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Surgical correction of flexible pes planovalgus often involves reestablishing the length of the lateral column. This is a review of a cohort of patients who underwent an opening cuboid osteotomy with interpositional graft for triplanar correction of flexible pes planovalgus. The medical records of 35 patients involving 51 feet were reviewed. All patients were treated with an opening wedge osteotomy of the cuboid in combination with adjunctive procedures as needed for correction of the pes planovalgus deformity. Radiographs were obtained before and a minimum of 12 months after surgery. Preoperative and postoperative cuboid abduction and Meary's (lateral talometatarsal) angles were measured using the radiographs, and adjunctive procedures and complications were recorded. Mean follow-up was 46 (range, 12-85) months. The mean cuboid abduction angle improved from 20.3° (range, 8°-31°) to 6.6° (range, 0°-15°), and the mean Meary's angle improved from 10.5° (range, 0°-25°) to 2° (range, -3° to 15°). All patients also underwent adjunctive procedures at the time of cuboid osteotomy. In the 51 feet treated, there were 3 (6%) complications, including wound dehiscence, neuritis, and deep vein thrombosis. There were no recurrences. Triplanar correction of flexible pes planovalgus can be performed safely and successfully with an opening cuboid osteotomy as an alternative to the Evans Osteotomy.

Calls for interventions in early childhood that best prepare children with autism spectrum disorder (ASD) to have inclusive school experiences have been numerous. Although there is a developing literature on the efficacy of interactive book reading (IBR) for this population, it is still unclear which aspects of IBR benefit these children and in what way. To address this gap, we reanalyzed data from a recently completed experiment comparing IBR with other early literacy instruction for preschoolers with ASD. Our results showed that frequency of tutors’ use of completion prompts used during IBR was uniquely predictive of better gains in phonological awareness. In addition, tutors’ frequency using open-ended prompts was associated with increased gains in print knowledge. Furthermore, both findings held true after controlling for language gains. Results have implications for the types of structure and support that adults might provide young children with ASD during IBR.

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer’s disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer’s disease neuropathology may uncover novel therapeutic targets to treat Alzheimer’s disease. It is well established that there are sex differences in response to Alzheimer’s disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts of cognitive ageing, in vivo amyloid PET across two cohorts, and autopsy measures of amyloid neuritic plaque burden across two cohorts. These data were leveraged to build robust, continuous resilience phenotypes. With these phenotypes, we performed sex-stratified [n (males) = 2093, n (females) = 2931] and sex-interaction [n (both sexes) = 5024] genome-wide association studies (GWAS), gene and pathway-based tests, and genetic correlation analyses to clarify the variants, genes and molecular pathways that relate to resilience in a sex-specific manner. Estimated among cognitively normal individuals of both sexes, resilience was 20–25% heritable, and when estimated in either sex among cognitively normal individuals, resilience was 15–44% heritable. In our GWAS, we identified a female-specific locus on chromosome 10 [rs827389, β (females) = 0.08, P (females) = 5.76 × 10−09, β (males) = −0.01, P(males) = 0.70, β (interaction) = 0.09, P (interaction) = 1.01 × 10−04] in which the minor allele was associated with higher resilience scores among females. This locus is located within chromatin loops that interact with promoters of genes involved in RNA processing, including GATA3. Finally, our genetic correlation analyses revealed shared genetic architecture between resilience phenotypes and other complex traits, including a female-specific association with frontotemporal dementia and male-specific associations with heart rate variability traits. We also observed opposing associations between sexes for multiple sclerosis, such that more resilient females had a lower genetic susceptibility to multiple sclerosis, and more resilient males had a higher genetic susceptibility to multiple sclerosis. Overall, we identified sex differences in the genetic architecture of resilience, identified a female-specific resilience locus and highlighted numerous sex-specific molecular pathways that may underly resilience to Alzheimer’s disease pathology. This study illustrates the need to conduct sex-aware genomic analyses to identify novel targets that are unidentified in sex-agnostic models. Our findings support the theory that the most successful treatment for an individual with Alzheimer’s disease may be personalized based on their biological sex and genetic context.

