Combined impact of negative lifestyle factors on cardiovascular risk in children: a randomized prospective study.

PURPOSE: Negative lifestyle factors are known to be associated with increased cardiovascular risk (CVR) in children, but research on their combined impact on a general population of children is sparse. Therefore, we aimed to quantify the combined impact of easily assessable negative lifestyle factors on the CVR scores of randomly selected children after 4 years. METHODS: Of the 540 randomly selected 6- to 13-year-old children, 502 children participated in a baseline health assessment, and 64% were assessed again after 4 years. Measures included anthropometry, fasting blood samples, and a health assessment questionnaire. Participants scored one point for each negative lifestyle factor at baseline: overweight; physical inactivity; high media consumption; little outdoor time; skipping breakfast; and having a parent who has ever smoked, is inactive, or overweight. A CVR score at follow-up was constructed by averaging sex- and age-related z-scores of waist circumference, blood pressure, glucose, inverted high-density lipoprotein, and triglycerides. RESULTS: The age-, sex-, pubertal stage-, and social class-adjusted probabilities (95% confidence interval) for being in the highest CVR score tertile at follow-up for children who had at most one (n = 48), two (n = 64), three (n = 56), four (n = 41), or five or more (n = 14) risky lifestyle factors were 15.4% (8.9-25.3), 24.3% (17.4-32.8), 36.0% (28.6-44.2), 49.8% (38.6-61.0), and 63.5% (47.2-77.2), respectively. CONCLUSIONS: Even in childhood, an accumulation of negative lifestyle factors is associated with higher CVR scores after 4 years. These negative lifestyle factors are easy to assess in clinical practice and allow early detection and prevention of CVR in childhood.

Emotionally negative stimuli can overcome attentional deficits in patients with visuo-spatial hemineglect.

Left unilateral spatial neglect resulting from right brain damage is characterized by loss of awareness for stimuli in the contralesional side of space, despite intact visual pathways. We examined using fMRI whether patients with neglect are more likely to consciously detect in the neglected hemifield, emotionally negative complex scenes rather than visually similar neutral pictures and if so, what neural mechanisms mediate this effect. Photographs of emotional and neutral scenes taken from the IAPS were presented in a divided visual field paradigm. As expected, the detection rate for emotional stimuli presented in the neglected field was higher than for neutral ones. Successful detection of emotional scenes as opposed to neutral stimuli in the left visual field (LVF) produced activations in the parahippocampal and anterior cingulate areas in the right hemisphere. Detection of emotional stimuli presented in the intact right visual field (RVF) activated a distributed network of structures in the left hemisphere, including anterior and posterior cingulate cortex, insula, as well as visual striate and extrastriate areas. LVF-RVF contrasts for emotional stimuli revealed activations in right and left attention related prefrontal areas whereas RVF-LVF comparison showed activations in the posterior cingulate and extrastriate visual cortex in the left hemisphere. An additional analysis contrasting detected vs. undetected emotional LVF stimuli showed involvement of left anterior cingulate, right frontal and extrastriate areas. We hypothesize that beneficial role of emotion in overcoming neglect is achieved by activation of frontal and limbic lobe networks, which provide a privileged access of emotional stimuli to attention by top-down modulation of processing in the higher-order extrastriate visual areas. Our results point to the importance of top-down regulatory role of the frontal attentional systems, which might enhance visual activations and lead to greater salience of emotional stimuli for perceptual awareness.

Age above 60 years is not a negative predictive factor for combined antiviral therapy with pegylated interferon alpha and ribavirin in hepatitis C patients

