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ObjectiveTo determine if preterm birth is associated with adaptation of the hypothalamic–pituitary–adrenal (HPA) axis and whether HPA axis programming relates to the degree of prematurity (defined as extremely preterm birth at DesignThis study reports findings from a prospective birth cohort. Saliva cortisol concentrations were measured prevaccination and postvaccination, and in the morning and evening, at 4 months chronological age.SettingInfants born at a single Scottish hospital.Participants45 term-born, 42 very preterm and 16 extremely preterm infants.OutcomesCortisol stress response to vaccination (postvaccination minus prevaccination cortisol concentrations), diurnal slope (log-transformed morning minus log-transformed evening cortisol values) and mean log-transformed daily cortisol.ResultsCompared with infants born at term, infants born extremely preterm had a blunted cortisol response to vaccination (5.8 nmol/L vs 13.1 nmol/L, difference in means: −7.3 nmol/L, 95% CI −14.0 to −0.6) and a flattened diurnal slope (difference in geometric means: −72.9%, 95% CI −87.1 to −42.8). In contrast, the cortisol response to vaccination (difference in means −2.7 nmol/L, 95% CI −7.4 to 2.0) and diurnal slope at 4 months (difference in geometric means: −33.6%, 95% CI −62.0 to 16.0) did not differ significantly in infants born very preterm compared with infants born at term.ConclusionsInfants born extremely preterm have blunted cortisol reactivity and a flattened diurnal slope. These patterns of HPA axis regulation are commonly seen after childhood adversity and could contribute to later metabolic and neurodevelopmental phenotypes observed in this population.

Objective We examine how emergency department (ED) visits for serious cardiovascular conditions evolved in the coronavirus (COVID-19) pandemic over January–October 2020, compared to 2019, in a large sample of U.S. EDs. Methods We compared 2020 ED visits before and during the COVID-19 pandemic, relative to 2019 visits in 108 EDs in 18 states in 115,716 adult ED visits with diagnoses for five serious cardiovascular conditions: ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), ischemic stroke (IS), hemorrhagic stroke (HS), and heart failure (HF). We calculated weekly ratios of ED visits in 2020 to visits in 2019 in the pre-pandemic (Jan 1-March 10), early-pandemic (March 11–April 21), and later-pandemic (April 22–October 31) periods. Results ED visit ratios show that NSTEMI, IS, and HF visits dropped to lows of 56%, 64%, and 61% of 2019 levels, respectively, in the early-pandemic and gradually returned to 2019 levels over the next several months. HS visits also dropped early pandemic period to 60% of 2019 levels, but quickly rebounded. We find mixed evidence on whether STEMI visits fell, relative to pre-pandemic rates. Total adult ED visits nadired at 57% of 2019 volume during the early-pandemic period and have only party recovered since, to approximately 84% of 2019 by the end of October 2020. Conclusion We confirm prior studies that ED visits for serious cardiovascular conditions declined early in the COVID-19 pandemic for NSTEMI, IS, HS, and HF, but not for STEMI. Delays or non-receipt in ED care may have led to worse outcomes.

Intraoperative fluorescence angiography (FA) has been described as a useful adjunct to physical examination in predicting mastectomy skin flap viability for immediate breast reconstruction. Its use has been described as a screening tool for mastectomy skin flap viability as well as a test used only for patients at high risk for mastectomy skin flap loss. We performed a national database review of implant-based breast reconstruction surgeries to determine the practice patterns of FA in this patient cohort and to determine if this technology impacted clinical outcomes.A national insurance claims database was reviewed to select patients having undergone direct-to-implant (DTI) and immediate tissue expander (TE) placement with and without intraoperative FA as well as patients who had FA at the time of mastectomy without reconstruction. Patient characteristics that prompted FA and postoperative outcomes with and without FA were evaluated to determine its clinical impact in the observed practice pattern.Of the 48,464 patients identified, 836 had FA. More than twice as many patients undergoing DTI had FA than patients undergoing immediate TE placement (10.4% vs 5%, P0.0001). Twelve percent of patients receiving FA at the time of mastectomy had reconstruction delayed. Fluorescence angiography was associated with a trend toward lower overall complication rates in DTI patients (8.0% vs 11.9% without FA) but a significantly higher overall complication rate with immediate TE placement (13.8% vs 10.5% without FA, P = 0.018) and was associated with higher reoperation (12.0% vs 8.3% without FA, P = 0.037) in the TE group. There was no difference in other individual complications, readmission, or explantation for either clinical group with and without FA. Regression analysis identified obesity (odds ratio, 1.32; P0.001) and younger age (odds ratio, 1.74; P0.001) to be associated with performing FA, whereas obesity, diabetes, and tobacco use were associated with higher complication rates.Younger and otherwise healthier obese patients were more likely to have FA. A greater proportion of DTI patients had FA than TE patients with improved outcomes in the former group and worse outcomes in the latter group. Obesity, tobacco use, and diabetes were associated with worse outcomes, whereas only obesity was associated with FA use.

The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr-/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.

Study objective In 2014, Maryland launched a population-based payment model that replaced fee-for-service payments with global budgets for all hospital-based services. This global budget revenue program gives hospitals strong incentives to tightly control patient volume and meet budget targets. We examine the effects of the global budget revenue model on rates of admission to the hospital from emergency departments (EDs). Methods We used medical record and billing data to examine adult ED encounters from January 1, 2012, to December 31, 2015, in 25 hospital-based EDs, including 10 Maryland global budget revenue hospitals, 10 matched non-Maryland hospitals (primary control), and 5 Maryland Total Patient Revenue hospitals (secondary control). Total Patient Revenue hospitals adopted global budgeting in 2010 under a pilot Maryland program targeting rural hospitals. We conducted difference-in-differences analyses for overall ED admission rates, ED admission rates for ambulatory-care-sensitive conditions and non–ambulatory-care-sensitive conditions, and for clinical conditions that commonly lead to admission. Results In 3,175,210 ED encounters, the ED admission rate for Maryland global budget revenue hospitals decreased by 0.6% (95% confidence interval –0.8% to –0.4%) compared with that for non-Maryland controls after global budget revenue implementation, a 3.0% relative decline, and decreased by 1.9% (95% confidence interval –2.2% to –1.7%) compared with that for Total Patient Revenue hospitals, a 9.5% relative decline. Relative declines in ED admission rates were similar for ambulatory-care-sensitive-condition and non–ambulatory-care-sensitive-condition encounters. Admission rate declines varied across clinical conditions. Conclusion Implementation of the global budget revenue model led to statistically significant although modest declines in ED admission rates within its first 2 years, with declines in ED admissions most pronounced among certain clinical conditions.

Study objective Malpractice fear is a commonly cited cause for defensive medicine, but it is unclear whether being named in a malpractice claim changes physician practice patterns. We study whether there are changes in commonly used measures of emergency physician practice after being named in a malpractice claim. Methods We performed a retrospective difference-in-differences study comparing practice patterns of emergency physicians named in a malpractice claim and unnamed matched controls working contemporaneously in the same emergency departments (EDs), using data from a national emergency medicine management group (59 EDs in 11 US states from 2010 to 2015). We studied aggregate measures of care intensity (hospital admission rate and relative value units/visit), studied care speed (relative value units/hour and discharged patients' length of stay), and assessed patient experience (monthly physician Press Ganey percentile rank). Results A total of 65 emergency physicians named in at least 1 malpractice claim and 140 matched controls met inclusion criteria. After the malpractice claim filing date, there were no significant changes in measures of care intensity or speed. However, named emergency physicians' patient experience scores improved immediately after the malpractice claim filing date and showed sustained improvements by 6.52 Press Ganey percentile ranks (95% confidence interval 0.67 to 12.38), with the increase most prominent among those involved in the 46 failure-to-diagnose claims (10.52; 95% confidence interval 3.72 to 17.32). Conclusion We observed a temporal improvement in patient satisfaction scores for emergency physicians in this sample after their being named in a malpractice claim relative to matched controls. Measures of care intensity and speed did not significantly change.

Bundled reimbursement models for total knee arthroplasty (TKA) by the Center for Medicare and Medicaid Services have resulted in an effort to decrease the cost of care. However, these models may incentivize bias in patient selection to avoid excess cost of care. We sought to determine the impact of the Comprehensive Care for Joint Replacement (CJR) model at a single center.This is a retrospective review of primary TKA patients from July 2015 to December 2017. Patients were stratified by whether or not their surgery was performed before or after implementation of the CJR bundle. Patient demographic data including age, sex, and body mass index were collected in addition to Elixhauser comorbidities and American Society of Anesthesiologists score. In-hospital outcomes were then examined including surgery duration, length of stay, discharge disposition, and direct cost of care.A total of 1248 TKA patients (546 Medicare and 702 commercial insurance) were evaluated, with 27.0% undergoing surgery before the start of the bundle. Compared to patients following implementation of the bundle, there was no significant difference in age, gender, or body mass index. However, pre-CJR Medicare patients were more likely to have fewer Elixhauser comorbidities (P.001), prolonged length of stay (P.001), and greater discharges to inpatient facilities (P = .019). There was no significant difference in direct hospital costs or operative service time comparing pre-bundle and post-bundle patients.Implementation of the bundled reimbursement model did not result in biased patient selection at our institution; importantly, it also did not result in decreased hospital costs despite apparent improvement in value-based outcome metrics. This should be taken into consideration as future adaptations to reimbursement are made by the Center for Medicare and Medicaid Services.

