Incidence and evaluation of the risk of coronary disease. Prospective study in Paris]

The Paris prospective study in an epidemiological study of 7,453 middle-aged men born in France, and initially free from ischaemic heart disease. The current mean follow-up time is 4 years. The mean annual incidence is 5.1 per 1000, which is about one half that found in similar american studies. This incidence is related to the cholesterol level, to the blood pressure, to cigarette consumption when the smoke is inhaled, to diabetes mellitus, and to major abnormalities on the electrocardiogram. These five factors are mutually independant in their prediction of the risk of future illness. A formula has been derived by statistical analysis, and takes these five factors into account: the incidence of illness rises exponentially as a function of this formula. New cases of ischaemic heart disease are distributed, but with a very patchy incidence, in this population, of which only a very small number remain disease-free. A table has been drawn up to show the probability of a middle aged male contracting ischeamic heart disease within 4 years, and takes the 5 factors into account: this probability varies between 0.5 per cent and 34 per cent.     

Drinks of the father: father's maximum number of drinks consumed predicts externalizing disorders,substance use,and substance use disorders in preadolescent and adolescent offspring

BACKGROUND: The maximum number of drinks consumed in 24 hr seems to be an interesting phenotype related to alcoholism. The goal of the present study was to determine in an epidemiologic sample whether this measure of drinking history in fathers predicted externalizing behavioral disorders, substance use, and substance abuse in preadolescent and adolescent offspring and whether any such associations would be independent of paternal alcohol dependence diagnoses. METHODS: Subjects were male and female twins from both age cohorts of the Minnesota Twin Family Study, a population-based longitudinal study, and were approximately 11 or 17 years of age, respectively, upon study enrollment. In both age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder served as outcome measures. In addition, measures of lifetime substance use and of the presence of symptoms of substance abuse were derived for the 11-year-old cohort when subjects were approximately 14 years old and diagnoses of substance abuse were derived for the older cohort at age 17. An extension of logistic regression using generalized estimating equations served to assess whether paternal maximum alcohol consumption predicted filial outcome measures. RESULTS: Paternal maximum alcohol consumption was consistently associated with conduct disorder, substance use, and substance abuse or dependence in male and female offspring. These associations were not mediated by a primary effect of paternal alcoholism. CONCLUSIONS: Paternal maximum alcohol consumption was uniquely associated with those offspring characteristics most reliably found in adolescent children of alcoholic parents. This phenotype might supplement DSM diagnoses of alcohol dependence to reduce the number of false positives in genetic research.     

A method for high-throughput quantitative analysis of yeast chronological life span

Chronological aging in yeast has been studied by maintaining cells in a quiescent-like stationary phase culture and monitoring cell survival over time. The composition of the growth medium can have a profound influence on chronological aging. For example, dietary restriction accomplished by lowering the glucose concentration of the medium significantly increases life span. Here we report a novel high-throughput method for measuring yeast chronological life span by monitoring outgrowth of aging cells using a Bioscreen C MBR machine. We show that this method provides survival data comparable to traditional methods, but with decreased variability. In addition to reducing the glucose concentration, we find that elevated amino acid levels or increased osmolarity of the growth medium is sufficient to increase chronological life span. We also report that life-span extension from dietary restriction does not require any of the five yeast sirtuins (Sir2, Hst1, Hst2, Hst3, or Hst4) either alone or in combination.     

Evaluating NRC’s Recommendations for Educating Children with Autism a Decade Later

Background

Over a decade ago, the National Research Council (NRC) published the influential book, Educating Children with Autism.

Objective

To survey parents and state-level special education administrators to evaluate how NRC’s recommendations, as published in Educating Children with Autism, have impacted educational practices for children with autism in the US.

Methods

149 parents of children with autism and 35 state-level special education administrators from 35 states were surveyed on the degree to which they agreed with NRC’s recommendations and the degree to which they believed NRC’s recommendations have been implemented.