The present study seeks to further understand the relationship between implicit mindsets about the malleability of intelligence with achievement goal orientations, academic self-handicapping behaviors, and confidence in one’s intelligence among undergraduate students. A sample of 142 undergraduate students at two small, private liberal arts universities participated in this study. Using a Pearson correlation coefficient and a two-tailed test of significance, results confirmed hypotheses that having a growth mindset positively correlated with mastery-approach and mastery-avoidance achievement goals, as well as having a high confidence in intelligence. However, a growth mindset is negatively correlated with those who do not engage in self-handicapping behaviors, which refutes the first hypothesis in this study. Moreover, having a fixed mindset is positively correlated with performance-avoidance achievement goals, and having low confidence in one's intelligence, which supports the second hypothesis in this study. Yet, having a fixed mindset is negatively correlated with performance-approach achievement goals and self-handicapping behaviors; both of which refute the second hypothesis in this study. Overall, the study helps further understand the complex relationship between implicit mindsets and non-cognitive factors among undergraduate students. Using the findings in this study, college educators and professors will be better equipped to aid students who have differing mindsets and learning strategies.

Archaeological isotope studies have traditionally been anthropocentric, with animals analyzed either as proxies or as baseline data in human-focused studies of diet and behavior. However, the value of analyzing animals in their own right is becoming increasingly clear for understanding human-animal-environment relationships. This chapter presents the results of a multi-species, multi-isotope investigation of animal remains recovered from Fishbourne Roman Palace (Sussex, UK). This extraordinarily high-status site, located at the edge of the Roman Empire, appears to have been a node through which exotic animals and new cultural attitudes to the natural world entered Britain. Here, we show how isotope analysis can be used to explore these ideologies, and reconstruct changing relationships between people, animals, and their environments.

OBJECTIVE: Studies use different instruments to measure cognitirating cognitive tests permit direct comparisons of individuals across studies and pooling data for joint analyses. METHOD: We began our legacy item bank with data from the Adult Changes in Thought study (n = 5,546), the Alzheimer’s Disease Neuroimaging Initiative (n = 3,016), the Rush Memory and Aging Project (n = 2,163), and the Religious on such as the Mini-Mental State Examination, the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, the Wechsler Memory Scale, and the Boston Naming Test. CocalibOrders Study (n = 1,456). Our workflow begins with categorizing items administered in each study as indicators of memory, executive functioning, language, visuospatial functioning, or none of these domains. We use confirmatory factor analysis models with data from the most recent visit on the pooled sample across these four studies for cocalibration and derive item parameters for all items. Using these item parameters, we then estimate factor scores along with corresponding standard errors for each domain for each study. We added additional studies to our pipeline as available and focused on thorough consideration of candidate anchor items with identical content and administration methods across studies. RESULTS: Prestatistical harmonization steps such qualitative and quantitative assessment of granular cognitive items and evaluating factor structure are important steps when trying to cocalibrate cognitive scores across studies. We have cocalibrated cognitive data and derived scores for four domains for 76,723 individuals across 10 studies. CONCLUSIONS: We have implemented a large-scale effort to harmonize and cocalibrate cognitive domain scores across multiple studies of cognitive aging. Scores on the same metric facilitate meta-analyses of cognitive outcomes across studies or the joint analysis of individual data across studies. Our systematic approach allows for cocalibration of additional studies as they become available and our growing item bank enables robust investigation of cognition in the context of aging and dementia.

