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Background: Women are more likely to experience thyroid diseases than men. However, thyroid dysfunction risk in women undergoing the menopausal transition remains largely unknown. We explored the prevalence of thyroid dysfunction across menopausal stages. Methods: We conducted a cross-sectional study of 53,230 women aged 40 years or older who underwent health screening between 2014 and 2018. Menopausal stages were categorized into 4 based on the Stages of Reproductive Aging Workshop +10 criteria. A multinomial logistic regression model was used to estimate the prevalence ratios (PRs) with confidence intervals [CIs] for thyroid dysfunction in menopausal stages compared with that in premenopause. Results: The prevalence of overt hypothyroidism was significantly increased during late transition and postmenopause; it remained significant after further adjustments for potential confounders (age, center, year of examination, age at menarche, parity, education level, smoking status, alcohol consumption, physical activity, and body mass index) with corresponding multivariable-adjusted PRs [CI] of 1.61 [1.12-2.30] and 1.66 [1.16-2.37] in the late transition and postmenopausal stages, respectively. A significant increase in the prevalence of subclinical hypothyroidism was also observed in the late transition and postmenopausal stage with multivariable-adjusted PRs [CI] of 1.22 [1.06-1.40] and 1.24 [1.07-1.44], respectively. In contrast, subclinical and overt hyperthyroidism were not significantly associated with menopausal stages. Conclusions: In this study of pre- and perimenopausal Korean women, the prevalence of overt and subclinical hypothyroidism was significantly elevated in the late menopausal transition. Future prospective studies are warranted to investigate the clinical and prognostic significance of thyroid dysfunction in women during menopausal transition.

The role of alcohol consumption in the risk of vasomotor symptoms (VMS), the most cardinal climacteric symptoms, is not well established. We examined their relationship with early-onset VMS among premenopausal women. Moderately-to-severely bothersome VMS, the primary outcome, was assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. The alcohol consumption categories included lifetime abstainer, former drinker, or current drinker, categorized as light, moderate, heavy, and very heavy. Compared with the lifetime-abstinence (reference), the multivariable-adjusted odds ratio (95% CIs) for prevalent VMS in alcohol consumption of <10, 10−19, 20−39, and ≥40 g/day were 1.42 (1.02−1.99), 1.99 (1.27−3.12), 2.06 (1.19−3.57), and 3.52 (1.72−7.20), respectively (p trend <0.01). Compared with the lifetime-abstinence, the multivariable-adjusted hazard ratios (95% CIs) for incident bothersome VMS among average alcohol consumption of <10, 10−19, 20−39, and ≥40 g/day were 1.10 (0.85−1.41), 1.03 (0.70−1.51), 1.72 (1.06−2.78), and 2.22 (1.16−4.23), respectively (p trend = 0.02). Increased alcohol consumption positively and consistently showed a relationship with increased risk of both prevalent and incident early-onset VMS. Refraining from alcohol consumption may help prevent bothersome VMS in premenopausal women.