Results

Parents and administrators agreed with most NRC recommendations; however, disagreements between parents and administrators were evident regarding labeling of students with autism, intensity of services, and training of staff. Conversely, parents and administrators concurred that the recommendations had been poorly to modestly implemented, overall. Lowest levels of implementation were found for training of qualified staff, research-based curricula, and mental health supports for families. Qualitative analysis of parents’ comments highlighted that vigorous advocacy was necessary for their children to receive appropriate services consistent with NRC’s recommendations.

Conclusions

Over a decade following publication of Educating Children with Autism, most of NRC’s recommendations have not been fully implemented. Policy makers should focus particular attention on improving professional training, disseminating research-based practices, and providing mental health supports for families.     

Differential Disruption of Blood–Brain Barrier in Severe Traumatic Brain Injury

Background

Traumatic brain injury (TBI) is a significant cause of death and disability in young adults, but not much is known about the incidence and characteristics of blood–brain barrier (BBB) dysfunction in this group. In this proof of concept study, we sought to quantify the incidence of BBB dysfunction (defined as a cerebrospinal fluid (CSF)–plasma albumin quotient of ≥0.007) and examine the relationship between plasma and CSF levels of proteins and electrolytes, in patients with severe TBI.

Methods

We recruited 30 patients, all of whom were receiving hypertonic 20 % saline infusion for intracranial hypertension and had external ventricular drains in situ. Simultaneous CSF and blood samples were obtained. Biochemical testing was performed for sodium, osmolality, potassium, glucose, albumin, immunoglobulin-G, and total protein.

Results

Eleven patients (37 %) showed evidence of impairment of passive BBB function, with a CSF–plasma albumin quotient of ≥0.007. There were strong positive correlations seen among CSF–plasma albumin quotient and CSF–plasma immunoglobulin-G quotient and CSF–plasma total protein quotient (r = 0.967, P < 0.001 and r = 0.995, P < 0.001, respectively). We also found a higher maximum intracranial pressure (24 vs. 21 mmHg, P = 0.029) and a trend toward increased mortality (27 vs. 11 %, P = 0.33) in patients with BBB disruption.

Conclusions

In summary, passive BBB dysfunction is common in patients with severe TBI, and may have important implications for effectiveness of osmotherapy and long-term outcomes. Also, our results suggest that the CSF–plasma total protein quotient, a measurement which is readily available, can be used instead of the CSF–plasma albumin quotient for evaluating BBB dysfunction.     

Predictive factors for latency period and a prognostic model for survival in patients with therapy‐related acute myeloid leukemia

Therapy‐related acute myeloid leukemia (t‐AML) is an increasingly recognized sequela in patients receiving chemotherapy or radiotherapy for a primary malignancy or autoimmune disease. This study assessed factors related to the latency period (LP) between the antecedent disorder (AD) and t‐AML diagnosis and developed a comprehensive prognostic model to predict overall survival (OS). We evaluated a cohort of newly diagnosed t‐AML patients treated with cytarabine‐based induction therapy from 2001 to 2011. Multivariable linear and proportional hazards models were used to assess the impact of different classes of chemotherapy on the LP and to identify independent prognostic factors for OS. Of 730 treated AML patients, 58 (7.9%) had t‐AML. Median LP to t‐AML was 5.6 years (range, 0.5–38.4). 64% of patients achieved CR and median OS was 10.7 months. Independent prognostic factors of short LP were age at AD (P < 0.0001) and prior treatment with mitotic inhibitors (P = 0.05). Unfavorable cytogenetics (P = 0.004), antecedent hematologic or autoimmune disease (P = 0.01), age >60 (P = 0.03), and platelet count <30,000 μL (P = 0.04) at the time of t‐AML diagnosis were prognostic for inferior OS. A prognostic model using these factors was developed that risk stratified t‐AML patients into two groups: favorable and unfavorable. Patients in the favorable group had a median OS of 37.6 months compared with 6.4 months in patients comprising the unfavorable group (P < 0.0001). Multicomponent prognostic models integrating disease or treatment‐related covariates can help better understand how t‐AML evolves; and can be clinically useful in risk stratifying t‐AML patients undergoing induction therapy. Am. J. Hematol. 89:168–173, 2014. © 2013 Wiley Periodicals, Inc.