Eastern US Dryline Climatology and Synoptic-Scale Environment

The dryline is an important focal point for convection initiation, and the subject of many studies. While the most common location for drylines is the southern Great Plains, dryline passages and subsequent severe weather outbreaks have been documented in the Mississippi River Valley and into portions of the southeastern United States. Little is known about these “eastern” drylines or how often they occur, as no climatologies or detailed studies have been published on them. This thesis presents a fifteen-year climatology (1999-2013) of eastern drylines in an effort to identify how often and where they typically occur, and to identify synoptic patterns that result in drylines moving atypically far eastward. A computer algorithm was created that objectively identifies drylines from the North American Regional Reanalysis (NARR) dataset. Dryline events were divided into regional categories once the climatology of eastern drylines was compiled, and mean and anomaly synoptic composites were created of different variables for each regional category. Thirty-nine eastern drylines were identified through the study. These events occurred under synoptically-active conditions with amplified upper-air patterns, 500 mb shortwave troughs to the west or northwest of the drylines, and strong surface cyclones to the north. Advisor: Matthew Van Den Broek

Gene rearrangements in bone marrow cells of patients with acute myelogenous leukemia

At diagnosis, clonal gene rearrangement probes {[}retinoic acid receptor (RAR)-alpha, major breakpoint cluster region (M-bcr), immunoglobulin (Ig)-JH, T cell receptor (TcR)-beta, myeloid lymphoid leukemia (MLL) or cytokine genes (GM-CSF, G-CSF, IL-3)] were detected in bone marrow samples from 71 of 153 patients with acute myelogenous leukemia (AML) (46%): in 41 patients with primary AML (pAML) (58%) and in 30 patients with secondary AML (42%). In all cases with promyelocytic leukemia (AML-M3) RAR-alpha gene rearrangements were detected (n = 9). Gene rearrangements in the Ig-JH or the TcR-beta or GM-CSF or IL-3 or MLL gene were detected in 12, 10, 16 and 12% of the cases, respectively, whereas only few cases showed gene rearrangements in the M-bcr (6%) or G-CSF gene (3%). Survival of pAML patients with TcR-beta gene rearrangements was longer and survival of pAML patients with IL-3 or GM-CSF gene rearrangement was shorter than in patients without those rearrangements. No worse survival outcome was seen in patients with rearrangements in the MLL, Ig-JH or M-bcr gene. In remission of AML (CR), clonal gene rearrangements were detected in 23 of 48 cases (48%) if samples were taken once in CR, in 23 of 26 cases (88%) if samples were taken twice in CR and in 23 of 23 cases (100%) if samples were studied three times in CR. All cases with gene rearrangements at diagnosis showed the same kind of rearrangement at relapse of the disease (n = 12). Our data show that (1) populations with clonal gene rearrangements can be regularly detected at diagnosis, in CR and at relapse of AML. (2) Certain gene rearrangements that are detectable at diagnosis have a prognostic significance for the patients' outcome. Our results point out the significance of gene rearrangement analyses at diagnosis of AML in order to identify `poor risk' patients - independently of the karyotype. Moreover, the persistence of clonal cells in the further course of AML can be studied by gene rearrangement analysis. Copyright (C) 2000 S. Karger AG, Basel

Brain Development, Social Context and Justice Policy

Justice policy reform in the past decade has been driven by research evidence indicating that brain development is ongoing through adolescence, and that neurological and psychological immaturity likely contributes in important ways to teenagers’ involvement in crime. But despite the power of this trend, skeptics point out that many (perhaps most) adolescents do not engage in serious criminal activity; on this basis, critics argue that normative biological and psychological factors associated with adolescence are unlikely to play the important role in juvenile offending that is posited by supporters of the reform trend. This Article explains that features associated with biological and psychological immaturity alone do not lead teenagers to engage in illegal conduct. Instead the decision to offend, like much behavior in adolescence, is the product of dynamic interaction between the still-maturing individual and her social context. The Article probes the mechanisms through which particular tendencies and traits linked to adolescent brain development interact with environmental influences to encourage antisocial or prosocial behavior. Brain development in adolescence is associated with reward-seeking behavior and limited future orientation. Further, as compared to adults, adolescents are particularly sensitive to external stimuli (particularly peers), easily aroused emotionally, and less able to regulate strong emotions. The Article shows how these tendencies may be manifested in different teenagers in different ways, depending on many factors in the social context. By analyzing this intricate relationship, the Article clarifies how social environment influences adolescent choices in ways that incline or deter involvement in crime and in other risky behavior. Thus a teenager who lives in a high-crime neighborhood with many antisocial peers is more likely to get involved in criminal activity than one in a neighborhood with few such peers, even though the two may not differ in their tendencies and propensities for risk-taking. The Article’s interactive model offers powerful support for laws and policies that subject adolescent offenders to more lenient sanctions than adults receive and that tailor dispositions to juveniles’ developmental needs. Our examination confirms and illuminates the Supreme Court’s conclusion that juvenile offenders differ in important ways from adult counterparts; juveniles deserve less punishment because their offenses are driven by biological and psychological immaturity, and also because, as legal minors, they cannot extricate themselves from social contexts (neighborhoods, schools and families) that contribute to involvement in crime. The model also confirms that correctional facilities and programs, which constitute young offenders’ social settings, can support healthy development to adulthood in individual offenders, or affect their lives in harmful ways

Profiling Sterols in Cerebrotendinous Xanthomatosis: Utility of Girard Derivatization and High Resolution Exact Mass LC-ESI-MSn Analysis