Objectives:To examine factors that influence decision-making, preferences, and plans related to advance care planning (ACP) and end-of-life care among persons with dementia and their caregivers, and examine how these may differ by race.Design:Cross-sectional survey.Setting:13 geographically dispersed Alzheimer’s Disease Centers across the United States.Participants:431 racially diverse caregivers of persons with dementia.Measurements:Survey on “Care Planning for Individuals with Dementia.”Results:The respondents were knowledgeable about dementia and hospice care, indicated the person with dementia would want comfort care at the end stage of illness, and reported high levels of both legal ACP (e.g., living will; 87%) and informal ACP discussions (79%) for the person with dementia. However, notable racial differences were present. Relative to white persons with dementia, African American persons with dementia were reported to have a lower preference for comfort care (81% vs. 58%) and lower rates of completion of legal ACP (89% vs. 73%). Racial differences in ACP and care preferences were also reflected in geographic differences. Additionally, African American study partners had a lower level of knowledge about dementia and reported a greater influence of religious/spiritual beliefs on the desired types of medical treatments. Notably, all respondents indicated that more information about the stages of dementia and end-of-life health care options would be helpful.Conclusions:Educational programs may be useful in reducing racial differences in attitudes towards ACP. These programs could focus on the clinical course of dementia and issues related to end-of-life care, including the importance of ACP.

BackgroundHypothalamic-pituitary-adrenal (HPA) axis adaptation is a potential mechanism linking early life exposures with later adverse health. This study tested the hypothesis that preterm birth is associated with adaptation of diurnal cortisol regulation across infancy.MethodsA secondary analysis was conducted of saliva cortisol measured morning, midday and evening, monthly, across infancy, as part of a birth cohort conducted in Linköping, Sweden. Diurnal cortisol regulation of infants born extremely preterm (n=24), very preterm (n=27) and at term (n=130) were compared across infancy through random coefficients regression models.ResultsCompared with infants born at term, infants born extremely preterm (−17.2%, 95% CI: −30.7 to −1.2), but not very preterm (1.7%, 95% CI: −14.1 to 20.4), had a flattened diurnal slope across infancy.ConclusionsExtremely preterm birth is associated with a flattened diurnal slope in infancy. This pattern of cortisol regulation could contribute to adverse metabolic and neurodevelopmental phenotypes observed in this population.

Objective We determine how pediatric emergency department (ED) visits changed during the COVID-19 pandemic in a large sample of U.S. EDs. Methods Using retrospective data from January–June 2020, compared to a similar 2019 period, we calculated weekly 2020–2019 ratios of Non-COVID-19 ED visits for adults and children (age 18 years or less) by age range. Outcomes were pediatric ED visit rates before and after the onset of pandemic, by age, disposition, and diagnosis. Results We included data from 2,213,828 visits to 144 EDs and 4 urgent care centers in 18 U.S. states, including 7 EDs in children's hospitals. During the pandemic period, adult non-COVID-19 visits declined to 60% of 2019 volumes and then partially recovered but remained below 2019 levels through June 2020. Pediatric visits declined even more sharply, with peak declines through the week of April 15 of 74% for children age

Cartilage transmits and redistributes biomechanical loads in the knee joint during exercise. Exercise-induced loading alters cartilage hydration and is detectable using quantitative MRI, where T2 relaxation time (T2 ) is influenced by cartilage collagen composition, fiber orientation, and changes in extracellular matrix. This study characterized short-term transient responses of healthy knee cartilage to running-induced loading using bilateral scans and image registration. Eleven healthy female recreational runners (33.73±4.22 years) and four healthy female controls (27.25±1.38 years) were scanned on a 3T GE MRI scanner with qDESS before running over-ground (runner group) or resting (control group) for 40 minutes. Subjects were scanned immediately post-activity at five-minute intervals for 60 minutes. T2 times were calculated for femoral, tibial, and patellar cartilage at each time point and analyzed using a mixed-effects model and Bonferroni post-hoc. There were immediate decreases in T2 (mean±SEM) post-run in superficial femoral cartilage of at least 3.3±0.3% (P=0.002) between baseline and Time 0 that remained for 25 minutes, a decrease in superficial tibial cartilage T2 of 2.9±0.4% (P=0.041) between baseline and Time 0, and a decrease in superficial patellar cartilage T2 of 3.6±0.3% (P=0.020) 15 minutes post-run. There were decreases in the medial posterior region of superficial femoral cartilage T2 of at least 5.3±0.2% (P=0.022) within five minutes post-run that remained at 60 minutes post-run. Clinical Significance: These results increase understanding of transient responses of healthy cartilage to repetitive, exercise-induced loading and establish preliminary recommendations for future definitive studies of cartilage response to running. This article is protected by copyright. All rights reserved.

Study objective We examine the effect of Medicaid expansion on reimbursement for emergency physicians' professional services. Methods We conducted a retrospective study using data from a national emergency medicine group in a sample of 50 emergency departments (EDs) from July 1, 2012, to June 30, 2015. We categorized facilities in 14 states into full-expansion (23), partial-expansion (17), and nonexpansion (10) categories based on pre-expansion Medicaid eligibility criteria for all adults. We used a difference-in-differences design to assess the effect of Medicaid expansion on provider reimbursement per visit. Secondary outcomes included reimbursement per relative value unit and relative value units per visit, both overall and by payer type, controlling for age, sex, billing codes, and health system relationship. Results We studied greater than 6.7 million ED visits during July 2012 to December 2015, 3.0 million pre-expansion and 3.7 million postexpansion. After adjusting for covariates, reimbursement per visit increased 6.3% (95% confidence interval 1.4% to 11.1%) in full-expansion relative to nonexpansion states and did not change significantly in partial-expansion versus nonexpansion states. Reimbursement per visit for commercial insurance increased 17.1% (95% confidence interval 9.9% to 24.2%) in full-expansion versus nonexpansion states. Reimbursement for self-pay visits increased 9.7% (95% confidence interval 3.7% to 15.7%) in full-expansion versus nonexpansion states. Changes in payments were driven by higher reimbursement per relative value unit; relative value units per visit declined slightly in full-expansion compared with nonexpansion states. Conclusion In this sample, full Medicaid expansion increased payments for emergency physicians' professional services compared with reimbursement in nonexpansion states. Higher reimbursement was driven primarily by lower proportions of uninsured patients and increased reimbursement per visit for both commercially insured and self-pay patients in states with full Medicaid expansion.

The mechanisms linking maternal stress in pregnancy with infant neurodevelopment in a sexually dimorphic manner are poorly understood. We tested the hypothesis that maternal hypothalamic-pituitary-adrenal axis activity, measured by hair cortisol concentration (HCC), is associated with microstructure, structural connectivity, and volume of the infant amygdala. In 78 mother-infant dyads, maternal hair was sampled postnatally, and infants underwent magnetic resonance imaging at term-equivalent age. We found a relationship between maternal HCC and amygdala development that differed according to infant sex. Higher HCC was associated with higher left amygdala fractional anisotropy (β = 0.677, p=0.010), lower left amygdala orientation dispersion index (β = −0.597, p=0.034), and higher fractional anisotropy in connections between the right amygdala and putamen (β = 0.475, p=0.007) in girls compared to boys. Furthermore, altered amygdala microstructure was only observed in boys, with connectivity changes restricted to girls. Maternal cortisol during pregnancy is related to newborn amygdala architecture and connectivity in a sexually dimorphic manner. Given the fundamental role of the amygdala in the emergence of emotion regulation, these findings offer new insights into mechanisms linking maternal health with neuropsychiatric outcomes of children., eLife digest Stress during pregnancy, for example because of mental or physical disorders, can have long-term effects on child development. Epidemiological studies have shown that individuals exposed to stress in the womb are at higher risk of developmental and mood conditions, such as ADHD and depression. This effect is different between the sexes, and the biological mechanisms that underpin these observations are poorly understood. One possibility is that a baby’s developing amygdala, the part of the brain that processes emotions, is affected by a signal known as cortisol. This hormone is best known for its role in coordinating the stress response, but it also directs the growth of a fetus. Tracking fetal amygdala changes as well as cortisol levels in the pregnant individual could explain how stress during pregnancy affects development. To investigate, Stoye et al. recruited nearly 80 volunteers and their newborn children. MRI scans were used to examine the structure of the amygdala, and how it is connected to other parts of the brain. In parallel, the amount of cortisol was measured in hair samples collected from the volunteers around the time of birth, which reflects stress levels during the final three months of pregnancy. Linking the brain imaging results to the volunteers’ cortisol levels showed that being exposed to higher cortisol levels in the womb affected babies in different ways based on their sex: boys showed alterations in the fine structure of their amygdala, while girls displayed changes in the way that brain region connected to other neural networks. The work by Stoye et al. potentially reveals a biological mechanism by which early exposure to stress could affect brain development differently between the sexes, potentially informing real-world interventions.

