Evolutionary aspects of population structure for molecular and quantitative traits in the freshwater snail Radix balthica.

Detecting the action of selection in natural populations can be achieved using the QST-FST comparison that relies on the estimation of FST with neutral markers, and QST using quantitative traits potentially under selection. QST higher than FST suggests the action of directional selection and thus potential local adaptation. In this article, we apply the QST-FST comparison to four populations of the hermaphroditic freshwater snail Radix balthica located in a floodplain habitat. In contrast to most studies published so far, we did not detect evidence of directional selection for local optima for any of the traits we measured: QST calculated using three different methods was never higher than FST. A strong inbreeding depression was also detected, indicating that outcrossing is probably predominant over selfing in the studied populations. Our results suggest that in this floodplain habitat, local adaptation of R. balthica populations may be hindered by genetic drift, and possibly altered by uneven gene flow linked to flood frequency.

Blind docking of 260 protein-ligand complexes with EADock 2.0.

Molecular docking softwares are one of the important tools of modern drug development pipelines. The promising achievements of the last 10 years emphasize the need for further improvement, as reflected by several recent publications (Leach et al., J Med Chem 2006, 49, 5851; Warren et al., J Med Chem 2006, 49, 5912). Our initial approach, EADock, showed a good performance in reproducing the experimental binding modes for a set of 37 different ligand-protein complexes (Grosdidier et al., Proteins 2007, 67, 1010). This article presents recent improvements regarding the scoring and sampling aspects over the initial implementation, as well as a new seeding procedure based on the detection of cavities, opening the door to blind docking with EADock. These enhancements were validated on 260 complexes taken from the high quality Ligand Protein Database [LPDB, (Roche et al., J Med Chem 2001, 44, 3592)]. Two issues were identified: first, the quality of the initial structures cannot be assumed and a manual inspection and/or a search in the literature are likely to be required to achieve the best performance. Second the description of interactions involving metal ions still has to be improved. Nonetheless, a remarkable success rate of 65% was achieved for a large scale blind docking assay, when considering only the top ranked binding mode and a success threshold of 2 A RMSD to the crystal structure. When looking at the five-top ranked binding modes, the success rate increases up to 76%. In a standard local docking assay, success rates of 75 and 83% were obtained, considering only the top ranked binding mode, or the five top binding modes, respectively.

Global surveillance of cancer survival 1995-2009 : analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. FUNDING: Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

Spectroscopic ellipsometry study of the In1-x Gax Asy P1-y / InP Heterojunctions grown by metalorganic chemical-vapor deposition

The dielectric functions of InP, In0.53Ga0.47As, and In0.75Ga0.25As0.5P0.5 epitaxial layers have been measured using a polarization modulation spectroscopic ellipsometer in the 1.5 to 5.3 eV region. The oxide removal procedure has been carefully checked by comparing spectroscopic ellipsometry and x ray photoelectron spectroscopy measurements. These reference data have been used to investigate the structural nature of metalorganic chemical vapor deposition grown In0.53Ga0.47As/InP and In0.75Ga0.25As0.5P0.5/InP heterojunctions, currently used for photodiodes and laser diodes. The sharpness of the interfaces has been systematically compared for the two types of heterojunctions: In1 xGaxAsy/InP and InP/In1 xGaxAsyP1 y. The sharpest interface is obtained for InP growth on In0.75Ga0.25As0.5P0.5 where the interface region is estimated to be (10±10) Å thick. The importance of performing in situ SE measurements is emphasized.

Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with significantly increased cardiovascular morbidity and mortality. Fluid overload may promote obstructive sleep apnea in patients with ESRD through an overnight fluid shift from the legs to the neck soft tissues. Body fluid shift and severity of obstructive sleep apnea before and after hemodialysis were compared in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventeen patients with hemodialysis and moderate to severe obstructive sleep apnea were included. Polysomnographies were performed the night before and after hemodialysis to assess obstructive sleep apnea, and bioimpedance was used to measure fluid overload and leg fluid volume. RESULTS: The mean overnight rostral fluid shift was 1.27±0.41 L prehemodialysis; it correlated positively with fluid overload volume (r=0.39; P=0.02) and was significantly lower posthemodialysis (0.78±0.38 L; P<0.001). There was no significant difference in the mean obstructive apnea-hypopnea index before and after hemodialysis (46.8±22.0 versus 42.1±18.6 per hour; P=0.21), but obstructive apnea-hypopnea index was significantly lower posthemodialysis (-10.1±10.8 per hour) in the group of 12 patients, with a concomitant reduction of fluid overload compared with participants without change in fluid overload (obstructive apnea-hypopnea index +8.2±16.1 per hour; P<0.01). A lower fluid overload after hemodialysis was significantly correlated (r=0.49; P=0.04) with a lower obstructive apnea-hypopnea index. Fluid overload-assessed by bioimpedance-was the best predictor of the change in obstructive apnea-hypopnea index observed after hemodialysis (standardized r=-0.68; P=0.01) in multivariate regression analysis. CONCLUSIONS: Fluid overload influences overnight rostral fluid shift and obstructive sleep apnea severity in patients with ESRD undergoing intermittent hemodialysis. Although no benefit of hemodialysis on obstructive sleep apnea severity was observed in the whole group, the change in obstructive apnea-hypopnea index was significantly correlated with the change in fluid overload after hemodialysis. Moreover, the subgroup with lower fluid overload posthemodialysis showed a significantly lower obstructive sleep apnea severity, which provides a strong incentive to further study whether optimizing fluid status in patients with obstructive sleep apnea and ESRD will improve the obstructive apnea-hypopnea index.

Influence of Gilbert's syndrome on the formation of ethyl glucuronide.

A drinking experiment with participants suffering from Gilbert's syndrome was performed to study the possible influence of this glucuronidation disorder on the formation of ethyl glucuronide (EtG). Gilbert's syndrome is a rather common and, in most cases, asymptomatic congenital metabolic aberration with a prevalence of about 5 %. It is characterized by a reduction of the enzyme activity of the uridine diphosphate glucuronosyltransferase (UGT) isoform 1A1 up to 80 %. One of the glucuronidation products is EtG, which is formed in the organism following exposure to ethanol. EtG is used as a short-term marker for ethyl alcohol consumption to prove abstinence in various settings. After 2 days of abstinence from ethanol and giving a void urine sample, 30 study participants drank 0.1 L of sparkling wine (9 g ethanol). 3, 6, 12, and 24 h after drinking, urine samples were collected. 3 hours after drinking, an additional blood sample was taken, in which liver enzyme activities, ethanol, hematological parameters, and bilirubin were measured. EtG and ethyl sulfate (EtS), another short-term marker of ethanol consumption, were determined in the urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS); creatinine was measured photometrically. In all participants, EtG and EtS were detected in concentrations showing a wide range (EtG: 3 h sample 0.5-18.43 mg/L and 6 h sample 0.67-13.8 mg/L; EtS: 3 h sample 0.87-6.87 mg/L and 6 h sample 0.29-4.48 mg/L). No evidence of impaired EtG formation was found. Thus, EtG seems to be a suitable marker for ethanol consumption even in individuals with Gilbert's syndrome.

La compensation écologique : marché ou marchandage ?

Les "banques de conservation" sont fréquemment présentées comme de nouveaux instruments de marché au service de la conservation de la biodiversité. Il s'agit d'une modalité de mise en oeuvre de la compensation écologique d'abord développée aux Etats-Unis au début des années 2000 avant d'être plus globalement diffusée. Ce dispositif est perçu par ses promoteurs comme un marché en devenir, tandis que ses détracteurs y voient le dernier avatar du projet de marchandisation de la nature au coeur des politiques environnementales depuis deux décennies. Au-delà des discours, les arrangements institutionnels en jeu dans les banques de conservation sont mal connus. Cet article se propose de revenir sur leur statut économique en analysant le dispositif tel que décrit dans la réglementation fédérale qui lui est consacrée aux Etats-Unis et en évaluant sa mise en place à l'aune de critères et attributs constitutifs d'un marché, qui auront été préalablement définis.

Rectal enema is an alternative to full mechanical bowel preparation for primary rectal cancer surgery.

