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A transcriptional profile of multicellular development in Dictyostelium discoideum.

A distinct feature of development in the simple eukaryote Dictyostelium discoideum is an aggregative transition from a unicellular to a multicellular phase. Using genome-wide transcriptional analysis we show that this transition is accompanied by a dramatic change in the expression of more than 25% of the genes in the genome. We also show that the transcription patterns of these genes are not sensitive to the strain or the nutritional history, indicating that Dictyostelium development is a robust physiological process that is accompanied by stereotypical transcriptional events. Analysis of the two differentiated cell types, spores and stalk cells, and their precursors revealed a large number of differentially expressed genes as well as unexpected patterns of gene expression, which shed new light on the timing and possible mechanisms of cell-type divergence. Our findings provide new perspectives on the complexity of the developmental program and the fraction of the genome that is regulated during development.

Animals↗

Suicides by mentally ill people.

In 1992, following consultations with the Royal College of Psychiatrists, the confidential inquiry into homicides and suicides by mentally ill people was set up by the United Kingdom Department of Health. The inquiry collects detailed information on contact with secondary mental health services by means of a questionnaire from clinical audit or information departments from these organisations. In Leeds, however, a wider range of available records including Coroner Reports, police, social, educational, and all health records were consulted. This resulted in a series of health/life event histories of suicide cases that had been in contact with psychiatric services. This paper presents an exploratory analysis of these data. The Leeds suicide cases formed less than one-third of all suicide cases in Leeds; the remainder had not come into contact with psychiatric services. This proportion is consistent with the U.K. national figures. Records show that 46% of the sample"s first contact with the psychiatric services was through a first failed attempted suicide. Other results include the role of prescribed drugs in repeat suicide attempts, education levels, and employment stability. It is concluded that the link between mental illness and suicide is questionable. Life event history type data on all suicide cases is desperately required to study suicide as a social process.

Adult↗

Maturing out of alcohol dependence: the impact of transitional life events.

OBJECTIVE: The purpose of this study was to investigate the effects of transitional life events related to education, employment, and family formation on the likelihood of recovery from alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), distinguishing the short- and long-term effects of these events and potential effect modification by treatment history, gender, and severity of dependence. METHOD: This analysis is based on data from the Wave 1 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a cross-sectional, retrospective survey of a nationally representative sample of U.S. adults 18 years of age and older. The analytic sample consisted of 4,422 individuals with prior-to-past-year (PPY) onset of DSM-IV alcohol dependence. Time-dependent proportional hazards models were used to estimate the effects of completing school, starting full-time work, getting married, becoming separated/divorced/widowed, and becoming a parent on the outcomes of nonabstinent recovery (NR; e.g., low-risk asymptomatic drinking) and abstinent recovery (AR). RESULTS: Entry into and exit from a first marriage each increased the likelihood of NR during the first 3 years after those events occurred (hazard rate ratio [HRR] = 1.37 and 1.76, respectively). However, individuals who were still dependent 3 or more years after those events occurred had a decreased likelihood of subsequent NR (HRR = 0.70 for both events), as did those who were still dependent 3 or more years after completing schooling (HRR = 0.54). The likelihood of AR was more than doubled in the 3 years after first becoming a parent (HRR = 2.22) but was decreased among individuals still dependent 3 or more years after starting full-time work. For the outcome of NR, all of the negative effects associated with still being dependent 3 or more years after the occurrence of key life events were more strongly negative among individuals with less severe cases of dependence. CONCLUSIONS: Transitional life events demonstrate many effects on recovery, including both direct effects consistent with role socialization and associations more reflective of selectivity than causation. Taken as a whole, these events appear to contribute to (but by no means fully explain) the high rates of recovery from alcohol dependence that have been observed even in the absence of treatment.

Adult↗

Predictive power of duplex ultrasonography in asymptomatic carotid disease.

