3,720 research outputs found

    Dynamics of transcendental Hénon maps-II

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    Transcendental Henon maps are the natural extensions of the well investigated complex polynomial Henon maps to the much larger class of holomorphic automorphisms. We prove here that transcendental Henon maps always have non-trivial dynamical behavior, namely that they always admit both periodic and escaping orbits, and that their Julia sets are non-empty and perfect

    Delivering the promise of Sendai framework for disaster risk reduction in fragile and conflict-affected contexts (FCAC): A case study of the NGO GOAL's response to the Syria conflict

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    The Sendai Framework for Disaster Risk Reduction (SFDRR) has helped to reduce global disaster risk, but there has been a lack of progress in disaster risk reduction (DRR) for people living in fragile and conflict affected contexts (FCAC). Given the mounting evidence that DRR cannot be implemented through conventional approaches in FCAC, serious efforts must be made to understand how to meet SFDRR's goals. This paper offers a case study of international non-governmental organization GOAL's programming that responds to the protracted crisis in Syria, with a critical discussion on SFDRR and how to adapt humanitarian relief and disaster resilience

    Informality, violence, and disaster risks: Coproducing inclusive early warning and response systems in urban informal settlements in Honduras

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    Anticipatory disaster risk reduction (DRR) is an essential human right for the ~1 billion people living in informal settlements who are disproportionately exposed to climate-related hazards due to their high vulnerability. Participatory approaches are recognized as being critical for effective and sustainable disaster prevention, mitigation, and preparation through to response, but research on how to coproduce anticipatory DRR with people living and working in informal settlements is scant. Their exclusion is even more pronounced in challenging contexts, such as those characterized by social-political fragility and violence. As a result, a significant portion of the global population is left behind in best practices tied to global DRR ambitions, with DRR actions working neither with nor for the people most at risk. The signal case of urban informal settlements controlled by territorial gangs in Tegucigalpa, Honduras, illustrates the need for new thinking on how to inclusively mitigate, prepare for, and respond to natural hazard-related disasters. Our research examines the coproduction of early warning systems linked with response capacities for floods and landslides through the case study of the international NGO GOAL's work across the city with a focus on nine urban informal settlements with high levels of territorial gang violence. We explore how GOAL navigated informality and violent conflict to support the early warning and response system as an inclusive social process rather than a technical exercise. We identify four cross-cutting strategies employed by GOAL in support of local vulnerability reduction and capacity building based on a local systems approach. This research breaks new ground in identifying how to bridge the gap between knowledge and action in designing inclusive and sustainable early warning and response systems together with the millions of people around the world affected by the intersection of informality, violence, and disaster risks

    Background risk of breast cancer and the association between physical activity and mammographic density

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    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0

    Yield of comparative genomic hybridization microarray in pediatric neurology practice

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    OBJECTIVE: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes. METHODS: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records. An assessment of pathogenicity was made for each CNV, based on recent developments in the literature. RESULTS: Forty-seven patients were found to carry a pathogenic CNV, giving an overall diagnostic yield of 8.59%. Certain phenotypes predicted for the presence of a pathogenic CNV, including developmental delay (odds ratio [OR] 3.69 [1.30–10.51]), cortical visual impairment (OR 2.73 [1.18–6.28]), dysmorphism (OR 2.75 [1.38–5.50]), and microcephaly (OR 2.16 [1.01–4.61]). The combination of developmental delay/intellectual disability with dysmorphism and abnormal head circumference was also predictive for a pathogenic CNV (OR 2.86 [1.02–8.00]). For every additional clinical feature, there was an increased likelihood of detecting a pathogenic CNV (OR 1.18 [1.01–1.38]). CONCLUSIONS: the use of aCGH led to a pathogenic finding in 8.59% of patients. The results support the use of aCGH as a first tier investigation in children with diverse neurologic disorders, although whole-genome sequencing may replace aCGH as the detection method in the future. In particular, the yield was increased in children with developmental delay, dysmorphism, cortical visual impairment, and microcephaly

    Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation.

