Genetic assessment of additional endophenotypes from the Consortium on the Genetics of Schizophrenia Family Study.

The Consortium on the Genetics of Schizophrenia Family Study (COGS-1) has previously reported our efforts to characterize the genetic architecture of 12 primary endophenotypes for schizophrenia. We now report the characterization of 13 additional measures derived from the same endophenotype test paradigms in the COGS-1 families. Nine of the measures were found to discriminate between schizophrenia patients and controls, were significantly heritable (31 to 62%), and were sufficiently independent of previously assessed endophenotypes, demonstrating utility as additional endophenotypes.

Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History.

Objective: The Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton).

Treatment of Breast Cancer in the Elderly.

Despite the fact that the US population is aging and the numbers of older patients with breast cancer are increasing, many questions remain on how to optimally treat this patient population. Accrual of older cancer patients to clinical trials has been stagnant, and consequently, evidence-based recommendations are often limited by a lack of prospective data to inform decisions. Increasingly, one's functional status has been recognized as a critical factor in predicting for treatment toxicity, and tools such as the geriatric assessment will likely become a routine part of clinical practice over time.

Higher Stage of Disease Is Associated With Bilateral Mastectomy Among Patients With Breast Cancer: A Population-Based Survey.

Background: The reasons for increasing rates of bilateral mastectomy for unilateral breast cancer are incompletely understood, and associations of disease stage with bilateral surgery have been inconsistent. We examined associations of clinical and sociodemographic factors, including stage, with surgery type and reconstruction receipt among women with breast cancer.

Patients And Methods: We surveyed a diverse population-based sample of women from Northern California cancer registries with stage 0 to III breast cancer diagnosed during 2010-2011 (participation rate, 68.

The effect of Paget disease on axillary lymph node metastases and survival in invasive ductal carcinoma.

Background: The objective of this study was to examine the effect of Paget disease (PD) on axillary lymph node metastases and survival in patients who had concomitant invasive ductal carcinoma (PD-IDC).

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women who were diagnosed with PD-IDC from 2000 to 2011, comparing baseline demographic and tumor characteristics with those who were diagnosed with IDC alone during the same period. Multivariable logistic regression was used to examine the association of PD-IDC with axillary lymph node metastasis, and breast cancer-specific survival and overall survival were compared between the PD-IDC and IDC groups using the Kaplan-Meier method and Cox proportional hazards regression.

New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis.

Background: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders.

Modern Trends in the Surgical Management of Paget's Disease.

Purpose: We examined the incidence and modern national trends in the management of Paget's disease (PD), including the use of breast-conserving surgery (BCS), mastectomy, axillary surgery, and receipt of radiotherapy.

Methods: Using surveillance, epidemiology and end results (SEER) data, we identified 2631 patients diagnosed with PD during 2000-2011. Of these patients, 185 (7%) had PD of the nipple only, 953 (36.

Racial/Ethnic Differences in Patients' Selection of Surgeons and Hospitals for Breast Cancer Surgery.

Importance: Racial differences in breast cancer treatment may result in part from differences in the surgeons and hospitals from whom patients receive their care. However, little is known about differences in patients' selection of surgeons and hospitals.

Objective: To examine racial/ethnic differences in how women selected their surgeons and hospitals for breast cancer surgery.

Prenatal choline and the development of schizophrenia.

Background: The primary prevention of illness at the population level, the ultimate aim of medicine, seems out of reach for schizophrenia. Schizophrenia has a strong genetic component, and its pathogenesis begins long before the emergence of psychosis, as early as fetal brain development. Cholinergic neurotransmission at nicotinic receptors is a pathophysiological mechanism related to one aspect of this genetic risk.

How Do Payers Respond to Regulatory Actions? The Case of Bevacizumab.

Purpose: In February 2008, the US Food and Drug Administration (FDA) granted accelerated approval for bevacizumab for metastatic breast cancer. After public hearings in July 2010, and June 2011, the FDA revoked this approved indication in November 2011, on the basis of additional evidence regarding its risk/benefit profile. The Centers for Medicare and Medicaid Services, local Medicare contractors, and commercial payers varied in their stated intentions to cover bevacizumab after FDA's regulatory actions.

Racial differences in outcomes for patients with metastatic breast cancer by disease subtype.

Treatment advances have differed by breast cancer subtype. We examined the impact of race on survival of women with metastatic breast cancer by disease subgroup. Using surveillance, epidemiology, and end results -Medicare data, we included white and black patients aged ≥66 with de novo metastatic breast cancer diagnosed between 1998 and 2009.

Endophenotypes in Schizophrenia for the Perinatal Period: Criteria for Validation.

