Investigación de defectos genéticos en el sistema de la fosforilasa hepática en pacientes argentinos. Definición nosológica mediante una estrategia de análisis molecular. Investigation of genetic defects in the hepatic phosphorylase system in Argentinean patients. Nosological definition by molecular analysis strategy.

Las Enfermedades de Atesoramiento de Glucógeno (EAGs) también llamadas Glucogenosis comprenden un grupo de entidades causadas por una deficiencia enzimática específica relacionada con la vía de síntesis o degradación de esta macromolécula. La heterogeneidad fenotípica de los pacientes afectados dificulta la identificación de las diferentes variantes de EAG y por ende la correcta definición nosológica. En el Centro de Estudio de las Metabolopatías Congénitas, CEMECO, se fueron definiendo los diferentes tipos de Glucogenosis a través de una estrategia multidisciplinaria que integra distintos niveles de investigación clínica y complementaria, laboratorio metabólico especializado, enzimático, histomorfológico y de análisis molecular. Sin embargo, en algunos enfermos, entre los que se encuentran aquellos con defectos en el sistema de la fosforilasa hepática (EAG-VI y EAG-IX), la exacta definición nosológica aún no está resulta. La EAG-VI se refiere a un defecto en la fosforilasa hepática, enzima codificada por el gen PYGL, mientras que la EAG-IX es causada por un defecto genético en una de las subunidades de la fosforilasa b quinasa hepática codicadas por los genes PHKA2, PHKB y PHKG2, respectivamente. El objetivo del presente trabajo es propender a la definición nosológica de pacientes con defectos en el sistema de la fosforilasa mediante una estrategia de análisis molecular investigando los genes PYGL, PHKA2, PHKB y PHKG2. Los pacientes incluidos en este estudio deberán ser compatibles de padecer una EAG-VI o EAG-IX sobre la base de síntomas clínicos y hallazgos bioquímicos. La metodología incluirá la determinación de la enzima fosforilasa b quinasa en glóbulos rojos y dentro del análisis molecular la extracción de DNA genómico a partir de sangre entera para la amplificación por PCR de los exones más las uniones exon/intron de los genes PHKG2 y PYGL y la extracción de RNA total y obtención de cDNA para posterior amplificación de los cDNA PHKA2 y PHKB. Todos los fragmentos amplificados serán sometidos a análisis de secuencia de nucleótidos. Resultados esperados. Este trabajo, primero en Argentina, permitirá establecer las bases moleculares de los defectos del sistema de la fosforilasa hepática (EAG-VI y EAG-IX). El poder lograr este nivel de investigación traerá aparejado, una oferta integrativa en el vasto capítulo de las glucogenosis hepáticas, con extraordinaria significación en la práctica asistencial para el manejo, pronóstico y correspondiente asesoramiento genético. Hepatic glycogen storage diseases (GSDs) are a group of disorders produced by a deficiency in a specific protein involved in the metabolism of glycogen causing different types of GSDs. Phenotypic heterogeneity of affected patients difficult to identify the different GSD variants and therefore the correct definition of the disease. In the “Centro de Estudio de las Metabolopatías Congénitas”, CEMECO, were defined the different GSD types by a protocol which included complex gradual levels of clinical, biochemical, enzymatic and morphological investigation. However, in some patients, like those one with defects in the hepatic phosphorylase system (GSD-VI and GSD-IX) the exact definition of the disease has not yet been resolved. The GSD-VI is produced by a defect in the PYGL gen that encode the liver phosphorylase, while the GSD-IX is caused by a genetic defect in one of the Phosphorylase b kinase subunits, encoded by the PHKA2, PHKB and PHKG2 genes, respectively. The aim of the present study is to define the phosphorylase system defects in argentinian patients through a molecular strategy that involve the investigation of PYGL, PHKA2, PHKB and PHKG2 genes. Patients included in the present study must be compatible with a GSD-VI or GSD-IX on the bases of clinical symptoms and biochemical findings. The phosphorylase b kinase activity will be assay on in blood red cells. The molecular study will include genomic DNA extraction for the amplification of PHKG2 and PYGL genes and the total RNA extraction for amplification of the PHKA2 and PHKB cDNA by PCR. All PCR-amplified fragments will be subjected to direct nucleotide sequencing. This work, first in Argentina, will make possible to establish the molecular basis of the defects on the hepatic phosphorylase system (GSD-VI and GSD IX). To achieve this level of research will entail advance in the study of the hepatic glycogen storage disease, with extraordinary significance in the treatment, prognosis and the genetic counselling.

Reverse Auction: A Potential Strategy for Reduction of Pharmacological Therapy Cost

Background:Polypharmacy is a significant economic burden.Objective:We tested whether using reverse auction (RA) as compared with commercial pharmacy (CP) to purchase medicine results in lower pharmaceutical costs for heart failure (HF) and heart transplantation (HT) outpatients.Methods:We compared the costs via RA versus CP in 808 HF and 147 HT patients followed from 2009 through 2011, and evaluated the influence of clinical and demographic variables on cost.Results:The monthly cost per patient for HF drugs acquired via RA was $10.15 (IQ 3.51-40.22) versus $161.76 (IQ 86.05‑340.15) via CP; for HT, those costs were $393.08 (IQ 124.74-774.76) and $1,207.70 (IQ 604.48-2,499.97), respectively.Conclusion:RA may reduce the cost of prescription drugs for HF and HT, potentially making HF treatment more accessible. Clinical characteristics can influence the cost and benefits of RA. RA may be a new health policy strategy to reduce costs of prescribed medications for HF and HT patients, reducing the economic burden of treatment.

power network concept : a theoretical and empirical approach to strategy in the global network economy

Magdeburg, Univ., Fak. für Wirtschaftswiss., Diss., 2014

Reproductive strategy of a non-annual rivulid in a perennial wetland

ABSTRACT Atlantirivulus riograndensis (Costa & Lanés, 2009) is a fish registered to the basin of Patos lagoon and the adjacent coastal plains in southern states of Rio Grande do Sul and Santa Catarina, Brazil, found in shallow water courses with that have large quantities of aquatic vegetation and forest edges. The objective of this study was to investigate the reproductive strategy and tactics of this species including the sex ratio, the length at first maturity, spawning type, fecundity and the possible associations among reproduction and abiotic factors. Sampling of specimens occurred in perennial wetlands within the Banhado dos Pachecos wildlife refuge, in the city of Viamão, state of Rio Grande do Sul, Brazil, which is a conservation unit that belongs to an area of environmental protection in the Pampa Biome. The capture of 30 A. riograndensis specimens per month occurred from January to December of 2012. A total of 188 females and 172 males were captured and the total sex ratio was 1:1 in the sampled population. Sexual maturity of the species occurs after 13.59 and 11.92 mm (SL) for females and males, respectively. Both a multiple spawning and a long reproductive period (since August to March) were confirmed by the presence of post-ovulatory follicles that were observed through histological analysis and the values of the gonadosomatic index in females considered spawning capable. The average absolute fecundity of the species is of 19.33 (± 6.18) vitellogenic oocytes in mature ovaries. No significant relationship was found between mean GSI and the abiotic data. Reproductive tactics presented by A. riograndensis indicate a species with an opportunistic reproductive strategy, following the pattern of other species of the Rivulidae family.

On group strategy-proof mechanisms for a many-to-one matching model

For the many-to-one matching model in which firms have substitutable and quota q-separable preferences over subsets of workers we show that the workers-optimal stable mechanism is group strategy-proof for the workers. In order to prove this result, we also show that under this domain of preferences (which contains the domain of responsive preferences of the college admissions problem) the workers-optimal stable matching is weakly Pareto optimal for the workers and the Blocking Lemma holds as well. We exhibit an example showing that none of these three results remain true if the preferences of firms are substitutable but not quota q-separable.

Influence of seasons and sampling strategy on assessment of bioaerosols in sewage treatment plants in Switzerland

An assessment of sewage workers' exposure to airborne cultivable bacteria, fungi and inhaled endotoxins was performed at 11 sewage treatment plants. We sampled the enclosed and unenclosed treatment areas in each plant and evaluated the influence of seasons (summer and winter) on bioaerosol levels. We also measured personal exposure to endotoxins of workers during special operation where a higher risk of bioaerosol inhalation was assumed. Results show that only fungi are present in significantly higher concentrations in summer than in winter (2331 +/- 858 versus 329 +/- 95 CFU m(-3)). We also found that there are significantly more bacteria in the enclosed area, near the particle grids for incoming water, than in the unenclosed area near the aeration basins (9455 +/- 2661 versus 2435 +/- 985 CFU m(-3) in summer and 11 081 +/- 2299 versus 2002 +/- 839 CFU m(-3) in winter). All bioaerosols were frequently above the recommended values of occupational exposure. Workers carrying out special tasks such as cleaning tanks were exposed to very high levels of endotoxins (up to 500 EU m(-3)) compared to routine work. The species composition and concentration of airborne Gram-negative bacteria were also studied. A broad spectrum of different species within the Pseudomonadaceae and the Enterobacteriaceae families were predominant in nearly all plants investigated. [Authors]

Renal transplantation following aorto-iliac reconstruction is a safe a strategy

Introduction: Renal transplantation is considered the treatment of choice for end-stage renal disease. However, the association of occlusive aorto-iliac disease and chronic renal failure is frequent and aorto-iliac reconstruction may be necessary prior to renal transplantation. This retrospective study reviews the results of this operative strategy.Material and Methods: Between January 2001 and June 2010, 309 patients underwent renal transplantation at our institution and 8 patients had prior aorto-iliac reconstruction using prosthetic material. There were 6 men and 2 women with a median age of 62 years (range 51-70). Five aorto-bifemoral and 2 aorto-bi-iliac bypasses were performed for stage II (n=5), stage IV (n=1) and aortic aneurysm (n=1). In one patient, iliac kissing stents and an ilio-femoral bypass were implanted. 4 cadaveric and 4 living donor renal transplantations were performed with an interval of 2 months to 10 years after revascularization.The results were analysed with respect of graft and patients survival. Differences between groups were tested by the log rank method.Results: No complications and no death occurred in the post-operative period. All bypasses remained patent during follow-up. The median time of post transplantation follow-up was 46 months for all patients and 27 months for patients with prior revascularization. In the revascularized group and control group, the graft and patient survival at 1 year were respectively 100%/96%, 100%/99% and at 5 years 86%/86%, 86%/94%, without significant differences between both groups.Discussion: Our results suggest that renal transplantation following prior aorto-iliac revascularisation with prosthetic material is safe and effective. Patients with end-stage renal disease and concomitant aorto-iliac disease should therefore be considered for renal transplantation. However, caution in the interpretation of the results is indicated due to the small sample size of our study.

Which screening strategy using BMD measurements would be most cost effective for hip fracture prevention in elderly women? A decision analysis based on a Markov model.

INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. METHODS: A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. RESULTS: In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Ventricular arrhythmia in coronary artery disease: limits of a risk stratification strategy based on the ejection fraction alone and impact of infarct localization.

AIMS: Estimates of the left ventricular ejection fraction (LVEF) in patients with life-threatening ventricular arrhythmias related to coronary artery disease (CAD) have rarely been reported despite it has become the basis for determining patient's eligibility for prophylactic defibrillator. We aimed to determine the extent and distribution of reduced LVEF in patients with sustained ventricular tachycardia or ventricular fibrillation. METHODS AND RESULTS: 252 patients admitted for ventricular arrhythmia related to CAD were included: 149 had acute myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients had an old MI without residual ischaemia (Group III, 19%). 34% of the patients with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF evaluation, it can be estimated that less than one quarter of the whole study population had a known chronic MI with severely reduced LVEF. In Group III, the proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%; absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001), though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P = 0.0499). CONCLUSION: Patients included in defibrillator trials represent only a minority of the patients at risk of sudden cardiac death. By applying the current risk stratification strategy based on LVEF, more than one third of the patients with old MI would not have qualified for a prophylactic defibrillator. Our study also suggests that inferior scars may be more prone to ventricular arrhythmia compared to anterior scars.

Individual versus group strategy-proofness: when do they coincide?

A social choice function is group strategy-proof on a domain if no group of agents can manipulate its final outcome to their own benefit by declaring false preferences on that domain. Group strategy-proofness is a very attractive requirement of incentive compatibility. But in many cases it is hard or impossible to find nontrivial social choice functions satisfying even the weakest condition of individual strategy-proofness. However, there are a number of economically significant domains where interesting rules satisfying individual strategy-proofness can be defined, and for some of them, all these rules turn out to also satisfy the stronger requirement of group strategy-proofness. This is the case, for example, when preferences are single-peaked or single-dipped. In other cases, this equivalence does not hold. We provide sufficient conditions defining domains of preferences guaranteeing that individual and group strategy-proofness are equivalent for all rules defined on the

Extending contingency: the impact of strategy, technology, size and business environment on the organisational form of small Chinese firms

This paper is inspired by articles in the last decade or so that have argued for more attention to theory, and to empirical analysis, within the well-known, and long-lasting, contingency framework for explaining the organisational form of the firm. Its contribution is to extend contingency analysis in three ways: (a) by empirically testing it, using explicit econometric modelling (rather than case study evidence) involving estimation by ordered probit analysis; (b) by extending its scope from large firms to SMEs; (c) by extending its applications from Western economic contexts, to an emerging economy context, using field work evidence from China. It calibrates organizational form in a new way, as an ordinal dependent variable, and also utilises new measures of familiar contingency factors from the literature (i.e. Environment, Strategy, Size and Technology) as the independent variables. An ordered probit model of contingency was constructed, and estimated by maximum likelihood, using a cross section of 83 private Chinese firms. The probit was found to be a good fit to the data, and displayed significant coefficients with plausible interpretations for key variables under all the four categories of contingency analysis, namely Environment, Strategy, Size and Technology. Thus we have generalised the contingency model, in terms of specification, interpretation and applications area.

Lock-in, path dependence, and the Internationalization of QWERTY

This paper looks at the emergence of what is described here as the QWERTY family of standards (QWERTY and its international adaptations QZERTY, AZERTY, and QWERTZ). QWERTY has been described as an inferior solution and an accident of history. However, the analysis here finds that each member of the family represented highly efficient adaptations to specific user needs and technical challenges encountered in their own environments. These findings may be seen to have wider implications given QWERTY’s role as paradigm case in the literature on increasing returns and path dependence, and these are pursued in the paper