Objective:Understanding which characteristics of persons with dementia (PWD) and their caregivers are associated with unmet needs can inform strategies to address those needs. Our purpose was to determine the percentage of PWD having unmet needs and significant correlates of unmet needs in PWD.Design:Cross-sectional data were analyzed using bivariate and hierarchical multiple linear regression analyses.Setting:Participants lived in the greater Baltimore, Maryland and Washington DC suburban area.Participants:A sample of 646 community-living PWD and their informal caregivers participated in an in-home assessment of dementia-related needs.Measurements:Unmet needs were identified using the Johns Hopkins Dementia Care Needs Assessment. Correlates of unmet needs were determined using demographic, socioeconomic, clinical, functional and quality of life characteristics of the PWD and their caregivers.Results:PWD had a mean of 10.6 (±4.8) unmet needs out of 43 items (24.8%). Unmet needs were most common in Home/Personal Safety (97.4%), General Health Care (83.1%), and Daily Activities (73.2%) domains. Higher unmet needs were significantly related to non-white race, lower education, higher cognitive function, more neuropsychiatric symptoms, lower quality of life in PWD, and having caregivers with lower education or who spent fewer hours/week with the PWD.Conclusions:Unmet needs are common in community-living PWD, and most are non-medical. Home-based dementia care can identify and address PWD’s unmet needs by focusing on care recipients and caregivers to enable PWD to remain safely at home.

Chemical exchange saturation transfer of glycosaminoglycans (GAG), gagCEST, is a quantitative MR technique that has potential for assessing cartilage proteoglycan content at field strengths of 7 Tesla (T) and higher. However, its utility at 3T remains unclear. The objective of this work was to implement a rapid volumetric gagCEST sequence with higher gagCEST asymmetry at 3T to evaluate its sensitivity to osteoarthritic changes in knee articular cartilage and in comparison to T(2) and T(1ρ) measures. We hypothesize that gagCEST asymmetry at 3T decreases with increasing severity of osteoarthritis (OA). Forty-two human volunteers, including ten healthy subjects and thirty-two subjects with medial OA, were included in the study. Knee injury and Osteoarthritis Outcome Scores (KOOS) were assessed for all subjects and Kellgren-Lawrence grading was performed for OA volunteers. Healthy subjects were scanned consecutively at 3T to assess repeatability of the volumetric gagCEST sequence at 3T. For healthy and OA subjects, gagCEST asymmetry and T(2) and T(1ρ) relaxation times were calculated for the femoral articular to assess sensitivity to OA severity. Volumetric gagCEST imaging had higher gagCEST asymmetry than single slice acquisitions (p = 0.015). Average scan-rescan coefficient of variation was 6.8%. There were no significant differences in average gagCEST asymmetry between younger and older healthy controls (p = 0.655) or between healthy controls and OA subjects (p = 0.310). T(2) and T(1ρ) relaxation times were elevated in OA subjects (p < 0.001 for both) compared to healthy controls and both were moderately correlated with total KOOS scores (rho = −0.181 and rho = −0.332 respectively). The gagCEST technique developed here, with volumetric scan times under 10 minutes and high gagCEST asymmetry at 3T, did not vary significantly between healthy subjects and those with mild-moderate osteoarthritis. This further supports a limited utility for gagCEST imaging at 3T for assessment of early changes in cartilage composition in osteoarthritis.

Postpartum mammary gland involution is a mammalian tissue remodeling event that occurs after pregnancy and lactation to return the gland to the pre-pregnant state. This event is characterized by apoptosis and lysosomal-mediated cell death of the majority of the lactational mammary epithelium, followed by remodeling of the extracellular matrix, influx of immune cell populations (in particular, T helper cells, monocytes, and macrophages), and neo-lymphangiogenesis. This postpartum environment has been shown to be promotional for tumor growth and metastases and may partially account for why women diagnosed with breast cancer during the postpartum period or within 5 years of last childbirth have an increased risk of developing metastases when compared to their nulliparous counterparts. The lymphatics and macrophages present during mammary gland involution have been implicated in promoting the observed growth and metastasis. Of importance are the macrophages, which are of the “M2” phenotype and are known to create a pro-tumor microenvironment. In this report, we describe a subset of postpartum macrophages that express lymphatic proteins (PoEMs) and directly interact with lymphatic vessels to form chimeric vessels or “macphatics”. Additionally, these PoEMs are very similar to tumor-associated macrophages that also express lymphatic proteins and are present at the sites of lymphatic vessels where tumors escape the tissue and enter the lymphatic vasculature. Further characterizing these PoEMs may offer insight in preventing lymphatic metastasis of breast cancer, as well as provide information for how developmental programming of lymphatic endothelial cells and macrophages can contribute to different disease progression.

Postpartum mammary gland involution is a tissue remodeling event that occurs in all mammals in the absence of nursing or after weaning to return the gland to the pre-pregnant state. The tissue microenvironment created by involution has proven to be tumor promotional. Here we report that the GPI-linked protein semaphorin 7A (SEMA7A) is expressed on mammary epithelial cells during involution and use preclinical models to demonstrate that tumors induced during involution express high levels of SEMA7A. Overexpression of SEMA7A promoted the presence of myeloid-derived podoplanin (PDPN)-expressing cells in the tumor microenvironment and during involution. SEMA7A drove the expression of PDPN in macrophages, which led to integrin- and PDPN-dependent motility and adherence to lymphatic endothelial cells to promote lymphangiogenesis. In support of this mechanism, mammary tissue from SEMA7A-knockout mice exhibited decreased myeloid-derived PDPN-expressing cells, PDPN-expressing endothelial cells, and lymphatic vessel density. Furthermore, coexpression of SEMA7A, PDPN, and macrophage marker CD68 predicted for decreased distant metastasis-free survival in a cohort of over 600 cases of breast cancer as well as in ovarian, lung, and gastric cancers. Together, our results indicate that SEMA7A may orchestrate macrophage-mediated lymphatic vessel remodeling, which in turn drives metastasis in breast cancer. Signficance: SEMA7A, which is expressed on mammary cells during glandular involution, alters macrophage biology and lymphangiogenesis to drive breast cancer metastasis. Cancer Res; 78(22); 6473–85. ©2018 AACR.

Objective: The objective of this study was to validate the proof of concept of a computer-simulated cranial distraction, demonstrating accurate shape and end volume. Design: Detailed modeling was performed on pre- and postoperative computed tomographic (CT) scans to generate accurate measurements of intracranial volume. Additionally, digital distraction simulations were performed on the preoperative scan and the resultant intracranial volume and shape were evaluated. Setting: Tertiary Children’s Hospital. Patients, Participants: Preoperative and postoperative CT images were used from 10 patients having undergone cranial distraction for cephalocranial disproportion. Interventions: None; computer simulation. Main Outcome Measure: Computer simulation feasibility of cranial vault distraction was demonstrated through creation of digital osteotomies, simulating distraction through translating skull segments, followed by simulated consolidation. Accuracy of the model was evaluated through comparing the intracranial volumes of actual and simulated distracted skulls. Results: The developed digital distraction simulation was performed on the CT images of 10 patients. Plotting the relationship between the actual and simulated postdistraction volumes for the 10 patients yielded a slope of 1.0 and a correlation coefficient of 0.99. The average actual resultant volume change from distraction was 77.0 mL, compared to a simulated volume change of 76.9 mL. Conclusions: Digital simulation of cranial distraction was demonstrated through manipulation of the CT images and confirmed by comparing the actual to simulated volume change. This process may provide objective data in designing an individual distraction plan to optimize volume expansion and resultant cranial shape as well as patient education.

Supplemental Digital Content is available in the text., Background: Radiation exposure during fluoroscopically guided interventions such as endovascular aortic repair (EVAR) is a growing concern for operators. This study aimed to measure DNA damage/repair markers in operators perfoming EVAR. Methods: Expression of the DNA damage/repair marker, γ-H2AX and DNA damage response marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infrarenal, branched, and fenestrated) and open aortic repair using flow cytometry. These markers were separately measured in the same operators but this time wearing leg lead shielding in addition to upper body protection and compared with those operating with unprotected legs. Susceptibility to radiation damage was determined by irradiating operators’ blood in vitro. Results: γ-H2AX and pATM levels increased significantly in operators immediately after branched endovascular aortic repair/fenestrated endovascular aortic repair (P

IMPORTANCE: To control spending, the Centers for Medicare & Medicaid Services reduced Medicare fee-for-service (FFS) payments for noninvasive cardiac tests (NCTs) performed in provider-based office settings (ambulatory offices not administratively affiliated with hospitals) starting in 2005. Contemporaneously, payments for hospital-based outpatient testing increased. The association between differential payments by site and test location is unknown. OBJECTIVES: To quantify trends in differential Medicare FFS payments for NCTs performed in hospital-based and provider-based settings, determine the association between the hospital-based outpatient testing to provider-based office testing payment ratio and the proportion of hospital-based NCTs, and to examine trends in test location between Medicare FFS and 3 Medicare Advantage health maintenance organizations for which Centers for Medicare & Medicaid Services payments do not depend on testing location. DESIGN, SETTING, AND PARTICIPANTS: This observational claims-based study used Medicare FFS claims from 1999 to 2015 (5% random sample) and Medicare Advantage claims from 3 large health maintenance organizations (2005-2015) among Medicare FFS beneficiaries aged 65 years or older and a health maintenance organization control group. Statistical analysis was performed from May 1, 2017, to July 15, 2019. EXPOSURES: The weighted mean payment ratio of Medicare FFS hospital-based outpatient testing to provider-based office testing for outpatient NCTs. MAIN OUTCOMES AND MEASURES: Proportion of outpatient NCTs performed in the hospital-based setting and Medicare FFS costs. RESULTS: The data included a mean of 1.72 million patient-years annually in Medicare FFS (mean age, 75.2 years; 57.3% female in 2015) and a mean of 142 230 patient-years annually in the managed care control group (mean age, 74.8 years; 56.2% female in 2015). The Medicare payment ratio of FFS hospital-based outpatient testing to provider-based office testing increased from 1.05 in 2005 to 2.32 in 2015. The FFS hospital-based outpatient testing proportion increased from 21.1% in 2008 to 43.2% in 2015 and was correlated with the payment ratio (correlation coefficient with a 1-year lag, 0.767; P