Endophenotypes are disease-associated phenotypes that are thought to reflect the neurobiological or other mechanisms that underlie the more overt symptoms of a psychiatric illness. Endophenotypes have been critical in understanding the genetics, neurobiology, and treatment of schizophrenia. Because psychiatric illnesses have multiple causes, including both genetic and nongenetic risk factors, an endophenotype linked to one of the mechanisms may be expressed more frequently than the disease itself.

Black/White Disparities in Receipt of Treatment and Survival Among Men With Early-Stage Breast Cancer.

Purpose: To examine the extent of black/white disparities in receipt of treatment and survival for early-stage breast cancer in men age 18 to 64 and ≥ 65 years.

Patients And Methods: We identified 725 non-Hispanic black (black) and 5,247 non-Hispanic white (white) men diagnosed with early-stage breast cancer from 2004 to 2011 in the National Cancer Data Base. We used multivariable logistic regression and calculated standardized risk ratios to predict receipt of treatment and a proportional hazards model to estimate overall hazard ratios (HRs) in black versus white men age 18 to 64 and ≥ 65 years, separately.

Characterization of folding cores in the cyclophilin A-cyclosporin A complex.

Determining the folding core of a protein yields information about its folding process and dynamics. The experimental procedures for identifying the amino acids that make up the folding core include hydrogen-deuterium exchange and Φ-value analysis and can be expensive and time consuming. Because of this, there is a desire to improve upon existing methods for determining protein folding cores theoretically.

MBRRACE-UK: saving lives, improving mothers' care - implications for anaesthetists.

In December 2014, the latest UK Confidential Enquiry into Maternal Deaths report was published, covering the surveillance period from 2009 to 2012. This is the first report since a significant change in the organisational structure of the body responsible for surveillance and dissemination of reports. The Confidential Enquiry Reports are regarded as a gold standard worldwide and have contributed to quality improvement of maternity care both in the UK and elsewhere.

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function.

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is ubiquitously expressed in both the central nervous system and in the periphery. CHRNA7 is genetically linked to multiple disorders with cognitive deficits, including schizophrenia, bipolar disorder, ADHD, epilepsy, Alzheimer's disease, and Rett syndrome. The regulation of CHRNA7 is complex; more than a dozen mechanisms are known, one of which is a partial duplication of the parent gene.

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring.

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.

Factor structure and heritability of endophenotypes in schizophrenia: findings from the Consortium on the Genetics of Schizophrenia (COGS-1).

Background: Although many endophenotypes for schizophrenia have been studied individually, few studies have examined the extent to which common neurocognitive and neurophysiological measures reflect shared versus unique endophenotypic factors. It may be possible to distill individual endophenotypes into composite measures that reflect dissociable, genetically informative elements.

Methods: The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) is a multisite family study that collected neurocognitive and neurophysiological data between 2003 and 2008.

Racial/ethnic disparities in knowledge about one's breast cancer characteristics.

Background: Understanding tumor characteristics is likely important, but little is known about breast cancer patients' knowledge of their own disease. The authors assessed women's knowledge about their tumor characteristics, whether racial/ethnic disparities in knowledge exist, and whether education and health literacy influence associations.

Methods: A population-based cohort of women in Northern California with stage 0 through III breast cancers diagnosed from 2010 to 2011 (participation rate 68.

"Vasovagal" response during ventricular fibrillation: incidence and implications.

Background: The purpose of this study was to assess the relationship between changes in sinus node cycle length (SNCL) during ventricular fibrillation (VF) and the peripheral changes in blood pressure (BP) and sympathetic nerve activity (SNA) in human subjects. We hypothesized that patients with no SNCL shortening during VF have a vasovagal-like response with a greater decrease in BP and SNA when compared to patients with SNCL shortening.

Methods: SNCL, BP, and SNA recordings were attempted in 24 patients undergoing the implantation of a dual-chamber implantable defibrillator.

Efficient export of human growth hormone, interferon α2b and antibody fragments to the periplasm by the Escherichia coli Tat pathway in the absence of prior disulfide bond formation.

Numerous therapeutic proteins are expressed in Escherichia coli and targeted to the periplasm in order to facilitate purification and enable disulfide bond formation. Export is normally achieved by the Sec pathway, which transports proteins through the plasma membrane in a reduced, unfolded state. The Tat pathway is a promising alternative means of export, because it preferentially exports correctly folded proteins; however, the reducing cytoplasm of standard strains has been predicted to preclude export by Tat of proteins that contain disulfide bonds in the native state because, in the reduced state, they are sensed as misfolded and rejected.