Using Patient Registries to Identify Triggers of Rare Diseases

Mapping the distribution of patients and analyzing disease clusters is an effective method in epidemiology, where the non-random aggregation of patients is carefully investigated. This can aid in the search for clues to the etiology of diseases, particularly the rare ones. Indeed, with the increased incidence of rare diseases in certain populations and/or geographic areas and with proper analysis of common exposures, it is possible to identify the likely promoters/triggers of these diseases at a given time. In this chapter, we will highlight the appropriate methodology and demonstrate several examples of cluster analyses that lead to the recognition of environmental, occupational and communicable preventable triggers of several rare diseases

Choix multicritère de procédés d'épuration des eaux usées municipales

Les stations d'épuration des eaux usées municipales du Québec, comme ailleurs au Canada et aux États Unis, sont en général peu efficaces sur le plan énergétique. Il est donc possible de concevoir des hypothèses de chaînes épuratoires améliorées au plan de leur efficacité énergétique et de leur performance globale en y introduisant, d'une part, diverses MEEE et, d'autre part, certains procédés unitaires améliorant l'épuration. Cependant, le problème de choisir, parmi ces hypothèses de chaînes d'épuration, celle correspondant au procédé le plus adéquat pour prendre en charge une situation donnée, demeure entier. Cet article analyse ce problème de choix pour les stations d'épuration de capacité comprise entre 5,000 m3/d (≈ 5000 personnes) et 100,000 m3/d (≈ 100,000 personnes). En faisant l'hypothèse, d'un côté, que l'ajout des mesures d'efficacité énergétique peut améliorer la consommation énergétique d'une chaîne d'épuration, et d'un autre côté, que l'insertion de segments de procédés peut contribuer à améliorer leur performance globale, nous avons élaboré, à partir des stations d'épuration de types Biofiltration, Physico-chimique, Réacteurs Biologiques séquentiels (deux variantes), Boues activées et Étangs aérés, six (6) hypothèses de chaînes épuratoires (chaînes 1 à 6) respectant les exigences opérationnelles et épuratoires et nous les avons comparées entre elles, sur la base d'une analyse multicritère d'aide à la décision, en vue d'en déterminer les plus performantes. Cette analyse multicritère intègre les aspects techniques, énergétiques, économiques, etc. et prend en compte les préférences du(des) décideur(s) dans le processus de choix. Les résultats obtenus montrent que, parmi les six hypothèses de chaînes étudiées, les trois premières positions sont occupées par les chaînes 3, 1 et 4 respectivement. Ce type d'analyse pourrait jouer un rôle complémentaire à une étude technico-économique visant le choix de technologies d'épuration.Quebec municipal wastewater treatment facilities, like those elsewhere in Canada and the United States, generally are low efficiency energy consumers (ELECTRIC POWER RESEARCH INSTITUTE (EPRI), 1993; OWEN, 1982; ONTARIO-HYDRO, 1993; METCALF and EDDY, INC., 1992, SASSEVILLE et al., 1995). The work of METCALF and EDDY, INC. (1992) and of EPRI (1993) concluded that it would be possible to substantially reduce electricity demand and to improve the utilization of electrical energy in the municipal wastewater treatment processes by introducing Electricity Saving Measures (ESMs) in the processes and their management.In the province of Quebec, given the potential savings linked to the reduction of electricity consumption in municipal wastewater treatment facilities, and the progressive expansion of the province's wastewater treatment facilities, the adoption of energetically efficient wastewater treatment technologies is particularly timely. SASSEVILLE et al. (1995) estimated that it would be possible to save 5 M $at the present level of wastewater treatment, based on a cost of about 24 M$ for the 400 GWh of electricity annually consumed in the municipal wastewater treatment facilities. This saving would come solely from the implementation of appropriate energy-saving measures.In hypothesizing on one hand that adding energy-saving measures can improve the energy consumption of a wastewater treatment chain, and on the other hand that the introduction of segments of processes can contribute in improving overall performance, we have elaborated from existing wastewater treatment facilities six hypotheses of liquid treatment chains that respect operational and regulation requirements, on the basis of the experience developed in the operation of municipal wastewater treatment facilities. The six hypothetical treatment chains were elaborated from facilities of the following types: biofiltration (chain 1), physico-chemical (chain 2), sequencing biological (batch) reactors system A (chain 3), sequencing biological (batch) reactors system B (chain 4), activated sludge (chain 5) and aerated lagoons (chain 6). The energy-saving measures utilized in the elaboration of these hypothetical treatment chains were chosen on the basis of a conjunctive analysis (KIBI et al., 1997). However, the problem of choosing among these treatment chains the one corresponding to the most adequate process for a particular situation is still present. The present article analyzes this choice for wastewater treatment facilities of a capacity between 5 000 m3/d (≈ 5 000 persons) and 100 000 m3/d (≈ 100 000 persons).How then to choose the most efficient of these hypothetical municipal wastewater treatment chains?Generally, the choice of the treatment technologies is done on the basis of single-criterion mathematical models: for example, the reduction of construction costs, or of exploitation and maintenance costs (ECKENFELDER, 1982; PINEAU et al., 1985; WANG and WANG, 1979; TYTECA et al., 1977). There are other approaches based on dynamic simulation models or on technological and econometric analyses (HYDRO-QUÉBEC, 1993; MACRAE 1989; LESSARD, 1989; BROCKTON, 1987; HOLDREN, 1987; FOSBERG and MUKHOPADHYAY, 1981; REID, CROWTHER and PARTNERS, 1978; KLEMETSON and GRENNEY, 1976).These different approaches are often insufficient to distinguish the real value of the different technological options. Furthermore, they do not take into account many important factors (technological, economic, financial and environmental, ergonomic and socio-political) that affect their implementation and should be considered in identifying an acceptable and viable solution.The multicriteria approach of decision-making advocated in this article can mitigate this difficulty. It will take into account key factors in the conception and operation of treatment technologies, especially energy and environmental factors, likely to give rise to efficient treatment facilities from both an energy and a treatment point of view. However the analysis of decisional factors to consider in this multicriteria analysis gives rise to a particular problem. They affect the decision that can be appreciated by deterministic relationships, offering a high level of certainty as to its evaluation, while others have a non-deterministic nature (uncertainty and imprecision). Research using the multicriteria analysis approach has been performed in similar situations over the last twenty years, in some cases applied to the environmental and energy sectors (e.g. KEENEY and NAIR 1977; ROY and VINCKE 1981; TEGHEM and KUNSCH 1985; SIMOS 1990; HANSON 1991; ROUSSEAU and MARTEL 1994). Here again, these approaches have limits since the cases were treated either in a situation of certainty or a situation of uncertainty and imprecision. The proposed model deals with the case of certainty and uncertainty at the same time, therefore improving the applicability of the multicriteria approach in the situation under study. The solution retained consists of applying this type of modelling in order to classify from the best to the worst, the six hypothetical treatment chains. This approach utilizes in the modelling process, fourteen evaluation criteria, various criteria weights, quantitative and qualitative evaluations, as well as the indifference, preference and veto thresholds. The main steps of the model are the construction of evaluated outclass relationships and the exploitation of these outclass relationships. The multicriteria aggregation procedure utilizes an elaborated mathematical model based upon the methods of ELECTRE III (Roy, 1978) and PROMETHEE II (BRANS et al., 1984), as well as the works of DÉROT et al. (1994). The ranking of these treatment chain hypotheses, elaborated on an empirical level in consultation with the operators and others involved in wastewater treatment and obtained on the basis of this procedure, can discriminate among their overall performance characteristics rather well. It also emphasizes their energy efficiency, since the energy criteria have on average in the analysis a weight that is 28% higher than the other evaluation criteria. The results obtained show that the hypothetical chain 3 is ranked first, chain 1 occupies the second rank, whereas chain 4 is in the third rank. The last three ranks are occupied respectively by chains 6, 5 and 2.In a decisional and strategic approach, the first three treatment chain hypotheses can be considered overall as being the highest achievers. This result signifies that in the scope of investments related to the expansion of treatment facilities and the construction of facilities with a flow rate contained within the considered range, these three treatment chains (when considering different modification hypotheses), should be preferred over the other chains when the emphasis is on their overall performance including energy efficiency. However, other analyses would be necessary in the case of the construction of a new wastewater treatment facility with a flow rate above the level considered in this study.Generally, the results of this analysis can assist in discriminating among the behaviors of the technologies considered, and in judging their relative performance in the investments of the construction of new wastewater treatment facilities, in addition to a technico-economic analysis. Overall, the multicriteria model described in this study identified a compromise solution between evaluations of a different and conflicting nature. This result demonstrates that this type of analysis is appropriate for tackling multidimensional problems

