101 research outputs found
The Natural Gas Industry in Transition
10 pages (includes illustrations)
Loss Distribution Generation in Credit Portfolio Modeling
In the current paper we analyze several methods for generation of loss distribution for credit portfolios. Loss distributions play an important role in pricing of credit derivatives and in credit portfolio optimization. A loss distribution is a function of the number of entities in the portfolio, their credit ratings, the notional amount and recovery of each entity, default probabilities, loss given defaults, and the correlation/dependence structure between entities incorporated in the portfolio. Direct generation of loss distribution may require Monte Carlo simulation which is time consuming and is not effective when applied for credit portfolio optimization. To overcome computational complexity a number of approaches were undertaken based on assumptions imposed on the input parameters, goals of loss distributions generation, and the accepted level of tolerance and computational errors
Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration
In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life1, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge2 are regulated by the surrounding microenvironment, or niche3. The activation of such stem cells is cyclic, involving periodic -catenin activity4, 5, 6, 7. In the adult mouse, regeneration occurs in waves in a follicle population, implying coordination among adjacent follicles and the extrafollicular environment. Here we show that unexpected periodic expression of bone morphogenetic protein 2 (Bmp2) and Bmp4 in the dermis regulates this process. This BMP cycle is out of phase with the WNT/-catenin cycle, thus dividing the conventional telogen into new functional phases: one refractory and the other competent for hair regeneration, characterized by high and low BMP signalling, respectively. Overexpression of noggin, a BMP antagonist, in mouse skin resulted in a markedly shortened refractory phase and faster propagation of the regenerative wave. Transplantation of skin from this mutant onto a wild-type host showed that follicles in donor and host can affect their cycling behaviours mutually, with the outcome depending on the equilibrium of BMP activity in the dermis. Administration of BMP4 protein caused the competent region to become refractory. These results show that BMPs may be the long-sought 'chalone' inhibitors of hair growth postulated by classical experiments. Taken together, results presented in this study provide an example of hierarchical regulation of local organ stem cell homeostasis by the inter-organ macroenvironment. The expression of Bmp2 in subcutaneous adipocytes indicates physiological integration between these two thermo-regulatory organs. Our findings have practical importance for studies using mouse skin as a model for carcinogenesis, intra-cutaneous drug delivery and stem cell engineering studies, because they highlight the acute need to differentiate supportive versus inhibitory regions in the host skin
Preservation of the Bladder in Patients With Rhabdomyosarcoma
Purpose: To review the pathologic findings from children with gross residual rhabdomyosarcoma (RMS) of the bladder and compare the treatment outcome of those who underwent cystectomy with those who did not. Patients and Methods: Primary and follow-up records and pathology specimens for 28 patients with gross residual disease entered onto the Intergroup Rhabdomyosarcoma Study (IRS) III were reviewed. These patients were assigned to receive 20 weeks of multiagent induction chemotherapy and 4 weeks of radiotherapy. Future therapy decisions were based on clinical and histologic evaluation at 20 weeks. Results: All patients had a clinical and histologic response. Thirteen patients underwent cystectomy at intervals that ranged from 1.5 to 38 months after the start of therapy. All but one patient are alive and well without recurrence. Reasons for cystectomy included presumed evidence of tumor growth from imaging studies, findings at cystoscopy, or histologic interpretation of biopsies. In HE GOAL OF THE Intergroup Rhabdomyosarcoma Study (IRS) for patients with primary bladder or bladder/prostate rhabdomyosarcoma (RMS) is not only survival, but survival with an intact and functioning bladder.3 Retention of the bladder may also minimize some of the long-term problems of sexual dysfunction associated with cystectomy. The use of partial cystectomy has been fostered to attain this goal, but is applicable in a relatively limited number of cases. 4 5 Among patients in IRS III with gross residual disease after biopsy, subsequent cystectomies were performed most frequently in patients with intravesical primary tumors (43%), less often in those with prostatic primary tumors (36%), and least often in those with extravesical primary tumors that did not extend through the bladder wall (14%). Because more cystectomies were performed for intravesical primary tumors and subsequent biopsies more readily obtained at cystoscopy, this group was chosen for review. Pathologic review of primary and follow-up specimens was made, comparing findings between those patients who retained the bladder and those who underwent cystectomy. PATIENTS AND METHODS Patient Selection One hundred three patients were entered onto IRS III with primary tumors that involved the bladder between November 1984 and September 1988. There were 35 patients with positive biopsies from intravesical bladder sites, 24 with abdominal or pelvic masses with bladder attachment, and 44 with prostatic or bladder/prostate involvement. Among the 35 intravesical tumors, four were group I cases (no gross or microscopic residual disease after initial surgery) and all are living and well following partial cystectomy and chemotherapy. A single group II patient (microscopic residual disease) underwent cystectomy as primary therapy for an intravesical tumor that extended through the bladder wall to an abdominal mass. This patient died of pneumonia after 8 months of chemotherapy and radiotherapy. Two of 30 patients with group III disease died following 2 and 3 weeks of therapy from toxicity related to chemotherapy. The remaining 28 group III patients comprise the current study. Treatment After initial biopsy, patients with gross residual disease (group III) were scheduled to be treated with 20 weeks of induction chemo
Spatiotemporal dissemination of ESBL-producing Enterobacterales in municipal sewer systems: a prospective, longitudinal study in the city of Basel, Switzerland
BACKGROUND: The contribution of community and hospital sources to the transmission of extended-spectrum β-lactamase producing Enterobacterales (ESBL-PE) remains elusive.
