Prosecutorial Misconduct in Closing Argument: The Role of Intent in Appellate Review

This article is the first of two articles that discuss the concern of prosecutorial misconduct. This article focuses improper prosecutorial argument in the 1990s. The article examines a California Supreme Court reversal of a murder conviction and death sentence due to misconduct during the prosecutor’s closing argument. The article then discusses forty-five federal appellate court opinions addressing the issue of prosecutorial misconduct

Prosecutorial Misconduct in Closing Argument: The Role of Intent in Appellate Review

This article is the first of two articles that discuss the concern of prosecutorial misconduct. This article focuses improper prosecutorial argument in the 1990s. The article examines a California Supreme Court reversal of a murder conviction and death sentence due to misconduct during the prosecutor’s closing argument. The article then discusses forty-five federal appellate court opinions addressing the issue of prosecutorial misconduct

Vitamins and Perinatal Outcomes Among HIV-Negative Women in Tanzania.

Prematurity and low birth weight are associated with high perinatal and infant mortality, especially in developing countries. Maternal micronutrient deficiencies may contribute to these adverse outcomes. In a double-blind trial in Dar es Salaam, Tanzania, we randomly assigned 8468 pregnant women (gestational age of fetus, 12 to 27 weeks) who were negative for human immunodeficiency virus infection to receive daily multivitamins (including multiples of the recommended dietary allowance) or placebo. All the women received prenatal supplemental iron and folic acid. The primary outcomes were low birth weight (<2500 g), prematurity, and fetal death. The incidence of low birth weight was 7.8% among the infants in the multivitamin group and 9.4% among those in the placebo group (relative risk, 0.82; 95% confidence interval [CI], 0.70 to 0.95; P=0.01). The mean difference in birth weight between the groups was modest (67 g, P<0.001). The rates of prematurity were 16.9% in the multivitamin group and 16.7% in the placebo group (relative risk, 1.01; 95% CI, 0.91 to 1.11; P=0.87), and the rates of fetal death were 4.3% and 5.0%, respectively (relative risk, 0.87; 95% CI, 0.72 to 1.05; P=0.15). Supplementation reduced both the risk of a birth size that was small for gestational age (<10th percentile; 10.7% in the multivitamin group vs. 13.6% in the placebo group; relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.001) and the risk of maternal anemia (hemoglobin level, <11 g per deciliter; relative risk, 0.88; 95% CI, 0.80 to 0.97; P=0.01), although the difference in the mean hemoglobin levels between the groups was small (0.2 g per deciliter, P<0.001). Multivitamin supplementation reduced the incidence of low birth weight and small-for-gestational-age births but had no significant effects on prematurity or fetal death. Multivitamins should be considered for all pregnant women in developing countries. (ClinicalTrials.gov number, NCT00197548 [ClinicalTrials.gov].)

Geochemical stages at Jasper Seamount and the origin of intraplate volcanoes

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 19 (2009): Q02001, doi:10.1029/2008GC002236.Ocean intraplate volcanoes (OIVs) are formed in a sequence of stages, from large to small, that involve a systematic progression in mantle melting in terms of volumes and melt fractions with concomitant distinct mantle source signatures. The Hawaiian volcanoes are the best-known example of this type of evolution, even though they are extraordinarily large. We explore the Pb-Sr-Nd-Hf isotopic evolution of much smaller OIVs in the Fieberling-Guadalupe Seamount Trail (FGST) and small, near-ridge generated seamounts in the same region. In particular, we investigate whether we can extend the Hawaiian models to Jasper Seamount in the FGST, which displays three distinct volcanic stages. Each stage has characteristic variations in Pb-Sr-Nd-Hf isotopic composition and trace element enrichment that are remarkably similar to the systematics observed in Hawaii: (1) The most voluminous, basal “shield building” stage, the Flank Transitional Series (FTS), displays slightly isotopically enriched compositions compared to the common component C and the least enriched trace elements (143Nd/144Nd: 0.512866–0.512909, 206Pb/204Pb: 18.904–19.054; La/Sm: 3.71–4.82). (2) The younger and substantially less voluminous Flank Alkalic Series (FAS) is comparatively depleted in Sr, Nd, and Hf isotope compositions plotting on the side of C, near the least extreme values for the Austral Islands and St. Helena. Trace elements are highly enriched (143Nd/144Nd: 0.512912–0.512948, 206Pb/204Pb: 19.959–20.185; La/Sm: 9.24). (3) The Summit Alkalic Series (SAS) displays the most depleted Sr, Nd, and Hf isotope ratios and is very close in isotopic composition to the nearby near-ridge seamounts but with highly enriched trace elements (143Nd/144Nd: 0.512999–0.513050, 206Pb/204Pb: 19.080–19.237; La/Sm: 5.73–8.61). These data fit well with proposed multicomponent melting models for Hawaii, where source lithology controls melt productivity. We examine the effect of melting a source with dry peridotite, wet peridotite, and pyroxenite, calculating melt productivity functions with depth to evaluate the effect of potential temperature and lithospheric thickness. This type of melting model appears to explain the isotopic variation in a range of small to large OIVs, in particular for OIVs occurring far from the complicating effects of plate boundaries and continental crust, constraining their geodynamic origin.JBT acknowledges financial support from the French Institut National des Sciences de l’Univers. The isotope work at SDSU was made possible by NSF and Keck grants to BBH

Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver

Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT), white adipose (WAT) and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05) up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver). Gene ontology analysis revealed for the first time significant (P<0.05) down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production

Predictive and Prognostic Roles of BRAF Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803

Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colon and rectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer

Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis

The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery applications. Statement of Significance The surface topography of synthetic biomaterials plays important roles in material-driven osteogenesis. The data presented herein have shown that the surface topography of calcium phosphate ceramics regulates mesenchymal stromal cells (e.g., human bone marrow mesenchymal stromal cells, hBMSCs) with respect to morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation in vitro. Together with bone formation in vivo, our results suggested a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery by the bioengineering control of osteogenesis via primary cilia modulation

Attenuating Effect of Vigorous Physical Activity on the Risk for Inherited Obesity: A Study of 47,691 Runners

Objective: Physical activity has been shown to attenuate the effect of the FTO polymorphism on body weight, and the heritability of body weight in twin and in family studies. The dose-response relationship between activity and the risk for inherited obesity is not well known, particularly for higher doses of vigorous exercise. Such information is needed to best prescribe an exercise dose for obesity prevention in those at risk due to their family history. Design: We therefore analyzed self-reported usual running distance, body mass index (BMI), waist circumference, and mother’s and father’s adiposity (1 = lean, 2 = normal, 3 = overweight, and 4 = very overweight) from survey data collected on 33,480 male and 14,211 female runners. Age-, education-, and alcohol-adjusted regression analyses were used to estimate the contribution of parental adiposities to the BMI and waist circumferences in runners who ran an average of,3, 3–6, 6–9, $9 km/day. Results: BMI and waist circumferences of runners who ran,3 km/day were significantly related to their parents adiposity (P,10 215 and P,10 211, respectively). These relationships (i.e., kg/m 2 or cm per increment in parental adiposity) diminished significantly with increasing running distance for both BMI (inheritance6exercise interaction, males: P,10 210; females: P,10 25) and waist circumference (inheritance6exercise interaction, males: P,10 29; females: P = 0.004). Compared to,3 km/day, the parental contribution to runners who averaged$9 km/day was diminished by 48 % for male BMI, 58 % for female BMI, 55 % for male waist circumference, and 58 % for female waist circumference. These results could not b

Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the associations between 16 specific single nucleotide polymorphisms (SNPs) in 8 obesity-related genes and overall and cause-specific mortality. We also examined the associations between the SNPs and body mass index (BMI) and change in BMI over time.</p> <p>Methods</p> <p>Data were analyzed from 9,919 individuals who participated in two large community-based cohort studies conducted in Washington County, Maryland in 1974 (CLUE I) and 1989 (CLUE II). DNA from blood collected in 1989 was genotyped for 16 SNPs in 8 obesity-related genes: monoamine oxidase A (<it>MAOA</it>), lipoprotein lipase (<it>LPL</it>), paraoxonase 1 and 2 (<it>PON1 </it>and <it>PON2</it>), leptin receptor (<it>LEPR</it>), tumor necrosis factor-α (<it>TNFα</it>), and peroxisome proliferative activated receptor-γ and -δ (<it>PPARG </it>and <it>PPARD</it>). Data on height and weight in 1989 (CLUE II baseline) and at age 21 were collected from participants at the time of blood collection. All participants were followed from 1989 to the date of death or the end of follow-up in 2005. Cox proportional hazards regression was used to obtain the relative risk (RR) estimates and 95% confidence intervals (CI) for each SNP and mortality outcomes.</p> <p>Results</p> <p>The results showed no patterns of association for the selected SNPs and the all-cause and cause-specific mortality outcomes, although statistically significant associations (p < 0.05) were observed between <it>PPARG </it>rs4684847 and all-cause mortality (CC: reference; CT: RR 0.99, 95% CI 0.89, 1.11; TT: RR 0.60, 95% CI 0.39, 0.93) and cancer-related mortality (CC: reference; CT: RR 1.01, 95% CI 0.82, 1.25; TT: RR 0.22, 95% CI 0.06, 0.90) and <it>TNFα </it>rs1799964 and cancer-related mortality (TT: reference; CT: RR 1.23, 95% CI 1.03, 1.47; CC: RR 0.83, 95% CI 0.54, 1.28). Additional analyses showed significant associations between SNPs in <it>LEPR </it>with BMI (rs1137101) and change in BMI over time (rs1045895 and rs1137101).</p> <p>Conclusion</p> <p>Findings from this cohort study suggest that the selected SNPs are not associated with overall or cause-specific death, although several <it>LEPR </it>SNPs may be related to BMI and BMI change over time.</p