BACKGROUND: Duplex ultrasonography is considered a valid measure of stenosis of the carotid arteries, but the prognostic value of repeated ultrasonographic examinations is unknown. OBJECTIVE: To determine the ability of serial ultrasonographic measurements to predict cerebrovascular events in patients with asymptomatic carotid disease. DESIGN: Secondary analysis of data from a natural history study of asymptomatic carotid disease. PATIENTS: Asymptomatic patients with cervical bruits. MEASUREMENTS: Duplex ultrasonography of the carotid arteries was done at study enrollment and biannually thereafter. Multivariable Cox proportional hazards models with fixed and time-dependent covariates were used for analysis. RESULTS: 61 transient ischemic attacks (TIAs) and 38 strokes occurred in 715 participants over a mean follow-up period of 3.2 years; 4 strokes were disabling, and no deaths from stroke occurred. Sixty percent of strokes occurred in persons who did not have severe stenosis. One fifth of participants had stenosis progression. Baseline carotid stenosis was a significant predictor of the outcome "TIA or stroke" (relative risk, 1.5 [95% CI, 1.2 to 1.7]) and retained its predictive ability for more than 3 years. Progression of stenosis to 80% or more significantly increased the risk for cerebrovascular events and death. The sensitivity and positive predictive value of progression as an independent predictor of TIA or stroke were low. CONCLUSION: Severe carotid stenosis is associated with a higher risk for cerebrovascular events, but the power of repeated ultrasonography to predict ischemic events is limited by low incidence rates and low rates of progression. The evidence does not support the routine use of serial ultrasonography to determine the risk for stroke in unselected patients with asymptomatic carotid disease.

Adult↗

Perioperative and long-term prognostic value of intravenous dipyridamole thallium scintigraphy in patients with peripheral vascular disease.

The prognostic value of long-term risk stratification of patients with peripheral vascular disease who undergo intravenous dipyridamole thallium scintigraphy has not been well studied. We screened 131 patients with peripheral vascular disease who underwent intravenous dipyridamole thallium testing to determine cardiac event rates over an average follow-up of 18 +/- 10 months. Of the 131 patients, 111 subsequently had peripheral vascular surgery. The patients with abnormal thallium scans after dipyridamole had a significantly higher risk of death or myocardial infarction, both in the perioperative phase (7% versus 0%; p less than 0.001) and at late follow-up (17% versus 6%; p less than 0.01). The risk of a cardiac event was two-fold greater when a reversible as compared to a fixed thallium defect was present. Multivariate analysis selected the number of thallium segments with perfusion defects, prior history of angina pectoris, and chest pain during dipyridamole testing as perioperative predictors of a cardiac event. A reversible thallium defect was the only predictor of death or nonfatal myocardial infarction during late follow-up. Thus intravenous dipyridamole thallium scintigraphy is a useful noninvasive test for risk stratification of patients before peripheral vascular surgery and provides prognostic information as to the risk of a cardiac event in the 2-year period after the test. A reversible thallium defect is associated with a significant increased risk and would indicate that coronary angiography should be considered and preoperative coronary revascularization.

Aged↗

Noninvasive cardiac risk stratification of diabetic and nondiabetic uremic renal allograft candidates using dipyridamole-thallium-201 imaging and radionuclide ventriculography.

The ability of noninvasive risk stratification using dipyridamole-thallium-201 (Tl-201) imaging and radionuclide ventriculography to predict perioperative and long-term cardiac events (myocardial infarction or cardiac death) was evaluated in 36 uremic diabetic and 29 nondiabetic candidates for renal allograft surgery. Of the 35 patients who underwent renal allograft surgery 8 +/- 7 months after the study, none had transient Tl-201 defects (although 13 had depressed left ventricular ejection fraction) and none developed perioperative cardiac events. During a mean follow-up of 23 +/- 11 months, 6 (9%) patients developed cardiac events. Logistic regression analysis was used to compare the predictive value of clinical data (including age, sex, diabetes, chest pain history, allograft recipient) and radionuclide data. Presence of transient Tl-201 defect and left ventricular ejection fraction were the only significant predictors of future cardiac events (p less than 0.01). No other patient variables, including diabetes or receiving a renal allograft, had either univariate or multivariate predictive value. All 3 patients with transient Tl-201 defects had cardiac events compared with only 3 of 62 (5%) patients without transient Tl-201 defect (p less than 0.0001). Mean left ventricular ejection fraction was lower in patients with cardiac events (44 +/- 13%) compared with patients without cardiac events (57 +/- 9%, p less than 0.005). Overall, 5 of 6 patients with cardiac events had either transient Tl-201 defects or depressed left ventricular ejection fraction. Dipyridamole-Tl-201 imaging and radionuclide ventriculography may be helpful in identifying uremic candidates for renal allograft surgery who are at low risk for perioperative and long-term cardiac events.

Adult↗

Risk of thromboembolic events in patients with atrial flutter.

