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Mutations in BRCA1 and BRCA2 predispose individuals to certain cancers.sup.1-3, and disease-specific screening and preventative strategies have reduced cancer mortality in affected patients.sup.4,5. These classical tumour-suppressor genes have tumorigenic effects associated with somatic biallelic inactivation, although haploinsufficiency may also promote the formation and progression of tumours.sup.6,7. Moreover, BRCA1/2-mutant tumours are often deficient in the repair of double-stranded DNA breaks by homologous recombination.sup.8-13, and consequently exhibit increased therapeutic sensitivity to platinum-containing therapy and inhibitors of poly-(ADP-ribose)-polymerase (PARP).sup.14,15. However, the phenotypic and therapeutic relevance of mutations in BRCA1 or BRCA2 remains poorly defined in most cancer types. Here we show that in the 2.7% and 1.8% of patients with advanced-stage cancer and germline pathogenic or somatic loss-of-function alterations in BRCA1/2, respectively, selective pressure for biallelic inactivation, zygosity-dependent phenotype penetrance, and sensitivity to PARP inhibition were observed only in tumour types associated with increased heritable cancer risk in BRCA1/2 carriers (BRCA-associated cancer types). Conversely, among patients with non-BRCA-associated cancer types, most carriers of these BRCA1/2 mutation types had evidence for tumour pathogenesis that was independent of mutant BRCA1/2. Overall, mutant BRCA is an indispensable founding event for some tumours, but in a considerable proportion of other cancers, it appears to be biologically neutral--a difference predominantly conditioned by tumour lineage--with implications for disease pathogenesis, screening, design of clinical trials and therapeutic decision-making. Analysis of more than 17,000 tumours suggests that the contribution of germline and somatic mutations in the BRCA1 and BRCA2 genes to oncogenesis depends on tumour lineage., Author(s): Philip Jonsson [sup.1] [sup.2] [sup.3] , Chaitanya Bandlamudi [sup.1] , Michael L. Cheng [sup.4] [sup.7] , Preethi Srinivasan [sup.5] , Shweta S. Chavan [sup.1] , Noah D. Friedman [sup.2] [...]

PROFESSOR JAN NARVESON objects to my claim that abortion on demand up to the moment of birth is not a policy prescription that follows naturally from the basic principles that [...]

Shakespeare's Corioianus contains a significant amount of homoerotic material, much of it linked to the Roman protagonist's bond with his Volscian opponent, Aufidius. However, this homoeroticism did not begin to [...]

INTRODUCTION I. THE SCOPE AND IMPACT OF SETTLEMENTS A. The Conflict Between Settlements and the Aims of Title VII B. The Role of the EEOC II. THE SPLIT ON SUBSTANTIVE [...]

Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging (¹HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally in typically developing (TD) children at 3-4, 6-7 and 9-10 years-of-age. A total of 239 studies from 130 unique participants (54ASD, 22DD, 54TD) were acquired. ¹HMRS and MRI revealed no evidence for brain mitochondrial dysfunction in the children with ASD. Findings do not support a substantive role for brain mitochondrial abnormalities in the etiology or symptom expression of ASD, nor the widespread use of hyperbaric oxygen treatment that has been advocated on the basis of this proposed relationship. Keywords: Autism * Developmental disorders * MRS * MRI * Mitochondrial disorders * Brain metabolism * Lactate, Introduction Brain mitochondrial dysfunction has been implicated in a number of neurodegenerative disorders (Calabrese et al. 2001; Mancuso et al. 2006) and has been proposed to be a contributing factor [...]

This study discusses the pretest and posttest results of a batterer's intervention program (BIP) implemented within a California state prison substance abuse program (SAP), with a recommendation for further programs to be implemented within correctional institutions. The efficacy of utilizing correctional facilities to reach offenders who self-report domestic violence behaviors is evaluated. The 52-week curriculum was designed to address the unique environment of a correctional setting and the characteristics of the participants, using established psycho-educational and cognitive-behavioral methods. A repeated measurement design was used to evaluate the participants' cognitive changes, including acceptance of personal responsibility for abusive behaviors. Using a modified Abusive Behavior Inventory along with Criminal Thinking Scales, participants were tested at intake and again at 18 sessions. Their responses were statistically significant to p < .01. KEYWORDS batterer interventions, domestic violence, prison programs, spousal abusers, tertiary prevention DOI: 10.1080/10509674.2010.510770

Advance publicity and reviews of the film V for Vendetta frequently repeated the rumor that the plan to release the movie on 5 November 2005, the four-hundredth anniversary of the [...]