This cohort study assesses whether changes in overall rates of use of diagnostic cardiovascular tests were associated with changes in high-value testing recommended by guidelines and low-value testing that is expected to provide minimal benefits among a 5% national sample of Medicare beneficiaries between 2000 and 2006., Key Points Question Are changes in annual rates of diagnostic cardiovascular tests associated with changes in rates of high- and low-value testing? Findings In this cohort study of a 5% national sample of Medicare beneficiaries, annual rates of overall testing appeared to increase from 2000 to 2008 and then declined until 2016. Rates of low-value tests (preoperative stress testing and routine stress testing after coronary revascularization) appeared to have increased and then decreased, whereas rates of high-value tests (assessing left ventricular systolic function among patients hospitalized with acute myocardial infarction and heart failure) appeared to increase throughout the study period. Meaning Payment changes intended to reduce spending on overall testing may not have adversely affected testing recommended by guidelines., Importance Owing to a rapid increase in rates of diagnostic cardiovascular testing in the 1990s and early 2000s, the Centers for Medicare & Medicaid Services implemented a series of payment changes intended to reduce overall spending on fee-for-service testing. Whether guideline-concordant testing has been subsequently affected is unknown to date. Objective To determine whether changes in overall rates of use of diagnostic cardiovascular tests were associated with changes in high-value testing recommended by guidelines and low-value testing that is expected to provide minimal benefits. Design, Setting, and Participants This retrospective cohort study assessed a national 5% random sample of Medicare fee-for-service beneficiaries aged 65 to 95 years from January 1, 1999, through December 31, 2016. Data were analyzed from February 15, 2018, through August 15, 2019. Exposures Eligibility to receive high-value testing (assessment of left ventricular systolic function among patients hospitalized with acute myocardial infarction or heart failure) and low-value testing (stress testing before low-risk noncardiac surgery and routine stress testing within 2 years of coronary revascularization not associated with acute care visits). Main Outcomes and Measures Age- and sex-adjusted annual rates of overall, high-value, and low-value diagnostic cardiovascular testing. Results Mean (SD) age was similar over time (75.57 [7.32] years in 2000-2003; 74.82 [7.79] years in 2012-2016); the proportion of women slightly declined over time (63.23% in 2000 to 2003; 57.27% in 2012 to 2016). The rate of overall diagnostic cardiovascular testing per 1000 patient-years among the 5% sample of Medicare beneficiaries increased from 275 in 2000 to 359 in 2008 (P

In 2010 Maryland replaced fee-for-service payment for some rural hospitals with "global budgets" for hospital-provided services called Total Patient Revenue (TPR). A principal goal was to incentivize hospitals to manage resources efficiently. Using a difference-in-differences design, we compared eight TPR hospitals to seven similar non-TPR Maryland hospitals to estimate how TPR affected hospital-provided services. We also compared health care use by "treated" patients in TPR counties to that of patients in counties containing control hospitals. Inpatient admissions and outpatient services fell sharply at TPR hospitals, increasingly so over the period that TPR was in effect. Emergency department (ED) admission rates declined 12 percent, direct (non-ED) admissions fell 23 percent, ambulatory surgery center visits fell 45 percent, and outpatient clinic visits and services fell 40 percent. However, for residents of TPR counties, visits to all Maryland hospitals fell by lesser amounts and Medicare spending increased, which suggests that some care moved outside of the global budget. Nonetheless, we could not assess the efficiency of these shifts with our data, and some care could have moved to more efficient locations. Our evidence suggests that capitation models require strong oversight to ensure that hospitals do not respond by shifting costs to other providers.

Adult hair glucocorticoid concentrations reflect months of hypothalamic-pituitary-adrenal axis activity. However, little is known about the determinants of neonatal hair glucocorticoids. We tested associations between perinatal exposures and neonatal hair glucocorticoids. Cortisol and cortisone were measured by LC-MS/MS in paired maternal and infant hair samples collected within 10 days of birth (n = 49 term, n = 47 preterm), with neonatal samples collected at 6-weeks in n = 54 preterm infants. We demonstrate cortisol accumulation in hair increases with fetal maturity, with hair cortisol being higher in term than preterm born infants after delivery (median 401 vs 106 pg/mg; p, Highlights • Neonatal hair cortisol is higher after term compared to preterm birth. • Neonatal hair cortisol reflects fetal growth, maternal cortisol and birth exposures. • Hair sampled at 6 weeks reflects postnatal exposures in preterm infants.

In 2014 twenty-eight states and the District of Columbia had expanded Medicaid eligibility while federal and state-based Marketplaces in every state made subsidized private health insurance available to qualified individuals. As a result, about seventeen million previously uninsured Americans gained health insurance in 2014. Many policy makers had predicted that Medicaid expansion would lead to greatly increased use of hospital emergency departments (EDs). We examined the effect of insurance expansion on ED use in 478 hospitals in 36 states during the first year of expansion (2014). In difference-in-differences analyses, Medicaid expansion increased Medicaid-paid ED visits in those states by 27.1 percent, decreased uninsured visits by 31.4 percent, and decreased privately insured visits by 6.7 percent during the first year of expansion compared to nonexpansion states. Overall, however, total ED visits grew by less than 3 percent in 2014 compared to 2012-13, with no significant difference between expansion and nonexpansion states. Thus, the expansion of Medicaid coverage strongly affected payer mix but did not significantly affect overall ED use, even though more people gained insurance coverage in expansion states than in nonexpansion states. This suggests that expanding Medicaid did not significantly increase or decrease overall ED visit volume.

Background: High tibial osteotomy is a surgical procedure to treat medial compartment osteoarthritis in varus knees. The reported success rates of the procedure are inconsistent, which may be due to sagittal plane alignment of the osteotomy. The objective of this study was to determine the effect of changing tibial slope, for a range of tibial wedge angles in high tibial osteotomy, on knee joint contact pressure location and kinematics during continuous loaded flexion/extension. Methods: Seven cadaveric knee specimens were cycled through flexion and extension in an Oxford knee-loading rig. The osteotomy on each specimen was adjusted to seven clinically relevant wedge and slope combinations. We used pressure sensors to determine the position of the centre of pressure in each compartment of the tibial plateau and infrared motion capture markers to determine tibiofemoral and patellofemoral kinematics. Findings: In early knee flexion, a 5 degree increase in tibial slope shifted the centre of pressure in the medial compartment anteriorly by 7mm for a 15 degree wedge (p