In this study we profile free 3-oxo sterols present in plasma from patients affected with the neurodegenerative disorder of sterol and bile acid metabolism cerebrotendinous xanthomatosis (CTX), utilizing a combination of charge-tagging and LC-ESI-MSn performed with an LTQ-Orbitrap Discovery instrument. In addition, we profile sterols in plasma from 24-month-old cyp27A1 gene knockout mice lacking the enzyme defective in CTX. Charge-tagging was accomplished by reaction with cationic Girard\u27s P (GP) reagent 1-(carboxymethyl) pyridinium chloride hydrazide, an approach uniquely suited to studying the 3-oxo sterols that accumulate in CTX, as Girard\u27s reagent reacts with the sterol oxo moiety to form charged hydrazone derivatives. The ability to selectively generate GP-tagged 3-oxo-4-ene and 3-oxo-5(H) saturated plasma sterols enabled ESI-MSn analysis of these sterols in the presence of a large excess (3 orders of magnitude) of cholesterol. Often cholesterol detected in biological samples makes it challenging to quantify minor sterols, with cholesterol frequently removed prior to analysis. We derivatized plasma (10μl) without SPE removal of cholesterol to ensure detection of all sterols present in plasma. We were able to measure 4-cholesten-3-one in plasma from untreated CTX patients (1207±302ng/ml, mean±SD, n=4), as well as other intermediates in a proposed pathway to 5α-cholestanol. In addition, a number of bile acid precursors were identified in plasma using this technique. GP-tagged sterols were identified utilizing high resolution exact mass spectra (±5ppm), as well as MS2 ([M]+→) spectra that possessed characteristic neutral loss of 79Da (pyridine) fragment ions, and MS3 ([M]+→[M-79]+→) spectra that provided additional structurally informative fragment ions. © 2010 Elsevier B.V

Lung Cancer in a U.S. Population with Low to Moderate Arsenic Exposure

BackgroundLittle is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 microg/L) in drinking water.ObjectivesWe examined associations between arsenic and lung cancer.MethodsA population-based case-control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled-plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level).ResultsArsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00-7.57] for toenail arsenic concentration > or = 0.114 microg/g, versus < 0.05 microg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39-5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic > or = 0.05 microg/g (OR = 4.78; 95% CI, 1.87-12.2) than among individuals with low toenail arsenic and no history of lung disease.ConclusionAlthough this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies

Environmental And Occupational Exposures And Amyotrophic Lateral Sclerosis In New England

Background: Recent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS). Objective: To evaluate environmental and occupational exposures as risk factors for sporadic ALS. Methods: We performed a case control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodegenerative illness. Results: Self-reported job-or hobby-related exposure to one or more chemicals, such as pesticides, solvents, or heavy metals, increased the risk of ALS (adjusted OR 2.51; 95% CI 1.64-3.89). Industries with a higher toxicant exposure potential (construction, manufacturing, mechanical, military, or painting) were associated with an elevated occupational risk (adjusted OR 3.95; 95% CI 2.04-8.30). We also identified increases in the risk of ALS associated with frequent participation in water sports, particularly waterskiing (adjusted OR 3.89; 95% C11.97-8.44). Occupation and waterskiing both retained independent statistical significance in a composite model containing age, gender, and smoking status. Conclusions: Our study contributes to a growing body of literature implicating occupational-and hobby-related toxicant exposures in ALS etiology. These epidemiologic study results also provide motivation for future evaluation of water-body-related risk factors. (C) 2017 S. Karger AG, Base

ExMed: An AI Tool for Experimenting Explainable AI Techniques on Medical Data Analytics

Local Interpretable Model-Agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP) algorithms have been widely discussed by the Explainable AI (XAI) community but their application to wider domains are rare, potentially due to the lack of easy-to-use tools built around these methods. In this paper, we present ExMed, a tool that enables XAI data analytics for domain experts without requiring explicit programming skills. It supports data analytics with multiple feature attribution algorithms for explaining machine learning classifications and regressions. We illustrate its domain of applications on two real world medical case studies, with the first one analysing COVID-19 control measure effectiveness and the second one estimating lung cancer patient life expectancy from the artificial Simulacrum health dataset. We conclude that ExMed can provide researchers and domain experts with a tool that both concatenates flexibility and transferability of medical sub-domains and reveal deep insights from data

Pancreatitis and pancreatic cancer in two large pooled case–control studies

The association between duration of pancreatitis and pancreatic cancer has not been well characterized in large population-based studies. We conducted detailed analyses to determine the association between pancreatitis onset and pancreatic cancer risk. Data from two case–control studies of pancreatic cancer (n = 4515) in the San Francisco Bay Area and the M.D. Anderson Cancer Center were pooled for analysis (1,663 cases, 2,852 frequency-matched controls). Adjusted odds ratios (OR) were estimated using a random-effects model. In the pooled multivariable model, history of pancreatitis was associated with a 7.2-fold increased risk estimate for pancreatic cancer [95% confidence interval (CI): 4.0, 13]. The risk estimate was nearly 10-fold in participants aged <55 years (OR = 9.9, 95% CI: 3.5, 28). A shorter temporal history of pancreatitis was more closely associated with pancreatic cancer than was a longer temporal history: <3 years (OR = 29, 95% CI: 12, 71), 3–10 years (OR = 2.6, 95% CI: 1.5, 5.6), and >10 years (OR = 1.8, 95% CI: 0.7, 4.5, p trend < 0.001). A short temporal history of pancreatitis was highly associated with pancreatic cancer, suggesting that pancreatitis may be an early manifestation of pancreatic cancer in some individuals. Pancreatic cancer should be considered in the differential diagnosis of individuals with an episode of pancreatitis

Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study

We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk

Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with malignant hernatological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hernatological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes {[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hernatological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease. Copyright (c) 2006 S. Karger AG, Basel