The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up.

BACKGROUND: The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established. PATIENTS AND METHODS: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features. RESULTS: At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58-1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03). CONCLUSIONS: After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.

Reduction of the bull: cow ratio in the Brazilian Pantanal

This work was conducted to study alternatives for reduction of the bull:cow ratio in the Brazilian lowland and, therefore, lower the production costs for the local beef cattle industry. The ratios 1:10, 1:25, and 1:40 were used in native pastures with a mean stocking rate of 0.27 mature animal unit per hectare over two consecutive breeding seasons. Statistical analysis did not show any effect (P>0.05) of year (P = 0.2097), animal category (P = 0.0773), bull:cow ratio (0.8134) on reproductive performance. However, the pregnancy rate in a multiple bull system was higher (P = 0.0228) than in the individual bull system. An evaluation of the economic impact of this management system in the extensive Lowland herds showed that at the ratio of 1:10 the bulls were sub utilized.

Effect of Video Camera-Based Remote Roadway Condition Monitoring on Snow Removal-Related Maintenance Operations. 2014

Remote monitoring through the use of cameras is widely utilized for traffic operation, but has not been utilized widely for roadway maintenance operations. The Utah Department of Transportation (UDOT) has implemented a new remote monitoring system, referred to as a Cloud-enabled Remote Video Streaming (CRVS) camera system for snow removal-related maintenance operations in the winter. The purpose of this study was to evaluate the effectiveness of the use of the CRVS camera system in snow removal-related maintenance operations. This study was conducted in two parts: opinion surveys of maintenance station supervisors and an analysis on snow removal-related maintenance costs. The responses to the opinion surveys mostly displayed positive reviews of the use of the CRVS cameras. On a scale of 1 (least effective) to 5 (most effective), the average overall effectiveness given by the station supervisors was 4.3. An expedition trip for this study was defined as a trip that was made to just check the roadways if snow-removal was necessary. The average of the responses received from surveys was calculated to be a 33 percent reduction in expedition trips. For the second part of this study, an analysis was performed on the snow removal-related maintenance cost data provided by UDOT to see if the installation of a CRVS camera had an effect in reducing expedition trips. This expedition cost comparison was performed for 10 sets of maintenance stations within Utah. It was difficult to make any definitive inferences from the comparison of expedition costs over the years for which precipitation and expedition cost data were available; hence a statistical analysis was performed using the Mixed Model ANOVA. This analysis resulted in an average of 14 percent higher ratio of expedition costs at maintenance stations with a CRVS camera before the installation of the camera compared to the ratio of expedition costs after the installation of the camera. This difference was not proven to be statistically significant at the 95 percent confident level, but indicated that the installation of CRVS cameras was on the average helpful in reducing expedition costs and may be considered practically significant. It is recommended that more detailed and consistent maintenance cost records be prepared for accurate analysis of cost records for this type of study in the future.

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type.

AIM: To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). METHODS AND RESULTS: Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES  vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). CONCLUSION: A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).

The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression.

Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21 932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.

Assessing the possible direct effect of birth weight on childhood blood pressure : a sensitivity analysis.

To estimate the possible direct effect of birth weight on blood pressure, it is conventional to condition on the mediator, current weight. Such conditioning can induce bias. Our aim was to assess the potential biasing effect of U, an unmeasured common cause of current weight and blood pressure, on the estimate of the controlled direct effect of birth weight on blood pressure, with the help of sensitivity analyses. We used data from a school-based study conducted in Switzerland in 2005-2006 (n = 3,762; mean age = 12.3 years). A small negative association was observed between birth weight and systolic blood pressure (linear regression coefficient βbw = -0.3 mmHg/kg, 95% confidence interval: -0.9, 0.3). The association was strengthened upon adjustment for current weight (βbw|C = -1.5 mmHg/kg, 95% confidence interval: -2.1, -0.9). Sensitivity analyses revealed that the negative conditional association was explained by U only if U was relatively strongly associated with blood pressure and if there was a large difference in the prevalence of U between low-birth weight and normal-birth weight children. This weakens the hypothesis that the negative relationship between birth weight and blood pressure arises only from collider-stratification bias induced by conditioning on current weight.

Effect of an ectoparasite on reproduction in great tits.