Introduction During the COVID pandemic, at the San Francisco VA Healthcare System (VASFHS), positive airway pressure (PAP) set-up visits transitioned from in person to a mix of in person and telehealth for patients newly diagnosed sleep apnea. As part of a larger study examining the clinical outcomes resulting from telehealth versus in-person PAP initiation, we performed a cost analysis of these two treatment pathways within VASFHS. Methods The telehealth pathway included mailing of PAP machines to patients (initially from VASFHS and later through a centralized national distributor), with follow-up video/phone education by respiratory therapists (RTs) and registered sleep technicians (RSTs). We used a bottom-up analysis to examine the total variable direct cost of telehealth versus in-person PAP initiation at various points through the COVID pandemic for patients newly diagnosed with sleep apnea at VASFHS. Results The total variable direct cost of telehealth PAP initiation was $49.66 per patient mid-pandemic (Feb-Dec 2020) compared to $31.02 per patient post-pandemic (Oct-Dec 2022). The total variable direct cost of in-person PAP initiation was $16.76 per patient pre-pandemic (Jan-Dec 2019) compared to $22.71 per patient post-pandemic. The reduction in costs (37.5%) for telehealth PAP initiation mid- to post-pandemic was due to 25% less RT/RST time required and elimination of PAP shipping costs as PAP distribution became nationally centralized. The increase in costs (35.5%) for in-person PAP initiation pre- to post-pandemic was largely due to elimination of group PAP initiation sessions (33.3% more RT/RST time required for individual PAP initiation). Post-pandemic, telehealth PAP initiation cost was 36.6% more than in-person due to 25% more RT/RST time required and five times as much troubleshooting help required for the telehealth pathway. Conclusion With integration of telehealth for PAP initiation, as RT/RSTs gained more expertise with this interface through the pandemic and as distribution of PAP machines/supplies became centralized, costs were significantly reduced, making telehealth a financially sustainable workflow. Future cost analysis can evaluate if group rather than individual telehealth PAP initiation would yield additional cost savings, placing it on par with the cost of in-person PAP initiation. Support (if any) VA OCC FY21 RFA, VAGLAHS GRECC, K24HL143055

Objectives To characterize the extent to which brief cognitive assessments administered in the population-representative U.S. Health and Retirement Study (HRS) and its International Partner Studies can be considered to be measuring a single, unidimensional latent cognitive function construct. Methods Cognitive function assessments were administered in face-to-face interviews in 12 studies in 26 countries (N = 155,690), including the U.S. HRS and selected International Partner Studies. We used the time point of the first cognitive assessment for each study to minimize differential practice effects across studies and documented cognitive test item coverage across studies. Using confirmatory factor analysis models, we estimated single-factor general cognitive function models and bifactor models representing memory-specific and nonmemory-specific cognitive domains for each study. We evaluated model fits and factor loadings across studies. Results Despite relatively sparse and inconsistent cognitive item coverage across studies, all studies had some cognitive test items in common with other studies. In all studies, the bifactor models with a memory-specific domain fit better than single-factor general cognitive function models. The data fit the models at reasonable thresholds for single-factor models in 6 of the 12 studies and for the bifactor models in all 12 of the 12 studies. Discussion The cognitive assessments in the U.S. HRS and its International Partner Studies reflect comparable underlying cognitive constructs. We discuss the assumptions underlying our methods, present alternatives, and future directions for cross-national harmonization of cognitive aging data.

Historians and social scientists have for years identified the current era as a new capital-dominant Gilded Age on the basis of economic trends (particularly rising inequality, now at a higher peak than in the early twentieth century), the coalescence of political elites (this time on a neoliberal, rather than protectionist agenda), and speculations about political upheaval on the horizon.

Improving Access to Psychological Therapies (IAPT) services were set up in 2008 as part of primary care to support patients with common mental health difficulties, including anxiety and depression. Practitioners within IAPT deliver evidence based psychological therapies including cognitive-behavioural therapy (CBT). IAPT services have recently expanded to support people with long-term conditions (LTC), including diabetes, respiratory and cardiac disease, and medically unexplained symptoms (MUS). Current guidance states that LTC-IAPT services should be developed alongside existing health care services, with clear arrangements for joint working with physical health teams (National Collaborating Centre for Mental Health, 2018). ‘Time to Talk Health’ is an LTC-IAPT service within Sussex Community NHS Foundation Trust that offers a service model requiring staff to engage in three hours of consultation with physical health care teams each week. The nature of the consultation work undertaken with physical health care professionals and their patients is explored within the current article. There is a need for future research to evaluate the effectiveness of this collaborative working in relation to outcomes for both health care professionals and patients.