Tosatto, Silvio/0000-0003-4525-7793; Zhang, Feng/0000-0003-3447-897X; Gonzalez, Jose Maria Fernandez/0000-0002-4806-5140; Devignes, Marie-Dominique/0000-0002-0399-8713; Wass, Mark/0000-0001-5428-6479; Falda, Marco/0000-0003-2642-519X; Thurlby, Natalie/0000-0002-1007-0286; Zosa, Elaine/0000-0003-2482-0663; Dessimoz, Christophe/0000-0002-2170-853X; Yunes, Jeffrey/0000-0003-1869-3231; Hamid, Md Nafiz/0000-0001-8681-6526; Hoehndorf, Robert/0000-0001-8149-5890; Dogan, Tunca/0000-0002-1298-9763; NOTARO, MARCO/0000-0003-4309-2200; Cozzetto, Domenico/0000-0001-6752-5432; Lewis, Kimberley/0000-0003-3010-8453; Roche, Daniel/0000-0002-9204-1840; Martin, Maria-Jesus/0000-0001-5454-2815; Tress, Michael/0000-0001-9046-6370; Tolvanen, Martti/0000-0003-3434-7646; Cheng, Jianlin/0000-0003-0305-2853; Rose, Peter/0000-0001-9981-9750; Renaux, Alexandre/0000-0002-4339-2791; Kacsoh, Balint/0000-0001-9171-0611; O'Donovan, Claire/0000-0001-8051-7429; Kulmanov, Maxat/0000-0003-1710-1820; Friedberg, Iddo/0000-0002-1789-8000; Zhou, Naihui/0000-0001-6268-6149, WOS: 000498615000001, PubMed ID: 31744546, Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens., National Science FoundationNational Science Foundation (NSF) [DBI1564756, DBI-1458359, DBI-1458390, DMS1614777, CMMI1825941, NSF 1458390]; Gordon and Betty Moore FoundationGordon and Betty Moore Foundation [GBMF 4552]; National Institutes of Health NIGMSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P20 GM113132]; Cystic Fibrosis Foundation [CFRDP STANTO19R0]; BBSRCBiotechnology and Biological Sciences Research Council (BBSRC) [BB/K004131/1, BB/F00964X/1, BB/M025047/1, BB/M015009/1]; Consejo Nacional de Ciencia y Tecnologia Paraguay (CONACyT)Consejo Nacional de Ciencia y Tecnologia (CONACyT) [14-INV-088, PINV15-315]; NSFNational Science Foundation (NSF) [1660648, DBI 1759934, IIS1763246, DBI-1458477, 0965768, DMR-1420073, DBI-1458443]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01GM093123, DP1MH110234, UL1 TR002319, U24 TR002306]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy-EXC 2155 "RESIST"German Research Foundation (DFG) [39087428]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01GM123055, R01GM60595, R15GM120650, GM083107, GM116960, AI134678, NIH R35-GM128637, R00-GM097033]; ERCEuropean Research Council (ERC) [StG 757700]; Spanish Ministry of Science, Innovation and Universities [BFU2017-89833-P]; Severo Ochoa award; Centre of Excellence project "BioProspecting of Adriatic Sea"; Croatian Government; European Regional Development FundEuropean Union (EU) [KK.01.1.1.01.0002]; ATT Tieto kayttoon grant; Academy of FinlandAcademy of Finland; University of Turku; CSC-IT Center for Science Ltd.; University of Miami; National Cancer Institute of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [U01CA198942]; Helsinki Institute for Life Sciences; Academy of FinlandAcademy of Finland [292589]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31671367, 31471245, 91631301, 61872094, 61572139]; National Key Research and Development Program of China [2016YFC1000505, 2017YFC0908402]; Italian Ministry of Education, University and Research (MIUR) PRIN 2017 projectMinistry of Education, Universities and Research (MIUR) [2017483NH8]; Shanghai Municipal Science and Technology Major Project [2017SHZDZX01, 2018SHZDZX01]; UK Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [BB/N019431/1, BB/L020505/1, BB/L002817/1]; Elsevier; Extreme Science and Engineering Discovery Environment (XSEDE) award [MCB160101, MCB160124]; Ministry of Education, Science and Technological Development of the Republic of Serbia [173001]; Taiwan Ministry of Science and Technology [106-2221-E-004-011-MY2]; Montana State University; Bavarian Ministry for Education; Simons Foundation; NIH NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [1R21NS103831-01]; University of Illinois at Chicago (UIC) Cancer Center award; UIC College of Liberal Arts and Sciences Faculty Award; UIC International Development Award; Yad Hanadiv [9660/2019]; National Institute of General Medical Science of the National Institute of Health [GM066099, GM079656]; Research Supporting Plan (PSR) of University of Milan [PSR2018-DIP-010-MFRAS]; Swiss National Science FoundationSwiss National Science Foundation (SNSF) [150654]; EMBL-European Bioinformatics Institute core funds; CAFA BBSRC [BB/N004876/1]; European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grantEuropean Union (EU) [778247]; COST ActionEuropean Cooperation in Science and Technology (COST) [BM1405]; NIH/NIGMSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01 GM071749]; National Human Genome Research Institute of the National of Health [U41 HG007234]; INB Grant (ISCIII-SGEFI/ERDF) [PT17/0009/0001]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [EEEAG-116E930]; KanSil [2016K121540]; Universita degli Studi di Milano; 111 ProjectMinistry of Education, China - 111 Project [B18015]; key project of Shanghai Science Technology [16JC1420402]; ZJLab; project Ribes Network POR-FESR 3S4H [TOPP-ALFREVE18-01]; PRID/SID of University of Padova [TOPP-SID19-01]; NIGMSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R15GM120650]; King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) [URF/1/3454-01-01, URF/1/3790-01-01]; "the Human Project from Mind, Brain and Learning" of the NCCU Higher Education Sprout Project by the Taiwan Ministry of Education; National Center for High-performance ComputingIstanbul Technical University, The work of IF was funded, in part, by the National Science Foundation award DBI-1458359. The work of CSG and AJL was funded, in part, by the National Science Foundation award DBI-1458390 and GBMF 4552 from the Gordon and Betty Moore Foundation. The work of DAH and KAL was funded, in part, by the National Science Foundation award DBI-1458390, National Institutes of Health NIGMS P20 GM113132, and the Cystic Fibrosis Foundation CFRDP STANTO19R0. The work of AP, HY, AR, and MT was funded by BBSRC grants BB/K004131/1, BB/F00964X/1 and BB/M025047/1, Consejo Nacional de Ciencia y Tecnologia Paraguay (CONACyT) grants 14-INV-088 and PINV15-315, and NSF Advances in BioInformatics grant 1660648. The work of JC was partially supported by an NIH grant (R01GM093123) and two NSF grants (DBI 1759934 and IIS1763246). ACM acknowledges the support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy -EXC 2155 "RESIST" - Project ID 39087428. DK acknowledges the support from the National Institutes of Health (R01GM123055) and the National Science Foundation (DMS1614777, CMMI1825941). PB acknowledges the support from the National Institutes of Health (R01GM60595). GB and BZK acknowledge the support from the National Science Foundation (NSF 1458390) and NIH DP1MH110234. FS was funded by the ERC StG 757700 "HYPER-INSIGHT" and by the Spanish Ministry of Science, Innovation and Universities grant BFU2017-89833-P. FS further acknowledges the funding from the Severo Ochoa award to the IRB Barcelona. TS was funded by the Centre of Excellence project "BioProspecting of Adriatic Sea", co-financed by the Croatian Government and the European Regional Development Fund (KK.01.1.1.01.0002). The work of SK was funded by ATT Tieto kayttoon grant and Academy of Finland. JB and HM acknowledge the support of the University of Turku, the Academy of Finland and CSC -IT Center for Science Ltd. TB and SM were funded by the NIH awards UL1 TR002319 and U24 TR002306. The work of CZ and ZW was funded by the National Institutes of Health R15GM120650 to ZW and start-up funding from the University of Miami to ZW. The work of PWR was supported by the National Cancer Institute of the National Institutes of Health under Award Number U01CA198942. PR acknowledges NSF grant DBI-1458477. PT acknowledges the support from Helsinki Institute for Life Sciences. The work of AJM was funded by the Academy of Finland (No. 292589). The work of FZ and WT was funded by the National Natural Science Foundation of China (31671367, 31471245, 91631301) and the National Key Research and Development Program of China (2016YFC1000505, 2017YFC0908402]. CS acknowledges the support by the Italian Ministry of Education, University and Research (MIUR) PRIN 2017 project 2017483NH8. SZ is supported by the National Natural Science Foundation of China (No. 61872094 and No. 61572139) and Shanghai Municipal Science and Technology Major Project (No. 2017SHZDZX01). PLF and RLH were supported by the National Institutes of Health NIH R35-GM128637 and R00-GM097033. JG, DTJ, CW, DC, and RF were supported by the UK Biotechnology and Biological Sciences Research Council (BB/N019431/1, BB/L020505/1, and BB/L002817/1) and Elsevier. The work of YZ and CZ was funded in part by the National Institutes of Health award GM083107, GM116960, and AI134678; the National Science Foundation award DBI1564756; and the Extreme Science and Engineering Discovery Environment (XSEDE) award MCB160101 and MCB160124.; The work of BG, VP, RD, NS, and NV was funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Project No. 173001. The work of YWL, WHL, and JMC was funded by the Taiwan Ministry of Science and Technology (106-2221-E-004-011-MY2). YWL, WHL, and JMC further acknowledge the support from "the Human Project from Mind, Brain and Learning" of the NCCU Higher Education Sprout Project by the Taiwan Ministry of Education and the National Center for High-performance Computing for computer time and facilities. The work of IK and AB was funded by Montana State University and NSF Advances in Biological Informatics program through grant number 0965768. BR, TG, and JR are supported by the Bavarian Ministry for Education through funding to the TUM. The work of RB, VG, MB, and DCEK was supported by the Simons Foundation, NIH NINDS grant number 1R21NS103831-01 and NSF award number DMR-1420073. CJJ acknowledges the funding from a University of Illinois at Chicago (UIC) Cancer Center award, a UIC College of Liberal Arts and Sciences Faculty Award, and a UIC International Development Award. The work of ML was funded by Yad Hanadiv (grant number 9660/2019). The work of OL and IN was funded by the National Institute of General Medical Science of the National Institute of Health through GM066099 and GM079656. Research Supporting Plan (PSR) of University of Milan number PSR2018-DIP-010-MFRAS. AWV acknowledges the funding from the BBSRC (CASE studentship BB/M015009/1). CD acknowledges the support from the Swiss National Science Foundation (150654). CO and MJM are supported by the EMBL-European Bioinformatics Institute core funds and the CAFA BBSRC BB/N004876/1. GG is supported by CAFA BBSRC BB/N004876/1. SCET acknowledges funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 778247 (IDPfun) and from COST Action BM1405 (NGP-net). SEB was supported by NIH/NIGMS grant R01 GM071749. The work of MLT, JMR, and JMF was supported by the National Human Genome Research Institute of the National of Health, grant numbers U41 HG007234. The work of JMF and JMR was also supported by INB Grant (PT17/0009/0001 - ISCIII-SGEFI/ERDF). VA acknowledges the funding from TUBITAK EEEAG-116E930. RCA acknowledges the funding from KanSil 2016K121540. GV acknowledges the funding from Universita degli Studi di Milano - Project "Discovering Patterns in Multi-Dimensional Data" and Project "Machine Learning and Big Data Analysis for Bioinformatics". SZ is supported by the National Natural Science Foundation of China (No. 61872094 and No. 61572139) and Shanghai Municipal Science and Technology Major Project (No. 2017SHZDZX01). RY and SY are supported by the 111 Project (NO. B18015), the key project of Shanghai Science & Technology (No. 16JC1420402), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01), and ZJLab. ST was supported by project Ribes Network POR-FESR 3S4H (No. TOPP-ALFREVE18-01) and PRID/SID of University of Padova (No. TOPP-SID19-01). CZ and ZW were supported by the NIGMS grant R15GM120650 to ZW and start-up funding from the University of Miami to ZW. The work of MK and RH was supported by the funding from King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) under Award No. URF/1/3454-01-01 and URF/1/3790-01-01. The work of SDM is funded, in part, by NSF award DBI-1458443.