Objective: To explore the prevalence of and relationship between caregiver-reported sleep problems and sleep-related desired areas of change in young children (0-36 months) in a multinational sample., Methods: Caregivers (96.5% mothers) of 2219 young children (birth to 3 years; M = 13.7 mos; 49.8% male) completed an online survey including an abbreviated Brief Infant Sleep Questionnaire-Revised (BISQ-R) and questions about desired areas of change regarding their child's sleep. Data were collected in six countries (Indonesia, Japan, New Zealand, Singapore, Thailand, and United States)., Results: Overall, 35% of caregivers reported a sleep problem and nearly all (96%) indicated a desired area of change, with 76% endorsing changes in 3 or more categories (bedtime/falling asleep, overnight, morning, and naps). Desiring a change in their child's sleep was universal across age group and country, with those perceiving a sleep problem more likely to endorse an area of change than those without a sleep problem. Overall, the top change categories were bedtime (80%), naps (74%), and overnight (67%). Top specific areas of change related to sleeping for longer stretches, waking up later in the morning, and having an earlier bedtime., Conclusions: Although one-third of caregivers perceived that their child had a sleep problem, nearly all caregivers identified desired areas of change related to their child's sleep, across the first three years of life and all countries. Sleep education, such as normalizing sleep challenges that are developmentally appropriate, is warranted for all families of young children, regardless of whether sleep problems are endorsed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aims: Pancreatic ductal adenocarcinoma is an aggressive disease most often diagnosed after local progression or metastatic dissemination, precluding resection and resulting in a high mortality rate. For individuals with elevated personal risk of the development of pancreatic cancer, EUS is a frequently used advanced imaging and diagnostic modality. However, variability in the expertise and definition of EUS findings exists among gastroenterologists, as well as a lack of standardized reporting of relevant findings at the time of examination. Adoption of standardized EUS reporting, using a universally accepted and agreed on terminology, is needed., Methods: A consensus statement designed to create a standardized reporting template was authored by a multidisciplinary group of experts in pancreatic diseases that includes gastroenterologists, radiologists, surgeons, oncologists, and geneticists. This statement was developed using a modified Delphi process as part of the Pancreatic Cancer Early Detection Consortium, and >75% agreement was required to reach consensus., Results: We identified reporting elements and present standardized reporting templates for EUS indications, procedural data, EUS image capture, and descriptors of findings, tissue sampling, and postprocedural assessment of adequacy., Conclusions: Adoption of this standardized EUS reporting template should improve consistency in clinical decision-making for individuals with elevated risk of pancreatic cancer by providing complete and accurate reporting of pancreatic abnormalities. Standardization will also help to facilitate research and clinical trial design by using clearly defined and consistent imaging descriptions, thus allowing for comparison of results across different centers., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: There are limited data on cervical screen results from female-to-male (FTM) transgender patients. Herein, we compiled demographic information and cervical screen testing on FTM transgender patients and compared with age-appropriate controls., Methods: A search of our previous and current databases was performed for Papanicolaou (Pap) tests from patients taking testosterone and/or with a diagnosis of gender dysphoria, transsexualism, or transvestism. Patient data were reviewed. Relative risks of abnormal Pap smear and human papillomavirus (HPV) infection were calculated against age-matched controls., Results: Eighty-nine Pap tests from FTM transgender individuals were identified, with a mean age of 31.3 years (range, 21-60 years). The Pap test diagnoses were distributed as follows: negative for intraepithelial lesion (n = 84, 94.4%), atypical squamous cells of undetermined significance (n = 0), low-grade intraepithelial lesion (n = 4, 4.5%), and high-grade squamous intraepithelial lesion (n = 1, 1.1%). Fifty (56.2%) patients had concurrent high-risk HPV testing with four (8%) positive results. Relative risk was 0.625 (95% confidence interval [CI], 0.25-1.59; P = .32) for an abnormal Pap test and 0.55 (95% CI, 0.19-1.52; P = .24) for HPV compared with 267 age-matched controls. Of note, 13.5% of patients older than 21 years had documentation of never having a prior Pap test in our medical record., Conclusions: In our study, FTM transgender individuals were not at a higher or lower risk of HPV infection or abnormal Pap test result compared with women. However, larger studies are needed to support our findings., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We report a novel NIPBL-NACC1 gene fusion in a rare primary hepatic neoplasm previously described as the "cholangioblastic variant of intrahepatic cholangiocarcinoma." The 2 index cases were identified within our consultation files as morphologically distinctive primary hepatic neoplasms in a 24-year-old female and a 54-year-old male. The neoplasms each demonstrated varied architecture, including trabecular, organoid, microcystic/follicular, and infiltrative glandular patterns, and biphasic cytology with large, polygonal eosinophilic cells and smaller basophilic cells. The neoplasms had a distinctive immunoprofile characterized by diffuse labeling for inhibin, and patchy labeling for neuroendocrine markers (chromogranin and synaptophysin) and biliary marker cytokeratin 19. RNA sequencing of both cases demonstrated an identical fusion of NIBPL exon 8 to NACC1 exon 2, which was further confirmed by break-apart fluorescence in situ hybridization assay for each gene. Review of a tissue microarray including 123 cases originally diagnosed as well-differentiated neuroendocrine neoplasm at one of our hospitals resulted in identification of a third case with similar morphology and immunophenotype in a 52-year-old male, and break-apart fluorescence in situ hybridization probes confirmed rearrangement of both NIPBL and NACC1. Review of The Cancer Genome Atlas (TCGA) sequencing data and digital images from 36 intrahepatic cholangiocarcinomas (www.cbioportal.org) revealed one additional case with the same gene fusion and the same characteristic solid, trabecular, and follicular/microcystic architectures and biphasic cytology as seen in our genetically confirmed cases. The NIPBL-NACC1 fusion represents the third type of gene fusion identified in intrahepatic cholangiocarcinoma, and correlates with a distinctive morphology described herein., Competing Interests: Conflicts of Interest and Source of Funding: Supported in part by Biliary Cancer Research Fund at Johns Hopkins (P.A.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Clinical scores are frequently used in the diagnosis and management of stroke. While medical calculators are increasingly important support tools for clinical decisions, the uptake and use of common medical calculators for stroke remain poorly characterized., Objective: We aimed to describe use patterns in frequently used stroke-related medical calculators for clinical decisions from a web-based support system., Methods: We conducted a retrospective study of calculators from MDCalc, a web-based and mobile app-based medical calculator platform based in the United States. We analyzed metadata tags from MDCalc's calculator use data to identify all calculators related to stroke. Using relative page views as a measure of calculator use, we determined the 5 most frequently used stroke-related calculators between January 2016 and December 2018. For all 5 calculators, we determined cumulative and quarterly use, mode of access (eg, app or web browser), and both US and international distributions of use. We compared cumulative use in the 2016-2018 period with use from January 2011 to December 2015., Results: Over the study period, we identified 454 MDCalc calculators, of which 48 (10.6%) were related to stroke. Of these, the 5 most frequently used calculators were the CHA 2 DS 2 -VASc score for atrial fibrillation stroke risk calculator (5.5% of total and 32% of stroke-related page views), the Mean Arterial Pressure calculator (2.4% of total and 14.0% of stroke-related page views), the HAS-BLED score for major bleeding risk (1.9% of total and 11.4% of stroke-related page views), the National Institutes of Health Stroke Scale (NIHSS) score calculator (1.7% of total and 10.1% of stroke-related page views), and the CHADS 2 score for atrial fibrillation stroke risk calculator (1.4% of total and 8.1% of stroke-related page views). Web browser was the most common mode of access, accounting for 82.7%-91.2% of individual stroke calculator page views. Access originated most frequently from the most populated regions within the United States. Internationally, use originated mostly from English-language countries. The NIHSS score calculator demonstrated the greatest increase in page views (238.1% increase) between the first and last quarters of the study period., Conclusions: The most frequently used stroke calculators were the CHA 2 DS 2 -VASc, Mean Arterial Pressure, HAS-BLED, NIHSS, and CHADS 2 . These were mainly accessed by web browser, from English-speaking countries, and from highly populated areas. Further studies should investigate barriers to stroke calculator adoption and the effect of calculator use on the application of best practices in cerebrovascular disease., (©Benjamin Kummer, Lubaina Shakir, Rachel Kwon, Joseph Habboushe, Nathalie Jetté. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 02.08.2021.)