Introduction Telehealth has been widely integrated into healthcare systems during the COVID-19 pandemic and is likely to remain a part of routine clinical care. At the VA Greater Los Angeles Healthcare System (VAGLAHS), positive airway pressure (PAP) set-up visits transitioned from in person to telehealth for newly diagnosed sleep apnea patients during the pandemic. The telehealth pathway included mailing of PAP machines to patients with follow-up video/phone education by respiratory therapists (RTs). As part of a larger study examining the clinical outcomes resulting from telehealth versus in-person PAP initiation, we performed a cost analysis of these two treatment pathways within VAGLAHS. Methods We examined the total variable direct cost of telehealth versus in-person PAP initiation for patients newly diagnosed with sleep apnea at VAGLAHS between March and October 2021 (n = 2,662 PAP set-ups) using a bottom-up analysis. There was an average of 16 PAP set-ups per day with 11 set-ups (68.7%) via telehealth and 5 set-ups (31.3%) in person. Results The total variable direct cost of telehealth PAP initiation was $98.87 per patient. The total variable direct cost of in-person PAP initiation was $50.58 per patient. For telehealth, there was an additional cost of mailing the PAP machine and 31.2% more RT time spent on educating patients compared to the in-person pathway. After the initial PAP set-up visit, a larger subset of patients required additional troubleshooting help from RTs about proper PAP use after telehealth compared to in-person set-ups (5% versus 1%). Conclusion The telehealth PAP initiation pathway was nearly two times the cost of in-person PAP initiation. This resulted from the additional cost of mailing the PAP machine, more RT time spent on education, and a greater need for troubleshooting after the visit. Telehealth visits may need to be supplemented by written educational materials or web-based resources to reduce the need for additional support after the initial visit. Support (If Any) OCC study funding, VAGLAHS GRECC

The American South has been something of an anomaly in most studies of the connection between voting and policy outcomes. The South remained solidly Democratic from the end of Reconstruction until the middle 1960s, largely unaffected by the realigning elections of 1896 or 1932. Welfare benefits in the South have always been extremely low. The discretion available to the local welfare office permitted the welfare system to be manipulated according to the needs of the local economic elite. Plantation counties were often willing to make selected welfare programs available to their poor populations. The manipulation of local welfare systems to suit the needs of the plantation economy is an old practice in the South. Expansion of the welfare rolls was most dramatic in the black belt and, particularly, in counties with substantial numbers of black elected officials. The poor are significantly less relevant to the southern agricultural economy in 1981 than they were in 1965.

Admission of a child to the pediatric intensive care unit (PICU) has long been recognized as a significant source of stress for both the child and their caregivers. However, it is increasingly recognized that the results of these stresses may last long beyond the date that the patient is discharged from the PICU or hospital. Child life specialists receive special training in child development, family systems, and coping strategies, and this unique set of skills offers an avenue of treatment to the critically ill child not typically able to be provided by other bedside caregivers. Specific interventions that can be provided include developmentally appropriate preparation for procedures needing to be performed in the PICU, a non-clinician presence for the alone child due to parental/family absence, and distraction and/or play therapies designed to provide a degree of “normality” to an abnormal situation. They can also be especially helpful in sitting down with patients/families who are having difficulty coping with the need for a PICU admission and/or the course of illness progression is poor or even maladaptive. By aiding in the development of improved comfort and coping mechanisms, child life therapists can further facilitate an easier transition out of the PICU and return to the home environment. They may also offer an added source of comfort when the outcome requires end-of-life care. Consequently, child life therapists must be considered an integral part of the PICU care team, and their involvement as early as possible following PICU admission should be encouraged.

Introduction Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults. Methods We used item response theory to derive composite measures for language (ADNI‐Lan) and visuospatial functioning (ADNI‐VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress. Results ADNI‐Lan and ADNI‐VS were able to detect change over time and predict conversion from MCI to AD. They were associated with most of the pre‐specified magnetic resonance imaging measures. ADNI‐Lan had strong associations with a cerebrospinal fluid biomarker pattern. Discussion ADNI‐Lan and ADNI‐VS may be useful composites for language and visuospatial functioning in ADNI.