Insurance authorization of reduction mammoplasty can be a challenging process. Despite copious evidence of the benefits of this operation and evidence that specimen weight does not correlate with symptomatic relief, most insurance providers require estimated resection weights. Many formulas and techniques to predict resection weight are inconsistent or not specific to the vertical technique. This study describes a simple method for generating a surgeon-specific equation for accurately predicting vertical reduction mammoplasty resection weight using 2 breast surface measurements.

Objective To provide a critical review of a multipronged recruitment approach used to identify, recruit, and enroll a diverse community-based sample of persons with memory disorders into an 18-month randomized, controlled dementia care coordination trial. Methods Descriptive analysis of a recruitment approach comprised five strategies: community liaison ("gatekeepers") method, letters sent from trusted community organizations, display and distribution of study materials in the community, research registries, and general community outreach and engagement activities. Participants were 55 community organizations and 63 staff of community organizations in Baltimore, Maryland. Participant referral sources, eligibility, enrollment status, demographics, and loss to follow-up were tracked in a relational access database. Results In total, 1,275 referrals were received and 303 socioeconomically, cognitively, and racially diverse community-dwelling persons with cognitive disorders were enrolled. Most referrals came from letters sent from community organizations directly to clients on the study's behalf (39%) and referrals from community liaison organizations (29%). African American/black enrollees were most likely to come from community liaison organizations. Conclusion A multipronged, adaptive approach led to the successful recruitment of diverse community-residing elders with memory impairment for an intervention trial. Key factors for success included using a range of evidence-supported outreach strategies, forming key strategic community partnerships, seeking regular stakeholder input through all research phases, and obtaining "buy-in" from community stakeholders by aligning study objectives with perceived unmet community needs.

Many cancer survivors experience fatigue as a nagging symptom lasting years after treatment. To learn of the relevant biological pathways involved in fatigue among cancer survivors, the authors tested for an association between fatigue levels and leukocyte gene expression profiles and determined the specific mediating immune cell types.A sample of 89 Hispanic/Latino adults aged 60.5 years, 62% of whom were male, who were diagnosed with colorectal cancer and were 2.9 years since diagnosis provided blood for transcriptome profiling and completed a validated measure of fatigue (Multidimensional Fatigue Symptom Inventory-Short Form). The authors applied genome-wide transcriptional profiling of leukocyte RNA to identify gene expression activity associated with fatigue, tested for the activity of specific transcription factors involved in previously established markers of inflammation and immunologic activation, and identified the specific cell types mediating these transcriptional alterations.In analyses adjusting for demographic and behavioral health risk factors, results linked fatigue with increased activation of B lymphocytes and CD8-positive T cells, as well as several transcription factors involved in immune activation (nuclear factor κB [NF-κB], signal transducer and activator of transcription [STAT], and cAMP responsive element-binding protein [CREB]). Results also replicated several specific genomic effects previously observed in fatigued cancer survivors, including upregulated expression of α-synuclein (SNCA) and hemoglobin subunits (HBA and HBB).Cancer survivors' heightened fatigue levels may be partially explained by activation of specific immune cell subsets, thereby providing a potential molecular biomarker for clinical interventions targeting the remediation of fatigue. Cancer 2018;124:2637-44. © 2018 American Cancer Society.

OBJECTIVE We compare case mix, hospitalization rates, length of stay (LOS), and resource use in independent freestanding emergency departments (FSEDs) and hospital-based emergency departments (H-EDs). METHODS Data from 74 FSEDs (2013-2015) in Texas and Colorado were compared to H-ED data from the 2013-2014 National Hospital Ambulatory Medical Care Survey. In the unrestricted sample, large differences in visit characteristics (e.g., payer and case mix) were found between patients that use FSEDs compared to H-EDs. Therefore, we restricted our analysis to patients commonly treated in both settings (

Life under threat of deportation What is the effect on a child of having parents who are at risk of deportation as unauthorized immigrants? Hainmueller et al. developed a quasi-experimental protocol to address this complicated question. They selected mothers who had birthdates either just before or just after the cutoff for the United States' Deferred Action for Childhood Arrivals (DACA) program. Children whose mothers were protected from deportation by DACA had 50% fewer diagnoses of adjustment and anxiety disorder than children with mothers whose birthdates, by coincidence, preceded the cutoff and who thus were not protected. Science , this issue p. 1041

Immunosuppression following solid organ transplantation reduces T cell-mediated immune control of Epstein–Barr Virus (EBV), which may then drive development of post-transplant lymphoproliferative disease. Serology plays a key role in determination of risk of outgrowth of such lesions following transplantation. The study compared the VIDAS ® (bioMerieux) and LIAISON ® (DiaSorin) enzyme immunoassays (EIAs) and immunofluorescence assays (IFA; MBL-Bion) in the kidney transplantation setting. Sera from 100 live kidney donors [51 males; age range 20–82 years (mean 51.2 years)] and 100 cadaveric kidney recipients [70 males; age range 17–77 years (mean 51.0 years)] were tested. Overall proportional agreement ranged from 96% to 100% for VIDAS ® and LIAISON ® . Sensitivity ranged from 91% to 100% and 92% to 100% for VIDAS ® /IFA and LIAISON ® /IFA, respectively. The VIDAS ® and LIAISON ® approaches gave similar results. Such automated random access EIAs are well suited to busy clinical virology laboratories and rapid determination of donor and recipient EBV serostatus prior to transplantation.

Little is known about the presentation of mental health symptoms among South Asians living in the US.To explore mental health symptom presentation in South Asians in the US and to identify facilitators and barriers to treatment.Focus group study.Four focus groups were conducted with 7-8 participants in each group. All participants (N = 29) were clinicians who had been involved in the care of South Asian patients with emotional problems and/or mental illness in the US.Qualitative content analysis.Key themes identified included: generational differences in symptom presentation, stress was the most common symptom for younger South Asians (40 years of age), while major mental illnesses such as severe depression, psychosis and anxiety disorder were the primary symptoms for older South Asians (40 years of age). Substance abuse and verbal/physical/sexual abuse were not uncommon but were often not reported spontaneously. Stigma and denial of mental illness were identified as major barriers to treatment. Facilitators for treatment included use of a medical model and conducting systematic but patient-centered evaluations.South Asians living in the US present with a variety of mental health symptoms ranging from stress associated with acculturation to major mental illnesses. Facilitating the evaluation and treatment of South Asians with mental illness requires sensitivity to cultural issues and use of creative solutions to overcome barriers to treatment.

SummaryAims Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM). This randomised, double-blind, placebo-controlled, Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM. Methods Patients (N = 469) received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period and a 26-week extension. Prespecified primary end-point was change in HbA1c at 26 weeks. Secondary end-points included change in HbA1c at week 52 as well as proportion of patients achieving HbA1c

Objective To investigate effects of a novel dementia care coordination program on health services utilization. Data Sources/Study Setting A total of 303 community-dwelling adults aged ≥70 with a cognitive disorder in Baltimore, Maryland (2008–2011). Study Design Single-blind RCT evaluating efficacy of an 18-month care coordination intervention delivered through community-based nonclinical care coordinators, supported by an interdisciplinary clinical team. Data Collection/Extraction Methods Study partners reported acute care/inpatient, outpatient, and home- and community-based service utilization at baseline, 9, and 18 months. Principal Findings From baseline to 18 months, there were no significant group differences in acute care/inpatient or total outpatient services use, although intervention participants had significantly increased outpatient dementia/mental health visits from 9 to 18 months (p = .04) relative to controls. Home and community-based support service use significantly increased from baseline to 18 months in the intervention compared to control (p = .005). Conclusions While this dementia care coordination program did not impact acute care/inpatient services utilization, it increased use of dementia-related outpatient medical care and nonmedical supportive community services, a combination that may have helped participants remain at home longer. Future care model modifications that emphasize delirium, falls prevention, and behavior management may be needed to influence inpatient service use.