AIM: According to the French GRECCAR III randomized trial, full mechanical bowel preparation (MBP) for rectal surgery decreases the rate of postoperative morbidity, in particular postoperative infectious complications, but MBP is not well tolerated by the patient. The aim of the present study was to determine whether a preoperative rectal enema (RE) might be an alternative to MBP. METHODS: An analysis was performed of 96 matched cohort patients undergoing rectal resection with primary anastomosis and protective ileostomy at two different university teaching hospitals, whose rectal cancer management was comparable except for the choice of preoperative bowel preparation (MBP or RE). Prospective databases were retrospectively analysed. RESULTS: Patients were well matched for age, gender, body mass index and Charlson index. The surgical approach and cancer characteristics (level above anal verge, stage and use of neoadjuvant therapy) were comparable between the two groups. Anastomotic leakage occurred in 10% of patients having MBP and in 8% having RE (P = 1.00). Pelvic abscess formation (6% vs 2%, P = 0.63) and wound infection (8% vs 15%, P = 0.55) were also comparable. Extra-abdominal infection (13% vs 13%, P = 1.00) and non-infectious abdominal complications such as ileus and bleeding (27% and 31%, P = 0.83) were not significantly different. Overall morbidity was comparable in the two groups (50% vs 54%, P = 0.83). CONCLUSION: A simple RE before rectal surgery seems not to be associated with more postoperative infectious complications nor a higher overall morbidity than MBP.

Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.

BACKGROUND: Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. AIM: To evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients. METHODS: Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. RESULTS: Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE-related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. CONCLUSIONS: Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263.

The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation.

Intestinal helminths are potent regulators of their host's immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production. Transfer of the Hpb-modified microbiota alone was sufficient to mediate protection against allergic asthma. The helminth-induced anti-inflammatory cytokine secretion and regulatory T cell suppressor activity that mediated the protection required the G protein-coupled receptor (GPR)-41. A similar alteration in the metabolic potential of intestinal bacterial communities was observed with diverse parasitic and host species, suggesting that this represents an evolutionary conserved mechanism of host-microbe-helminth interactions.

Female common lizards (Lacerta vivipara) do not adjust their sex-biased investment in relation to the adult sex ratio.

Sex allocation theory predicts that facultative maternal investment in the rare sex should be favoured by natural selection when breeders experience predictable variation in adult sex ratios (ASRs). We found significant spatial and predictable interannual changes in local ASRs within a natural population of the common lizard where the mean ASR is female-biased, thus validating the key assumptions of adaptive sex ratio models. We tested for facultative maternal investment in the rare sex during and after an experimental perturbation of the ASR by creating populations with female-biased or male-biased ASR. Mothers did not adjust their clutch sex ratio during or after the ASR perturbation, but produced sons with a higher body condition in male-biased populations. However, this differential sex allocation did not result in growth or survival differences in offspring. Our results thus contradict the predictions of adaptive models and challenge the idea that facultative investment in the rare sex might be a mechanism regulating the population sex ratio.

Robotic-Assisted Surgery Improves the Quality of Total Mesorectal Excision for Rectal Cancer Compared to Laparoscopy: Results of a Case-Controlled Analysis.

BACKGROUND: The use of a robotic surgical system is claimed to allow precise traction and counter-traction, especially in a narrow pelvis. Whether this translates to improvement of the quality of the resected specimen is not yet clear. The aim of the study was to compare the quality of the TME and the short-term oncological outcome between robotic and laparoscopic rectal cancer resections. METHODS: 20 consecutive robotic TME performed in a single institution for rectal cancer (Rob group) were matched 1:2 to 40 laparoscopic resections (Lap group) for gender, body mass index (BMI), and distance from anal verge on rigid proctoscopy. The quality of TME was assessed by 2 blinded and independent pathologists and reported according to international standardized guidelines. RESULTS: Both samples were well matched for gender, BMI (median 25.9 vs. 24.2 kg/m(2), p = 0.24), and level of the tumor (4.1 vs. 4.8 cm, p = 0.20). The quality of the TME was better in the Robotic group (complete TME: 95 vs. 55 %; p = 0.0003, nearly complete TME 5 vs. 37 %; p = 0.04, incomplete TME 0 vs. 8 %, p = 0.09). A trend for lower positive circumferential margin was observed in the Robotic group (10 vs. 25 %, p = 0.1). CONCLUSIONS: These results suggest that robotic-assisted surgery improves the quality of TME for rectal cancer. Whether this translates to better oncological outcome needs to be further investigated.