Hirsch Index and Truth Survival in Clinical Research

BACKGROUND: Factors associated with the survival of truth of clinical conclusions in the medical literature are unknown. We hypothesized that publications with a first author having a higher Hirsch' index value (h-I), which quantifies and predicts an individual's scientific research output, should have a longer half-life. METHODS AND RESULTS: 474 original articles concerning cirrhosis or hepatitis published from 1945 to 1999 were selected. The survivals of the main conclusions were updated in 2009. The truth survival was assessed by time-dependent methods (Kaplan Meier method and Cox). A conclusion was considered to be true, obsolete or false when three or more observers out of the six stated it to be so. 284 out of 474 conclusions (60%) were still considered true, 90 (19%) were considered obsolete and 100 (21%) false. The median of the h-I was=24 (range 1-85). Authors with true conclusions had significantly higher h-I (median=28) than those with obsolete (h-I=19; P=0.002) or false conclusions (h-I=19; P=0.01). The factors associated (P<0.0001) with h-I were: scientific life (h-I=33 for>30 years vs. 16 for<30 years), -methodological quality score (h-I=36 for high vs. 20 for low scores), and -positive predictive value combining power, ratio of true to not-true relationships and bias (h-I=33 for high vs. 20 for low values). In multivariate analysis, the risk ratio of h-I was 1.003 (95%CI, 0.994-1.011), and was not significant (P=0.56). In a subgroup restricted to 111 articles with a negative conclusion, we observed a significant independent prognostic value of h-I (risk ratio=1.033; 95%CI, 1.008-1.059; P=0.009). Using an extrapolation of h-I at the time of article publication there was a significant and independent prognostic value of baseline h-I (risk ratio=0.027; P=0.0001). CONCLUSIONS: The present study failed to clearly demonstrate that the h-index of authors was a prognostic factor for truth survival. However the h-index was associated with true conclusions, methodological quality of trials and positive predictive values

Human Movement Is Both Diffusive and Directed

Understanding the influence of the built environment on human movement requires quantifying spatial structure in a general sense. Because of the difficulty of this task, studies of movement dynamics often ignore spatial heterogeneity and treat movement through journey lengths or distances alone. This study analyses public bicycle data from central London to reveal that, although journey distances, directions, and frequencies of occurrence are spatially variable, their relative spatial patterns remain largely constant, suggesting the influence of a fixed spatial template. A method is presented to describe this underlying space in terms of the relative orientation of movements toward, away from, and around locations of geographical or cultural significance. This produces two fields: one of convergence and one of divergence, which are able to accurately reconstruct the observed spatial variations in movement. These two fields also reveal categorical distinctions between shorter journeys merely serving diffusion away from significant locations, and longer journeys intentionally serving transport between spatially distinct centres of collective importance. Collective patterns of human movement are thus revealed to arise from a combination of both diffusive and directed movement, with aggregate statistics such as mean travel distances primarily determined by relative numbers of these two kinds of journeys

Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet

Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy

Increased mRNA expression levels of ERCC1, OGG1 and RAI in colorectal adenomas and carcinomas

BACKGROUND: The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If an increase in DNA repair expression is detected in both early adenomas and carcinomas it may indicate that low repair capacity in the normal mucosa is a risk factor for adenoma formation. METHODS: We have examined mRNA expression of two DNA repair genes, ERCC1 and OGG1 as well as the putative apoptosis controlling gene RAI, in normal tissues and lesions from 36 cases with adenomas (mild/moderat n = 21 and severe n = 15, dysplasia) and 9 with carcinomas. RESULTS: Comparing expression levels of ERCC1, OGG1 and RAI between normal tissue and all lesions combined yielded higher expression levels in lesions, 3.3-fold higher (P = 0.005), 5.6-fold higher(P < 3·10(-5)) and 7.7-fold higher (P = 0.0005), respectively. The levels of ERCC1, OGG1 and RAI expressions when comparing lesions, did not differ between adenomas and CRC cases, P = 0.836, P = 0.341 and P = 0.909, respectively. When comparing expression levels in normal tissue, the levels for OGG1 and RAI from CRC cases were significantly lower compared to the cases with adenomas, P = 0.012 and P = 0.011, respectively. CONCLUSION: Our results suggest that increased expression of defense genes is an early event in the progression of colorectal adenomas to carcinomas

Spatial memory in the grey mouse lemur (Microcebus murinus)

Wild animals face the challenge of locating feeding sites distributed across broad spatial and temporal scales. Spatial memory allows animals to find a goal, such as a productive feeding patch, even when there are no goal-specific sensory cues available. Because there is little experimental information on learning and memory capabilities in free-ranging primates, the aim of this study was to test whether grey mouse lemurs (Microcebus murinus), as short-term dietary specialists, rely on spatial memory in relocating productive feeding sites. In addition, we asked what kind of spatial representation might underlie their orientation in their natural environment. Using an experimental approach, we set eight radio-collared grey mouse lemurs a memory task by confronting them with two different spatial patterns of baited and non-baited artificial feeding stations under exclusion of sensory cues. Positional data were recorded by focal animal observations within a grid system of small foot trails. A change in the baiting pattern revealed that grey mouse lemurs primarily used spatial cues to relocate baited feeding stations and that they were able to rapidly learn a new spatial arrangement. Spatially concentrated, non-random movements revealed preliminary evidence for a route-based restriction in mouse lemur space; during a subsequent release experiment, however, we found high travel efficiency in directed movements. We therefore propose that mouse lemur spatial memory is based on some kind of mental representation that is more detailed than a route-based network map

