis. However, the long-term connection with a wide range of psychiatric disorders is largely unknown. STUDY DESIGN, SIZE, DURATION/METHODS:This study employed a matched-pair design within the UK Biobank (UKB) cohort, including 3893 females with a diagnosis of infertility and 15 603 matched female controls, totaling 19 496 participants. PARTICIPANTS/MATERIALS, SETTING, METHODS/METHODS:Female UKB participants with a diagnosis of infertility were matched to females without the diagnosis in a 1:4 ratio based on year of birth, index of deprivation of their residency area, and primary care data linkage status. The diagnosis of female infertility was identified by the first occurrence of a primary or secondary diagnosis in either primary care or hospital records. Additional analyses explored interactions between infertility diagnosis and both miscarriage and childbearing status on psychiatric conditions. MAIN RESULTS AND THE ROLE OF CHANCE/RESULTS:Diagnosis of infertility was associated with higher risks of mood disorders, anxiety- and stress-related disorders, and behavioral syndromes with physical components, but not with schizophrenia or other psychotic disorders. The most notable increases in the risk of psychiatric diagnoses were observed 9 years after the first infertility diagnosis. No significant interactions were found between infertility diagnosis and either miscarriage or childbearing status on psychiatric conditions. Sensitivity analysis confirmed the robustness of these associations across different data sources for infertility diagnosis and psychiatric condition ascertainment. LIMITATIONS, REASONS FOR CAUTION/CONCLUSIONS:The study's limitations include the racial homogeneity and the overall healthier status of the UKB cohort compared to the general UK population and the potential underestimation of associations due to misclassification of subfecund women. WIDER IMPLICATIONS OF THE FINDINGS/CONCLUSIONS:These results emphasize the need for integrated mental health support in infertility care and long-term monitoring of infertility patients for psychiatric risks. STUDY FUNDING/COMPETING INTEREST(S)/BACKGROUND:None. No competing interests were declared. TRIAL REGISTRATION NUMBER/BACKGROUND:n/a.

BACKGROUND:Child growth failure (CGF), which includes underweight, wasting, and stunting, is among the factors most strongly associated with mortality and morbidity in children younger than 5 years worldwide. Poor height and bodyweight gain arise from a variety of biological and sociodemographic factors and are associated with increased vulnerability to infectious diseases. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to estimate CGF prevalence, the risk of infectious diseases associated with CGF, and the disease mortality, morbidity, and overall burden associated with CGF. METHODS:In this analysis we estimated the all-cause and cause-specific (diarrhoea, lower respiratory tract infections, malaria, and measles) disability-adjusted life-years (DALYs) lost and mortality associated with stunting, wasting, underweight, and CGF in aggregate. We combined the burden associated with mild, moderate, and severe forms of CGF: stunting was defined as height-for-age Z scores (HAZ) less than -1, underweight was defined as weight-for-age Z scores (WAZ) less than -1, and wasting was defined as weight-for-height Z scores (WHZ) less than -1, according to WHO Child Growth Standards. Population-level continuous distributions of HAZ, WAZ, and WHZ were estimated for 2000 to 2023 using data from surveys, literature, and individual-level study data. The risk of incidence of, and mortality due to, diarrhoea, lower respiratory infections, malaria, and measles was separately estimated in a meta-regression framework from longitudinal cohort data for Z scores less than -1. Finally, fatal outcomes associated with these diseases were estimated with vital registration, verbal autopsy, and case-fatality data, while non-fatal outcomes were estimated with surveys as well as health-care utilisation and case reporting data. The exposure prevalence and relative risk estimates were from continuous distributions, allowing for direct assessment of the attributable fractions for mild, moderate, and severe stunting, underweight, wasting, and the combined impact of child growth failure within populations. All estimates were age-specific, sex-specific, geography-specific, and year-specific. FINDINGS/RESULTS:We estimated that, in children younger than 5 years in 2023, CGF was associated with 79·4 million (95% uncertainty interval [UI] 47·0-106) DALYs lost and 880 000 (517 000-1 170 000) deaths. This represented 17·9% (10·6-23·8) of 444 million (434-457) total under-5 DALYs and 18·8% (11·1-25·0) of all 4·67 million (4·59-4·75) under-5 deaths. Compared to stunting (33·0 million [24·1-42·2] DALYs, 373 000 [272 000-477 000] deaths) and wasting (39·2 million [23·8-53·0] DALYs, 428 000 [256 000-583 000] deaths), childhood underweight was associated with the largest share of CGF-related disease burden: 52·2 million (21·9-75·1) DALYs and 573 000 (236 000-824 000) deaths in children younger than 5 years in 2023. INTERPRETATION/CONCLUSIONS:CGF remains a leading factor associated with death and disability in children younger than 5 years, despite global attention and focused interventions to reduce the prevalence of associated CGF indicators. Our findings underscore the need for policies, strategies, and interventions that focus on all indicators of CGF to reduce its associated health burden. FUNDING/BACKGROUND:Gates Foundation.

Systemic mastocytosis is a rare condition caused by the accumulation of abnormal mast cells (MC) in various organs, including the bone. The diagnosis of mastocytosis is sometimes challenging because of the incidence rate, the heterogeneity of clinical manifestations, and the varying sensitivity of diagnostic tools. While mastocytosis is an uncommon cause of osteoporosis, conversely, systemic mastocytosis (SM) is often associated with bone loss, resulting in low bone mineral density (osteopenia or osteoporosis) and fractures, particularly vertebral fractures. SM must be ruled out in young patients with fragility fractures, mainly vertebral fracture, or unexplained low bone mineral density accompanied by suspected SM symptoms or signs. Other bone manifestations of SM include bone pain, osteolytic lesions, and even osteosclerosis. The putative mechanisms of bone loss and damage in SM include the secretion of vasoactive mediators and inflammatory markers, bone mediators released from bone cells (osteoblast, osteoclast, and osteocyte) such as RANKL, OPG, sclerostin, and DKK1, and neoplastic infiltration of MCs. Usually, early diagnosis with appropriate therapeutic intervention can impact the outcome of this disease and its skeletal-related complications. Fracture prediction can be improved by considering risk factors and using bone mineral density, FRAX, and TBS values. High-resolution peripheral quantitative CT may not be feasible but provides more information. The first step is the detection of high-risk patients in SM by recognizing the risk factors for fragility fractures such as older age, male sex, lower hip BMD, increased mast cell mass, or KIT mutation in bone biopsies, and then estimating the risk of SM progression in order to determine the best type of medication for bone loss mastocytosis and for osteoporosis. The current medications for the treatment of mastocytosis itself include anti-inflammatory or mast cell stabilizers (ketotifen, cromolyn sodium, antihistamines, leukotriene antagonists, and anti-IgE monoclonal antibody). Anti-osteoporosis medications (bisphosphonates, denosumab, and teriparatide) and cytoreductive agents (interferon, chemotherapeutic agents, or tyrosine kinase inhibitors) are also used. Although controlling the underlying disease is usually most effective, the benefits and risks of each therapeutic approach should be balanced if needed.

After decades of efforts by academic and professional organizations and by governmental agencies to promote advance care planning, less than half of adults in the USA have formally executed advance directives. For patients who have completed these documents, studies find limited impact on end-of-life care. In this paper, we discussed ways in which bias towards certain values in the health care enterprise including ethnocentrism, the centering of one set of cultural norms, may contribute to the public's ambivalence and the relative inefficacy of advance directives. We offer a more expansive perspective on this aspect of clinical care with the goal of serving all patients more effectively.