Health care transition: How adolescent survival, interruption of care, and continuity of care can inform health care transition programs for young adults with sickle cell disease

Sickle cell disease (SCD) is a genetic disorder that causes acute and chronic complications throughout the lifespan with morbidity and mortality increasing in young adulthood. Health care transition is important to promote continuous care throughout young adulthood. The aim of this dissertation was to inform transition programs for young adults with SCD by assessing survival among adolescents and young adults (AYA), analyzing an interruption period between pediatric and adult care, and evaluating a transition program for its effect on retention in adult care. The objective was to better inform health care transition protocols to improve overall wellness in young adults.In the first aim, the mortality of AYA with SCD born in West Tennessee from 19932019 was assessed. The probability of surviving into adulthood (i.e., greater than 18 years) was greater than 0.97. In the second aim, the effect of an interruption of care between pediatric and adult care was evaluated for its effect on health care utilization in adult care. Two sites were included in this analysis: Methodist Comprehensive Sickle Cell Center (Methodist) and Duke Sickle Cell Center (Duke). Among patients at Methodist, those with a longer interruption experienced increased rates of acute healthcare encounters in the first two years of adult care compared to those with a shorter interruption period; however, the opposite association was observed among patients at Duke. In the third aim, a healthcare transition program focused on continuity of care was evaluated for its effect on adult care retention. Those who participated in the transition program had 1.94 times the odds of being retained in adult care after 24 months compared to those who did not participate in the program (95%CI: 1.01, 3.70).As nearly all SCD patients are now surviving into adulthood, it is important to have protocols in place that support a successful transition to adult care. Two measures for successful transition might include a reduced interruption period between pediatric and adult care and improved retention in adult care. These factors indicate that patients receive consistent care throughout young adulthood, which might maintain or improve health

The morbidity and mortality following a diagnosis of peripheral arterial disease: Long-term follow-up of a large database

BACKGROUND: Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need. METHODS: Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations. RESULTS: Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events. CONCLUSION: A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased

The Role of Uncertainty, Worry, and Control in Well-Being: Evidence From the COVID-19 Outbreak and Pandemic in U.S. and China

Uncertainty about the future often leads to worries about what the future will bring, which can have negative consequences for health and well-being. However, if worry can act as a motivator to promote efforts to prevent undesirable future outcomes, those negative consequences of worry may be mitigated. In this article, we apply a novel model of uncertainty, worry, and perceived control to predict psychological and physical well-being among four samples collected in China (Study 1; during the early COVID-19 outbreak in China) and the United States (Studies 2–4, during 4 weeks in May 2020, 4 weeks in November 2020, and crosssectionally between April and November 2020). Grounded in the feeling-is-for-doing approach to emotions, we hypothesized (and found) that uncertainty about one’s COVID-19 risk would predict greater worry about the virus and one’s risk of contracting it, and that greater worry would in turn predict poorer well-being. We also hypothesized, and found somewhat mixed evidence, that perceptions of control over 1’s COVID-19 risk moderated the relationship between worry and well-being such that worry was related to diminished well-being when people felt they lacked control over their risk for contracting the virus. This study is one of the first to demonstrate an indirect path from uncertainty to well-being via worry and to demonstrate the role of control in moderating whether uncertainty and worry manifest in poor well-being

Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator

A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible “wait anaphase” signal to the vicinity of the spindle

The Lantern, 2018-2019

The Treasure Buried in Ponce de Leon\u27s Fountain of Youth Archaeological Park • High Cards on the Low River • Sestina of a Vagina left in the microwave too long • Keeps on Tripping • The Auction • Nuclear Meltdown on Seedship C5B.6 • Cock Fight • An Interview with God • Minimum Wage • Star-Crossed Lovers • Romeo Echo Alpha • PM Entertainment, or Action Beats • The Gospel of Aggregates • Hel Hath no Fury • Crossing the Line • Mango de la hora • Stress Judgment • Perception (Part 2) • Rain Falling Up • Church: the Italian Market • Landscape with the Fall of Hillary • Forced to Ponder • Morally Upright • Adulthood • Migration in Tandem • Hospital Bed • To Autumn (After Keats) • Selected Tweets • Hidden Moments • Mysteries are Wrong • Jukebox Memory • Flames • A Simple Moment • The Farmhouse • Lord, Let Me Catch a Fish • Sun-Kissed • Five • The Thing • The Moons of Mars • You are Weak • You Kept Me Quiet • Offer Her a Seat • Sacraments • Cigar • The Lake George Mafia • Houses • Spun Out • To Romanticize the Restless • 12/25/17 • skylight • lanternflies • Goo Girls • Toi Le • Lovers, Thinkers, Rebels • home in paradise • Irreverence • The Fisherman • St Mary Episcopal Cathedral, Edinburgh • Mirror 2https://digitalcommons.ursinus.edu/lantern/1187/thumbnail.jp

The Gravity Collective: A Search for the Electromagnetic Counterpart to the Neutron Star-Black Hole Merger GW190814

We present optical follow-up imaging obtained with the Katzman Automatic Imaging Telescope, Las Cumbres Observatory Global Telescope Network, Nickel Telescope, Swope Telescope, and Thacher Telescope of the LIGO/Virgo gravitational wave (GW) signal from the neutron star-black hole (NSBH) merger GW190814. We searched the GW190814 localization region (19 deg$^{2}$ for the 90th percentile best localization), covering a total of 51 deg$^{2}$ and 94.6% of the two-dimensional localization region. Analyzing the properties of 189 transients that we consider as candidate counterparts to the NSBH merger, including their localizations, discovery times from merger, optical spectra, likely host-galaxy redshifts, and photometric evolution, we conclude that none of these objects are likely to be associated with GW190814. Based on this finding, we consider the likely optical properties of an electromagnetic counterpart to GW190814, including possible kilonovae and short gamma-ray burst afterglows. Using the joint limits from our follow-up imaging, we conclude that a counterpart with an $r$-band decline rate of 0.68 mag day$^{-1}$, similar to the kilonova AT 2017gfo, could peak at an absolute magnitude of at most $-17.8$ mag (50% confidence). Our data are not constraining for ''red'' kilonovae and rule out ''blue'' kilonovae with $M>0.5 M_{\odot}$ (30% confidence). We strongly rule out all known types of short gamma-ray burst afterglows with viewing angles $<$17$^{\circ}$ assuming an initial jet opening angle of $\sim$$5.2^{\circ}$ and explosion energies and circumburst densities similar to afterglows explored in the literature. Finally, we explore the possibility that GW190814 merged in the disk of an active galactic nucleus, of which we find four in the localization region, but we do not find any candidate counterparts among these sources.Comment: 86 pages, 9 figure

Meta-Analysis of the Alzheimer\u27s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.

We present a consensus atlas of the human brain transcriptome in Alzheimer\u27s disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington\u27s disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead