A Wolf-Rayet-like progenitor of SN 2013cu from spectral observations of a stellar wind.

The explosive fate of massive Wolf-Rayet stars (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections. Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 10(12) centimetres, as expected for some WRSs. The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions.

An outburst from a massive star 40 days before a supernova explosion.

Some observations suggest that very massive stars experience extreme mass-loss episodes shortly before they explode as supernovae, as do several models. Establishing a causal connection between these mass-loss episodes and the final explosion would provide a novel way to study pre-supernova massive-star evolution. Here we report observations of a mass-loss event detected 40 days before the explosion of the type IIn supernova SN 2010mc (also known as PTF 10tel). Our photometric and spectroscopic data suggest that this event is a result of an energetic outburst, radiating at least 6 × 10(47) erg of energy and releasing about 10(-2) solar masses of material at typical velocities of 2,000 km s(-1). The temporal proximity of the mass-loss outburst and the supernova explosion implies a causal connection between them. Moreover, we find that the outburst luminosity and velocity are consistent with the predictions of the wave-driven pulsation model, and disfavour alternative suggestions.

Supernova 2007bi as a pair-instability explosion.

Stars with initial masses such that 10M[symbol: see text] or= 140M[symbol: see text] (if such exist) develop oxygen cores with masses, M(core), that exceed 50M[symbol: see text], where high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs before oxygen ignition and leads to a violent contraction which triggers a nuclear explosion that unbinds the star in a pair-instability supernova. Transitional objects with 100M[symbol: see text] < M(initial) < 140M[symbol: see text] may end up as iron-core-collapse supernovae following violent mass ejections, perhaps as a result of brief episodes of pair instability, and may already have been identified. Here we report observations of supernova SN 2007bi, a luminous, slowly evolving object located within a dwarf galaxy. We estimate the exploding core mass to be M(core) approximately 100M[symbol: see text], in which case theory unambiguously predicts a pair-instability supernova. We show that >3M[symbol: see text] of radioactive (56)Ni was synthesized during the explosion and that our observations are well fitted by models of pair-instability supernovae. This indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic stellar mass limit, which perhaps result from processes similar to those that created the first stars in the Universe.

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms.

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage (European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region.

CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy.

A homozygous mutation of the CNTNAP2 gene has been associated with a syndrome of focal epilepsy, mental retardation, language regression and other neuropsychiatric problems in children of the Old Order Amish community. Here we report genomic rearrangements resulting in haploinsufficiency of the CNTNAP2 gene in association with epilepsy and schizophrenia. Genomic deletions of varying sizes affecting the CNTNAP2 gene were identified in three non-related Caucasian patients. In contrast, we did not observe any dosage variation for this gene in 512 healthy controls. Moreover, this genomic region has not been identified as showing large-scale copy number variation. Our data thus confirm an association of CNTNAP2 to epilepsy outside the Old Order Amish population and suggest that dosage alteration of this gene may lead to a complex phenotype of schizophrenia, epilepsy and cognitive impairment.

Atrial emptying with orthotopic heart transplantation using bicaval and pulmonary venous anastomoses: a magnetic resonance imaging study.

OBJECTIVES: We hypothesized that orthotopic heart transplantation with bicaval and pulmonary venous anastomoses preserves atrial contractility. BACKGROUND: The standard biatrial anastomotic technique of orthotopic heart transplantation causes impaired function and enlargement of the atria. Cine magnetic resonance imaging (MRI) allows assessment of atrial size and function. METHODS: We studied 16 patients who had undergone bicaval (n = 8) or biatrial (n = 8) orthotopic heart transplantation without evidence of rejection and a control group of 6 healthy volunteers. For all three groups, cine MRI was performed by combining coronal and axial gated spin echo and gradient echo cine sequences. Intracardiac volumes were calculated with the Simpson rule. Atrial emptying fraction was defined as the difference between atrial diastolic and systolic volumes, divided by atrial diastolic volume, expressed in percent. All patients had right heart catheterization. RESULTS: Right atrial emptying fraction was significantly higher in the bicaval (mean [+/- SD] 37 +/- 9%) than in the biatrial group (22 +/- 11%, p < 0.05) and similar to that in the control group (48 +/- 4%). Left atrial emptying fraction was significantly higher in the bicaval (30 +/- 5%) than in the biatrial group (15 +/- 4%, p < 0.05) and significantly lower in both transplant groups than in the control group (47 +/- 5%, p < 0.05). The left atrium was larger in the biatrial than in the control group (p < 0.05). Cardiac index, stroke index, heart rate and blood pressure were similar in the transplant groups. CONCLUSIONS: Left and right atrial emptying fractions are significantly depressed with the biatrial technique and markedly improved with the bicaval technique of orthotopic heart transplantation. The beneficial effects of the latter technique on atrial function could improve allograft exercise performance.

Alzheimer's disease. Morbid risk among first-degree relatives approximates 50% by 90 years of age.

The morbid risk of Alzheimer's disease was studied in first-degree relatives of 50 patients who met contemporary clinical research diagnostic criteria and 45 matched controls. Relatives of patients showed a 46% cumulative incidence of probable Alzheimer's disease by 86 years of age. The risk, which was four times the control value, is consistent with other recent reports using similar, modern methods. Although not conclusive, the data suggest the operation of a relatively common, dominant autosomal gene for Alzheimer's disease, the expression of which is delayed until late old age but is largely complete by 90 years of age.

Familial correlates of reduced central serotonergic system function in patients with personality disorders.

BACKGROUND: To test the hypothesis that evidence of reduced central serotonergic (5-HT) system function in probands with personality disorders is associated with an elevated morbid risk of psychopathological conditions putatively associated with 5-HT dysfunction in first-degree relatives of these probands. METHODS: Data were collected during a study of the 5-HT correlates of behavior in male patients with DSM-III personality disorders conducted at a Veterans Affairs medical center. Probands in this study were selected from those patients who had undergone both a fenfluramine hydrochloride challenge and a family history assessment. Axis II diagnosis were made according to DSM-III criteria after a structured interview of the proband, using the Structured Interview for Diagnosing Personality Disorders, given by two raters and a similar interview with a knowledgeable informant by another rater. RESULTS: Reduced prolactin responses to the 5-HT releasing/uptake inhibiting agent fenfluramine was associated with an elevated morbid risk of impulsive personality disorder traits in the first-degree relatives of patients with a primary DSM-III diagnosis of a personality disorder. Quantitative scores on assessments of impulsive aggression in the probands were not correlated with an increased morbid risk for impulsive personality disorder traits. A trend in the same direction was noted for affective personality disorder traits and alcoholism. CONCLUSIONS: These results suggest that a central 5-HT system abnormality in probands is associated with an increased risk of impulsive aggression in their first-degree relatives, and that assessment of central 5-HT system function in probands may be a more sensitive parameter for identification of this familial trait than the presence of impulsive aggressive behaviors in the proband.

Patterns of risk in first-degree relatives of patients with Alzheimer's disease.

BACKGROUND: Although an increased cumulative risk for primary progressive dementia (PPD) has been repeatedly demonstrated in relatives of probands with Alzheimer's disease (AD), an examination of their rates of illness at different ages has not been previously undertaken. Such an examination might reveal possible age-related characteristics associated with a more familial variety of AD. METHODS: Using family history interviews and survival analysis, the cumulative risk for and 5-year age-specific hazard rates of PPD were assessed in the first-degree relatives of 200 probands with AD and two nondemented control groups--179 elderly ascertained through the Alzheimer's Disease Research Center (ADRC-derived controls) and 427 elderly ascertained from community senior centers (community controls). RESULTS: The PPD risk curve for the relatives of probands with AD rose to about 30% and was significantly higher than the curves for the relatives of the ADRC-derived and community controls, where comparable rates were observed (approximately 12%). The age-specific hazard rates of PPD were calculated in three groups of relatives for each 5-year interval from ages 45 to 49 years through ages 85 to 89 years. The age-specific relative risk (RRi) for PPD in the relatives of probands with AD began to steadily diminish from the 75- to 79-year age interval (RRi = 13.49) through the 85- to 89-year age interval (RRi = 0.96) compared with the relatives of ADRC-derived controls and from the 60- to 64-year age interval (RRi = 16.15) through the 85- to 89-year age interval (RRi = 2.03) compared with the relatives of the community controls. CONCLUSIONS: These data indicate that, for relatives of probands with AD, while the lifetime risk for PPD is greater than in relatives of controls, the familial contribution to the risk for PPD decreases with increasing age. The higher risk for PPD in relatives of probands with AD may be substantially diminished or even eliminated by the latter half of the ninth decade.

Increased morbid risk for schizophrenia-related disorders in relatives of schizotypal personality disordered patients.

To evaluate whether probands from a clinical sample diagnosed as having DSM-III schizotypal and/or paranoid personality disorder have a familial relationship to the schizophrenia-related disorders, the morbid risk for schizophrenia-related disorders and other psychiatric disorders were evaluated in the first-degree relatives of patients with schizotypal and/or paranoid personality disorder and compared with the corresponding risk for these disorders in the first-degree relatives of patients with other non-schizophrenia-related personality disorders. The morbid risk for all schizophrenia-related disorders, and specifically for schizophrenia-related personality disorders, was significantly greater among the relatives of the probands with schizotypal and/or paranoid personality disorder than among the relatives of probands with other personality disorder. The morbid risk for other psychiatric disorders did not differ significantly between the first-degree relatives of the schizotypal/paranoid personality disorder and the other personality disorder control proband samples. These results suggest a specific familial association between schizophrenia-related disorders, particularly schizophrenia-related personality disorders, and clinically diagnosed schizotypal patients.

Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia.

BACKGROUND: Biological relatives of patients with schizophrenia demonstrate an increased prevalence of schizotypal personality disorder symptoms, eye tracking deficits, and attentional disturbances. We investigated whether these hypothesized components of a schizophrenia-related phenotype are associated with one another or are independent in nonpsychotic relatives of patients with schizophrenia. METHODS: Eighty-three nonpsychotic first-degree relatives of 38 patients with schizophrenia and 45 control subjects without a psychiatric diagnosis underwent clinical evaluation, eye tracking evaluation, and the Continuous Performance Test (CPT) of visual attention. RESULTS: Eye tracking qualitative rating was more powerful than quantitative eye tracking measures or CPT measures in discriminating relatives of patients with schizophrenia from control subjects. Correlations between neurocognitive variables and DSM-III-R schizotypal personality disorder symptom clusters suggested that CPT errors of omission are associated with positive schizotypal symptoms. Eye tracking measures were not significantly correlated with schizotypal symptoms or CPT errors in relatives of patients with schizophrenia. CONCLUSIONS: Eye tracking deficits in the relatives of patients with schizophrenia are unrelated to CPT deficits and schizotypal symptoms. Eye tracking deficits and disturbances in visual attention may be separate components of a schizophrenia-related phenotype and should be considered as independent factors in genetic studies of schizophrenia.

Lateral ventricular enlargement in schizophrenic probands and their siblings with schizophrenia-related disorders.

BACKGROUND: To investigate possible genetic determinants of ventricular enlargement in schizophrenia, we compared lateral ventricle/brain ratios (VBRs) in schizophrenic patients with their own siblings, some with and some without other schizophrenia-related disorders [e.g., schizotypal personality disorder (SPD)], as well as with a group of unrelated normal controls. METHODS: VBRs, measured by computed tomography, were compared in both groupwise and within-sibship analyses, the latter method providing a measure of control over familial/genetic factors related to VBR, but unrelated to schizophrenia. RESULTS: The VBRs were significantly different across the groups, but the only significant pairwise group comparison was between the schizophrenia and no-SRD family member groups. In the within-sibship analyses, however, the VBRs of those with SPD and schizophrenia were similar, and both groups had significantly larger VBRs than their own siblings without SRD. In addition, siblings with a negative family history for SRD had larger VBRs than family history positive siblings. CONCLUSIONS: The results suggest that specific schizophrenia-related genetic factors may help determine ventricular enlargement in familial schizophrenia. The larger VBRs in family history negative siblings might be attributable to genetic factors not specifically associated with schizophrenia, but which nevertheless increase its susceptibility.

Genetic antecedents of dopamine dysfunction in schizophrenia.

BACKGROUND: Relatives of schizophrenic probands frequently manifest attenuated features of this illness including the negative symptoms and the milder positive psychotic symptoms. These two symptom dimensions are hypothesized to be associated with decreased and increased brain dopamine (DA) functions, respectively, raising the possibility that DA abnormalities may be present in the relatives of schizophrenic probands. METHODS: Plasma homovanillic acid (HVA), the major DA metabolite and an indicator of brain DA activity, was measured in nonpsychotic, physically healthy first-degree relatives (n = 55) of schizophrenic probands and in normal subjects (n = 20) without a family history of schizophrenia. RESULTS: Plasma HVA inversely correlated with negative symptoms and positively correlated with attenuated positive symptoms. Also, relatives had decreased plasma HVA compared to normal subjects, consistent with the fact that these relatives are characterized by negative symptoms. These findings were not related to major peripheral factors that could affect plasma HVA suggesting that the findings may reflect changes in brain DA activity. CONCLUSIONS: Negative symptoms indicating a genetic diathesis to schizophrenia in relatives may have a biologic basis in reduced DA activity and the DA dysfunction of schizophrenia may have genetic antecedents. This opens an important new avenue for further study of DA in this illness.

Cognitive decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients.

BACKGROUND: Geriatric schizophrenic patients with a chronic course of institutionalization manifest cognitive and functional impairments that implicate decline at some time point after the onset of illness. The rate of change in cognitive and functional status in these patients has not yet been identified with a longitudinal study. METHODS: Three hundred and twenty-six schizophrenic patients entered a 30-month follow-up study with two separate assessments of the patients. Overall functional and cognitive status was indexed with the Clinical Dementia Rating (CDR). Survival analysis was used to examine changes in cognitive and functional status, including worsening for the less impaired patients and improvements on the part of more impaired patients. RESULTS: Approximately 30% of the patients who had baseline scores in the less impaired range manifested a worsening of their CDR ratings to a score of 2.0 (moderate) or more severe, whereas only 7% of the sample with lower scores at baseline appeared to improve in their functioning. Several characteristics of the patients at baseline assessment predicted increased risk for cognitive and functional decline, including lower levels of education, older age, and more severe positive symptoms. CONCLUSIONS: Cognitive and functional decline can be detected in a short-term follow-up in a subset of geriatric long-stay patients with schizophrenia. This decline appears distributed across patients and not due to the presence of progressive degenerative dementing conditions. Later research will have to identify the causes of this decline, possibly on the basis of the risk factors identified in this study.

Genetic studies of typical Alzheimer's disease.

Typical, late-onset Alzheimer's disease is familial but shows no clear Mendelian pattern of inheritance. Strategies that could help to reveal its genetics are: 1) identification of genetically homogeneous phenotypes, 2) identification of early or alternate manifestations of AD gene expression in relatives, and 3) use of small multiplex families with cases of typical AD for linkage studies.

Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias.

The investigation of genetic and other causes of Alzheimer's disease requires reliable and valid methods of gathering historical data on elderly relatives. To assess the reliability of the family history method in the study of late-onset dementing illness, the authors studied families with Alzheimer's disease probands and control families. The results indicated that family history data obtained from multiple informants with standardized instruments are consistent across informants. The rate of Alzheimer's disease in the families studied was similar to rates found in previous studies.

Age at onset and familial risk in Alzheimer's disease.

OBJECTIVE: The authors investigated the relationship between probands' age at onset of Alzheimer's disease with the risk of primary progressive dementia in the probands' first-degree relatives. METHOD: Two hundred probands with clinically diagnosed Alzheimer's disease and 179 nondemented elderly probands were recruited from the Mount Sinai Alzheimer's Disease Research Center, located at Mount Sinai Hospital and the Bronx Veterans Affairs Medical Center. Demographic and diagnostic data were collected on 1,398 of the first-degree relatives of the probands with Alzheimer's disease and 955 first-degree relatives of the nondemented probands. RESULTS: Cox proportional hazards regression analysis showed a significant inverse relationship between age at onset of Alzheimer's disease in probands and greater familial risk in their relatives. Follow-up analyses indicated that the most commonly used age at onset cutoff point--65 years--was one of the points where an association with familial aggregation is least likely to be revealed; other onset cutoff ages (e.g., 55, 70, and 75) better identified Alzheimer's disease groups with differing familial/genetic risks. CONCLUSIONS: The authors conclude that patients with an earlier age at onset of Alzheimer's disease are more likely to have relatives with Alzheimer's disease than are patients with a later age at onset of the disease. An onset age of 70 best differentiated probands whose relatives were at higher risk from those whose relatives were at lower risk.

Affective and impulsive personality disorder traits in the relatives of patients with borderline personality disorder.

OBJECTIVE: This study tested the hypothesis that the risk for affective and impulsive personality disorder traits commonly found in patients with borderline personality disorder would be greater in the first-degree relatives of probands with borderline personality disorder than in two comparison groups. METHOD: Blind family history interviews were conducted with family informants to assess the extent to which first-degree relatives of 29 probands with borderline personality disorder, 22 probands with other personality disorders who met three or fewer of the criteria for borderline personality disorder, and 43 probands with schizophrenia fulfilled operationalized criteria for the two kinds of personality disorder traits and for other diagnostic categories. The crude proportions of adult relatives with each diagnosis, as well as the age-adjusted morbid risks, were assessed in the three groups of relatives. RESULTS: The risks for affective and impulsive personality disorder traits were independently greater in the 129 relatives of the borderline probands than in the 105 relatives of the probands with other personality disorders and the 218 relatives of the schizophrenic probands. There was no similarly greater risk for any other psychiatric disorder assessed, including major affective disorder. In addition, the relatives of borderline probands with current or past major depressive disorder showed a greater risk for major affective disorders than the relatives of never-depressed probands with other personality disorders but not the relatives of never-depressed borderline probands. CONCLUSIONS: These results suggest familial transmission of the hallmark borderline-related personality characteristics and raise the possibility that these familial traits may be partially independent.