Background: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral hepatitis C therapy. However, elderly patients often show relevant fibrosis or cirrhosis which is a known negative predictive factor, making it difficult to interpret age as an independent predictive factor. Methods: From the framework of the Swiss hepatitis C cohort (SCCS), we collected data from 545 antiviral hepatitis C therapies, including data from 67 hepatitis C patients ≥ 60 y who had been treated with PEG-interferon and ribavirin. We analyzed host factors (age, gender, fibrosis, haemoglobin, depression, earlier hepatitis C treatment), viral factors (genotype, viral load) and treatment course (early virological response, end of treatment response, SVR). Generalised estimating equations (GEE) regression modelling was used for the primary end point (SVR), with age ≥ 60 y and < 60 y as independent variable and gender, presence of cirrhosis, genotype, earlier treatment and viral load as confounders. SVR was analysed in young and elderly patients after matching for these confounders. Additionally, classification tree analysis was done in elderly patients using these confounders. Results: SVR analyzed in 545 patients was 55%. In genotype 1/4, SVR was 42.9% in 259 patients < 60 y and 26.1% in 46 patients ≥ 60 y. In genotype 2/3, SVR was 74.4% in 215 patients < 60 y and 84% in 25 patients ≥ 60 y. However, GEE model showed that age had no influence on achieving SVR (Odds ratio 0.91). Confounders influenced SVR as known from previous studies (cirrhosis, genotype 1/4, previous treatment and viral load >600'000 IE/ml as negative predictive factors). When young and elderly patients were matched (analysis in 59 elderly patients), SVR was not different in these patient groups (54.2% and 55.9%, resp.; p=0.795 in binomial test). The classification tree-derived best criterion for SVR in elderly patients was genotype, with no further criteria relevant for predicting SVR in genotype 2/3. In patients with genotype 1/4, further criteria were presence of cirrhosis and low viral load <600'000 IE/ml in non-cirrhotic patients. Conclusions: Age is not a relevant predictive factor for achieving SVR, when confounders were taken into account. In terms of effectiveness of antiviral therapy, age does not play a major role and should not be regarded as relevant negative predictive factor. Since life expectancy in Switzerland at age 60 is more than 22 y, hepatitis C therapy is reasonable in elderly patients with known relevant fibrosis or cirrhosis, because interferon-based hepatitis C therapy improves survival and reduces carcinogenesis.

β-Glucan Antigenemia Anticipates Diagnosis of Blood Culture-Negative Intraabdominal Candidiasis.

Rationale: Life-threatening intraabdominal candidiasis (IAC) occurs in 30 to 40% of high-risk surgical intensive care unit (ICU) patients. Although early IAC diagnosis is crucial, blood cultures are negative, and the role of Candida score/colonization indexes is not established. Objectives: The aim of this prospective Fungal Infection Network of Switzerland (FUNGINOS) cohort study was to assess accuracy of 1,3-β-d-glucan (BG) antigenemia for diagnosis of IAC. Methods: Four hundred thirty-four consecutive adults with abdominal surgery or acute pancreatitis and ICU stay 72 hours or longer were screened: 89 (20.5%) at high risk for IAC were studied (68 recurrent gastrointestinal tract perforation, 21 acute necrotizing pancreatitis). Diagnostic accuracy of serum BG (Fungitell), Candida score, and colonization indexes was compared. Measurements and Main Results: Fifty-eight of 89 (65%) patients were colonized by Candida; 29 of 89 (33%) presented IAC (27 of 29 with negative blood cultures). Nine hundred twenty-one sera were analyzed (9/patient): median BG was 253 pg/ml (46-9,557) in IAC versus 99 pg/ml (8-440) in colonization (P < 0.01). Sensitivity and specificity of two consecutive BG measurements greater than or equal to 80 pg/ml were 65 and 78%, respectively. In recurrent gastrointestinal tract perforation it was 75 and 77% versus 90 and 38% (Candida score ≥ 3), 79 and 34% (colonization index ≥ 0.5), and 54 and 63% (corrected colonization index ≥ 0.4), respectively. BG positivity anticipated IAC diagnosis (5 d) and antifungal therapy (6 d). Severe sepsis/septic shock and death occurred in 10 of 11 (91%) and 4 of 11 (36%) patients with BG 400 pg/ml or more versus 5 of 18 (28%, P = 0.002) and 1 of 18 (6%, P = 0.05) with BG measurement less than 400 pg/ml. β-Glucan decreased in IAC responding to therapy and increased in nonresponse. Conclusions: BG antigenemia is superior to Candida score and colonization indexes and anticipates diagnosis of blood culture-negative IAC. This proof-of-concept observation in strictly selected high-risk surgical ICU patients deserves investigation of BG-driven preemptive therapy.

Market rewards to patterns on increasing earnings: do cash flow patterns, accruals manipulation and real activities manipulation matter?

This study explores whether firms have differential price-earnings multiples associated with their means of achieving a sequential pattern of increasing positive earnings. Our main findings show that market participants assign higher price-earnings multiples to firms when their pattern of increasing earnings is supported by the same pattern of increasing cash flows. Market participants assign lower price-earnings multiples to firms suspect of having engaged in accrual-based earnings management, sales manipulation, and overproduction to achieve the earnings pattern. We find, however, that market participants do not penalize firms suspect of having achieved the earnings pattern through the opportunistic reduction of discretionary expenses.

