Angiotensin II blockade and aortic-root dilation in Marfan's syndrome

Background: Progressive enlargement of the aortic root, leading to dissection, is the main cause of premature death in patients with Marfan's syndrome. Recent data from mouse models of Marfan's syndrome suggest that aortic-root enlargement is caused by excessive signaling by transforming growth factor (beta) (TGF-(beta)) that can be mitigated by treatment with TGF-(beta) antagonists, including angiotensin II-receptor blockers (ARBs). We evaluated the clinical response to ARBs in pediatric patients with Marfan's syndrome who had severe aortic-root enlargement. Methods: We identified 18 pediatric patients with Marfan's syndrome who had been followed during 12 to 47 months of therapy with ARBs after other medical therapy had failed to prevent progressive aortic-root enlargement. The ARB was losartan in 17 patients and irbesartan in 1 patient. We evaluated the efficacy of ARB therapy by comparing the rates of change in aortic-root diameter before and after the initiation of treatment with ARBs. Results: The mean (+/-SD) rate of change in aortic-root diameter decreased significantly from 3.54+/-2.87 mm per year during previous medical therapy to 0.46+/-0.62 mm per year during ARB therapy (P<0.001). The deviation of aortic-root enlargement from normal, as expressed by the rate of change in z scores, was reduced by a mean difference of 1.47 z scores per year (95% confidence interval, 0.70 to 2.24; P<0.001) after the initiation of ARB therapy. The sinotubular junction, which is prone to dilation in Marfan's syndrome as well, also showed a reduced rate of change in diameter during ARB therapy (P<0.05), whereas the distal ascending aorta, which does not normally become dilated in Marfan's syndrome, was not affected by ARB therapy. Conclusions: In a small cohort study, the use of ARB therapy in patients with Marfan's syndrome significantly slowed the rate of progressive aortic-root dilation. These findings require confirmation in a randomized trial

Male mastodon landscape use changed with maturation (late Pleistocene, North America)

Under harsh Pleistocene climates, migration and other forms of seasonally patterned landscape use were likely critical for reproductive success of mastodons (Mammut americanum) and other megafauna. However, little is known about how their geographic ranges and mobility fluctuated seasonally or changed with sexual maturity. We used a spatially explicit movement model that coupled strontium and oxygen isotopes from two serially sampled intervals (5+ adolescent years and 3+ adult years) in a male mastodon tusk to test for changes in landscape use associated with maturation and reproductive phenology. The mastodon’s early adolescent home range was geographically restricted, with no evidence of seasonal preferences. Following inferred separation from the matriarchal herd (starting age 12 y), the adolescent male’s mobility increased as landscape use expanded away from his natal home range (likely central Indiana). As an adult, the mastodon’s monthly movements increased further. Landscape use also became seasonally structured, with some areas, including northeast Indiana, used only during the inferred mastodon mating season (spring/summer). The mastodon died in this area (\u3e150 km from his core, nonsummer range) after sustaining a craniofacial injury consistent with a fatal blow from a competing male’s tusk during a battle over access to mates. Northeast Indiana was likely a preferred mating area for this individual and may have been regionally significant for late Pleistocene mastodons. Similarities between mammutids and elephantids in herd structure, tusk dimorphism, tusk function, and the geographic component of male maturation indicate that these traits were likely inherited from a common ancestor

Associations Between Daily Affect and Sleep Vary by Sleep Assessment Type: What Can Ambulatory EEG Add to the Picture?

Objective/Background Disrupted sleep can be a cause and a consequence of affective experiences. However, daily longitudinal studies show sleep assessed via sleep diaries is more consistently associated with positive and negative affect than sleep assessed via actigraphy. The objective of the study was to test whether sleep parameters derived from ambulatory electroencephalography (EEG) in a naturalistic setting were associated with day-to-day changes in affect. Participants/Method Eighty adults (mean age = 32.65 years, 63% female) completed 7 days of affect and sleep assessments. We examined bidirectional associations between morning positive affect and negative affect with sleep assessed via diary, actigraphy, and ambulatory EEG. Results Mornings with lower positive affect than average were associated with higher diary- and actigraphy-determined sleep efficiency that night. Mornings with higher negative affect than average were associated with longer actigraphy-determined total sleep time that night. Nights with longer diary-determined total sleep time, greater sleep efficiency, and shorter sleep onset latency than average were associated with higher next-morning positive affect, and nights with lower diary-determined wake-after-sleep-onset were associated with lower next-morning negative affect. EEG-determined sleep and affect results were generally null in both directions: only higher morning negative affect was associated with longer rapid eye movement (REM) sleep that night. Conclusions Self-reported sleep and affect may occur in a bidirectional fashion for some sleep parameters. EEG-determined sleep and affect associations were inconsistent but may still be important to assess in future studies to holistically capture sleep. Single-channel EEG represents a novel, ecologically valid tool that may provide information beyond diaries and actigraphy

