Niche dynamics in space and time.

Niche conservatism, the tendency of a species niche to remain unchanged over time, is often assumed when discussing, explaining or predicting biogeographical patterns. Unfortunately, there has been no basis for predicting niche dynamics over relevant timescales, from tens to a few hundreds of years. The recent application of species distribution models (SDMs) and phylogenetic methods to analysis of niche characteristics has provided insight to niche dynamics. Niche shifts and conservatism have both occurred within the last 100 years, with recent speciation events, and deep within clades of species. There is increasing evidence that coordinated application of these methods can help to identify species which likely fulfill one key assumption in the predictive application of SDMs: an unchanging niche. This will improve confidence in SDM-based predictions of the impacts of climate change and species invasions on species distributions and biodiversity.

Error and complexity of random walk Monte Carlo radiosity

The author studies the error and complexity of the discrete random walk Monte Carlo technique for radiosity, using both the shooting and gathering methods. The author shows that the shooting method exhibits a lower complexity than the gathering one, and under some constraints, it has a linear complexity. This is an improvement over a previous result that pointed to an O(n log n) complexity. The author gives and compares three unbiased estimators for each method, and obtains closed forms and bounds for their variances. The author also bounds the expected value of the mean square error (MSE). Some of the results obtained are also shown

Drugs Associated with Hepatotoxicity and their Reporting Frequency of Liver Adverse Events in VigiBase (TM) Unified List Based on International Collaborative Work

BACKGROUND Challenges exist in the clinical diagnosis of drug-induced liver injury (DILI) and in obtaining information on hepatotoxicity in humans. OBJECTIVE (i) To develop a unified list that combines drugs incriminated in well vetted or adjudicated DILI cases from many recognized sources and drugs that have been subjected to serious regulatory actions due to hepatotoxicity; and (ii) to supplement the drug list with data on reporting frequencies of liver events in the WHO individual case safety report database (VigiBase). DATA SOURCES AND EXTRACTION (i) Drugs identified as causes of DILI at three major DILI registries; (ii) drugs identified as causes of drug-induced acute liver failure (ALF) in six different data sources, including major ALF registries and previously published ALF studies; and (iii) drugs identified as being subjected to serious governmental regulatory actions due to their hepatotoxicity in Europe or the US were collected. The reporting frequency of adverse events was determined using VigiBase, computed as Empirical Bayes Geometric Mean (EBGM) with 90% confidence interval for two customized terms, 'overall liver injury' and 'ALF'. EBGM of >or=2 was considered a disproportional increase in reporting frequency. The identified drugs were then characterized in terms of regional divergence, published case reports, serious regulatory actions, and reporting frequency of 'overall liver injury' and 'ALF' calculated from VigiBase. DATA SYNTHESIS After excluding herbs, supplements and alternative medicines, a total of 385 individual drugs were identified; 319 drugs were identified in the three DILI registries, 107 from the six ALF registries (or studies) and 47 drugs that were subjected to suspension or withdrawal in the US or Europe due to their hepatotoxicity. The identified drugs varied significantly between Spain, the US and Sweden. Of the 319 drugs identified in the DILI registries of adjudicated cases, 93.4% were found in published case reports, 1.9% were suspended or withdrawn due to hepatotoxicity and 25.7% were also identified in the ALF registries/studies. In VigiBase, 30.4% of the 319 drugs were associated with disproportionally higher reporting frequency of 'overall liver injury' and 83.1% were associated with at least one reported case of ALF. CONCLUSIONS This newly developed list of drugs associated with hepatotoxicity and the multifaceted analysis on hepatotoxicity will aid in causality assessment and clinical diagnosis of DILI and will provide a basis for further characterization of hepatotoxicity.

Prediction of postpartum depression using multilayer perceptrons and pruning.

OBJECTIVE. The main goal of this paper is to obtain a classification model based on feed-forward multilayer perceptrons in order to improve postpartum depression prediction during the 32 weeks after childbirth with a high sensitivity and specificity and to develop a tool to be integrated in a decision support system for clinicians. MATERIALS AND METHODS. Multilayer perceptrons were trained on data from 1397 women who had just given birth, from seven Spanish general hospitals, including clinical, environmental and genetic variables. A prospective cohort study was made just after delivery, at 8 weeks and at 32 weeks after delivery. The models were evaluated with the geometric mean of accuracies using a hold-out strategy. RESULTS. Multilayer perceptrons showed good performance (high sensitivity and specificity) as predictive models for postpartum depression. CONCLUSIONS. The use of these models in a decision support system can be clinically evaluated in future work. The analysis of the models by pruning leads to a qualitative interpretation of the influence of each variable in the interest of clinical protocols.