1. The effect of a haematophageous ectoparasite, the hen flea, on quality an number of offspring was experimentally investigated in the great tit. The experiment consisted of a controlled infestation of a random sample of nests with the parasitic flea and of a regular treatment of control nests with Microwaves in order to eliminate the naturally occurring fleas. 2. To assess the effects of fleas on variables related to offspring number, we considered the number of hatchlings and fledglings, the mortality between hatching and fledging, and the hatching and fledging success. For assessment of offspring quality, we measured body mass, tarsus and wing length, and calculated the nutritional condition of, nestlings as the ratio of body mass to tarsus length. A physiological variable, the haematocrit level, was also measured. 3. Hatching success and hatchling numbers did not differ between the two experimental groups. Offspring mortality between hatching and fledging was significantly higher in the infested broods (xBAR = 0.22 chicks dead per day) than in the parasite-free broods (xBAR = 0.07 dead per day). Fledging success was 83% in the parasite-free broods, but only 53% in the infested ones. The number of fledglings in infested broods (xBAR = 3.7 fledglings +/-2.1 SD) was significantly lower than in the parasite-free (xBAR = 4.9 +/- 1.1 SD) broods. 4. Body mass of chicks in the infested broods was significantly smaller than in the parasite-free broods both 14 days and 17 days after hatching. The chicks in the infested broods reached a significantly smaller tarsus length than the ones in the parasite-free broods. Close to fledging, the nutritional condition of chicks was significantly lower in infested broods. Haematocrit levels were significantly lower in the infested broods. 5. Brood size correlated differently with body mass and condition of chicks in infested and parasite-free nests. In parasite-free broods both body mass and condition of chicks at age 17 days, i.e. close to fledging, were significantly higher in small broods than in large ones. However, in the infested broods chicks were of the same body mass and condition in large as in small broods. Therefore, in parasite-free broods fitness can potentially be gained through offspring quality or number or both, whereas in infested broods it can be gained through offspring quantity only. In other words, a trade-off between quality and number of offspring is feasible only in the absence of the parasitic hen flea. 6. These results emphasize the need to study the effects of ectoparasites on ecological, behavioural and evolutionary traits of their bird hosts. A knowledge of these effects is essential for the understanding of population dynamics, behaviour and life-history traits of the hosts.

The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals.

OBJECTIVE: To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication. DESIGN: A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication. RESULTS: Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001). CONCLUSION: We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.

Sex differences in hospital readmission among colorectal cancer patients.

Background: While several studies have analysed sex and socioeconomic differences in cancer incidence and mortality, sex differences in oncological health care have been seldom considered. Objective: To investigate sex based inequalities in hospital readmission among patients diagnosed with colorectal cancer. Design: Prospective cohort study. Setting: Hospital Universitary in L¿Hospitalet (Barcelona, Spain). Participants: Four hundred and three patients diagnosed with colorectal between January 1996 and December 1998 were actively followed up until 2002. Main outcome measurements and methods: Hospital readmission times related to colorectal cancer after surgical procedure. Cox proportional model with random effect (frailty) was used to estimate hazard rate ratios and 95% confidence intervals of readmission time for covariates analysed. Results: Crude hazard rate ratio of hospital readmission in men was 1.61 (95% CI 1.21 to 2.15). When other significant determinants of readmission were controlled for (including Dukes¿s stage, mortality, and Charlson¿s index) a significant risk of readmission was still present for men (hazard rate ratio: 1.52, 95% CI 1.17 to 1.96). Conclusions: In the case of colorectal cancer, women are less likely than men to be readmitted to the hospital, even after controlling for tumour characteristics, mortality, and comorbidity. New studies should investigate the role of other non-clinical variable such as differences in help seeking behaviours or structural or personal sex bias in the attention given to patients.

Empirical study of correlated survival times for recurrent events with proportional hazards margins and the effect of correlation and censoring.

Background: In longitudinal studies where subjects experience recurrent incidents over a period of time, such as respiratory infections, fever or diarrhea, statistical methods are required to take into account the within-subject correlation. Methods: For repeated events data with censored failure, the independent increment (AG), marginal (WLW) and conditional (PWP) models are three multiple failure models that generalize Cox"s proportional hazard model. In this paper, we revise the efficiency, accuracy and robustness of all three models under simulated scenarios with varying degrees of within-subject correlation, censoring levels, maximum number of possible recurrences and sample size. We also study the methods performance on a real dataset from a cohort study with bronchial obstruction. Results: We find substantial differences between methods and there is not an optimal method. AG and PWP seem to be preferable to WLW for low correlation levels but the situation reverts for high correlations. Conclusions: All methods are stable in front of censoring, worsen with increasing recurrence levels and share a bias problem which, among other consequences, makes asymptotic normal confidence intervals not fully reliable, although they are well developed theoretically.

Urinary saturation and nephrocalcinosis in preterm infants: effect of parenteral nutrition.

Urinary lithogenic and inhibitory factors were studied in 27 preterm infants; 16 had total parenteral nutrition (TPN) and 11 had breastmilk with an additional glucose-sodium chloride infusion. Urines were collected for 24 hours on day 2 (period A), day 3 (B), and once between days 4 and 10 (C). Urinary calcium oxalate saturation was calculated by the computer program EQUIL 2. Renal ultrasonography was performed every second week until discharge. The calcium/creatinine ratio increased in infants on TPN (A 0.91; C 1.68 mol/mol) and was significantly higher at period C than that in infants on breastmilk/infusion (A 0.52; C 0.36). The oxalate/creatinine ratio was persistently higher with TPN (203 mmol/mol) than with breastmilk/infusion (98; 137). The citrate/creatinine remained constant with TPN (0.44 mol/mol), whereas it increased significantly with breastmilk/infusion (0.26; 0.49). Calcium/citrate rose considerably with TPN, but decreased with breastmilk/infusion to a significantly lower level than with TPN. The urinary calcium oxalate saturation increased with TPN (2.4; 4.5) and decreased with breastmilk/infusion (2.1; 1.5) to a significantly lower value than with TPN. Nephrocalcinosis developed in two infants on TPN. Mean daily calcium intake was similar in both groups, whereas protein, sodium, and phosphorus intake were significantly higher on TPN. It is concluded that the increase in urinary calcium oxalate saturation observed with TPN is due to the combined effect of an increased urinary calcium excretion and higher urinary oxalate/creatinine and calcium/citrate ratios. The changes observed are likely to be caused by TPN itself, which differs in several respects from breastmilk feeding.