Our recent study of early-onset unclassified eosinophilic renal cell carcinoma (RCC) demonstrated that two third of cases could be reclassified by performing a limited number of immunohistochemistry stains. Following the same approach, we aimed to investigate what proportion of adult unclassified RCC could be reclassified. We identified 79 cases. The mean age at presentation was 58 years (range, 29 to 84 y). Tumors were grouped based on their predominant morphologic features as oncocytic (n=23); papillary (n=22); clear cell (n=22); mucinous tubular and spindle cell (MTSC; n=5); rhabdoid (n=4); or lacking a dominant pattern (n=3). By reviewing the morphologic features and performing ancillary studies, we were able to reclassify 10 cases (13%). Four cases were positive for CK20 and showed morphologic features consistent with eosinophilic solid and cystic RCC. Four cases were reclassified as MTSC based on VSTM2A expression by RNA in situ hybridization. One case was negative for SDHB and reclassified as succinate dehydrogenase-deficient RCC. None of the cases showed loss of expression of fumarate hydratase. One case was diffusely positive for CK7 and negative for CD117 and reclassified as a low-grade oncocytic tumor. Four cases were positive for both cathepsin-K and TFE3 by immunohistochemistry, although fluorescence in situ hybridization failed to identify rearrangement in either TFE3 or TFEB genes. Of the tumors that remained unclassified, those with oncocytic features were less likely to be a high grade (odds ratio [OR]=0.22, P=0.013) or advanced stage (OR=0.19, P=0.039) and were more common in women (OR=3.4, P=0.05) compared with those without oncocytic features. Tumors with rhabdoid morphology were associated with advanced stage (relative risk=3.6, P=0.009), while tumors with clear cell or papillary features had a wide range of grades and stages at presentation. In summary, the most frequent reclassified entity is eosinophilic solid and cystic RCC. Investigation of expression of succinate dehydrogenase or fumarate hydratase in individuals older than 35 years with unclassifiable tumors is low yield in the absence of specific morphologic features. A subset of MTSC without well-developed morphologic features can be reclassified by using RNA-ISH for VSTM2A. Recognition of more-recently described RCC subtypes allows for their distinction from the unclassified subtype and improves the prognostic information provided., Competing Interests: Conflicts of Interest and Source of Funding: Supported in part by the Joseph C. Eggleston Award in Surgical Pathology to R.K. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that renders it largely refractory to immunotherapy. We implemented a multimodal analysis approach to elucidate the immune landscape in PDA. Using a combination of CyTOF, single-cell RNA sequencing, and multiplex immunohistochemistry on patient tumors, matched blood, and non-malignant samples, we uncovered a complex network of immune-suppressive cellular interactions. These experiments revealed heterogeneous expression of immune checkpoint receptors in individual patient's T cells and increased markers of CD8 + T cell dysfunction in advanced disease stage. Tumor-infiltrating CD8 + T cells had an increased proportion of cells expressing an exhausted expression profile that included upregulation of the immune checkpoint TIGIT , a finding that we validated at the protein level. Our findings point to a profound alteration of the immune landscape of tumors, and to patient-specific immune changes that should be taken into account as combination immunotherapy becomes available for pancreatic cancer., Competing Interests: Competing interests: The authors have declared that no conflict of interest exists.

Background: Clinical efficacy of T cell-based cancer immunotherapy is limited by the lack of T cell infiltration in the tumor mass, especially in solid tumors. Our group demonstrated previously that leukocyte-specific protein 1 (LSP1), an intracellular signal regulator, negatively regulates T cell infiltration in inflamed tissues., Methods: To determine the immuno-regulatory effects of LSP1 in T cells on tumor progression, we investigated the growth of B16 melanoma in Lsp1 knockout (KO) mice and T cell-specific Lsp1 transgenic (Tg) mice. The immune cell subpopulation infiltrated into the tumor mass as well as the expression of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in T cells was assessed by flow cytometry and/or immunohistochemistry. Chemotactic migration was assayed with Lsp1 KO and Lsp1 Tg T cells. Adoptive transfer of Lsp1 KO or Lsp1 Tg T cells was performed in B16 melanoma-challenged Rag1 KO mice., Results: Lsp1 KO mice showed decreased growth of B16 melanoma and increased infiltration of T cells in the tumor mass, which were completely reversed in T cell-specific Lsp1 Tg mice. Lsp1 KO CD8 + T cells also exhibited elevated migratory capacity in response to CXCL9 and CXCL10, whereas Lsp1 Tg CD8 + T cells did the opposite. LSP1 expression was increased in tumor-infiltrating T cells and could be induced by T cell receptor activation. Intriguingly, gene expression profiling of Lsp1 KO T cells suggested enhanced cytotoxicity. Indeed, expression of IFN-γ and TNF-α was increased in tumor-infiltrating CD4 + and CD8 + T cells of Lsp1 KO mice, while it was markedly reduced in those of Lsp1 Tg mice. Adoptive transfer of Lsp1 KO T cells to Rag1 KO mice was more effective in suppressing melanoma growth than transfer of Lsp1 Tg T cells. Of note, when treated with antiprogrammed cell death protein 1 (PD-1) antibody, inhibition of melanoma growth was more pronounced in Lsp1 KO mice than in Lsp1- sufficient mice, suggesting that Lsp1 depletion additively increases the antitumor effects of anti-PD-1 antibody., Conclusions: LSP1 in T cells regulates the growth of B16 melanoma in mice, possibly by affecting migration and infiltration of T cells into the tumor and by modulating production of antitumor effector cytokines by CD8 + T cells. These findings provide evidence that LSP1 can be a target to improve the efficacy of T cell-based immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: A systematic review was conducted to update and provide a comprehensive overview on the psychological effects of antenatal yoga on pregnancy compared to standard prenatal care., Study Design: Four databases were searched using keywords "yoga", "pregnancy", "perinatal care", "prenatal care", "postnatal care", "postpartum period", "peripartum period", "patient outcome assessment", "outcome assessment", "pregnancy outcome", "treatment outcome". Trials were considered if they were randomized controlled trials (RCTs) published from 2011 to 2018 and evaluated an antenatal yoga intervention. All studies were assessed for risk of bias using the Cochrane criteria. Trial characteristics and outcomes were extracted and synthesized descriptively where possible. Due to heterogeneity, meta-analysis was not possible., Results: Of the 175 non-duplicated studies, 16 met criteria for full-text review. Five RCTs met the inclusion criteria and were included in the systematic review. The findings of the RCTs suggest antenatal yoga may be safe and may effectively decrease stress levels, anxiety scores, depression scores, and pain response as well as increasing maternal immunity and emotional-wellbeing., Conclusion: Yoga appears to be safe and may improve psychological and pregnancy outcomes. However, due to the limited number of studies, more high-quality, large RCTs are needed to draw conclusions about improvement in other pregnancy outcomes., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Idiopathic basal ganglia calcification (IBGC), also known as Fahr disease, is a rare neurodegenerative disorder characterized by the accumulation of extensive parenchymal and vascular calcifications in the basal ganglia, with variable calcifications elsewhere in the brain. Typically, IBGC presents with neurologic and psychiatric symptoms in middle-aged adults. Recent genetic studies have identified alterations in 4 genes causing IBGC, including alterations in SLC20A2 on chromosome 8p11.2. Currently, there are no clinical descriptions of patients with IBGC occurring within the context of a complex genetic syndrome. Here, we present a case of pediatric 8p11 deletion with IBGC, hereditary spherocytosis, vitreoretinopathy, and focal cortical dysplasia. We review multiple cases of IBGC with pediatric onset due to SLC20A2 deletion in the literature, and raise the consideration of IBGC in the evaluation of pediatric patients with 8p11.2 deletion syndromes., (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)