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    BackgroundMucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.MethodsThis 2-year open-label pilot study of laronidase included ten patients (age 5-13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls.ResultsThe two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients.ConclusionsLaronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made

    Activation of peroxisome proliferator-activated receptors by chlorinated hydrocarbons and endogenous steroids.

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    Trichloroethylene (TCE) and related hydrocarbons constitute an important class of environmental pollutants whose adverse effects on liver, kidney, and other tissues may, in part, be mediated by peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors belonging to the steroid receptor superfamily. Activation of PPAR induces a dramatic proliferation of peroxisomes in rodent hepatocytes and ultimately leads to hepatocellular carcinoma. To elucidate the role of PPAR in the pathophysiologic effects of TCE and its metabolites, it is important to understand the mechanisms whereby PPAR is activated both by TCE and endogenous peroxisome proliferators. The investigations summarized in this article a) help clarify the mechanism by which TCE and its metabolites induce peroxisome proliferation and b) explore the potential role of the adrenal steroid and anticarcinogen dehydroepiandrosterone 3beta-sulfate (DHEA-S) as an endogenous PPAR activator. Transient transfection studies have demonstrated that the TCE metabolites trichloroacetate and dichloroacetate both activate PPAR alpha, a major liver-expressed receptor isoform. TCE itself was inactive when tested over the same concentration range, suggesting that its acidic metabolites mediate the peroxisome proliferative potential of TCE. Although DHEA-S is an active peroxisome proliferator in vivo, this steroid does not stimulate trans-activation of PPAR alpha or of two other PPAR isoforms, gamma and delta/Nuc1, when evaluated in COS-1 cell transfection studies. To test whether PPAR alpha mediates peroxisomal gene induction by DHEA-S in intact animals, DHEA-S has been administered to mice lacking a functional PPAR alpha gene. DHEA-S was thus shown to markedly increase hepatic expression of two microsomal P4504A proteins associated with the peroxisomal proliferative response in wild-type mice. In contrast, DHEA-S did not induce these hepatic proteins in PPAR alpha-deficient mice. Thus, despite its unresponsiveness to steroidal peroxisome proliferators in transfection assays, PPAR alpha is an obligatory mediator of DHEA-S-stimulated hepatic peroxisomal gene induction. DHEA-S, or one of its metabolites, may thus serve as an important endogenous regulator of liver peroxisomal enzyme expression

    Altered Cardiac Repolarization in Association with Air Pollution and Air Temperature among Myocardial Infarction Survivors

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    Background: Epidemiological studies have shown that ambient particulate matter (PM) and changes in air temperature are associated with increased cardiopulmonary events. Objective: We hypothesized that patients with previous myocardial infarction (MI) experience changes in heart rate (HR) and repolarization parameters, such as Bazett-corrected QT interval (QTc), and T-wave amplitude (Tamp), in association with increases in air pollution and temperature changes. Methods: Between May 2003 and February 2004, 67 MI survivors from the Augsburg KORA-MI registry repeatedly sent 16 sec electrocardiograms (ECGs) with a personal transmitter (Viapac) via telephone to the Philips Monitoring Center, where ECG parameters were immediately analyzed. Meteorological data and air pollutants were acquired from fixed monitoring sites on an hourly basis. Additive mixed models were used for analysis. Effect modification by patient characteristics was investigated. Results: The analysis of the 1,745 ECGs revealed an increased HR associated with interquartile range (IQR) increases in PM levels among participants not using beta-adrenergic receptor blockers and among those with body mass index ≥ 30 kg/m2. We observed a 24- to 47-hr lagged QTc prolongation [0.5% change (95% confidence interval, 0.0–1.0%)] in association with IQR increases in levels of PM ≤ 2.5 µm in aerodynamic diameter, especially in patients with one [0.6% (0.1–1.0%)] or two [1.2% (0.4–2.1%)] minor alleles of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) single-nucleotide polymorphism rs2364725. Positive immediate (0–23 hr) and inverse delayed (48–71 hr up to 96–119 hr) associations were evident between PM and Tamp. We detected an inverse U-shaped association between temperature and Tamp, with a maximum Tamp at 5°C. Conclusions: Increased air pollution levels and temperature changes may lead to changes in HR and repolarization parameters that may be precursors of cardiac problems.The AIRGENE study was funded as part of the European Union’s 5th Framework Programme, key action 4: “Environment and Health,” contract QLRT-2002-02236. This research has been funded wholly or in part by the U.S. Environmental Protection Agency through Science to Achieve Results grants RD827354 and RD832415 to the University of Rocheste