The objective of this randomized clinical experiment was to test the influence of a mindfulness meditation practice, when delivered during 1 session of active chemotherapy administration, on the acute salivary cortisol response as a marker of neuroendocrine system activity in cancer patients.A mindfulness, attention-control, or resting exposure was assigned to 57 English- or Spanish-speaking colorectal cancer patients at 1 county oncology clinic and 1 university oncology clinic at the start of chemotherapy. Saliva samples were collected at the start of chemotherapy and at subsequent 20-minute intervals during the first 60 minutes of chemotherapy (4 samples in all). Self-reporting on biobehavioral assessments after chemotherapy included distress, fatigue, and mindfulness.An area-under-the-curve analysis (AUC) showed a relative increase in cortisol reactivity in the mindfulness group after adjustments for biological and clinical measures (β = 123.21; P = .03). More than twice as many patients in the mindfulness group versus the controls displayed a cortisol rise from the baseline to 20 minutes (69% vs 34%; P = .02). AUC values were uncorrelated with biobehavioral measure scores, although mindfulness scores were inversely correlated with fatigue (r = -0.46; P .01) and distress scores (r = -0.54; P .01).Findings suggest that mindfulness practice during chemotherapy can reduce the blunting of neuroendocrine profiles typically observed in cancer patients. Implications include support for the use of mindfulness practice in integrative oncology. Cancer 2017;123:3088-96. © 2017 American Cancer Society.

Previous studies have reported conflicting findings on the relationship between race and cognitive decline in elders with dementia. Few studies have examined the role of race in cognitive decline in mild cognitive impairment (MCI). We investigate the relationship between race and cognitive decline in participants with MCI in a community-based, longitudinal study of cognitively impaired elders.Based on a validated method utilizing a neuropsychiatric battery, 133 subjects [mean age: 78.7 years (SD = 6.5); female: 112 (76.7%); black: 59 (44.4%)] out of 512 participants in the Memory and Medical Care Study were diagnosed with MCI. The main outcome measure was the Telephone Interview for Cognitive Status (TICS) score over three years. Other baseline subject characteristics (demographics, health-related variables, behavioral, and psychiatric symptoms) were included in the analysis.Overall, the three-year decline in mean TICS score was significantly higher among African Americans than non-African Americans [3.31 (SD: 7.5) versus 0.96 (SD: 3.0), t-value = 1.96, p-value = 0.05]. General estimating equation analyses revealed that African American race was associated with a faster rate of cognitive decline in all models.The rate of cognitive decline in MCI appears to be faster in African Americans than non-African Americans in the community. Diagnosis of MCI among African American elders could lead to early interventions to prevent or delay cognitive decline in the future.

Background—Innovative approaches to the widespread delivery of evidence-based dementia care are needed. The aims of this study were to determine whether a telephone screening method could efficiently identify individuals in the community in need of care for dementia and to develop a multidimensional needs assessment tool for identifying the type and frequency of unmet needs related to memory disorders in the home setting. Methods—This was a cross-sectional evaluation of 292 community-residing individuals aged 70 and older in Maryland. Participants were given a brief cognitive telephone screen. A subsample (n=43) received a comprehensive in-home assessment for dementia and dementia-related needs. Cognitive, functional, behavioral, and clinical factors were assessed. The Johns Hopkins Dementia Care Needs Assessment was used to identify unmet needs related to dementia. Results—Telephone screening for the sample took 350 hours, and 27% screened positive for dementia. Virtually all participants with dementia who received an in-home assessment had at least one unmet need, with the most frequent unmet needs being for a dementia workup, general medical care, environmental safety, assistance with ADL impairments, and access to meaningful activities. Caregivers, when present, also had a number of unmet needs, with the most common being caregiver education about dementia, knowledge of community resources, and caregiver mental health care. Conclusions—Effective and efficient means for identifying community-residing individuals with dementia are needed so that Dementia Care interventions can be provided to address unmet care needs of patients and their caregivers.

We investigated the relationship between architectural space syntax measures describing the spatial layout of a home and activities of daily living (ADL) among people with dementia. We visited the homes of 82 participants in a dementia care comparative effectiveness clinical trial and measured the space syntax variables intelligibility and convexity along with several clinical variables, including ADLs. In regression models, we estimated the cross-sectional association between space syntax measures and ADLs. Higher convexity was associated with worse performance of basic but not instrumental ADLs (adjusted β =19.2, P = .02). Intelligibility was not associated with ADLs. These results imply that enclosed rooms with a clearly legible meaning and function might be better memorized and associated with the spatial layout of the home resulting in better basic ADL performance. These results warrant further research on space syntax measures in the home environment of people with dementia, including longitudinal study, which we are pursuing.

IMPORTANCE: Physicians often report practicing defensive medicine to reduce malpractice risk, including performing expensive but marginally beneficial tests and procedures. Although there is little evidence that malpractice reform affects overall health care spending, it may influence physician behavior for specific conditions involving clinical uncertainty. OBJECTIVE: To examine whether reducing malpractice risk is associated with clinical decisions involving coronary artery disease testing and treatment. DESIGN, SETTING, AND PARTICIPANTS: Difference-in-differences design, comparing physician-specific changes in coronary artery disease testing and treatment in 9 new-cap states that adopted damage caps between 2003 and 2005 with 20 states without caps. We used the 5% national Medicare fee-for-service random sample between 1999 and 2013. Physicians (n = 75 801; 36 647 in new-cap states) who ordered or performed 2 or more coronary angiographies. Data were analyzed from June 2015 to January 2018. MAIN OUTCOMES AND MEASURES: Changes in ischemic evaluation rates for possible coronary artery disease, type of initial evaluation (stress testing or coronary angiography), progression from stress test to angiography, and progression from ischemic evaluation to revascularization (percutaneous coronary intervention or coronary artery bypass grafting). RESULTS: We studied 36 647 physicians in new-cap states and 39 154 physicians in no-cap states. New-cap states had younger populations, more minorities, lower per-capita incomes, fewer physicians per capita, and lower managed care penetration. Following cap adoption, new-cap physicians reduced invasive testing (angiography) as a first diagnostic test compared with control physicians (relative change, −24%; 95% CI, −40% to −7%; P = .005) with an offsetting increase in noninvasive stress testing (7.8%; 95% CI, −3.6% to 19.3%; P = .17), and referred fewer patients for angiography following stress testing (−21%; 95% CI, −40% to −2%; P = .03). New-cap physicians also reduced revascularization rates after ischemic evaluation (−23%; 95% CI, −40% to −4%; P = .02; driven by fewer percutaneous coronary interventions). Changes in overall ischemic evaluation rates were similar for new-cap and control physicians (−0.05%; 95% CI, −8.0% to 7.9%; P = .98). CONCLUSIONS AND RELEVANCE: Physicians substantially altered their approach to coronary artery disease testing and follow-up after initial ischemic evaluations following adoption of damage caps. They performed a similar number of ischemic evaluations but conducted fewer initial left heart catheterizations, referred fewer stress-tested patients for left heart catheterizations, and referred fewer patients for revascularization. These findings suggest that physicians tolerate greater clinical uncertainty in coronary artery disease testing and treatment if they face lower malpractice risk.

Background: Approximately 25% of individuals with dementia live alone, yet little is known about the cognitive and functional factors that impact detection of impairment.Methods: Subjects with dementia (n = 349) from a community study of dementia management were administered the Mini-mental State Examination (MMSE) and were asked to rate their cognitive status. Each participant's knowledgeable informant (KI) was interviewed to provide information about the subject's mental health and levels of cognitive and functional impairment. Subjects with dementia living alone (n = 97, 27.8%) were compared to subjects living with others (n = 252, 72.2%) regarding functional impairment, psychiatric symptoms, cognitive functioning, and dementia recognition.Results: While subjects with dementia living alone had significantly fewer ADL impairments (p < 0.0001) and less cognitive impairment (p < 0.0001) than subjects with dementia who were living with others, nearly half of subjects living alone had two or more IADL impairments. Both knowledgeable informants (p < 0.001) and primary care physicians (p < 0.009) were less likely to detect dementia in subjects living alone, while 77.3% of subjects with dementia living alone rated their cognitive abilities as “good” or “a little worse”. Subjects with dementia living alone and those living with others had similar rates of psychosis (p = 0.2792) and depressive symptoms (p = 0.2076).Conclusions: Lack of awareness of cognitive impairment by individuals with dementia living alone as well as their knowledgeable informants and physicians, combined with frequent functional impairment and psychiatric symptoms, heightens risk for adverse outcomes. These findings underscore the need for increased targeted screening for dementia and functional impairment among older persons living alone.

Objectives Obtaining assent and respecting dissent are widely adopted safeguards when conducting dementia research involving individuals who lack consent capacity, but there is no consensus on how assent and dissent should be defined or what procedures should be used regarding them. Our objective was to provide recommendations on these issues based on the opinions of knowledgeable key informants. Design Cross-sectional qualitative research. Setting University research institutions. Participants Forty informants, including 1) nationally known experts on dementia and research ethics, 2) dementia researchers, and 3) dementia caregivers and advocates. Measurements Semistructured individual and focus group interviews, audio recorded, and transcribed for content analysis. Results Assent and dissent should be defined broadly and based on an assessment of how adults who lack consent capacity can express or indicate their preferences verbally, behaviorally, or emotionally. Assent requires the ability to indicate a meaningful choice and at least a minimal level of understanding. Assent should be required whenever an individual has the ability to assent, and dissent should be binding if it is unequivocal or sustained after an effort to relieve concerns and/or distress. Standards for seeking assent and respecting dissent should not be linked to the risks or potential benefits of a study. Lacking the ability to assent and/or dissent should not automatically preclude research participation. Conclusions Obtaining assent and respecting dissent from individuals who lack consent capacity for dementia research allows them to participate, to the extent possible, in the consent process. Assent and dissent are important independent ethical constructs.