Relationships between Levels of Serum IgE, Cell-Bound IgE, and IgE-Receptors on Peripheral Blood Cells in a Pediatric Population

Background: Elevated serum immunoglobulin (Ig) E is a diagnostic marker of immediate-type allergic reactions. We hypothesize that serum IgE does not necessarily reflect total body IgE because in vivo IgE can be bound to cell surface receptors such as FcεRI and FcεRII (CD23). The aim of this study was to analyze the relationships between levels of serum IgE, cell-bound IgE, and IgE-receptors on peripheral blood cells in a pediatric population. Methodology: Whole blood samples from 48 children (26 boys, 22 girls, mean age 10,3±5,4 years) were analyzed by flow cytometry for FcεRI, CD23, and cell-bound IgE on dendritic cells (CD11c+MHC class II+), monocytes (CD14+), basophils (CD123+MHC class II-) and neutrophils (myeloperoxidase+). Total serum IgE was measured by ELISA and converted into z-units to account for age-dependent normal ranges. Correlations were calculated using Spearman rank correlation test. Principal Findings: Dendritic cells, monocytes, basophils, and neutrophils expressed the high affinity IgE-receptor FcεRI. Dendritic cells and monocytes also expressed the low affinity receptor CD23. The majority of IgE-receptor positive cells carried IgE on their surface. Expression of both IgE receptors was tightly correlated with cell-bound IgE. In general, cell-bound IgE on FcεRI+ cells correlated well with serum IgE. However, some patients carried high amounts of cell-bound IgE despite low total serum IgE levels. Conclusion/Significance: In pediatric patients, levels of age-adjusted serum IgE, cell-bound IgE, and FcεRI correlate. Even in the absence of elevated levels of serum IgE, cell-bound IgE can be detected on peripheral blood cells in a subgroup of patients

A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a danish prospective case-cohort study

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs <it>ASE-1 </it>G-21A, <it>RAI </it>IVS1 A4364G and <it>ERCC1 </it>Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of <it>RAI </it>IVS1 A4364G^A, <it>ERCC1 </it>Asn118Asn^Tand <it>ASE-1 </it>G-21A^G. We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal cancer, and investigated gene-environment associations between the polymorphisms and the haplotype and smoking status at enrolment, smoking duration, average smoking intensity and alcohol consumption, respectively, in relation to risk of colorectal cancer.</p> <p>Methods</p> <p>Associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were examined, as well as gene-environment interaction, in a Danish case-cohort study including 405 cases and a comparison group of 810 persons. Incidence rate ratio (IRR) were estimated by the Cox proportional hazards model stratified according to gender, and two-sided 95% confidence intervals (CI) and p-values were calculated based on robust estimates of the variance-covariance matrix and Wald's test of the Cox regression parameter.</p> <p>Results</p> <p>No consistent associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed.</p> <p>Conclusion</p> <p>Our results suggest that the <it>ASE-1 </it>G-21A, <it>RAI </it>IVS1 A4364G and <it>ERCC1 </it>Asn118Asn polymorphisms and the previously identified haplotype are not associated with risk of colorectal cancer. We found no evidence of gene-environment interaction between the three polymorphisms and the haplotype and smoking intensity and alcohol consumption, respectively, in relation to the risk of colorectal cancer.</p

Incidence of epidural haematoma and neurological injury in cardiovascular patients with epidural analgesia/anaesthesia: systematic review and meta-analysis

BACKGROUND: Epidural anaesthesia is used extensively for cardiothoracic and vascular surgery in some centres, but not in others, with argument over the safety of the technique in patients who are usually extensively anticoagulated before, during, and after surgery. The principle concern is bleeding in the epidural space, leading to transient or persistent neurological problems. METHODS: We performed an extensive systematic review to find published cohorts of use of epidural catheters during vascular, cardiac, and thoracic surgery, using electronic searching, hand searching, and reference lists of retrieved articles. RESULTS: Twelve studies included 14,105 patients, of whom 5,026 (36%) had vascular surgery, 4,971 (35%) cardiac surgery, and 4,108 (29%) thoracic surgery. There were no cases of epidural haematoma, giving maximum risks following epidural anaesthesia in cardiac, thoracic, and vascular surgery of 1 in 1,700, 1 in 1,400 and 1 in 1,700 respectively. In all these surgery types combined the maximum expected rate would be 1 in 4,700. In all these patients combined there were eight cases of transient neurological injury, a rate of 1 in 1,700 (95% confidence interval 1 in 3,300 to 1 in 850). There were no cases of persistent neurological injury (maximum expected rate 1 in 4,600). CONCLUSION: These estimates for cardiothoracic epidural anaesthesia should be the worst case. Limitations are inadequate denominators for different types of surgery in anticoagulated cardiothoracic or vascular patients more at risk of bleeding