AIM: To investigate the extent of community dissemination and the contribution of hospitals to the spread of ESBL-PE by exploring their spatiotemporal distribution in municipal wastewater of the central European city of Basel.
METHODS: Wastewater samples were collected monthly for two consecutive years throughout Basel, Switzerland, including 21 sites across 10 postcode areas of the city collecting either community wastewater (urban sites, n = 17) or community and hospital wastewater (mixed sites, n = 4). Presumptive ESBL-PE were recovered by selective culture methods. Standard methodologies were applied for species identification, ESBL-confirmation, and quantification.
RESULTS: Ninety-five percent (477/504) of samples were positive for ESBL-PE. Among these isolates, Escherichia coli (85%, 1,140/1,334) and Klebsiella pneumoniae (11%, 153/1,334) were most common. They were recovered throughout the sampling period from all postcodes, with E. coli consistently predominating. The proportion of K. pneumoniae isolates was higher in wastewater samples from mixed sites as compared to samples from urban sites, while the proportion of E. coli was higher in samples from urban sites (p = 0.003). Higher numbers of colony forming units (CFUs) were recovered from mixed as compared to urban sites (median 3.2 × 10 vs. 1.6 × 10 CFU/mL). E. coli-counts showed moderate correlation with population size (rho = 0.44), while this correlation was weak for other ESBL-PE (rho = 0.21).
CONCLUSION: ESBL-PE are widely spread in municipal wastewater supporting that community sources are important reservoirs entertaining the spread of ESBL-PE. Hospital-influenced abundance of ESBL-PE appears to be species dependent
Extended-spectrum β-lactamase-producing Enterobacterales in diverse foodstuffs: a prospective, longitudinal study in the city of Basel, Switzerland
BackgroundThe involvement of non-human-to-human transmission of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) remains elusive. Foodstuffs may serve as reservoirs for ESBL-PE and contribute to their spread.AimWe aimed to systematically investigate the presence and spatiotemporal distribution of ESBL-PE in diverse unprocessed foodstuffs of different origin purchased in a central European city.MethodsChicken and green (herbs, salad, sprouts, vegetables) samples were collected monthly for two consecutive years, from June 2017 to June 2019, from large supermarket chains and small local food retailers, representing all ten postcode areas of the City of Basel (Switzerland), and the kitchen of the University Hospital Basel (Basel, Switzerland). After enrichment, presumptive ESBL-PE were isolated by selective culture methods and identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ESBL production was confirmed by phenotypic testing.ResultsAmong 947 food samples, 14.8% were positive for ESBL-PE isolate/s belonging to eight different ESBL-producing bacterial species. Escherichia coli and Serratia fonticola were predominant across samples (9 and 2%, respectively). Higher ESBL-PE prevalence was observed in chicken (25.9%) than in green (3.8%) samples (p < 0.001). Among greens, ESBL-PE were most frequently isolated from sprouts (15.2%). High ESBL-PE species diversity was observed among chicken samples, with E. coli as predominant (17.6%). ESBL-producing Enterobacter cloacae was detected among different greens. Yet, ESBL-producing Klebsiella pneumoniae was predominant in sprouts (12.1%). In total, 20.5% of samples from organic farming and 14.2% of samples from conventionally raised animals harbored an ESBL-producing isolate. Detection of ESBL-PE across samples differed between organic and non-organic when stratified by food source (p < 0.001), particularly among greens (12.5% organic, 2.4% conventional). High proportion of organic chicken samples was positive for ESBL-E. coli (33.3%), while the detection of several species characterized the conventional chicken samples. No significant differences in ESBL-PE frequences were detected between national (13.4%) and international samples (8.0%) (p = 0.122). Instead, differences were observed between regions of food production and countries (p < 0.001). No significant differences were found when comparing the proportion of ESBL-PE positive samples across districts, shop sizes and the hospital kitchen. The percentage of ESBL-PE positive samples did not differ monthly across the two-year sampling period (p = 0.107).ConclusionOur findings indicate moderate dissemination of ESBL-PE in foodstuffs, especially between chicken products and sprouts. Chicken meat represents a source for several ESBL-producing Enterobacterales, especially E. coli, while greens are more prone to carry ESBL-K. pneumoniae and E. cloacae. We disclose the importance of food type, food production system and production origin when assessing the risk of contamination with different ESBL-PE species
ARIA 2016 : Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle
The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.Peer reviewe
Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.Peer reviewe
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