Leavitt, Gregory C. Class Conflict: The Pursuit and History of American Justice. New Brunswick, N. J.: Transaction Publishers, 2013. 249 pages. Cloth, $49.95. Americans tend to imagine that the 1787 [...]

Guidelines are presented for creating an effective, beneficial work-life balance. The process consists of experiments including tracking and reflecting, rejuvenating and restoring, delegating and developing, and exploring and venturing.

A research is conducted to find the prevalence of preoperative anemia and polythemia and their effect on postoperative outcomes in elderly patients undergoing noncardiac surgery.

A new vision of management in the 21 st century must address how organization members align their core values with their actions. Recent trends have changed the landscape on which business leaders pursue interests of various stakeholders. To be successful in the 21st century, business leaders at all levels must possess three important capacities--authenticity, integrity, and creativity--and enact them at work, in their families, in their communities, and in their personal growth. Building these capacities requires innovative means for educating and developing leaders. This article discusses the author's approach to realizing this goal--total leadership--which aims to help participants increase business results by enriching lives, to learn to lead in new ways that integrate work, home, community, and self for mutual gain. This article reviews the principles and skills of total leadership and describes experiments undertaken by participants to produce changes in both their leadership identity and their performance in all life domains. Keywords: leadership development; business education; work/life; human resource management; organization change

Objective: Heavy alcohol drinking is associated with increased prevalence of systemic hypertension (HTN), but the relationship between moderate drinking and HTN remains unclear. We explored the possible role of underreporting among moderate drinkers. Method: In a cross-sectional analysis of 105,378 persons, we defined a subset among persons reporting three or fewer drinks per day that was likely to include a disproportionate number of underreporters. This subset included persons who, on another occasion, indicated intake of three or more drinks per day or who ever had a diagnosis of an alcohol-related condition; these persons are called 'positive?' Persons who never reported three or more drinks per day and who had no alcohol-related diagnosis were called 'negative' Logistic regression models estimated the odds ratios (ORs) for prevalent HTN (140/90 mm Hg or greater) in the positive and negative subgroups, compared with lifelong abstainers as referent. All persons and four race-gender groups were studied, and they were controlled for age, education, smoking, and body mass index. We also studied the relationship of blood liver transaminase enzyme levels in the positive and negative subgroups at specific alcohol intake strata. Results: For persons reporting one to two drinks per day, the OR (95% confidence interval) of HTN was 1.32 (1.21-1.43) for positive persons and 1.16 (1.09-1.25) for negative persons. For those reporting less than one drink per day, the ORs were 0.97 (0.89-1.06) for positives and 0.92 (0.87-0.98) for negatives. For those reporting one to two drinks per day, positive/negative comparisons showed approximately a 75% increased prevalence of high liver transaminase enzymes. For those reporting less than one drink per day, the positive/negative difference was approximately 30%. Conclusion: In these data, increased prevalence of HTN among persons reporting one to two drinks per day appears to be partially due to underreporting of alcohol intake., PERSONS REPORTING AN INTAKE of three or more standard-sized alcoholic drinks per day have an increased prevalence of systemic hypertension (HTN) in cross-sectional analyses and an increased incidence in prospective [...]

Various patients are examined to investigate the prognostic significance of a common symptom dyspnea among patients consulting for cardiac stress check-up. The study reveals that a subgroup of otherwise asymptomatic patients who reported dyspnea were in great danger of death from cardiac or other causes, and hence testing for dyspnea is considered necessary while examining cardiac patients.

Although research and service contributions are important, it is a love for teaching that motivates many college faculty members. Excellent teachers often inspired faculty to pursue careers in higher education, [...]