Consumer's guide : fruits and vegetables and other farm fresh products, 1992

Lincoln University at Jefferson City, University of Missouri and the U. S. Department of Agriculture cooperating. Rufus Jones, 1890 Administrator. Distributed in futherance of the Food and Agriculture kt., 1977 PL 95-113 Section 1444 and 1445, as amended by PL 97-98 December 1981

New and improved demonstrations, each illustrating a single scientific paper

Thesis (Ed.M.)--Boston Universit

A Core Outcome Set for multimorbidity research (COSmm)

PURPOSE: We aimed to develop a consensus-based set of core outcomes specifically for studies in multimorbidity. METHODS: We undertook a consensus study following the COS-STAR (Core Outcome Set-STAndards for Reporting) guidelines for the design and reporting of core outcome sets. A Delphi panel of experts completed a web-based survey with 2 rounds. Panelists were presented with a range of outcomes that had been identified in previous workshops and a related systematic review. They indicated their level of agreement on whether each outcome should be included in the core set using a 5-point Likert scale, and outcomes reaching a prespecified consensus level were included. RESULTS: Of 30 individuals invited to be panelists, 26 from 13 countries agreed. All 26 completed both rounds of the survey. The Delphi panel reached consensus on 17 outcomes for inclusion in a core outcome set for multimorbidity (COSmm). The highest-ranked outcomes were health-related quality of life, mental health outcomes, and mortality. Other outcomes were grouped into overarching themes of patient-reported impacts and behaviors (treatment burden, self-rated health, self-management behavior, self-efficacy, adherence); physical activity and function (activities of daily living, physical function, physical activity); consultation related (communication, shared decision making, prioritization); and health systems (health care use, costs, quality of health care). CONCLUSIONS: This consensus study involved a wide range of international experts who identified a large number of outcomes for multimorbidity intervention studies. Our results suggest that quality of life, mental health outcomes, and mortality should be regarded as essential core outcomes. Researchers should, however, also consider the full range of outcomes when designing studies to capture important domains in multimorbidity depending on individual study aims and interventions

Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells

Orientador: Iverson LadewigMonografia (licenciatura) - Universidade Federal do Paraná. Setor de Ciências Biológicas. Curso de Educação Física

Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA

Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA