Questions and Answers

"I was curious about websites because we’re now beginning to accumulate websites and we were thinking about using a website service so it makes it very simple just to find it, click it, ship it and we have archival access to it. But the problem of course is these websites are so complicated and you don’t actually know what you’re fully accessing because there are lots of links; there are lots of portions that may go unexamined. Have you had any experiences with websites that are essentially transnational, that are essentially built in this country but linked to things that are governed by laws outside of U.S. control?

A balanced complex chromosomal rearrangement (BCCR) in a family with reproductive failure

Balanced complex chromosomal rearrangements are very rare events in the human population. Translocations involving three or more chromosomes frequently lead to a severe reproductive impairment secondary to meiotic disturbance in males and to chromosomal imbalance in gametes of females. We report a new familial case of complex chromosome anomaly involving chromosomes 13, 14 and 22. Cytogenetic investigations showed a complex chromosomal chromosome rearrangement involving: (i) a Robertsonian translocation between chromosomes 13 and 14; and (ii) a reciprocal translocation between the long arms of chromosome 14 and the long arm of chromosome 22. The aetiology of the translocation was characterized by conventional fluorescence in‐situ hybridization (FISH) studies and routine R‐ and G‐banding (RTBG and GBTG) combined with α and β satellite centromeric FISH probes. Predicted configuration of the hexavalent at pachytene stage of meiosis was used to consider the modes of segregation; only two configurations resulted in a normal or balanced gamete karyotype. Reproductive management and genetic counselling are discusse

WHEN SHOULD RANDOM EFFECTS BE INCLUDED IN ESTIMABLE FUNCTIONS AND WHEN THEY SHOULD NOT?

In the mixed model, the behavior of linear functions of the fixed and random effects is examined. It is found that inclusion of certain functions of random effects can lead to estimators which are equivalent to those under a fixed effects model and are inconsistent with the inherent structure of the mixed model. Three examples are presented which illustrate the behavior of linear functions of the fixed and random effects. These functions represent the broad, narrow and intermediate inference spaces as introduced by McLean, Sanders and Stroup (1991). Which random effects should be included in the model is discussed. Random effects representing experimental error units are candidates for inclusion in estimable functions. Inclusion of experimental unit effects in estimable functions can lead to misleading results

Exploring the Factors Associated with Online Financial and Performance Disclosure in Nonprofits

Informed by theories of technological innovation, this paper develops and empirically tests a web disclosure adoption model. In order to test the model, a questionnaire was administered to a sample of 775 organizations in an eight-county regional area in the Northeastern United States. Results reveal that Chief Executive Officer (CEO) and organizational characteristics are related to web disclosure adoption. Specifically, there is more disclosure of performance information online when the CEO believes that the web is useful for promoting transparency and accountability when the organization views the web as a communication or strategic tool, when more employees have technical expertise, and when the board of directors is more supportive of web technology. We found more web disclosure of financial information when the organization possesses the technological readiness for web disclosure. This paper contributes to research by identifying the main factors that facilitate web disclosure adoption in nonprofit contexts

The lipoatrophic caveolin-1 deficient mouse model reveals autophagy in mature adipocytes

Adipose tissue lipoatrophy caused by caveolin gene deletion in mice is not linked to defective adipocyte differentiation. We show that adipose tissue development cannot be rescued by endothelial specific caveolin-1 re-expression, indicating primordial role of caveolin in mature adipocytes. Partial or total caveolin deficiency in adipocytes induced broad protein expression defects, including but not limited to previously described downregulation of insulin receptor. Global alterations in protein turnover, and accelerated degradation of long-lived proteins were found in caveolin-deficient adipocytes. Lipidation of endogenous LC3 autophagy marker and distribution of GFP-LC3 into aggregates demonstrated activated autophagy in the absence of caveolin-1 in adipocytes. Furthermore, electron microscopy revealed autophagic vacuoles in caveolin-1 deficient but not control adipocytes. Surprisingly, significant levels of lipidated LC3-II were found around lipid droplets of normal adipocytes, maintained in nutrient-rich conditions or isolated from fed mice, which do not display autophagy. Altogether, these data indicate that caveolin deficiency induce autophagy in adipocytes, a feature that is not a physiological response to fasting in normal fat cells. This likely resulted from defective insulin and lipolytic responses that converge in chronic nutrient shortage in adipocytes lacking caveolin-1. This is the first report of a pathological situation with autophagy as an adaptative response to adipocyte failure

