An Eight-Week Trial Investigating the Efficacy and Tolerability of Atorvastatin for Children and Adolescents With Heterozygous Familial Hypercholesterolemia

This study aimed to assess the efficacy and tolerability of atorvastatin in Tanner stage (TS) 1 patients ages 6 to 10 years and TS ≥2 patients ages 10 to <18 years with genetically confirmed heterozygous familial hypercholesterolemia (HeFH) and a low density lipoprotein cholesterol (LDL-C) level of 4 mmol/l (155 mg/dl) or higher. In this open-label, 8-week study, 15 TS 1 children were treated initially with atorvastatin 5 mg/day and 24 TS ≥2 children with 10 mg/day. Doses were doubled at week 4 if the LDL-C target (<3.35 mmol/l [130 mg/dl]) was not achieved. The efficacy variables were the percentage change from baseline in LDL-C, total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), and apolipoprotein (Apo) A-I and Apo B. Safety evaluations included clinical monitoring, subject-reported adverse events (AEs), vital signs, and clinical laboratory tests. The mean values for LDL-C, TC, VLDL-C, and Apo B decreased by week 2 among all TS 1 and TS ≥2 patients, whereas TG, HDL-C, and Apo A-I varied considerably from week to week. After 8 weeks, the mean reduction in LDL-C was −40.7% ± 8.4 for the TS 1 children and −39.7% ± 10.3 for the TS ≥2 children. For the TS 1 patients, the mean reductions were −34.1% ± 6.9 for TC and −6.0% ± 32.1 for TG. The corresponding changes for the TS ≥2 patients were −35.6% ± 9.5 for TC and −21.1% ± 29.7 for TG. Four patients experienced mild to moderate treatment-related AEs. No serious AEs or discontinuations were reported. Overall, no difference in safety or tolerability was observed between the younger and older cohorts. Across the range of exposures after atorvastatin 5 to 10 mg (TS 1) or atorvastatin 10 to 20 mg (TS ≥2) doses for 8 weeks, clinically meaningful reductions in LDL-C, TC, VLDL-C, and Apo were observed with atorvastatin in pediatric patients who had HeFH. Atorvastatin also was well tolerated in this population

Geographic variation in social organization of Galápagos mockingbirds: ecological correlates of group territoriality and cooperative breeding

To investigate ecological influences on cooperative social organization, I studied the four allopatric species of mockingbirds ( Nesomimus spp.) endemic to the Galápagos archipelago on four islands. On three small, low and arid islands (Genovesa, Champion and Española), mockingbird territories filled all terrestrial habitat, mean group size varied from 4.5 to 14.2 adults, maximum group size ranged from seven to 24 birds, and 70–100% of groups contained more than two birds. San Cristóbal is larger and higher, and it supports a broader range of habitats. At one highland and two coastal sites on this island, mockingbirds did not hold territories in all available habitats, group size averaged 2.2 adults, only 25% of groups were larger than two, and none included more than three adults. Adults dispersed into vacant habitat to establish new territories only on San Cristóbal. Helping behavior has not yet been observed on San Cristóbal, but it occurs on the other three islands. These results support the hypothesis that social groups and cooperative breeding are maintained where limited availability of preferred habitat constrains dispersal. The mechanism relaxing habitat saturation on San Cristóbal, however, remains undetermined. Predation by introduced rats and cats may reduce survival and indirectly reduce group size; these predators are absent from Genovesa, Champion and Española. Differences in food supplies could also affect interand intra-island variation in population density. Variation in social organization among arid coastal sites on the four islands, and similarity between climatically different sites on San Cristóbal, suggest that climatic conditions are less important as determinants of dispersal and breeding. Skews in adult sex ratios also fail to account for inter-island variation in sociality. Although they live in a climatically variable environment, territorial behavior and the physical limits of suitable habitat have an overriding influence on cooperative social organization in Galápagos mockingbirds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46894/1/265_2004_Article_BF00302932.pd

