Influential research on the negative effects of living in a disadvantaged neighborhood assumes that its residents are socially isolated from nonpoor or “mainstream” neighborhoods, but the extent and ...nature of such isolation remain in question. We develop a test of neighborhood isolation that improves on static measures derived from commonly used census reports by leveraging fine-grained dynamic data on the everyday movement of residents in America’s 50 largest cities. We analyze 650 million geocoded Twitter messages to estimate the home locations and travel patterns of almost 400,000 residents over 18 mo. We find surprisingly high consistency across neighborhoods of different race and income characteristics in the average travel distance (radius) and number of neighborhoods traveled to (spread) in the metropolitan region; however, we uncover notable differences in the composition of the neighborhoods visited. Residents of primarily black and Hispanic neighborhoods—whether poor or not—are far less exposed to either nonpoor or white middle-class neighborhoods than residents of primarily white neighborhoods. These large racial differences are notable given recent declines in segregation and the increasing diversity of American cities. We also find that white poor neighborhoods are substantially isolated from nonpoor white neighborhoods. The results suggest that even though residents of disadvantaged neighborhoods travel far and wide, their relative isolation and segregation persist.
BACKGROUND Polycystic ovary syndrome (PCOS) is considered to be the most common endocrine disorder in women of reproductive age, yet debate over appropriate diagnostic criteria and design limitations ...with sampling methodology have left some doubt as to the actual prevalence in the community. The objective of this study was to create a representative prevalence estimate of PCOS in the community under the National Institutes of Health (NIH) criteria and the more recent Rotterdam consensus criteria and Androgen Excess Society (AES) criteria. METHODS A retrospective birth cohort study was carried out in which 728 women born during 1973–1975 in a single maternity hospital were traced and interviewed in adulthood (age = 27–34 year; n = 728). Symptoms of PCOS (hyperandrogenism, menstrual dysfunction and polycystic ovaries) were identified by examination and the presence of polycystic ovaries in those that did not consent to the ultrasound were imputed. RESULTS The estimated prevalence of PCOS in this birth cohort using the NIH criteria was 8.7 ± 2.0% (with no need for imputation). Under the Rotterdam criteria, the prevalence was 11.9 ± 2.4% which increased to 17.8 ± 2.8% when imputed data were included. Under the AES recommendations, PCOS prevalence was 10.2 ± 2.2%, and 12.0 ± 2.4% with the imputed data. Of the women with PCOS, 68–69% did not have a pre-existing diagnosis. CONCLUSIONS The Rotterdam and AES prevalence estimates were up to twice that obtained with the NIH criteria in this, as well other prevalence studies. In addition, this study also draws attention to the issue of many women with PCOS in the community remaining undiagnosed.
In this trial involving patients with relapsing–remitting multiple sclerosis, BG-12 (dimethyl fumarate) reduced the annualized relapse rate and number of MRI lesions but not disability progression. ...BG-12 was associated with flushing, diarrhea, and decreased lymphocyte counts.
Multiple sclerosis is a chronic demyelinating and neurodegenerative disease of the central nervous system, which is commonly treated with parenteral agents (interferon beta and glatiramer acetate). Oxidative stress and proinflammatory stimuli are important pathologic factors in multiple sclerosis.
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Experimental data suggest that BG-12, an oral formulation of dimethyl fumarate, has antiinflammatory and cytoprotective properties that are mediated through activation of the nuclear factor (erythroid-derived 2)–like 2 transcriptional pathway, among others.
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Here, we report the results of the Comparator and an Oral Fumarate in Relapsing–Remitting Multiple Sclerosis (CONFIRM) trial, a randomized, multicenter, double-blind, 2-year study evaluating the efficacy and . . .
The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to stable genetic events, epigenetic states are reversible and sensitive to ...the microenvironment, prompting the question whether epigenetic information can similarly be used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes transcriptionally upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution.
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•Dramatic loss of DNA methylation during the progression of low-grade gliomas to GBM•Phenotypic convergence of genomic and epigenomic evolution on cell cycle defects•Phyloepigenetics recapitulates the phylogenetics of tumor evolution•Robust model of gliomagenesis from tumor initiation through malignant progression
Mazor et al. show that spatial and temporal patterns of DNA methylation and somatic mutations during the progression of low-grade gliomas to high-grade tumors produce remarkably similar evolutionary histories and both converge to deregulate the cell cycle.
Intensification of the global hydrological cycle, ranging from larger individual precipitation events to more extreme multiyear droughts, has the potential to cause widespread alterations in ...ecosystem structure and function. With evidence that the incidence of extreme precipitation years (defined statistically from historical precipitation records) is increasing, there is a clear need to identify ecosystems that are most vulnerable to these changes and understand why some ecosystems are more sensitive to extremes than others. To date, opportunistic studies of naturally occurring extreme precipitation years, combined with results from a relatively small number of experiments, have provided limited mechanistic understanding of differences in ecosystem sensitivity, suggesting that new approaches are needed. Coordinated distributed experiments (CDEs) arrayed across multiple ecosystem types and focused on water can enhance our understanding of differential ecosystem sensitivity to precipitation extremes, but there are many design challenges to overcome (e.g., cost, comparability, standardization). Here, we evaluate contemporary experimental approaches for manipulating precipitation under field conditions to inform the design of ‘Drought‐Net’, a relatively low‐cost CDE that simulates extreme precipitation years. A common method for imposing both dry and wet years is to alter each ambient precipitation event. We endorse this approach for imposing extreme precipitation years because it simultaneously alters other precipitation characteristics (i.e., event size) consistent with natural precipitation patterns. However, we do not advocate applying identical treatment levels at all sites – a common approach to standardization in CDEs. This is because precipitation variability varies >fivefold globally resulting in a wide range of ecosystem‐specific thresholds for defining extreme precipitation years. For CDEs focused on precipitation extremes, treatments should be based on each site's past climatic characteristics. This approach, though not often used by ecologists, allows ecological responses to be directly compared across disparate ecosystems and climates, facilitating process‐level understanding of ecosystem sensitivity to precipitation extremes.