    Socioeconomic profile of diabetic patients with and without foot problems

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    Introduction: To identify the differences in a socioeconomic profile between two cohorts of diabetic patients – one with diabetic foot problems and another without diabetic foot problems. Materials and methods: The cohort with diabetic foot problems (including cellulitis, abscess, osteomyelitis, septic arthritis, gangrene, ulcers, or Charcot joint disease) consisted of 122 diabetic patients, while the other cohort without foot problems consisted of 112 diabetic patients. Both were seen at the National University Hospital from January to April 2007. A detailed protocol was designed and the factors studied included patient profile, average monthly household income, education, compliance to diabetic medication, attendance at clinics for diabetic treatment, exercise, smoking, alcohol consumption, gender, and glycosylated haemoglobin (HbA1C) level. These were studied for significant differences using univariate and stepwise multivariate logistic regression analysis. Results: With multivariate analysis, Malay ethnicity (p<0.001), education of up to secondary school only (p=0.021), low average monthly household income of less than SGD $2,000 (p=0.030), lack of exercise (at least once a week, p=0.04), and elevated HbA1C level (>7.0%; p=0.015) were found to be significantly higher in the cohort with diabetic foot problems than the cohort without. Conclusions: There are significant differences in the socioeconomic factors between diabetic patients with diabetic foot problems and those without

    A patient with metastatic melanoma presenting with gastrointestinal perforation after dacarbazine infusion: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>We report a rare case of gastrointestinal perforation following dacarbazine infusion for metastatic melanoma. The condition is attributed to a responding malignant melanoma in the gastrointestinal tract.</p> <p>Case presentation</p> <p>A 52-year-old Caucasian man presented with abdominal pain and distension, malaise, night sweats, dysphagia and early satiety. A computed tomography scan showed massive ascites, lymphadenopathy and liver lesions suspect for metastases. An upper gastrointestinal endoscopy was performed and revealed multiple dark lesions of 5 mm to 10 mm in his stomach and duodenum.</p> <p>When his skin was re-examined, an irregular pigmented lesion over the left clavicle measuring 15 mm × 8 mm with partial depigmentation was found. Histological examination of a duodenal lesion was consistent with a diagnosis of metastatic melanoma. The patient deteriorated and his level of lactate dehydrogenase rapidly increased. The patient was started on systemic treatment with dacarbazine 800 mg/m<sup>2 </sup>every three weeks and he was discharged one day after the first dose. On the sixth day he was readmitted with severe abdominal pain. A chest X-ray showed the presence of free intraperitoneal air that was consistent with gastrointestinal perforation. His lactate dehydrogenase level had fallen from 6969U/L to 1827U/L, supporting the conclusion that the response of gastrointestinal metastases to dacarbazine had resulted in the perforation of the patient's bowel wall. A laparotomy was discussed with the patient and his family but he decided to go home with symptomatic treatment. He died 11 days later.</p> <p>Conclusion</p> <p>Melanoma can originate in, as well as metastasize to, the gastrointestinal tract. Gastrointestinal perforations due to responding tumors are a well-known complication of systemic treatment of gastrointestinal lymphomas. However, as the response rate of metastatic melanoma to dacarbazine is only 10% to 20%, and responses are usually only partial, perforation due to treatment response in metastatic melanoma is rare.</p> <p>Medical oncologists should be aware of the risk of bowel perforation after starting cytotoxic chemotherapy on patients with gastrointestinal metastases.</p
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