Rural waste generation: a geographical survey at local scale

"The paper examines the per capita waste generation rates from from rural areas of Neamț County (Romania) using thematic cartography. Geographical approach of this issue is difficult because the lack of a geostatistic database at commune scale. Spatial analysis of waste indicators reveals several disparities between localities. Comparability of data between communes located in various geographical conditions must be carrefully made according to local waste management systems. Several dysfunctionalities are outlined in order to compare these results, on the one hand, between localities and on the one hand, between recent years. Geographical analysis of waste generation rates is imperative for a proper monitoring of this sector. Data from 2009, 2010 and 2012 shows that rural waste management is in a full process of change towards a more organized, stable and efficient system." (author's abstract

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial)

Background: Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome.Methods/design: This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditio

Environmentally controlled phenotypic plasticity of morphology and polypeptide expression in two populations of Daphnia pulex (Crustacea: cladocera)

Two local Daphnia pulex populations which are subject to different types of seasonally varying predation pressures were studied. Individuals from both populations were raised in laboratory environments which simulated either summer or winter temperatures and photoperiods. When individuals from the same parthenogenetic clone were raised in different seasonal environments, each clone exhibited phenotypic variation specific to each of the seasonal environments. Intraclonal phenotypic plasticity was found in both populations at two different levels: variation in morphological characters, and variation in the expressed polypeptide phenotypes. Summer environmental conditions induced predator-resistant morphological traits, while winter conditions induced predator-susceptible ones. From 65% to 71% of over 200 major polypeptides were specifically expressed in either one seasonal environment or the other. This is evidence for the existence of environmentally induced switching between alternate developmental programs. Clones from the population with the least year to year predictability of seasonal predation pressure showed more interclonal variation in environment specific phenotypic expression than clones from the more predictably fluctuating environment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47754/1/442_2004_Article_BF00379879.pd

Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity

Robin A Laskey,1 Scott D Richard,2 Ashlee L Smith,1 Jeff F Lin,1 Tiffany L Beck,3 Jamie L Lesnock,1 Joseph L Kelley 3rd,1 Alexander B Olawaiye,1 Paniti Sukumvanich,1 Thomas C Krivak4 1Division of Gynecologic Oncology, Magee-Womens Hospital of UPMC, Pittsburgh, 2Division of Gynecologic Oncology, Drexel University College of Medicine/Hahnemann University Hospital, Philadelphia, 3Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital of UPMC, Pittsburgh, 4Division of Gynecologic Oncology, Western Pennsylvania Hospital, Pittsburgh, PA, USA Purpose: Bevacizumab (Bev) is associated with improved progression-free survival in advanced epithelial ovarian cancer. The use of Bev in patients with gynecologic malignancy is increasing; however, little is known about cumulative toxicity and response in patients retreated with Bev. Our goal was to determine cumulative side effects and response in patients retreated with Bev. Patients and methods: Women with recurrent gynecologic malignancy treated with Bev between January 2007 and March 2012 at a single institution were identified, including a subset who received Bev in a subsequent regimen. The primary outcome was Bev-associated toxicity, and the secondary outcome was response. Results: Of 83 patients that received Bev for recurrent disease, 23 were retreated with Bev and four received Bev maintenance. Three patients (13%) developed grade 3 or 4 hypertension; all had a history of chronic hypertension. One (4.3%) patient developed grade 3 proteinuria, and one (4.3%) developed an enterovaginal fistula. Four patients discontinued Bev secondary to toxicity. Toxicity was not related to the cumulative number of cycles. Twenty-six percent of patients responded to Bev retreatment. On univariate analysis, there was a significant (P=0.003) overall survival advantage when the Bev-free interval was &gt;9 months (95% confidence interval [CI] 4.9&ndash;43.7) compared to &le;9 months (95% CI 2.1&ndash;11.5), 24.3 months, and 6.8 months. Conclusion: Retreatment of patients with recurrent gynecologic malignancy with Bev did not increase morbidity and was associated with treatment response. Physicians treating women with recurrent disease may consider a Bev-containing regimen even if prior regimen(s) included Bev. Future studies should prospectively evaluate the efficacy of this treatment strategy. Keywords: bevacizumab, gynecologic malignancy, cumulative toxicity, treatment respons