An Amendment to this paper has been published and can be accessed via a link at the top of the paper., Author(s): Philip Jonsson [sup.1] [sup.2] [sup.3] , Chaitanya Bandlamudi [sup.1] , Michael L. Cheng [sup.4] [sup.7] , Preethi Srinivasan [sup.5] , Shweta S. Chavan [sup.1] , Noah D. Friedman [sup.2] [...]

Comprehensive medical and psychosocial services are essential to quality addiction treatment, but their availability declined in the 1980s. To determine whether this downward trend in the availability of comprehensive services continued in the 1990s, we analyzed data from a national panel study of outpatient substance abuse treatment units in 1990, 1995, and 2000. Response rates were greater than 85%. Regarding the availability of comprehensive services, including physical examinations, routine medical care, mental health services, financial counseling and employment counseling, administrators reported whether any substance abuse treatment client received the service in the past year. With the exception of physical examinations, whose reported availability increased from 1990 to 1995, and financial counseling, whose reported availability decreased during the same time, the reported availability of comprehensive services changed little during the 1990s. These findings highlight the continuing need to monitor access to comprehensive services and other quality markers in addiction treatment over time. Keywords: Health services accessibility; Substance abuse treatment centers; Substance-related disorders; Trends

SINCE the publication of Stephen Orgel's 'The Authentic Shakespeare' in 1988, the concept of authenticity has taken a beating in performance-oriented Shakespeare criticism. (1) Due to the recent emphasis on [...]

For several hundred years, one of the great glories of the common law system of criminal justice has been the requirement that prosecution witnesses give their testimony in the presence [...]

Cambridge: Cambridge University Press, 1999. Pp. xvi + 289. $69.95 cloth. $24.95 paper. In the third chapter of Recovering Shakespeare's Theatrical Vocabulary (1995), Alan Dessen imagines 'a dictionary or handbook [...]

I. INTRODUCTION We live in a world of monopoly monies--in two senses. First, most trade takes place between people who are physically close to each other; thus, money is usually [...]

A comparison is presented between the motion picture 'Independence Day', William Shakespeare's play 'Henry V' and the biblical story of King David. Parallels include how each work incorporates aspects of the popular culture of the era, and in turn influences the development of popular culture.

Cigar smoking can increase the risk of lung and heart disease as well as cancer of the upper digestive tract. This was the conclusion of a study that followed cigar smokers and non-smokers for almost 25 years. Compared to non-smokers, cigar smokers had twice the risk of lung cancer and upper digestive tract cancer. They also had a 25% to 50% higher risk of coronary heart disease and chronic obstructive lung disease. Use of cigars and alcohol seemed to increase the risk of these diseases.

Byline: Xingping Kang, Daniel S. Berman, Howard Lewin, Romalisa Miranda, Jacob Erel, John D. Friedman, Aman M. Amanullah Abstract: Background Diabetics generally have more frequent and extensive silent myocardial ischemia than nondiabetics, increasing the importance of noninvasive detection of coronary artery disease (CAD) in this cohort. However, little is known regarding the diagnostic accuracy of myocardial perfusion single-photon emission computed tomography (SPECT) in patients with diabetes. This study was undertaken to compare the diagnostic value of rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion SPECT in patients with and without diabetes. Methods Of the 203 patients with diabetes and 260 patients without diabetes who underwent dual-isotope myocardial perfusion SPECT with exercise or pharmacologic stress testing, 138 diabetics (12% type 1 diabetics) and 188 nondiabetics had coronary angiography within 6 months of the nuclear test, and 65 diabetics and 72 nondiabetics had a low likelihood ( Author Affiliation: Departments of Imaging (Division of Nuclear Medicine) and Medicine (Division of Cardiology), Cedars-Sinai Medical Center, The CSMC Burns & Allen Research Institute, and Department of Medicine, University of California Los Angeles, School of Medicine. Los Angeles, Calif Article History: Received 22 June 1998; Accepted 17 August 1998 Article Note: (footnote) [star] Reprint requests: Daniel S. Berman, MD, Department of Imaging, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Room A042, Los Angeles, CA 90048., [star][star] 0002-8703/99/$8.00 + 0 4/1/93935

Evidence Law Adrift. By Mirjan R. Damaska. New Haven: Yale University Press, 1997. Pp. x, 160. $27.50. Difference, as well as distance, yields perspective. A comparison of legal systems may [...]