Background: Mass shootings are an increasingly common phenomenon in the United States. However, there is little research on whether the recent growth of income inequality is associated with this rise of mass shootings. We thus build on our prior research to explore the connection between income inequality and mass shootings across counties in the United States., Methods: We assemble a panel dataset of 3144 counties during the years 1990 to 2015. Socioeconomic data are extracted from the U.S. Bureau of the Census. Mass shootings data are from three databases that compile its information from the Federal Bureau of Investigation and media sources, respectively. These data are analyzed using random effects negative binomial regressions, while controlling for seven additional predictors of crime., Results: Counties experiencing a one standard deviation growth of income inequality witnessed 0.43 more mass shootings when using the definition of three or more victim injuries (incidence rate ratio [IRR] = 1.43; 95% confidence interval [CI] = 1.24, 1.66; P < .001) and 0.57 more mass shootings when using the designation of four or more victim deaths (IRR = 1.57; 95% CI = 1.26, 1.96; P < .001)., Conclusions: Counties with growing levels of income inequality are more likely to experience mass shootings. We assert that one possibility for this finding is that income inequality fosters an environment of anger and resentment that ultimately leads to violence.

Many scholars argue that liberalization increases both economic growth and income inequality in developed economies. However, there is limited research on how liberal economic policies shape the earnings of different income groups in the national economy. The current study thus attempts to fill this gap in the literature by examining a panel dataset of 15 advanced industrial societies during the years 1970-2010. According to the results, long-run measures of liberalization increase the incomes of the top 0.1%, but does not return significant results for the incomes of the top 1.0% and top 10%. Furthermore, no discernible effect of liberalization is observed for the incomes of the bottom 90%. When taken together, although most researchers focus on inter-group inequality by examining how liberalization augments the incomes of top earners vis-à-vis bottom earners, the evidence of this study indicates scholars should also focus on intra-group inequality among top earners, as liberalization seems to benefit only a very small segment of elite earners in the national economy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The Ottawa subarachnoid hemorrhage rule is used to rule out subarachnoid hemorrhage in patients with headache.

Background: Although the outcome of pediatric hematopoietic stem cell transplantation (HSCT) has significantly improved, it remains to be associated with high mortality. Identifying patients at high risk of mortality may potentially help to triage clinical management. The primary objective of this study is to evaluate risk factors associated with mortality of patients who received HSCT and admitted to ICU using pediatric sequential organ failure assessment (pSOFA), one of pediatric severity scoring systems in intensive care unit (ICU)., Methods: We performed retrospective review of electronic medical records of pediatric patients who received HSCT and were admitted to ICU in our institution between January 2010 and June 2018. Incidence of mortality was obtained, and risk factors associated with the mortality were examined using univariate and multivariable analyses., Results: The mortality rate of pediatric HSCT patients who were admitted to ICU as a whole was 27.9%. Patients were divided into three groups based on the number of HSCT required and timing of ICU admission. Patients who received first HSCT and admitted to ICU during the same hospital stay were the majority of the study population (Group A). d(pSOFA), which was defined as the difference between maximum pSOFA and admission pSOFA, greater than and equal to 7 best predicted mortality of Group A (the area under the ROC curve 0.850; 95% CI: 0.733-0.966). Univariate and multivariable analyses showed that an increase in neurologic and cardiovascular sub scores were independently associated with higher mortality (odds ratio (OR) 2.27; 95% CI: 1.32-3.93, and OR 2.69; 95% CI: 1.21-5.99, respectively)., Discussion: In our single center study, pediatric HSCT patients who were admitted to ICU demonstrated a high mortality. Risk factor analysis demonstrated that patients with the progression of neurologic and cardiovascular injuries probed by pSOFA scoring system during their ICU stay were strongly associated with mortality., Competing Interests: Conflict of Interest None