Based on multiple studies, clear, guided anticoagulation therapy is recommended for patients with atrial fibrillation. The value of anticoagulation therapy in patients with atrial flutter, however, is less well established. Little is known about the incidence of thromboembolism in patients with atrial flutter. We evaluated the risk of thromboembolism in 191 consecutive unselected patients referred for treatment of atrial flutter. A history of embolic events was noted in 11 patients. Acute embolism (<48 hours) occurred in 4 patients (3 after direct current cardioversion, 1 after catheter ablation). During follow-up of 26+/-18 months, 9 patients experienced thromboembolic events. During the follow-up, the overall embolic event rate (including acute embolism and thromboembolic events during follow-up) was 7 % in this patient population. Risk indicators for an embolic event in an univariate analysis were organic heart disease (p = 0.037), depressed left ventricular function (p = 0.02), history of systemic hypertension (p = 0.004), and diabetes mellitus (p = 0.0038). Using multivariate analysis, a history of hypertension was the only independent predictor for elevated embolic risk in this patient population (odds ratio = 6.5; 95% confidence intervals 1.5 to 45). Thus, the thromboembolic risk is higher than previously recognized for patients with atrial flutter. Anticoagulation therapy may decrease this risk.

Aged↗

Risk factors for a major coronary event after myocardial infarction in the Scandinavian Simvastatin Survival Study (4S). Impact of predicted risk on the benefit of cholesterol-lowering treatment.

AIMS: To analyse (1) the prognostic importance of clinical findings and lipids in patients with a previous myocardial infarction and (2) the relative and absolute benefit of simvastatin in patients at low, medium and high predicted risk. METHODS: The 4S was a double-blind, randomized, clinical trial of long-term treatment with simvastatin or matching placebo in patients with myocardial infarction or angina pectoris, serum total cholesterol 5.5-8.0 mmol x l(-1), and serum triglycerides <or=2.5 mmol x l(-1). The present study only deals with those 3525 patients who had a previous myocardial infarction. End-points comprised coronary death, definite and probable hospital verified myocardial infarction, and resuscitated cardiac arrest. Because there were few women the primary analyses were performed among men. RESULTS: A Cox model analysis in the placebo group identified the following independent predictors of coronary events: a history of hypertension (P=0.023), diabetes (P=0.0001), smoking after the myocardial infarction (P=0.010), total cholesterol (P=0.020), and HDL cholesterol (P=0.062). The relative reduction of risk by simvastatin treatment in patients at low, medium and high predicted risk was 38%, 39% and 42%, respectively, but the corresponding absolute benefit per 100 patients treated for 6 years increased from 7.9 to 16.2. CONCLUSION: In addition to serum lipids, clinical variables contributed significantly to prediction. The relative benefit from simvastatin treatment was independent of predicted risk, but the absolute benefit increased from low to high risk.

Anticholesteremic Agents↗

Relationship between duration of HIV disease and diagnostic history.

The duration of being infected with HIV, i.e., chronicity, is a unique factor that can affect coping and psychological outcomes. In a secondary data analysis, 50 HIV-positive adults between 30 and 57 years were administered the Centers for Epidemiological Studies-Depression scale, the UCLA Loneliness Scale-Revised, and the HIV Stigma Scale, along with questions about their diagnostic history. Analysis indicated that those diagnosed longer with HIV reported ruminating less on the events leading up to their diagnosis (r=-.36), reported less trauma by their diagnosis initially (r=-.31), and reported fewer depressive symptoms (r=-.30). Implications for addressing chronicity in research are posited.

Adaptation, Psychological↗

[Sex-specific effects in the intergenerational transmission of divorce risks].

"In an empirical analysis the article investigates the intergenerational transmission of divorce risk with multivariate event-history techniques using data on the 10,000 respondents of the German Family Survey. In both younger and older cohorts the transmission effect is confirmed. Surprisingly, however, there are huge sex differences in the impact of parents' divorces on their children. Sons of divorced parents have a much higher risk of divorce than girls.... The transmission effect cannot be explained by the decreased standard of living typically observed in all types of single-parent families. The data suggest, however, that differences in intervening variables may partially explain the transmission effect." (SUMMARY IN ENG)

Age Factors↗

[Genetic polymorphisms in X-ray repair cross-complementing gene 1 and susceptibility to papillary thyroid carcinoma].