The Alzheimer’s Disease-Related Quality of Life (ADRQL) instrument was developed to assess health-related quality of life in people with Alzheimer’s disease (AD) using assessments from family caregivers or professional staff. Validity and reliability of the ADRQL in its original form and a revised version are assessed in a sample consisting of persons in three residential settings (community, assisted living, nursing home). The ADRQL exhibits good item internal consistency (67.5% of items met .40 standard); high correlation of items to hypothesized scales (85% of items met criteria for 4 of 5 subscales and the overall instrument); a good range of scores (21.6 to 100 for total sample revised instrument); very low missing data; and internal-consistency reliability coefficients exceeding the minimum reliability standard for group comparisons (.86 for total scores; range of .56 to .83 for subscales). In a community sample, the ADRQL discriminates between groups and is responsive over time in hypothesized directions. Characteristics of caregiver raters (community sample) including demographics and self-rated health were largely unrelated to scores. The results support the use of the ADRQL to evaluate health-related quality of life in persons with Alzheimer’s disease across various care settings and various stages of the disease. Modest correlations with cognitive and functional disability levels suggest that the ADRQL provides insight into other important dimensions of life experience in persons with dementia. The revised version has improved measurement properties and is recommended for use over the original.

Objectives: This study examines how surrogate decision makers for dementia patients developed an understanding of patient preferences about end-of-life (EOL) care and patient wishes. Methods: Semistructured interviews were conducted with 34 surrogate decision makers for hospice-eligible nursing home patients with dementia. The data were content analyzed. Results: Most surrogates reported that patients had previously completed an advance directive (59%), discussed preferences for EOL care (56%), or done both (38%). Catalysts for and barriers to completing an advance directive or having EOL care discussions included factors that were both intrinsic and extrinsic to the patient. The most commonly reported wish for EOL care was to not be kept alive by “machines” or “extraordinary measures.” Discussion: Health care providers may be able to assist patients and families by normalizing discussions of dying, encouraging advance care planning, helping them identify goals for EOL care, and providing information to support treatment decisions consistent with patients' wishes.

Neuropsychiatric symptoms (NPS) are common in dementia, although little is known about their prevalence and treatment near the end of life. This study used a retrospective review of the medical records of 123 hospice-eligible nursing home residents with advanced dementia to investigate the prevalence of NPS and NPS-targeted pharmacological and non-pharmacological treatments. The most prevalent NPS were agitation or aggression (50.4%), depression (45.5%), and withdrawal/lethargy (43.1%). Of the 105 (85.4%) residents who exhibited one or more NPS, 90.5% were receiving at least one NPS-targeted treatment, yet 41.9% received no documented nonpharmacological NPS-targeted care. The majority of documented nonpharmacological care focused on safety and explanations or instructions given to residents. Given the high prevalence of comorbidities, associated risks for medication interactions or serious side effects, and potential low-risk benefits of psychobehavioral care, these findings raise concerns about how to best increase the provision and documentation of nonpharmacological care in advanced dementia.

In addition to hepatic expression, cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are expressed by human macrophages. The combined actions of these proteins have profound effects on HDL structure and function. It is not known how these HDL changes influence atherosclerosis. To elucidate the role of leukocyte-derived HL on atherosclerosis in a background of CETP expression, we studied low density lipoprotein receptor-deficient mice expressing human CETP (CETPtgLDLr -/-) with a leukocyte-derived HL deficiency (HL -/- BM). HL(-/-) bone marrow (BM), CETPtgLDLr(-/-) mice were generated via bone marrow transplantation. Wild-type bone marrow was transplanted into CETPtgLDLr(-/-) mice to generate HL +/+ BM, CETPtgLDLr(-/-) controls. The chimeras were fed a high-fat, high-cholesterol diet for 14 weeks to promote atherosclerosis. In female HL(-/-) BM, CETPtgLDLr(-/-) mice plasma HDL-cholesterol concentration during high-fat feeding was decreased 27% when compared with HL +/+ BM, CETPtgLDLr(-/-) mice (P0.05), and this was associated with a 96% increase in en face aortic atherosclerosis (P0.05). In male CETPtgLDLr(-/-) mice, leukocyte-derived HL deficiency was associated with a 16% decrease in plasma HDL-cholesterol concentration and a 25% increase in aortic atherosclerosis. Thus, leukocyte-derived HL in CETPtgLDLr(-/-) mice has an atheroprotective role that may involve increased HDL levels.

Previous studies have shown that a high level of dietary lipid (corn oil) exacerbates UV-carcinogenic expression in hairless mice. Furthermore, it was demonstrated that this effect occurs at the postinitiation, or promotion, stage of UV-carcinogenesis--a stage believed to be modulated immunologically. Thus, we sought to examine the influence of dietary lipid on specific immune parameters at various times within a UV-carcinogenic protocol, with the purpose of detecting potential relationships to UV carcinogenesis. Hairless mice were fed either a high- (12%, wt/wt, corn oil) or low-fat (0.75%, wt/wt, corn oil) diet for 2 weeks prior to start of the UV or experimental protocols. Animals were sensitized to dinitrochlorobenzene (DNCB) hapten and delayed-type hypersensitivity (DTH) was assessed. Delayed-type hypersensitivity was significantly suppressed (P = 0.01) in the high-fat group, even before UV irradiation. Although both groups exhibited UV-induced suppression of this response, the high-fat group was totally suppressed after 3 weeks of UV, whereas the low-fat group exhibited reactivity through week 8. The splenic T-lymphocyte (Thy 1.2+) population had declined by about 50% at the time of UV termination (11 weeks). Dietary lipid exerted no apparent influence upon this T-cell population. However, after 6 weeks of UV, I-J+ cells (a marker shown to be acquired adaptively by suppressor T lymphocytes) began to increase. By week 15 (4 weeks post-UV) I-J+ cells had increased by about 65% in the high-fat group, twice the % increase that occurred in the low-fat group. When UV-induced tumors were transplanted to recipient animals receiving various periods (0, 6, 11 weeks) of UV irradiation, no significant differences in median tumor rejection times between the two dietary groups occurred at 0 or 6 weeks. After 11 weeks of UV, the low-fat group exhibited a tumor rejection time that was comparable to that of nonirradiated animals, i.e. 21 days. However, median tumor rejection time for the high-fat group was greater than 63 days, significantly (P = 0.01) longer than that of the low-fat group. Thus, suppression of tumor rejection by high fat occurred at a time when high fat had been shown to exacerbate carcinogenic expression and when I-J+ cells had markedly increased. These data demonstrate that level of dietary lipid modulates immunoresponsiveness in UV-irradiated animals and is compatible with the thesis that immune suppression may account for the exacerbation of carcinogenic expression elicited by high dietary fat.

Objective To describe medication usage in nursing home residents with advanced dementia, to identify how this usage changed as patients advanced towards death, and to identify correlates of increased medication usage. Methods Prospective cohort study (CareAD) during which data on medication prescription were extracted from medical records at regular intervals using standardized extraction procedures. Results Patients (n = 125) were prescribed a mean of 14.6 medications during the 6 months prior to study enrollment. In a subgroup of patients who died during the study (n = 88), as the time of death approached, the total number of medications prescribed did not vary but the types of medications prescribed did change, with an increase in palliative medications such as opiate analgesics and a decrease in other medication classes such as antibiotics, anti-dementia agents, cardiovascular agents, and psychotropic agents, among others. In linear regression analyses, total medication prescription at study entry was associated with study site, antibiotic treatment, presence of cardiovascular disease, and treatment of gastrointestinal or dermatological conditions. Conclusions Nursing home residents with advanced dementia are prescribed a large number of medications from numerous medication classes and prescribing patterns change over time. Further study is needed to determine the ideal approach to treating chronic medical problems at the end of life in this patient population. Copyright © 2007 John Wiley & Sons, Ltd.

Malformations of the craniofacial skeleton are common. Restoration of anatomic shape, size, and position has been traditionally accomplished using autologous bone grafting to fill gaps created by surgery and segmental movement. The authors present their practice using distraction in many different ages and settings over 20 years. A retrospective review was performed of all craniofacial patients treated using distraction osteogenesis for mandible, midface, and calvarium. The authors identified 205 patient. Mandible: 112 patients were treated at an average age of 3.4 years. 18.8% of patients required repeat distraction. There was no difference in the neonatal versus older group (P = 0.71). There were significantly higher reoperation rates in syndromic children (P < 0.01). Midface: 58 patients underwent Lefort III distraction at an average age of 13.6 years. One (1.7%) required repeat distraction (Miller syndrome). Five (8.6%) patients underwent subsequent Lefort I advancement for occlusal changes. Calvarium: 33 patients were treated at an average age of 4.7 years. No repeat distractions were performed. One patient required an additional advancement procedure. Distraction demonstrates successful long-term correction of defects in the craniofacial skeleton with the versatility and control needed to treat the wide spectrum of deformity.