Serum ficolin-2 correlates worse than fecal calprotectin and CRP with endoscopic Crohn's disease activity.

BACKGROUND AND AIMS: Ficolin-2 is an acute phase reactant produced by the liver and targeted to recognize N-acetyl-glucosamine which is present in bacterial and fungal cell walls. We recently showed that ficolin-2 serum levels were significantly higher in CD patients compared to healthy controls. We aimed to evaluate serum ficolin-2 concentrations in CD patients regarding their correlation with endoscopic severity and to compare them with clinical activity, fecal calprotectin, and CRP. METHODS: Patients provided fecal and blood samples before undergoing ileo-colonoscopy. Disease activity was scored clinically according to the Harvey-Bradshaw Index (HBI) and endoscopically according to the simplified endoscopic score for CD (SES-CD). Ficolin-2 serum levels and fecal calprotectin levels were measured by ELISA. RESULTS: A total of 136 CD patients were prospectively included (mean age at inclusion 41.5±15.4 years, 37.5% females). Median HBI was 3 [2-6] points, median SES-CD was 5 [2-8], median fecal calprotectin was 301 [120-703] μg/g, and median serum ficolin-2 was 2.69 [2.02-3.83] μg/mL. SES-CD correlated significantly with calprotectin (R=0.676, P<0.001), CRP (R=0.458, P<0.001), HBI (R=0.385, P<0.001), and serum ficolin-2 levels (R=0.171, P=0.047). Ficolin-2 levels were higher in CD patients with mild endoscopic disease compared to patients in endoscopic remission (P=0.015) but no difference was found between patients with mild, moderate, and severe endoscopic disease. CONCLUSIONS: Ficolin-2 serum levels correlate worse with endoscopic CD activity when compared to fecal calprotectin or CRP.

Inverse relation between FASN expression in human adipose tissue and the insulin resistance level.

BACKGROUND Adipose tissue is a key regulator of energy balance playing an active role in lipid storage and may be a dynamic buffer to control fatty acid flux. Just like PPARgamma, fatty acid synthesis enzymes such as FASN have been implicated in almost all aspects of human metabolic alterations such as obesity, insulin resistance or dyslipemia. The aim of this work is to investigate how FASN and PPARgamma expression in human adipose tissue is related to carbohydrate metabolism dysfunction and obesity. METHODS The study included eighty-seven patients which were classified according to their BMI and to their glycaemia levels in order to study FASN and PPARgamma gene expression levels, anthropometric and biochemical variables. RESULTS The main result of this work is the close relation between FASN expression level and the factors that lead to hyperglycemic state (increased values of glucose levels, HOMA-IR, HbA1c, BMI and triglycerides). The correlation of the enzyme with these parameters is inversely proportional. On the other hand, PPARgamma is not related to carbohydrate metabolism. CONCLUSIONS We can demonstrate that FASN expression is a good candidate to study the pathophysiology of type II diabetes and obesity in humans.

An unexpected role of semaphorin3a-neuropilin-1 signaling in lymphatic vessel maturation and valve formation.

RATIONALE: Lymphatic vasculature plays important roles in tissue fluid homeostasis maintenance and in the pathology of human diseases. Yet, the molecular mechanisms that control lymphatic vessel maturation remain largely unknown. OBJECTIVE: We analyzed the gene expression profiles of ex vivo isolated lymphatic endothelial cells to identify novel lymphatic vessel expressed genes and we investigated the role of semaphorin 3A (Sema3A) and neuropilin-1 (Nrp-1) in lymphatic vessel maturation and function. METHODS AND RESULTS: Lymphatic and blood vascular endothelial cells from mouse intestine were isolated using fluorescence-activated cell sorting, and transcriptional profiling was performed. We found that the axonal guidance molecules Sema3A and Sema3D were highly expressed by lymphatic vessels. Importantly, we found that the semaphorin receptor Nrp-1 is expressed on the perivascular cells of the collecting lymphatic vessels. Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1 but not with an antibody that blocks VEGF-A binding to Nrp-1 resulted in a complex phenotype of impaired lymphatic vessel function, enhanced perivascular cell coverage, and abnormal lymphatic vessel and valve morphology. CONCLUSIONS: Together, these results reveal an unanticipated role of Sema3A-Nrp-1 signaling in the maturation of the lymphatic vascular network likely via regulating the perivascular cell coverage of the vessels thus affecting lymphatic vessel function and lymphatic valve development.

Kinematics and dynamic complexity of postural transitions in frail elderly subjects.