Mass shootings are becoming a more common occurrence in the United States. Data show that mass shootings increased steadily over the past nearly 50 years. Crucial is that the wide-ranging adverse effects of mass shootings generate negative mental health outcomes on millions of Americans, including fear, anxiety, and ailments related to such afflictions. This study extends previous research that finds a strong positive relationship between income inequality and mass shootings by examining the effect of household income as well as the interaction between inequality and income. To conduct our analyses, we compile a panel dataset with information across 3,144 counties during the years 1990 to 2015. Mass shootings was measured using a broad definition of three or more victim injuries. Income inequality was calculated using the post-tax version of the Gini coefficient. Our results suggest that while inequality and income alone are both predictors of mass shootings, their impacts on mass shootings are stronger when combined via interaction. Specifically, the results indicate areas with the highest number of mass shootings are those that combine both high levels of inequality and high levels of income. Additionally, robustness checks incorporating various measures of mass shootings and alternative regression techniques had analogous results. Our findings suggest that to address the mass shootings epidemic at its core, it is essential to understand how to stem rising income inequality and the unstable environments that we argue are created by such inequality.

The TASH Score predicts the need for massive transfusion based on clinical and laboratory data.

Background: Unrestrained use of expensive, high-risk interventions runs counter to the idea of a limited medical commons., Objective: To examine the effect of displaying the total first-year cost of implanting a left ventricular assist device (LVAD) on a hypothetical treatment decision and whether this effect differs when choosing for oneself versus for another person., Design: We conducted an online survey in February 2016. The survey described the clinical course of end-stage heart failure and the risks and benefits of an LVAD. Participants were randomized to 1 of 4 scenarios, which varied by patient identity (oneself versus another person) and description of total cost., Measurements: This study measured acceptance of LVAD implantation. Reasoning and attitudes were secondarily explored., Results: We received 1211 valid responses. The mean age was 38.3 y (±12.8); 53.5% were female and 84.4% were white. Participants were more likely to accept an LVAD when shown the total cost (66.2% v. 58.0%, P = 0.003) or when choosing for another (68.0 % v. 56.4%, P < 0.001). Open-ended responses indicated that acceptors wanted to extend survival while decliners feared poor quality of life with LVAD therapy. Acceptors and decliners agreed that consumers can help lower the cost of health care, but decliners were more likely to consider cost when making health care decisions ( P < 0.001)., Limitations: Limitations include the use of a hypothetical scenario, the use of paid participants, and differences between the respondents and the typical patient facing an LVAD decision., Conclusions: In this sample, being shown the total cost increased the likelihood of accepting an expensive, high-risk treatment. The results question how well consumers understand the relationship between expensive treatments and the commons.

Multi-racial (mixed-race) people constitute a growing percentage of the United States (US) population. The study reported in this paper used residential segregation measures as a proxy for social distance, to examine whether segregation levels of multi-racial groups differ from those of mono-racial groups in the US in 2010. First, we find that all multi-racial groups considered in the study experience lower levels of segregation at county level than their mono-racial counterparts. However, black-whites and Hispanic-whites experience higher levels of segregation than other multi-racial groups. Second, we find region and minority composition of counties are associated significantly with segregation levels for multi-racial groups, but relative income is not.

Lung cancer is the most frequent cause of cancer-related deaths worldwide. Every year, 1·8 million people are diagnosed with lung cancer, and 1·6 million people die as a result of the disease. 5-year survival rates vary from 4-17% depending on stage and regional differences. In this Seminar, we discuss existing treatment for patients with lung cancer and the promise of precision medicine, with special emphasis on new targeted therapies. Some subgroups, eg-patients with poor performance status and elderly patients-are not specifically addressed, because these groups require special treatment considerations and no frameworks have been established in terms of new targeted therapies. We discuss prevention and early detection of lung cancer with an emphasis on lung cancer screening. Although we acknowledge the importance of smoking prevention and cessation, this is a large topic beyond the scope of this Seminar., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

For almost 20 years the physical nature of globally propagating waves in the solar corona (commonly called "EIT waves") has been controversial and subject to debate. Additional theories have been proposed over the years to explain observations that did not agree with the originally proposed fast-mode wave interpretation. However, the incompatibility of observations made using the Extreme-ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory with the fast-mode wave interpretation was challenged by differing viewpoints from the twin Solar Terrestrial Relations Observatory spacecraft and data with higher spatial and temporal resolution from the Solar Dynamics Observatory . In this article, we reexamine the theories proposed to explain EIT waves to identify measurable properties and behaviours that can be compared to current and future observations. Most of us conclude that the so-called EIT waves are best described as fast-mode large-amplitude waves or shocks that are initially driven by the impulsive expansion of an erupting coronal mass ejection in the low corona., Competing Interests: of Potential Conflicts of Interest The authors declare that they have no conflicts of interest.

The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients, recruited from 5 different institutions, and relevant control groups. We characterized the performance of the current best serological biomarker for pancreatic cancer, CA 19-9, using plasma samples from the reference set to provide a benchmark for future biomarker studies and to further our knowledge of CA 19-9 in early-stage pancreatic cancer and the control groups. CA 19-9 distinguished pancreatic cancers from the healthy and chronic pancreatitis groups with an average sensitivity and specificity of 70-74%, similar to previous studies using all stages of pancreatic cancer. Chronic pancreatitis patients did not show CA 19-9 elevations, but patients with benign biliary obstruction had elevations nearly as high as the cancer patients. We gained additional information about the biomarker by comparing two distinct assays. The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis. Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9.