Lack of CB1 receptor activity impairs serotonergic negative feedback

Serotonergic and endocannabinoid systems are important substrates for the control of emotional behavior and growing evidence show an involvement in the pathophysiology of mood disorders. In the present study, the absence of the activity of the CB1 cannabinoid receptor impaired serotonergic negative feedback in mice. Thus, in vivo microdialysis experiments revealed increased basal 5-HT extracellular levels and attenuated fluoxetine-induced increase of 5-HT extracellular levels in the prefrontal cortex of CB1 knockout compared to wild-type mice. These observations could be related to the significant reduction in the 5-HT transporter binding site density detected in frontal cortex and hippocampus of CB1 knockout mice. The lack of CB1 receptor also altered some 5-HT receptors related to the 5-HT feedback. Extracellular recordings in the dorsal raphe nucleus revealed that the genetic and pharmacological blockade of CB1 receptor induced a 5-HT1A autoreceptor functional desensitization. In situ hybridization studies showed a reduction in the expression of the 5-HT2C receptor within several brain areas related to the control of the emotional responses, such as the dorsal raphe nucleus, the nucleus accumbens and the paraventricular nucleus of the hypothalamus, whereas an overexpression was observed in the CA3 area of the ventral hippocampus. These results reveal that the lack of CB1 receptor induces a facilitation of the activity of serotonergic neurons in the dorsal raphe nucleus by altering different components of the 5-HT feedback as well as an increase in 5-HT extracellular levels in the prefrontal cortex in mice.

Delayed referral and gram-negative organisms increase the conversion thoracotomy rate in patients undergoing video-assisted thoracoscopic surgery for empyema

BACKGROUND: The role of video-assisted thoracoscopic surgery in the treatment of pleural empyema was assessed in a consecutive series of 328 patients between 1992 and 2002. An analysis of the predicting factors for conversion thoracotomy in presumed stage II empyema was performed. METHODS: Empyema stage III with pleural thickening and signs of restriction on computer tomography imaging was treated by open decortication, whereas a thoracoscopic debridement was attempted in presumed stage II disease. Conversion thoracotomy was liberally used during thoracoscopy if stage III disease was found at surgery. Predictive factors for conversion thoracotomy were calculated in a multivariate analysis among several variables such as age, sex, time interval between onset of symptoms and surgery, involved microorganisms, and underlying cause of empyema. RESULTS: Of the 328 patients surgically treated for stage II and III empyema, 150 underwent primary open decortication for presumed stage III disease. One hundred seventy-eight patients with presumed stage II empyema underwent a video-assisted thoracoscopic approach. Of these 178 patients, thoracoscopic debridement was successful in 99 of 178 patients (56%), and conversion thoracotomy and open decortication was judged necessary in 79 of 178 patients (44%). The conversion thoracotomy rate was higher in parapneumonic empyema (55%) as compared with posttraumatic (32%) or postoperative (29%) empyema; however, delayed referral (p < 0.0001) and gram-negative microorganisms (p < 0.01) were the only significant predictors for conversion thoracotomy in a multivariate analysis. CONCLUSIONS: Video-assisted thoracoscopic debridement offers an elegant, minimally invasive approach in a number of patients with presumed stage II empyema. However, to achieve a high success rate with the video-assisted thoracoscopic approach, early referral of the patients to surgery is required. Conversion thoracotomy should be liberally used in case of chronicity, especially after delayed referral (> 2 weeks) and in the presence of gram-negative organisms.

Node-negative T1-T2 anal cancer: radiotherapy alone or concomitant chemoradiotherapy?

PURPOSE: To evaluate the influence of concomitant chemotherapy on loco-regional control (LRC) and cancer-specific survival (CSS) in patients with T1-T2 N0 M0 anal cancer treated conservatively by primary radiotherapy (RT). MATERIALS AND METHODS: Between 1976 and 2008, 146 patients with T1 (n=29) or T2 (n=117) N0 M0 anal cancer were treated curatively by RT alone (n=71) or by combined chemoradiotherapy (CRT) (n=75) consisting of mitomycin C±5-fluorouracil. Univariate and multivariate analyses were performed to assess patient-, tumor- and treatment-related factors influencing LRC and CSS. RESULTS: With a median follow-up of 62.5 months (interquartilerange, 26-113 months), 122 (84%) patients were locally controlled. The five-year actuarial LRC, CSS and overall survival for the population were 81.4%±3.6%, 91.9%±2.6%, and 75.4%±3.9%, respectively. The five-year LRC and CSS for patients treated with RT alone and with CRT were 75.5%±6.0% vs. 86.8%±4.1% (p=0.155) and 88.5%±4.5% vs. 94.9%±2.9% (p=0.161), respectively. In the multivariate analysis, no clinical or therapeutic factors were found to significantly influence the LRC and CSS, while the addition of chemotherapy was of borderline significance (p=0.065 and p=0.107, respectively). CONCLUSIONS: In the management of node negative T1-T2 anal cancer, LRC and CSS tend to be superior in patients treated by combined CRT, even though the difference was not significant. Randomized studies are warranted to assess definitively the role of combined treatment in early-stage anal carcinoma.