The aim of this study was to propose a methodology allowing a detailed characterization of body sit-to-stand/stand-to-sit postural transition. Parameters characterizing the kinematics of the trunk movement during sit-to-stand (Si-St) postural transition were calculated using one initial sensor system fixed on the trunk and a data logger. Dynamic complexity of these postural transitions was estimated by fractal dimension of acceleration-angular velocity plot. We concluded that this method provides a simple and accurate tool for monitoring frail elderly and to objectively evaluate the efficacy of a rehabilitation program.

Modern cataract surgery for radiation-induced cataracts in retinoblastoma.

Background Surgery of radiation-induced cataracts in children with retinoblastoma (RB) is a challenge as early intervention is weighted against the need to delay surgery until complete tumour control is obtained. This study analyses the safety and functional results of such surgery. Methods In a retrospective, non-comparative, consecutive case series, we reviewed medical records of RB patients </=14 y of age who underwent either external beam radiotherapy or plaque treatment and were operated for radiation-induced cataract between 1985 and 2008. Results In total, 21 eyes of 20 RB patients were included and 18 out of the 21 eyes had Reese-Ellsworth stage V or ABC classification group D/E RB. Median interval between last treatment for RB and cataract surgery was 21.5 months, range 3-164 months. Phacoaspiration was performed in 13 eyes (61%), extra-capsular cataract extraction in 8 (39%) and intraocular lens implantation in 19 eyes (90%). The majority of cases, 11/21 (52%), underwent posterior capsulorhexis or capsulotomy and 6/21 (28%) an anterior vitrectomy. Postoperative visual acuity was >/=20/200 in 13 eyes and <20/200 in 5 eyes. Intraocular tumour recurrence was noted in three eyes. Mean postoperative follow up was 90 months+/-69 months. Conclusions Modern cataract surgery, including clear cornea approach, lens aspiration with posterior capsulotomy, anterior vitrectomy and IOL implantation is a safe procedure for radiation-induced cataract as long as RB is controlled. The visual prognosis is limited by initial tumour involvement of the macula and by corneal complications of radiotherapy. We recommend a minimal interval of 9 months between completion of treatment of retinoblastoma and cataract surgery.

Structural and functional studies of nonstructural protein 2 of the hepatitis C virus reveal its key role as organizer of virion assembly.

Non-structural protein 2 (NS2) plays an important role in hepatitis C virus (HCV) assembly, but neither the exact contribution of this protein to the assembly process nor its complete structure are known. In this study we used a combination of genetic, biochemical and structural methods to decipher the role of NS2 in infectious virus particle formation. A large panel of NS2 mutations targeting the N-terminal membrane binding region was generated. They were selected based on a membrane topology model that we established by determining the NMR structures of N-terminal NS2 transmembrane segments. Mutants affected in virion assembly, but not RNA replication, were selected for pseudoreversion in cell culture. Rescue mutations restoring virus assembly to various degrees emerged in E2, p7, NS3 and NS2 itself arguing for an interaction between these proteins. To confirm this assumption we developed a fully functional JFH1 genome expressing an N-terminally tagged NS2 demonstrating efficient pull-down of NS2 with p7, E2 and NS3 and, to a lower extent, NS5A. Several of the mutations blocking virus assembly disrupted some of these interactions that were restored to various degrees by those pseudoreversions that also restored assembly. Immunofluorescence analyses revealed a time-dependent NS2 colocalization with E2 at sites close to lipid droplets (LDs) together with NS3 and NS5A. Importantly, NS2 of a mutant defective in assembly abrogates NS2 colocalization around LDs with E2 and NS3, which is restored by a pseudoreversion in p7, whereas NS5A is recruited to LDs in an NS2-independent manner. In conclusion, our results suggest that NS2 orchestrates HCV particle formation by participation in multiple protein-protein interactions required for their recruitment to assembly sites in close proximity of LDs.

The multifaceted resources and microevolution of the successful human and animal pathogen methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important bacterial pathogens based on its incidence and the severity of its associated infections. In addition, severe MRSA infections can occur in hospitalised patients or healthy individuals from the community. Studies have shown the infiltration of MRSA isolates of community origin into hospitals and variants of hospital-associated MRSA have caused infections in the community. These rapid epidemiological changes represent a challenge for the molecular characterisation of such bacteria as a hospital or community-acquired pathogen. To efficiently control the spread of MRSA, it is important to promptly detect the mecA gene, which is the determinant of methicillin resistance, using a polymerase chain reaction-based test or other rapidly and accurate methods that detect the mecA product penicillin-binding protein (PBP)2a or PBP2’. The recent emergence of MRSA isolates that harbour a mecA allotype, i.e., the mecC gene, infecting animals and humans has raised an additional and significant issue regarding MRSA laboratory detection. Antimicrobial drugs for MRSA therapy are becoming depleted and vancomycin is still the main choice in many cases. In this review, we present an overview of MRSA infections in community and healthcare settings with focus on recent changes in the global epidemiology, with special reference to the MRSA picture in Brazil.