Goals: To describe the short-term and long-term outcomes in 34 consecutive decompensated cirrhotic patients with symptomatic gallbladder disease undergoing transpapillary gallbladder stent (TGS) placement., Background: Endoscopic TGS placement is a minimally invasive means of treating symptomatic gallbladder disease in poor surgical candidates., Study: Between June 2005 and June 2011, 34 patients with cirrhosis and symptomatic gallbladder disease underwent attempted TGS placement., Results: Median patient age was 52 years, 56% were hospitalized, and 48% were listed for liver transplantation. The median model for end-stage liver disease (MELD) score was 15 (range, 6 to 40) and 88% were Child-Turcotte-Pugh class B/C. A double pigtailed stent was successfully placed in 94% of the patients. At 1-month follow-up, clinical improvement was noted in 82% of the treated subjects and the MELD scores in 14 of 22 (64%) evaluable subjects improved or stabilized. Actuarial transplant-free survival was 53% in the liver transplant candidates with a mean follow-up of 352 days, whereas survival was 44% in the 18 nontransplant candidates with a mean follow-up of 1.5 years. Periprocedural complications included pancreatitis in 5 patients, cholangitis in 3, and 1 patient with cystic duct perforation. In addition, 2 subjects had symptomatic bleeding from traumatic duodenal ulcerations 2 years after TGS placement that necessitated stent removal., Conclusions: Endoscopic TGS placement was technically feasible in 94% of decompensated cirrhotics and was associated with a relatively low rate of periprocedural (26%) and long-term complications (6%). Stabilization or improvement in clinical status and MELD scores was seen in the majority of treated patients.

The aim of this study was to assess the relationship between young children's sleep and maternal sleep from both a developmental and a cross-cultural perspective. Mothers of 10,085 young children completed the Brief Infant/Child Sleep Questionnaire and the Pittsburgh Sleep Quality Index. Overall, there were significant relationships between maternal and child sleep for bedtime, waketime, number of night wakings, and total nighttime sleep time across ages and cultures, although these relationships were stronger with younger children than preschool-aged children. Mothers report that their child's sleep pattern significantly impacts their sleep and daytime function, and they do not feel confident in managing their child's sleep pattern. Thus, interventions to improve children's sleep and develop good sleep habits, especially in early childhood, are likely to improve the quality of life of the whole family., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Establishment of a consistent bedtime routine (the activities that occur right before lights out) is often recommended as part of healthy sleep habits. However, no studies have investigated the dose-dependent association of a bedtime routine with sleep outcomes, especially in young children for whom they are particularly recommended. Thus, the aim of this study was to examine the associations of a consistent bedtime routine with sleep outcomes in young children (ages 0 through 5 y) in a large global sample and assess whether there is a dose-dependent relationship between the frequency of a bedtime routine both concurrently and retrospectively with sleep outcomes., Participants: Mothers of 10,085 children (Australia-New Zealand, Canada, China, Hong Kong, India, Japan, Korea, Malaysia, Philippines, Singapore, Thailand, United Kingdom, United States) completed the Brief Infant/Child Sleep Questionnaire., Results: A consistent bedtime routine was associated with better sleep outcomes, including earlier bedtimes, shorter sleep onset latency, reduced night wakings, and increased sleep duration. Decreased parent-perceived sleep problems and daytime behavior problems were also related to institution of a regular bedtime routine. Furthermore, there was a dose-dependent relationship, with better outcomes associated with increased "doses" of having a bedtime routine, both currently and retrospectively, and was found within both predominantly Asian and predominantly Caucasian cultural regions., Conclusions: These results indicate that having a regular nightly bedtime routine is associated with improved sleep in young children, and suggests that the more consistently a bedtime routine is instituted and the younger started the better., (© 2015 Associated Professional Sleep Societies, LLC.)

