Pursuing Energy-Efficient Behavior in a Regulatory Environment: Motivating Policymakers, Program Administrators, and Program Implementers

This white paper examines how policymakers, program administrators, and program implementers can be motivated to pursue behavioral change in a regulatory environment. For the purposes of this report, behavior change is defined rather broadly, encompassing both behaviors associated with the purchase and installation of energy efficiency technologies as well as behaviors, decisions, and actions that might be thought of as more independent of technology. These include energy use habits, lifestyle choices, and consumption patterns. The insights and lessons discussed in this paper are drawn from a wide variety of sources including interviews with representatives from the energy and utility communities, and program documentation for energy-related programs and projects

Differences in visceral adipose tissue and biochemical cardiometabolic risk markers in elite rugby union athletes of Caucasian and Polynesian descent

Polynesian individuals are leaner with greater musculature than Caucasians of an equivalent size, and this genetically different morphology provides a physique that is often compatible with success in a number of sports, including rugby union. Evidence indicates that Polynesians have greater stores of absolute and relative abdominal fat mass and this is known to confer cardiometabolic risk. The aims of this study were to (1) explore the relationship between ethnicity, visceral adipose tissue (VAT), and cardiometabolic disease risk markers in elite Caucasian and Polynesian rugby union athletes, and (2) assess the impact of a pre-season training programme on these markers. Twenty-two professional rugby union athletes of Caucasian (n = 11) and Polynesian (n = 11) descent underwent physique assessment via surface anthropometry, dual-energy X-ray absorptiometry, and magnetic resonance imaging before and after an 11-week pre-season. A fasted blood test was undertaken at both time points. Compared to Caucasians, at baseline Polynesians displayed significantly higher VAT (771 ± 609 cm3 vs 424 ± 235 cm3; p = 0.043), triglycerides (1.0 ± 0.9 mmol/L vs 0.6 ± 0.2 mmol/L; p = 0.050), and low-density lipoprotein cholesterol (3.1 ± 0.9 mmol/L vs 2.3 ± 0.7 mmol/L; p = 0.019). Similar changes were observed in both groups over the pre-season period in VAT and blood biochemical markers. Polynesian rugby union athletes were more likely than Caucasians to exhibit risk factors associated with cardiometabolic disease, such as elevated VAT and unfavourable lipid profiles. Further longitudinal research is required to identify and explain the short- and long-term risk of cardiometabolic disease in athletes of Polynesian descent

Assessment of abdominal fat compartments using DXA in premenopausal women from anorexia nervosa to morbid obesity

Objective: The purpose of this study was to test a newly developed DXA method for abdominal fat depot quantification in subjects with AN, normal weight, and obesity using CT as a gold standard. Design and Methods 135 premenopausal women (overweight/obese: n=89, normal-weight: n=27, AN: n=19); abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) areas determined on CT and DXA. Results: There were strong correlations between DXA and CT measurements of abdominal fat compartments in all groups with the strongest correlation coefficients in the normal-weight and overweight/obese groups. Correlations of DXA and CT VAT measurements were strongest in the obese group and weakest in the AN group. DXA abdominal fat depots were higher in all groups compared to CT, with the largest % mean difference in the AN group and smallest in the obese group. Conclusions: A new DXA technique is able to assess abdominal fat compartments including VAT in premenopausal women across a large weight spectrum However, DXA measurements of abdominal fat were higher than CT, and this percent bias was most pronounced in the AN subjects and decreased with increasing weight, suggesting that this technique may be more useful in obese individuals

Individual Response to Risk As a Function of Normative Social Pressure: A Pilot Study of Seat Belt Use

The authors attempt to clarify some of the variables that influence whether people act appropriately when a Risk is substantial and subject to individual control. They do so by reporting results of a pilot study of seat belt use. Also, the authors believe their approach to be generalizable to problems such as encouraging people to test for radon, to use condoms to prevent AIDS or to quit smoking

CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism

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Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis.