Detecting, quantifying and adjusting for publication bias in meta-analyses: protocol of a systematic review on methods.

BACKGROUND: Health professionals and policymakers aspire to make healthcare decisions based on the entire relevant research evidence. This, however, can rarely be achieved because a considerable amount of research findings are not published, especially in case of 'negative' results - a phenomenon widely recognized as publication bias. Different methods of detecting, quantifying and adjusting for publication bias in meta-analyses have been described in the literature, such as graphical approaches and formal statistical tests to detect publication bias, and statistical approaches to modify effect sizes to adjust a pooled estimate when the presence of publication bias is suspected. An up-to-date systematic review of the existing methods is lacking. METHODS/DESIGN: The objectives of this systematic review are as follows:âeuro¢ To systematically review methodological articles which focus on non-publication of studies and to describe methods of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses.âeuro¢ To appraise strengths and weaknesses of methods, the resources they require, and the conditions under which the method could be used, based on findings of included studies.We will systematically search Web of Science, Medline, and the Cochrane Library for methodological articles that describe at least one method of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses. A dedicated data extraction form is developed and pilot-tested. Working in teams of two, we will independently extract relevant information from each eligible article. As this will be a qualitative systematic review, data reporting will involve a descriptive summary. DISCUSSION: Results are expected to be publicly available in mid 2013. This systematic review together with the results of other systematic reviews of the OPEN project (To Overcome Failure to Publish Negative Findings) will serve as a basis for the development of future policies and guidelines regarding the assessment and handling of publication bias in meta-analyses.

Feeding strategies and energy to protein ratio on tambaqui performance and physiology

The objective of this work was to evaluate the effect of feed deprivation and refeeding with diets containing different energy to protein ratios (E/P) on the performance and physiology of juvenile tambaqui (Colossoma macropomum). A 4x2 factorial arrangement with three replicates was used, with four E/P ratios (11.5, 10.5, 9.5, and 8.5 kcal g-1 digestible energy per protein) and two feeding regimens (with and without deprivation), during 60 days. Fish from the food-deprived group were fasted for 14 days and refed from the fifteenth to the sixtieth day, whereas the remaining fish were fed for 60 days. At the end of the experimental period, weight of fish subjected to food deprivation was lower than that of those continuously fed; however, this condition did not influence the physiological parameters analyzed. Tambaqui fed 11.5 kcal g-1 achieved lower final weight than those fed with the other diets, in both regimens. Among the physiological parameters, only plasma protein presented significant increase in fish fed 8.5 kcal g-1, in both feeding regimens, probably due to the higher dietary protein concentration. These results indicate that fish show a partial compensatory growth, and that 10.5 kcal g-1 can be recommended for the diet of juvenile tambaqui.

Effect of nitrogen and phosphorus supply on growth, chlorophyll content and tissue composition of the macroalga Chaetomorpha linum (O.F. Mull), Kutz, in a Mediterranean Coastal Lagoon

The effect of dissolved nutrients on growth, nutrient content and uptake rates of Chaetomorpha linum in a Mediterranean coastal lagoon (Tancada, Ebro delta, NE Spain) was studied in laboratory experiments. Water was enriched with distinct forms of nitrogen, such as nitrate or ammonium and phosphorus. Enrichment with N, P or with both nutrients resulted in a significant increase in the tissue content of these nutrients. N-enrichment was followed by an increase in chlorophyll content after 4 days of treatment, although the difference was only significant when nitrate was added without P. P-enrichment had no significant effect on chlorophyll content. In all the treatments an increase in biomass was obseved after 10 days. This increase was higher in the N+P treatments. In all the treatments the uptake rate was significantly higher when nutrients were added than in control jars. The uptake rate of N, as ammonium, and P were significantly higher when they were added alone while that of N as nitrate was higher in the N+P treatment. In the P-enriched cultures, the final P-content of macroalgal tissues was ten-fold that of the initial tissue concentrations, thereby indicating luxury P-uptake. Moreover, at the end of the incubation the N:P ratio increased to 80, showing that P rather than N was the limiting factor for C. linum in the Tancada lagoon. The relatively high availability of N is related to the N inputs from rice fields that surround the lagoon and to P binding in sediments.

In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis.

IMPORTANCE: There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). OBJECTIVE: To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. INTERVENTIONS: Valve replacement during index hospitalization (early surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES: In-hospital and 1-year mortality. RESULTS: Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE: Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.