Background: The RAINBOW trial established ramucirumab combined with paclitaxel as a second-line option in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. Ramucirumab was given on days 1 and 15 with paclitaxel on days 1, 8, and 15 of a 28-day cycle. The median overall survival (OS) was significantly longer with ramuciru­mab plus paclitaxel (p = 0.017), and it led to 41% grade 3 or higher neutropenia. We review our experience with both ramucirumab plus paclitaxel given biweekly (mRAINBOW) to assess efficacy and safety. Objectives: The primary objective was to assess OS. Secondary end points were progression-free survival (PFS), overall response, and safety. Methods: We identified 129 patients retrospectively from our database between November 2014 and May 2017. Patients were included if they were followed up at our institution. Results: Median doses given were ramucirumab 8 mg/kg i.v. plus paclitaxel 110 mg/m2 i.v. given once every 2 weeks. The median performance status was 1, and ∼60% had poorly differentiated histology; 55.8% had progression in < 6 months on first-line therapy, and the majority had measurable cancer. Median overall OS and PFS for the entire cohort was 9.4 months (95% CI: 8.05–10.74) and 3.68 months (95% CI: 2.73–4.5), respectively. Median OS was 9.46 months (95% CI: 8.05–14.95) and median PFS was 4.14 months (95% CI: 2.96–5.29) in those patients that received ramucirumab plus paclitaxel in the second-line setting. Conclusion: Biweekly administration of ramucirumab plus paclitaxel did not compromise efficacy. Delays, adjustments, or doses held were similar to the RAINBOW trial, with 31% requiring a dose or schedule modification.

Approximately 30% of older adults exhibit the neuropathologic features of Alzheimer’s disease (AD) without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively normal in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modeling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5,108 participants from a clinical trial of AD and three longitudinal cohort studies of cognitive aging. All analyses were run across all participants and repeated restricting the sample to individuals with normal cognition to identify variants at the earliest stages of disease. As expected, all resilience metrics were genetically correlated with cognitive performance and education attainment traits (p-values−20), and we observed novel correlations with neuropsychiatric conditions (p-values−4). Notably, neither resilience metric was genetically correlated with clinical AD (p-values>0.42) nor associated withAPOE(p-values>0.13). In single variant analyses, we observed a genome-wide significant locus among participants with normal cognition on chromosome 18 upstream ofATP8B1(index SNP rs2571244, MAF=0.08, p=2.3×10−8). The top variant at this locus (rs2571244) was significantly associated with methylation in prefrontal cortex tissue at multiple CpG sites, including one just upstream ofATPB81(cg19596477; p=2×10−13). Overall, this comprehensive genetic analysis of resilience implicates a putative role of vascular risk, metabolism, and mental health in protection from the cognitive consequences of neuropathology, while also providing evidence for a novel resilience gene along the bile acid metabolism pathway.Furthermore, the genetic architecture of resilience appears to be distinct from that of clinical AD, suggesting that a shift in focus to molecular contributors to resilience may identify novel pathways for therapeutic targets.

Donald Trump owes his election to post-1972 changes in party institutions and economic developments that were largely the result of presidential policies supported by both parties. Political scientists and pundits who relied on survey data and assumptions about motives and character of Trump supporters failed to understand the deep causes of the 2016 election outcome, and to inform the public and party leaders about strategic and coalition options for the future. Focusing on expressive protest and labeling are probably antithetical to party reorganization leading to genuine reform and reduction in inequality.

Introduction There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia. Methods We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments. Results During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE e4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants. Discussion A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia.