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology, including indications for endoscopic ultrasound guided fine-needle aspiration biopsy, techniques of the endoscopic retrograde cholangiopancreatography, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and postbiopsy management. All documents are based on the expertise of the authors, a review of literature, discussions of the draft document at several national and international meetings over an 18 month period and synthesis of online comments of the draft document on the Papanicolaou Society of Cytopathology website [www.papsociety.org]. This document presents the results of these discussions regarding the use of sampling techniques in the cytological diagnosis of biliary and pancreatic lesions. This document summarizes the current state of the art for techniques in acquiring cytology specimens from the biliary tree as well as solid and cystic lesions of the pancreas.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound guided fine-needle aspiration biopsy, techniques of the endoscopic retrograde cholangiopancreatography, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and postbiopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings over an 18-month period and synthesis of online comments of the draft document on the Papanicolaou Society of Cytopathology website [www.papsociety.org]. This document presents the results of these discussions regarding the use of ancillary testing in the cytological diagnosis of biliary and pancreatic lesions. This document summarizes the current state of the art for techniques in acquiring cytology specimens from the biliary tree as well as solid and cystic lesions of the pancreas., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: The aim of our study was to characterize cross-cultural sleep patterns and sleep problems in a large sample of preschool children ages 3-6years in multiple predominantly Asian (P-A) and predominantly Caucasian (P-C) countries/regions., Methods: Parents of 2590 preschool-aged children (P-A countries/regions: China, Hong Kong, India, Japan, Korea, Malaysia, Philippines, Singapore, Thailand; P-C countries: Australia-New Zealand, Canada, United Kingdom, United States) completed an Internet-based expanded version of the Brief Child Sleep Questionnaire (BCSQ)., Results: Overall, children from P-A countries had significantly later bedtimes, shorter nighttime sleep, and increased parental perception of sleep problems compared with those from P-C countries. Bedtimes varied from as early as 7:43pm in Australia and New Zealand to as late as 10:26pm in India, a span of almost 3h. There also were significant differences in daytime sleep with the majority of children in P-A countries continuing to nap, resulting in no differences in 24-h total sleep times (TST) across culture and minimal differences across specific countries. Bed sharing and room sharing are common in P-A countries, with no change across the preschool years. There also were a significant percentage of parents who perceived that their child had a sleep problem (15% in Korea to 44% in China)., Conclusions: Overall, our results indicate significant cross-cultural differences in sleep patterns, sleeping arrangements, and parent-reported sleep problems in preschool-aged children. Further studies are needed to understand the underlying bases for these differences and especially for contributors to parents' perceptions of sleep problems., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: To characterize cross-cultural sleep patterns and sleep problems in a large sample of mothers of children (ages birth to 6 years) in multiple predominantly Asian and predominantly Caucasian countries., Methods: Mothers of 10,085 young children (predominantly Asian countries/regions: China, Hong Kong, India, Korea, Japan, Malaysia, Philippines, Singapore, Thailand; predominantly Caucasian countries: Australia, Canada, New Zealand, United Kingdom, United States) completed an internet-based expanded version of the Pittsburgh Sleep Quality Index., Results: Mothers in predominantly Asian countries/regions had later bedtimes, decreased number and duration of night wakings, more nighttime sleep, and more total sleep than mothers from predominantly Caucasian countries, P < 0.001. More than half (54.7%) of mothers reported having poor sleep, ranging from 50.9% of mothers in Malaysia to 77.8% of mothers in Japan. Sleep disturbance symptoms were quite common, especially symptoms related to insomnia, and were more likely to be reported by mothers in predominantly Caucasian countries. However, psychosocial factors, including having children of a younger age, being unemployed, and having a lower education level were the best predictors of poor sleep, whereas culture was not a significant predictor., Conclusions: Overall, mothers in predominantly Asian countries/regions reported later bedtimes but sleeping better and longer than mothers from predominantly Caucasian countries, which is dissimilar to cross-cultural findings of young children. Psychosocial factors were found to be the best predictors of poor sleep, irrespective of culture. Further studies are needed to understand the impact of these findings.

Specific protein glycoforms may be uniquely informative about the pathological state of a cyst and may serve as accurate biomarkers. Here we tested that hypothesis using antibody-lectin sandwich arrays in broad screens of protein glycoforms and in targeted studies of candidate markers. We profiled 16 different glycoforms of proteins captured by 72 different antibodies in cyst fluid from mucinous and nonmucinous cysts (n = 22), and we then tested a three-marker panel in 22 addition samples and 22 blinded samples. Glycan alterations were not widespread among the proteins and were mainly confined to MUC5AC and endorepellin. Specific glycoforms of these proteins, defined by reactivity with wheat germ agglutinin and a blood group H antibody, were significantly elevated in mucinous cysts, whereas the core protein levels were not significantly elevated. A three-marker panel based on these glycoforms distinguished mucinous from nonmucinous cysts with 93% accuracy (89% sensitivity, 100% specificity) in a prevalidation sample set (n = 44) and with 91% accuracy (87% sensitivity, 100% specificity) in independent, blinded samples (n = 22). Targeted lectin measurements and mass spectrometry analyses indicated that the higher wheat germ agglutinin and blood group H reactivity was due to oligosaccharides terminating in GlcNAc or N-acetyl-lactosamine with occasional α1,2-linked fucose. The results show that MUC5AC and endorepellin glycoforms may be highly specific and sensitive biomarkers for the differentiation of mucinous from nonmucinous pancreatic cysts.

Significant efforts are underway to develop new biomarkers from pancreatic cyst fluid. Previous research has made use of cyst fluid collected from surgically removed cysts, but the clinical implementation of biomarkers would use cyst fluid collected by endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA). The purpose of this study was to investigate the clinical applicability of cyst fluid research obtained using surgical specimens. Matched pairs of operating-room collected (OR) and EUS-FNA samples from 12 patients were evaluated for the levels of three previously described biomarkers, CA 19-9, CEA, and glycan levels detected by wheat germ agglutinin on MUC5AC (MUC5AC-WGA). CA 19-9 and MUC5AC-WGA correlated well between the sample types, although CEA was more variable between the sample types for certain patients. The variability was not due to the time delay between EUS-FNA and OR collection or differences in total protein concentrations but may be caused by contamination of the cyst fluid with blood proteins. The classification of each patient based on thresholds for each marker was perfectly consistent between sample types for CA 19-9 and MUC5AC-WGA and mostly consistent for CEA. Therefore, results obtained using OR-collected pancreatic cyst fluid samples should reliably transfer to the clinical setting using EUS-FNA samples.

The use of videogames for non-entertainment purposes has interested educational and behavioral researchers for decades. Recent technology advances have increased the interactivity of games while maintaining reasonable costs, leading rehabilitation therapists to investigate gaming consoles as an adjunct to traditional techniques. Obstacles to large-scale trials exist, but the transformative potential of gaming consoles should motivate developers and healthcare professionals to find solutions.

