Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron

The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2] for the proton and neutron have been determined from measurements of polarised cross section asymmetries in deep inelastic scattering of 27.5 GeV longitudinally polarised positrons from polarised 1H and 3He internal gas targets. The data were collected in the region above the nucleon resonances in the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the proton the contribution to the generalised Gerasimov-Drell-Hearn integral was found to be substantial and must be included for an accurate determination of the full integral. Furthermore the data are consistent with a QCD next-to-leading order fit based on previous deep inelastic scattering data. Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte

Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction

Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark- antiquark fluctuations with the nuclear medium.Comment: RevTeX, 5 pages, 3 figure

Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease that increases significantly cardiovascular morbidity and mortality. It is associated with obesity, insulin resistance, beta-cell dysfunction, and hyperglucagonemia, the combination of which typically leads to hyperglycemia. Incretin-based treatment modalities, and in particular glucagon-like peptide 1 (GLP-1) receptor agonists, are able to successfully counteract several of the underlying pathophysiological abnormalities of T2DM. The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis. GLP-1 receptors are widely expressed throughout human body; thus, GLP-1-based therapies exert pleiotropic and multisystemic effects that extend far beyond pancreatic islets. A large body of experimental and clinical data have suggested a considerable protective role of GLP-1 analogs in the cardiovascular system (decreased blood pressure, improved endothelial and myocardial function, functional recovery of failing and ischemic heart, arterial vasodilatation), kidneys (increased diuresis and natriuresis), gastrointestinal tract (delayed gastric emptying, reduced gastric acid secretion), and central nervous system (appetite suppression, neuroprotective properties). The pharmacologic use of GLP-1 receptor agonists has been shown to reduce bodyweight and systolic blood pressure, and significantly improve glycemic control and lipid profile. Interestingly, weight reduction induced by GLP-1 analogs reflects mainly loss of abdominal visceral fat. The critical issue of whether the emerging positive cardiometabolic effects of GLP-1 analogs can be translated into better clinical outcomes for diabetic patients in terms of long-term hard endpoints, such as cardiovascular morbidity and mortality, remains to be elucidated with prospective, large-scale clinical trials

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Item does not contain fulltextBACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction &lt; 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Toward a 21st-century health care system: Recommendations for health care reform

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high risk, early breast cancer.

BACKGROUND: The randomized, double-blind OlympiA trial compared one year of the oral poly(adenosine diphosphate-ribose) polymerase) inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2 (HER2)-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive-disease-free survival (IDFS) and distant-disease-free survival (DDFS). The olaparib-group had fewer deaths than the placebo-group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: 1,836 patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy (N)ACT, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone-receptor-positive-cancers. Statistical significance for OS at this IA required P<0.015. RESULTS: With median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib-group relative to the placebo-group (HR, 0.68; 98.5% CI 0.47 to 0.97; P=0.009). Four-year OS was 89.8% in the olaparib-group and 86.4% in the placebo-group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for olaparib-group versus placebo-group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS). CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals

Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2

Características sensoriais, físicas e químicas e aceitação de arroz irrigado ou de terras altas

Resumo:O objetivo deste trabalho foi caracterizar química, física e sensorialmente três genótipos de arroz polido de cultivo irrigado e cinco de terras altas. Determinaram-se: a composição centesimal, o amido, a amilose, a temperatura de gelatinização (Tg), a absorção de água ao cozimento, a cor, a textura instrumental, o perfil sensorial e a aceitação de atributos. A composição centesimal e o teor de amido variaram entre os genótipos. O 'Moti' e a linhagem N2583 foram classificados como cerosos, 'Douradão' apresentou amilose muito baixa, e os demais genótipos, amilose baixa. 'Irga 417', 'Moti' e AB101002 apresentaram Tg baixa; 'Douradão', alta; e os demais, intermediária. O 'Moti' e a linhagem N2583 crus apresentaram os maiores valores de L*; no entanto, após o cozimento, esses valores diminuíram e foram idênticos em todos os genótipos. 'Arroz-da-terra' apresentou maior a*, 'BRS Primavera' e N2583 apresentaram maior b*; e após o cozimento, houve redução desses valores. Na análise sensorial, destacaram-se 'AN Cambará', por pontos escuros e formato alongado; AB101002, 'Irga 417' e 'BRS Primavera', pela firmeza, cor branca e grãos soltos, que foram bem aceitos; e o 'Moti', por ser pegajoso, macio e com brilho, foi o menos aceito. Os atributos sensoriais do arroz são mais associados a características químicas, intrínsecas ao genótipo, do que à atribuição de plantio a terras altas ou irrigadas