OBJECTIVE: To study the association of polymorphisms in the X-ray repair cross-complementing gene 1 (XRCC1) and papillary thyroid carcinoma (PTC). METHODS: A hospital based, matched case-control study was carried out. The polymorphisms in XRCC1 for 105 pairs of cases with PTC and controls were identified by PCR-RFLP. RESULTS: The frequencies of Arg/Arg, Arg/Trp and Trp/Trp genotypes at XRCC1 Arg194Trp site were 47.6%, 49.5% and 2.9% among cases compared to 45.7%, 48.6% and 5.7% among controls. There was no statistically significant difference between the two groups (chi(2) = 1.07, P = 0.59). The frequencies of Arg/Arg, Arg/Gln and Gln/Gln genotypes at XRCC1 Arg399Gln site were 46.7%, 41.9% and 11.4% among cases, while 54.2%, 42.9% and 2.9% among controls respectively. There was statistically significant difference between the two groups (chi(2) = 6.40, P = 0.04). Individuals with Gln/Gln genotype had a 3.65-fold increased risk of developing PTC compared to Arg/Arg genotype (OR = 4.65, 95% CI: 1.24 - 17.45). The multivariate conditional logistic regression analysis showed that the XRCC1 Arg399Gln polymorphism, negative life events and X-irradiation history were associated with PTC, with odds ratios of 2.71 (95% CI: 1.22 - 6.05), 5.34 (95% CI: 1.40 - 20.38) and 0.38 (95% CI: 0.12 - 0.72) respectively. However, XRCC1 Arg194Trp polymorphism, drinking tea, fruit and economic levels did not show statistically significant associations with PTC. CONCLUSION: The Gln/Gln genotype at XRCC1 Arg399Gln site and negative life events significantly increased while X-irradiation history decreased the risk of developing PTC.

Adult↗

Phylogenetic relationships, evolution, and genetic diversity of the domestic dog.

The spectacular diversity in size, conformation, and pelage that characterizes the domestic dog reflects not only the intensity of artificial selection but ultimately the genetic variability of founding populations. Here we review past molecular genetic data that are relevant to understanding the origin and phylogenetic relationships of the dog. DNA-DNA hybridization data show that the dog family Canidae diverged about 50 million years ago from other carnivore families. In contrast, the extant canids are very closely related and diverged from a common ancestor about 10 million years ago. The evidence supporting a close relationship of dogs with gray wolves is overwhelming. However, dogs are remarkably diverse in mitochondrial and nuclear genes. Mitochondrial DNA analysis suggests a more ancient origin of dogs than has been indicated by the fossil record. In addition, dogs have originated from or interbred with wolves throughout their history at different times and different places. We test the possibility of an independent domestication event in North America by analysis of mtDNA variation in the Xoloitzcuintli. This unusual breed is believed to have been kept isolated for thousands of years and may be one of the most ancient breeds in North America. Our results do not support a New World domestication of dogs nor a close association of the Xoloitzcuintli with other hair-less breeds of dogs. Despite their phenotypic uniformity, the Xoloitzcuintli has a surprisingly high level of mtDNA sequence variation. Other breeds are also genetically diverse, suggesting that dog breeds were often founded with a large number of dogs from outbred populations.

Animals↗

A Bayesian approach for the analysis of panel-count data with dependent termination.

We consider modeling and Bayesian analysis for panel-count data when the termination time for each subject may depend on its history of the recurrent events. We propose a fully specified semiparametric model for the joint distribution of the recurrent events and the termination time. For this model, we provide a natural motivation, derive several novel properties, and develop a Bayesian analysis based on a Markov chain Monte Carlo algorithm. Comparisons are made to other existing models and methods for panel-count data. We demonstrate the usefulness of our new models and methodologies through the reanalysis of a data set from a clinical trial.

Algorithms↗

[Biographical anamnesis and social amnesia. A review of medical history taking, exploration, clinical interview, biographical analysis and diagnostic-clinical consultation].

The article describes the historical roots of the development of anamnesis including life-event-research and offers an overview of objective, subjective and situative information levels during diagnostic interviews. The author proposes as method the narrative interview completed by the so-called regressive-progressive method from Sartre. He calls special attention to the interpersonal aspect and to the therapeutic function of anamnesis as well as autobiographical writing.

Humans↗

Pneumonia in the later years.

This lecture presents an outline of early historical observations on pulmonary disorders in relation to age, as well as current studies on respiratory-tract defense mechanisms, with particular reference to pneumonia. Special attention is paid to the prevention of pneumococcal pneumonia by means of vaccines. Although much remains to be learned about this vaccine and its efficacy in some segments of the population at high risk from pneumococcal infection, current knowledge regarding its safety and efficacy warrants it more extensive use. Included are interesting notes on Osler's ambivalent attitude toward pneumonia in old age and his stimulating ideas on retirement, patterned after Trollope's writings, which contain an early cost-benefit analysis for events set in 1980.

Aged↗

Predictors of long-term event-free survival after percutaneous balloon mitral valvuloplasty.