Objective: The purpose of this exploratory case study is to describe differences in rehabilitation outcomes for a 47-year-old male with bilateral lower extremity burns when using conventional therapy techniques alone versus such techniques in combination with Nintendo(®) Wii™ (Nintendo of America, Inc., Redmond, WA) videogames., Materials and Methods: The patient received three series of rehabilitation therapy over 2 weeks. During the second series, the Wii was introduced for a portion of the otherwise conventional therapy. Under standardized conditions and upon completion of each series, the Limits of Stability test with a SMART Balance Master(®) (NeuroCom(®), Clackamas, OR) was used to measure reaction time (RT), maximum excursion (MXE), endpoint excursion (EPE), movement velocity, and directional control. The Timed Up and Go (TUG) test for functional mobility and a questionnaire assessing level of motivation and interest were administered at the end of each day; these results formed mean scores for each series., Results: The patient performed better on RT and MXE during the series that combined conventional therapy with the Wii than during the two series using conventional therapy alone. Improvement on EPE was greater for combined therapy than for conventional therapy alone and continued to improve after combined therapy. The patient completed the TUG test faster during the combined Wii series. Additionally, the patient reported increased motivation and interest levels for the series using combined therapy., Conclusions: The Wii may be a feasible and valuable adjunct to traditional therapy. Improvements during the series with Wii were demonstrated for areas of balance and functional mobility. Trends toward improvement in motivation and interest with the Wii suggest its use may elicit increased patient engagement during burn rehabilitation.

Background: The management of incidental pancreatic cysts is not well established because of lack of information on their natural history. International Consensus Guidelines advocate observation of asymptomatic patients with small lesions, despite limited data to support this approach., Methods: To characterize clinical outcomes in a cohort of asymptomatic patients with incidental pancreatic cysts who underwent endoscopic ultrasound (EUS) evaluation+/-fine needle aspiration (FNA)., Results: Overall, 317 patients underwent EUS for evaluation of pancreatic cysts from 1995 to 2005. A total of 97/317 (31%) had asymptomatic, incidentally discovered pancreatic cysts; of 97 asymptomatic patients, 93 were contacted. Of these patients, 71/93 (76%) had lesions<3 cm and benign EUS features. All were followed without operative therapy. The mean follow-up was 44 months (range, 6-123). A total of 69/71 (97%) were alive and free of symptoms of pancreatic disease; 2 patients died of unrelated causes. Among these 71 patients with lesions<3 cm, FNA was performed in 33 patients and cytology was negative for malignant cells in all. Overall, 45/71 patients had either follow-up cross-sectional imaging or EUS. All of them had stable lesions. Surveillance studies were performed with a mean follow-up of 28 months (range, 4-120). The 22 patients with lesions >3 cm and/or concerning EUS features underwent resection. Pathologic analysis revealed that 2/22 patients had adenocarcinoma and that 60% had premalignant lesions., Conclusion: Endoscopic ultrasound is helpful in evaluation of patients with small incidental pancreatic cystic lesions. Asymptomatic cysts with benign radiographic and/or endosonographic features may safely be followed clinically and with serial imaging., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

The generation and sensation of mechanical force plays a role in many dynamic biological processes, including touch sensation. This paper presents a two-axis micro strain gauge force sensor constructed from multiple layers of SU-8 and metal on quartz substrates. The sensor was designed to meet requirements for measuring tactile sensitivity and interaction forces exerted during locomotion by small organisms such as the nematode Caenorhabditis elegans. The device is transparent and compatible with light microscopes, allowing behavioral experiments to be combined with quantitative force measurements. For the first time, we have characterized the scale of interaction forces generated in wild-type C. elegans in probing and responding to their environment during locomotion. The device features sub-microN force resolution from 1 Hz to 1 kHz, >25 microN range, kHz acquisition rates and biocompatibility.

We describe a technique that uses IntraLase-created zigzag incisions for deep anterior lamellar keratoplasty. In this technique, the laser creates a precise incision that extends to within 70 microm of the recipient Descemet membrane. The deep incision minimizes air escape into the peripheral cornea during big-bubble formation. In cases that require hand dissection, the deep incision provides a reference for gauging the dissection depth. The angled incision edge facilitates final stromal excision with scissors. Compared with standard vertical incisions, the zigzag incision provides an interlocking wound configuration and facilitates matching the donor and recipient anterior surfaces.

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability, various ibuprofen-loaded solid dispersions were prepared with water, HPMC and poloxamer. The effect of HPMC and poloxamer on aqueous solubility of ibuprofen was investigated. The dissolution and bioavailability of solid dispersion in rats were then evaluated compared to ibuprofen powder. When the amount of carrier increased with a decreased in HPMC/poloxamer ratio, the aqueous solubility of ibuprofen was elevated. The solid dispersion composed of ibuprofen/HPMC/poloxamer at the weight ratio of 10:3:2 improved the drug solubility approximately 4 fold. It gave significantly higher initial plasma concentration, AUC and Cmax of drug than did ibuprofen powder in rats. The solid dispersion improved the bioavailability of drug about 4-fold compared to ibuprofen powder. Thus, this ibuprofen-loaded solid dispersion with water, HPMC and poloxamer was a more effective oral dosage form for improving the bioavailability of poor water-soluble ibuprofen.

EEMR systems have become an integral part of the daily operation of many endoscopy units. Systems have evolved from simple endoscopy report generators to sophisticated endoscopy unit managers. Newer features of these systems may improve patient care and enhance endoscopy unit efficiency and productivity, but further studies are needed. The needs of the endoscopy unit, the staff, and the endoscopist should drive the selection process when choosing an EEMR. Extensive testing of the EEMR system capabilities, especially the ability to interface with existing software programs, is essential before purchasing an EEMR system.

NBI and MBI may enhance the diagnosis and characterization of mucosal lesions in the GI tract, particularly as adjunctive techniques to magnification endoscopy. Standardization of image characterization, further image-to-pathology correlation and validation, and the impact of these technologies on patient outcomes are necessary before endorsing the use of NBI and MBI in the routine practice of GI endoscopy.