Population Structure and Conservation Genetics of the Oregon Spotted Frog, Rana Pretiosa

The Oregon spotted frog (Rana pretiosa) is one of the most threatened amphibians in the Pacific Northwest. Here we analyzed data from 13 microsatellite loci and 298 bp of mitochondrial DNA in frogs collected from 23 of the remaining R. pretiosa populations in order to (1) assess levels of genetic diversity within populations of R. pretiosa, (2) identify the major genetic groups in the species, (3) estimate levels of genetic differentiation and gene flow among populations within each major group, and (4) compare the pattern of differentiation among R. pretiosa populations with that among populations of R. cascadae, a non-endangered congener that also occurs in Oregon and Washington. There is a strong, hierarchical genetic structure in R. pretiosa. That structure includes six major genetic groups, one of which is represented by a single remaining population. R. pretiosa populations have low genetic diversity (average He = 0.31) compared to R. cascadae (average He = 0.54) and to other ranid frogs. Genetic subdivision among populations is much higher in R. pretiosa than in R. cascadae, particularly over the largest geographic distances (hundreds of kilometers). A joint analysis of migration rates among populations and of effective sizes within populations (using MIGRATE) suggests that both species have extremely low migration rates, and that R. pretiosa have slightly smaller effective sizes. However, the slight difference in effective sizes between species appears insufficient to explain the large difference in genetic diversity and in large-scale genetic structure. We therefore hypothesize that low connectivity among the more widely-spaced R. pretiosa populations (owing to their patchier habitat), is the main cause of their lower genetic diversity and higher among-population differentiation. Conservation recommendations for R. pretiosa include maintaining habitat connectivity to facilitate gene flow among populations that are still potentially connected, and either expanding habitat or founding additional \u27backup\u27 populations to maintain diversity in the isolated populations. We recommend that special consideration be given to conservation of the Camas Prairie population in Northern Oregon. It is the most geographically isolated population, has the lowest genetic diversity (He = 0.14) and appears to be the only remaining representative of a major genetic group that is now almost extinct. Finally, because the six major groups within R. pretiosa are strongly differentiated, occupy different habitat types, and are geographically separate, they should be recognized as evolutionarily significant units for purposes of conservation planning

Weight-based antibiotic dosing in a real-world European study of complicated skin and soft-tissue infections due to methicillin-resistant <i>Staphylococcus aureus</i>

AbstractWe aimed to characterize real-world dosing of weight-based intravenous (IV) antibiotic therapy in patients hospitalized for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTIs). This was a subgroup analysis of a retrospective chart review that captured data from 12 European countries. The study included patients ≥18 years old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Patients treated with IV vancomycin, teicoplanin or daptomycin at any stage during hospitalization were included in this analysis. Analyses were conducted at the regimen level (dosing in mg/kg or in mg, frequency, and total daily dose (TDD)), with potentially multiple regimens per patient, and the patient level, categorizing patients into low, standard (labelled) and high dosing groups according to their initial MRSA-targeted regimen. Among the 1502 patients in the parent study, 998 patients contributed a total of 1050 daptomycin, teicoplanin or vancomycin regimens. Across all regimens, the mean initial TDDs were 6.3 ± 1.9 mg/kg for daptomycin, 10.5 ± 4.9 mg/kg for teicoplanin and 28.5 ± 11.5 mg/kg for vancomycin. A total of 789 patients received first-line therapy with one of the above antibiotics. The majority of patients receiving first-line teicoplanin and daptomycin (96% and 80%, respectively) received higher than labelled cSSTI doses, whereas vancomycin doses were lower than labelled doses in >40% of patients. These real-world data reveal significant deviation from labelled antibiotic dosing in 12 European countries and the potential for suboptimal outcomes in patients with MRSA cSSTIs