Triple Disadvantage Levy, Brian L.; Phillips, Nolan E.; Sampson, Robert J.
American sociological review,
12/2020, Letnik:
85, Številka:
6
Journal Article
Recenzirano
Odprti dostop
This article develops and assesses the concept of triple neighborhood disadvantage. We argue that a neighborhood’s well-being depends not only on its own socioeconomic conditions but also on the ...conditions of neighborhoods its residents visit and are visited by, connections that form through networks of everyday urban mobility. We construct measures of mobilitybased disadvantage using geocoded patterns of movement estimated from hundreds of millions of tweets sent by nearly 400,000 Twitter users over 18 months. Analyzing nearly 32,000 neighborhoods and 9,700 homicides in 37 of the largest U. S. cities, we show that neighborhood triple disadvantage independently predicts homicides, adjusting for traditional neighborhood correlates of violence, spatial proximity to disadvantage, prior homicides, and city fixed effects. Not only is triple disadvantage a stronger predictor than traditional measures, it accounts for a sizable portion of the association between residential neighborhood disadvantage and homicides. In turn, potential mechanisms such as neighborhood drug activity, interpersonal friction, and gun crime prevalence account for much of the association between triple disadvantage and homicides. These findings implicate structural mobility patterns as an important source of triple (dis) advantage for neighborhoods and have implications for a broad range of phenomena beyond crime, including community capacity, gentrification, transmission in a pandemic, and racial inequality.
Soft robotics is an emerging technology that has shown considerable promise in deep-sea marine biological applications. It is particularly useful in facilitating delicate interactions with fragile ...marine organisms. This study describes the shipboard design, 3D printing and integration of custom soft robotic manipulators for investigating and interacting with deep-sea organisms. Soft robotics manipulators were tested down to 2224m via a Remotely-Operated Vehicle (ROV) in the Phoenix Islands Protected Area (PIPA) and facilitated the study of a diverse suite of soft-bodied and fragile marine life. Instantaneous feedback from the ROV pilots and biologists allowed for rapid re-design, such as adding "fingernails", and re-fabrication of soft manipulators at sea. These were then used to successfully grasp fragile deep-sea animals, such as goniasterids and holothurians, which have historically been difficult to collect undamaged via rigid mechanical arms and suction samplers. As scientific expeditions to remote parts of the world are costly and lengthy to plan, on-the-fly soft robot actuator printing offers a real-time solution to better understand and interact with delicate deep-sea environments, soft-bodied, brittle, and otherwise fragile organisms. This also offers a less invasive means of interacting with slow-growing deep marine organisms, some of which can be up to 18,000 years old.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic ...features of 108 subjects. Methods Between September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US. Results Most subjects (88/108, 81%) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks. Conclusions Acute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.
The acute hepatic porphyrias are a group of four inherited disorders, each resulting from a deficiency in the activity of a specific enzyme in the heme biosynthetic pathway. These disorders present ...clinically with acute neurovisceral symptoms which may be sporadic or recurrent and, when severe, can be life‐threatening. The diagnosis is often missed or delayed as the clinical features resemble other more common medical conditions. There are four major subgroups: symptomatic patients with sporadic attacks (<4 attacks/year) or recurrent acute attacks (≥4 attacks/year), asymptomatic high porphyrin precursor excretors, and asymptomatic latent patients without symptoms or porphyrin precursor elevations. Given their clinical heterogeneity and potential for significant morbidity with suboptimal management, comprehensive clinical guidelines for initial evaluation, follow‐up, and long‐term management are needed, particularly because no guidelines exist for monitoring disease progression or response to treatment. The Porphyrias Consortium of the National Institutes of Health's Rare Diseases Clinical Research Network, which consists of expert centers in the clinical management of these disorders, has formulated these recommendations. These recommendations are based on the literature, ongoing natural history studies, and extensive clinical experience. Initial assessments should include diagnostic confirmation by biochemical testing, subsequent genetic testing to determine the specific acute hepatic porphyria, and a complete medical history and physical examination. Newly diagnosed patients should be counseled about avoiding known precipitating factors. The frequency of follow‐up depends on the clinical subgroup, with close monitoring of patients with recurrent attacks who may require treatment modifications as well as those with clinical complications. Comprehensive care should include subspecialist referrals when needed. Annual assessments include biochemical testing and monitoring for long‐term complications. These guidelines provide a framework for monitoring patients with acute hepatic porphyrias to ensure optimal outcomes. (Hepatology 2017;66:1314‐1322)
The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled ...cohort of patients referred to oncodermatology clinics.
A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed.
A total of 285 patients (median age, 65 years range, 17 to 89 years) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype (
= .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74
0.71;
< .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1;
= .043).
Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.
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