Dietary and body mass thresholds for reproduction in grasshoppers

An organism’s dietary protein should match its respective dietary needs to yield the most advantageous effects; an extended lifespan and increased reproductive output. The key challenge however, is how to tailor a specific diet to an organism’s individual needs. Applying the technique of Piper et. al, we can approximate the optimal diet of the lubber grasshopper, Romalea microptera, by using the AA profile of vitellogenin (Vg), the precursor to egg yolk protein. The lubber grasshopper, Romalea microptera, was selected because of its plasticity in reproductive responsiveness in response to diet quality and quantity. Each of the organisms were fed 1g of romaine lettuce, ad libitum (ad-lib) zero protein high carbohydrate artificial diet and a different experimentally manipulated diet. The 4 treatment groups, Vg-balanced AA, unbalanced AA, ad-lib lettuce, and dietary restriction (DR), dietary treatments were applied twice daily from day 2 of adulthood to egg laying. The experimental group was force-fed the balanced AA diet, which was derived from the AA composition of vitellogenin. The unbalanced AA group was fed an isonitrogenous diet with over representations of AA’s found in romaine. The ad lib group had unlimited access to romaine and was force-fed PBS. The DR group was fed a diet comprising of 1 gram of romaine and PBS. The results indicated ad-lib group had the highest yield, followed by Vg-balanced, unbalanced, and DR . In contrast, somatic mass and storage did not differ across 3 groups fed 1gm lettuce daily. Isonitrogenous diets exhibited difference in reproduction but not somatic growth

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Small-scale societies exhibit fundamental variation in the role of intentions in moral judgment

Intent and mitigating circumstances play a central role in moral and legal assessments in large-scale industrialized societies. Although these features of moral assessment are widely assumed to be universal, to date, they have only been studied in a narrow range of societies. We show that there is substantial cross-cultural variation among eight traditional small-scale societies (ranging from hunter-gatherer to pastoralist to horticulturalist) and two Western societies (one urban, one rural) in the extent to which intent and mitigating circumstances influence moral judgments. Although participants in all societies took such factors into account to some degree, they did so to very different extents, varying in both the types of considerations taken into account and the types of violations to which such considerations were applied. The particular patterns of assessment characteristic of large-scale industrialized societies may thus reflect relatively recently culturally evolved norms rather than inherent features of human moral judgment

Health benefi ts, costs, and cost-eff ectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models

Background New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. Methods We used several independent mathematical models in four settings—South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)—to assess the potential health benefi ts, costs, and cost-eff ectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost eff ective if the cost per DALY averted was less than the country’s 2012 per-head gross domestic product (GDP; South Africa:$8040; Zambia: $1425; India:$1489; Vietnam: $1407) and cost eff ective if the cost per DALY averted was less than three times the per-head GDP. Findings In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from$237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to$749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost eff ective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to$241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost eff ective. Interpretation Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost eff ective in lowincome and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets

Acoustic metamaterial for low frequency sound absorption in linear and nonlinear regimes

Acoustic metamaterial absorbers have been built and tested with focus on low frequency airborne sound absorption in linear and nonlinear regimes. The absorbers are made up of a series of piled up flat cavities, separated by thin walls and traversed by a perforation at their centre. A model for absorber effective properties is developed and compared with experimental data. The model is used to derive simple formulae for the frequency and the peak value of the absorption coefficient at the lowest frequency resonance, depending on the geometrical parameters of the structure. Different absorbers have been built with several cavity thicknesses to allow comprehensive comparisons with the model. Nonlinear properties of the absorbers are investigated experimentally using sine wave excitation around the resonance frequency with the amplitude of the incident wave up to 250 Pa. Flow resistivity measurements at low flow rates show that the periodic set of cavities does not modify resistivity significantly when compared to a simple perforated cylinder with same thickness. As flow rate increases, the flow resistivity grows linearly according to Forchheimer's law and has a significant dependence on the absorber thickness. A numerical model is developed accounting for the linear growth of flow resistivity with particle velocity amplitude in the central perforation and compared with the measurements at high amplitudes of the incident wave