Why are some individuals able to tolerate severe Alzheimer’s disease pathology without experiencing dementia? Dumitrescu et al. perform a large genome-wide analysis of resilience to Alzheimer’s disease and highlight several biological pathways that may protect the brain from the downstream consequences of amyloidosis., Approximately 30% of older adults exhibit the neuropathological features of Alzheimer’s disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer’s disease and three longitudinal cohort studies of cognitive ageing. All analyses were run across all participants and repeated restricting the sample to individuals with unimpaired cognition to identify variants at the earliest stages of disease. As expected, all resilience metrics were genetically correlated with cognitive performance and education attainment traits (P-values < 2.5 × 10−20), and we observed novel correlations with neuropsychiatric conditions (P-values < 7.9 × 10−4). Notably, neither resilience metric was genetically correlated with clinical Alzheimer’s disease (P-values > 0.42) nor associated with APOE (P-values > 0.13). In single variant analyses, we observed a genome-wide significant locus among participants with unimpaired cognition on chromosome 18 upstream of ATP8B1 (index single nucleotide polymorphism rs2571244, minor allele frequency = 0.08, P = 2.3 × 10−8). The top variant at this locus (rs2571244) was significantly associated with methylation in prefrontal cortex tissue at multiple CpG sites, including one just upstream of ATPB81 (cg19596477; P = 2 × 10−13). Overall, this comprehensive genetic analysis of resilience implicates a putative role of vascular risk, metabolism, and mental health in protection from the cognitive consequences of neuropathology, while also providing evidence for a novel resilience gene along the bile acid metabolism pathway. Furthermore, the genetic architecture of resilience appears to be distinct from that of clinical Alzheimer’s disease, suggesting that a shift in focus to molecular contributors to resilience may identify novel pathways for therapeutic targets.

Current imaging diagnostic techniques are often insensitive to the underlying pathological changes following mild traumatic brain injury (TBI) or concussion so much so that the explicit definition of these uncomplicated mild brain injuries includes the absence of radiological findings. In the US military, this is complicated by the natural tendency of service members to down play symptoms for fear of removal from their unit particularly in combat making it challenging for clinicians to definitively diagnose and determine course of treatment. Questions remain regarding the long-term impact of these war-time brain injuries. The objective of the current study was to evaluate the long-term imaging sequelae of blast concussion in active-duty US military and leverage previous longitudinal data collected in these same patients to identify predictors of sustained DTI signal change indicative of chronic neurodegeneration. In total, 50 blast TBI and 44 combat-deployed controls were evaluated at this 5-year follow up by advanced neuroimaging techniques including diffusion tensor imaging and quantitative volumetry. While cross-sectional analysis of regions of white matter on DTI images did not reveal significant differences across groups after statistical correction, an approach flexible to the heterogeneity of brain injury at the single-subject level identified 74% of the concussive blast TBI cohort to have reductions in fractional anisotropy indicative of chronic brain injury. Logistic regression leveraging clinical and demographic data collected in the acute/sub-acute and 1-year follow up to determine predictors of these long-term imaging changes determined that brain injury diagnosis, older age, verbal memory and verbal fluency best predicted the presence of DTI abnormalities 5 years post injury with an AUC of 0.78 indicating good prediction strength. These results provide supporting evidence for the evolution not resolution of this brain injury pathology, adding to the growing body of literature describing imaging signatures of chronic neurodegeneration even after mild TBI and concussion., Highlights • Design: prospective, observational, longitudinal research study • Patients: concussive blast (n = 50), combat-deployed control (n = 44) • Diffusion tensor imaging analyzed 5 yr post-injury, highly predicted by 1 yr outcomes. • Imaging abnormalities appear to evolve from sub-acute, to 1-year, to 5-year scan. • Findings indicate chronic neurodegeneration in majority of blast concussion patients.

Categorizing people with late-onset Alzheimer’s disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer’s disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p −5 and odds ratios more extreme than those previously reported for Alzheimer’s disease (1.30). There was substantial variation across studies in the proportions of people in each subgroup. In each study, higher proportions of people with isolated substantial relative memory impairment had ≥1 APOE ε4 allele than any other subgroup (overall p = 1.5 × 10−27). Across subgroups, there were 33 novel suggestive loci across the genome with p −5 and an extreme OR compared to controls, of which none had statistical evidence of heterogeneity and 30 had ORs in the same direction across all datasets. These data support the biological coherence of cognitively defined subgroups and nominate novel genetic loci.

Categorizing people with late-onset Alzheimer's disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer's disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p 10