Previous studies have shown that long-term event-free survival after percutaneous balloon mitral valvuloplasty (PBMV) could be predicted by several baseline characteristics. However, the extent of the predictive variables has not been defined accurately yet. In this study, 40 baseline demographic, clinical, echocardiographic, and hemodynamic variables of 128 consecutive patients with mitral stenosis who underwent PBMV in a single institution, were analyzed in order to predict long-term event-free survival, defined as absence of death, mitral valve replacement, or repeat PBMV. Univariate survival analysis showed that age (p = 0.03), history of commissurotomy or mitral valvuloplasty (p = 0.05), calcium grade (p = 0.008), echo score (p = 0.0001), preprocedure cardiac output (p = 0.03), preprocedure valve area (p = 0.0007), postprocedure mean left atrial pressure (p = 0.0001), postprocedure valve area (p = 0.0001), postprocedure valve gradient (p = 0.013), and postprocedural mitral regurgitation (p = 0.01) were statistically significant predictors of event-free survival. Additionally, the absolute and/or relative procedural change of the following variables were found to be statistically significant predictors of event-free survival: left atrial pressure (p = 0.01), valve area (p = 0.0001), and valve gradient (p = 0.02). Multivariate Cox proportional hazard analysis indicated that when only variables available before the procedure were considered, echo score (p = 0.002) and preprocedure valve area (p = 0.0002) were found to be independent predictors of event-free survival. When both pre- and postprocedure variables were considered, echo score (p = 0.002) and postprocedure valve area (p = 0.0001) were found to be independent predictors of event-free survival. In conclusion, mitral valve morphology reflected by echo score, and baseline and postprocedure mitral valve area were found to be the strongest independent predictors of event-free survival after PBMV.

Aged↗

What does transient global amnesia really mean? Review of the literature and thorough study of 142 cases.

Since the first reports of transient global amnesia (TGA) were published in 1956, several neuropsychological and functional imaging studies have shed light on different aspects of this neurological syndrome. By establishing diagnostic criteria, Hodges and Warlow (1990b) have made it far easier to identify clinical TGA-related features. However, no comprehensive survey has been yet carried out in order to validate their criteria/findings or provide information about previously unknown features. In the present paper, (i) we review the literature published since Hodges and Warlow's study and seek to characterize the demographic and clinical features of TGA more accurately, (ii) we report 142 personal TGA cases, with supplementary information regarding both episodes and patients, such as precipitating events, associated symptoms and personality, and (iii) we suggest the existence of different groups of TGA patients, on the basis of a hierarchical cluster analysis. This revealed that in women, episodes are mainly associated with an emotional precipitating event, a history of anxiety and a pathological personality. In men, they occur more frequently after a physical precipitating event. In younger patients, a history of headaches may constitute an important risk factor. No link was found with vascular risk factors. The relevance of each of the above-mentioned variables is discussed in the light of our classification. An extensive description of cases from both the literature and our patient population allows us to refine the characterization of clinical TGA features.

Adult↗

Barriers to antiretroviral adherence: the importance of depression, abuse, and other traumatic events.

Among HIV-infected persons, high-level adherence to antiretroviral medications (>90%-95%) is associated with improved immunologic, virologic, and clinical outcomes, and is necessary to prevent the emergence of viral resistance. This study examines whether lifetime traumatic events including physical and sexual abuse, are associated with antiretroviral nonadherence. We present a cross-sectional analysis of the Coping with HIV/AIDS in the Southeast (CHASE) Study, analyzing data from the enrollment interview and medical records of study subjects. The CHASE Study is a prospective cohort study of consecutively sampled HIV-infected subjects from infectious diseases clinics in five southern states; Alabama, Georgia, Louisiana, North Carolina, and South Carolina. Four hundred seventy-four (78%) of the 611 CHASE study subjects reported being treated with antiretroviral medications at enrollment and are included in this analysis. Nonadherence was defined as the patient's self-report of missing any doses of their antiretroviral medications over the previous 7 days. Among study subjects, 54% reported a history of physical and/or sexual abuse, 91% reported at least one lifetime traumatic event, and 24% reported nonadherence with their antiretrovirals. In multivariable logistic regression analysis, the number of categories of lifetime traumatic events (p = 0.03), the Addiction Severity Index (ASI) alcohol score (p = 0.02), and being uninsured (p = 0.04) were associated with antiretroviral nonadherence. The finding that lifetime traumatic events are associated with antiretroviral nonadherence, particularly among those who have been traumatized in multiple ways, highlights the complex and often persisting manifestations of such trauma and calls for further investigation.

Adult↗