A-8a Summary of Food Stamp Errors Active and Negative Cases, April-September 2004

A-8a Summary of Food Stamp Errors Active and Negative Cases, Apr. 2004 - Sept. 2004

A-8a Summary of Food Stamp Errors Active and Negative Cases, October 2004-March 2005

A-8a Summary of Food Stamp Errors Active and Negative Cases, Oct. 2004 - Mar. 2005

False-negative PCR result due to gene polymorphism: the example of Neisseria meningitidis.

Early treatment of meningococcal meningitis is mandatory but may negate the cerebrospinal fluid culture. Etiological diagnosis then mainly relies on PCR. Here, we report a case of false-negative results for real-time PCR for a Neisseria meningitidis serogroup B isolate with a polymorphism in the ctrA gene.

Renal and neurohormonal responses to increasing levels of lower body negative pressure in men.

BACKGROUND: The stimulation of efferent renal sympathetic nerve activity induces sequential changes in renin secretion, sodium excretion, and renal hemodynamics that are proportional to the magnitude of the stimulation of sympathetic nerves. This study in men investigated the sequence of the changes in proximal and distal renal sodium handling, renal and systemic hemodynamics, as well as the hormonal profile occurring during a sustained activation of the sympathetic nervous system induced by various levels of lower body negative pressure (LBNP). METHODS: Ten healthy subjects were submitted to three levels of LBNP ranging between 0 and -22.5 mm Hg for one hour according to a triple crossover design, with a minimum of five days between each level of LBNP. Systemic and renal hemodynamics, renal water and sodium handling (using the endogenous lithium clearance technique), and the neurohormonal profile were measured before, during, and after LBNP. RESULTS: LBNP (0 to -22.5 mm Hg) induced an important hormonal response characterized by a significant stimulation of the sympathetic nervous system and gradual activations of the vasopressin and the renin-angiotensin systems. LBNP also gradually reduced water excretion and increased urinary osmolality. A significant decrease in sodium excretion was apparent only at -22.5 mm Hg. It was independent of any change in the glomerular filtration rate and was mediated essentially by an increased sodium reabsorption in the proximal tubule (a significant decrease in lithium clearance, P < 0.05). No significant change in renal hemodynamics was found at the tested levels of LBNP. As observed experimentally, there appeared to be a clear sequence of responses to LBNP, the neurohormonal response occurring before the changes in water and sodium excretion, these latter preceding any change in renal hemodynamics. CONCLUSIONS: These data show that the renal sodium retention developing during LBNP, and thus sympathetic nervous stimulation, is due mainly to an increase in sodium reabsorption by the proximal segments of the nephron. Our results in humans also confirm that, depending on its magnitude, LBNP leads to a step-by-step activation of neurohormonal, renal tubular, and renal hemodynamic responses.

The Effect of occupational sex-composition on earnings: job-specialisation, sex-role attitudes and the division of domestic-labour in Spain

Important theoretical controversies remain unresolved in the literatire on occupational sex-segregation and the gender wage-gap. A useful way of summarising these controversies is viewing them as a debate between - cultural -socialisation. The paper discusses these theories in detail and carries out a preliminary test of the relative explanatory performance of some of their most consequential predictions. This is done by drawing on the Spanish sample of the second wave of the European Social Survey, ESS. The empirical analysis of ESS data illustrates the notable analytical pay-offs that can stem from using rich individual-level indicators, but also exemplifies the statistical llimitations generated by small sample size and high rates of non-response. Empirical results should, therefore, be taken as preliminary. They seem to suggest that the effect of occupational sex-segregation on wages could be explicable by workers' sex-role attitutes, their relative input in domestic production and the job-specific human capital requirements of their jobs. Of these three factors, job-specialisation seeems clearly the most important one.