Randomized controlled basket trials investigating drugs targeting a rare molecular alteration are challenging. Using patients as their own control overcomes some of these challenges. Growth modulation index (GMI) is the ratio of progression-free survival (PFS) on the current therapy to time to progression (TTP) on the last prior line of therapy; GMI ≥ 1.33 is considered a threshold of meaningful clinical activity. In a retrospective, exploratory analysis among patients with advanced tropomyosin receptor kinase (TRK) fusion cancer treated with the selective TRK inhibitor larotrectinib who received ≥1 prior line of therapy for locally advanced/metastatic disease, we determined the proportion of patients with GMI ≥ 1.33; patients who had not progressed by data cut-off were censored for PFS. Among 72 eligible patients, median GMI was 2.68 (range 0.01-48.75). Forty-seven patients (65%) had GMI ≥ 1.33; 13/25 patients (52%) with GMI < 1.33 had not yet progressed on larotrectinib. Kaplan-Meier estimates showed a median GMI of 6.46. The probability of attaining GMI ≥ 1.33 was 0.75 (95% confidence interval (CI), 0.65-0.85). Median TTP on previous treatment was 3.0 months (95% CI, 2.6-4.4). Median PFS on larotrectinib was not estimable ((NE); 95% CI, NE; hazard ratio, 0.220 (95% CI, 0.146-0.332)). This analysis suggests larotrectinib improves PFS for patients with TRK fusion cancer compared with prior therapy

The Role of γ-Tubulin in Centrosomal Microtubule Organization

As part of a multi-subunit ring complex, γ-tubulin has been shown to promote microtubule nucleation both in vitro and in vivo, and the structural properties of the complex suggest that it also seals the minus ends of the polymers with a conical cap. Cells depleted of γ-tubulin, however, still display many microtubules that participate in mitotic spindle assembly, suggesting that γ-tubulin is not absolutely required for microtubule nucleation in vivo, and raising questions about the function of the minus end cap. Here, we assessed the role of γ-tubulin in centrosomal microtubule organisation using three-dimensional reconstructions of γ-tubulin-depleted C. elegans embryos. We found that microtubule minus-end capping and the PCM component SPD-5 are both essential for the proper placement of microtubules in the centrosome. Our results further suggest that γ-tubulin and SPD-5 limit microtubule polymerization within the centrosome core, and we propose a model for how abnormal microtubule organization at the centrosome could indirectly affect centriole structure and daughter centriole replication

CXCR2 and CXCL4 regulate survival and self-renewal of hematopoietic stem/progenitor cells

The regulation of hematopoietic stem cell (HSC) survival and self-renewal within the bone marrow (BM) niche is not well understood. We therefore investigated global transcriptomic profiling of normal human hematopoietic stem/progenitor cells, revealing that several chemokine ligands (CXCL1-4, CXCL6, CXCL10, CXCL11, CXCL13) were up-regulated in human quiescent CD34+Hoescht-Pyronin Y- and primitive CD34+38-, as compared to proliferating CD34+Hoechst+Pyronin Y+ and CD34+38+ stem/progenitor cells. This suggested that chemokines may play an important role in the homeostasis of HSCs. In human CD34+ hematopoietic cells, knock-down of CXCL4 or pharmacological inhibition of the chemokine receptor CXCR2, significantly decreased cell viability and colony forming cell (CFC) potential. Studies on Cxcr2-/- mice demonstrated enhanced BM and spleen cellularity, with significantly increased numbers of HSC, hematopoietic progenitor cell (HPC)-1, HPC-2 and Lin-Sca-1+c-Kit+ sub-populations. Cxcr2-/- stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. Parallel studies on Cxcl4 demonstrated reduced numbers of CFC in primary and secondary assays following knock-down in murine c-Kit+ cells and Cxcl4-/- mice showed a decrease in HSC and reduced self-renewal capacity after secondary transplantation. These data demonstrate that the CXCR2 network and CXCL4 play a role in the maintenance of normal hematopoietic stem/progenitor cell fates, including survival and self-renewal