L'explotació de recursos forestals en el nord i en el sud des del punt de vista de la sostenibilitat

El present projecte té com a objectiu l’estudi de la sostenibilitat de l’explotació forestal que es realitza en l’hemisferi nord i en el sud. Per això, s’han escollit quatre països que disposen, dins de les seves fronteres, de grans extensions boscoses, cada un d’ells amb un tipus de bosc diferent: Brasil (Selva Amazònica), República Democràtica del Congo (Selva Equatorial), Canadà (Bosc Boreal) i Espanya (Bosc Mediterrani). Amb aquests països s’ha realitzat una comparativa tant de forma qualitativa com quantitativa. Pel que fa a l’anàlisi qualitatiu, s’han recollit dades del PIB per càpita dels diferents països de l’any 2010 i les principals metodologies d’explotació forestal que aquests realitzen. Així, els països amb més PIB per càpita eren també els països que utilitzaven mètodes d’explotació menys agressius i es consideren, per tant, els països amb una extracció dels seus recursos més sostenible. En quant a l’anàlisi quantitatiu, s’han utilitzat les dades de PIB per càpita, taxa de desforestació (ha/any) i taxa de creixement del bosc (ha/any) de cada tipus de bosc. Amb aquestes dades s’ha construït un índex, l’índex de sostenibilitat d’extracció, que pretén ser una eina d’estandardització per a la comparativa entre països i/o boscos diferents. El resultat ha estat el mateix en les dues anàlisis.

Coping specificities in bipolar affective disorder: relations with symptoms and therapeutic alliance

Ways to enhance research into coping have been suggested by Lazarus (2000). The issues of adaptiveness and conceptual structure of coping (Cramer, 1998; Skinner et al., 2003) are particularly relevant; thus, this study addresses them in a clinical research setting. A total of 30 inpatients presenting with Bipolar Affective Disorder (BD) have been interviewed twice, as well as the participants of a matched control group (N = 30). Self-report (CISS) and observerrater methods (CAP) of coping have been applied: low correlations were found between the instruments. Coping specificities in BD have been identified: opposition and support-seeking are most frequently practiced by BD patients, in comparison with controls. No significant link has been found between coping processes, symptom level and the therapeutic alliance. This study lends support for a quantitative definition of coping adaptiveness which is discussed, along with clinical implications on psychological treatments of BD (German J Psychiatry 2009; 12: 19-27).

Identification and in vitro reactivity of celiac immunoactive peptides in an apparent gluten-free beer.

Gluten content from barley, rye, wheat and in certain oat varieties, must be avoid in individuals with celiac disease. In most of the Western countries, the level of gluten content in food to be considered as gluten-free products is below 20 parts per million measured by ELISA based on specific anti-gluten peptide antibody. However, in beverages or food suffering complex hydrolytic processes as beers, the relative proportion of reactive peptides for celiac patients and the analytical techniques may differ, because of the diversity of the resulting peptide populations after fermentations. A beer below 20 parts per million of gluten but yet detectable levels of gluten peptides by anti-gliadin 33-mer antibodies (G12 and A1) was analyzed. We identified and characterized the relevant peptides for either antibody recognition or immunoactivity in celiac patients. The beer was fractionated by HPLC. The relative reactivity of the different HPLC fractions to the G12/A1 antibodies correlated to the reactivity of peripheral blood mononuclear cells isolated from 14 celiac individuals. Peptides from representative fractions classified according to the relative reactivity to G12/A1 antibodies were identified by mass spectrometry. The beer peptides containing sequences with similarity to those of previously described G12 and A1 epitopes were synthesized and confirmed significant reactivity for the antibodies. The most reactive peptides for G12/A1 also confirmed the highest immunogenicity by peripheral blood mononuclear cell activation and interferon γ production from celiac patients. We concluded that preparative HPLC combined with anti-gliadin 33-mer G12/A1 antibodies were very sensitive and specific methods to analyze the relevant immunogenic peptides in hydrolyzed gluten.

Moderate-Vigorous Physical Activity across Body Mass Index in Females: Moderating Effect of Endocannabinoids and Temperament.

BACKGROUND Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI. METHODS Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA. RESULTS Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039) and high MVPA levels were associated with elevated anandamide (AEA) levels (b = 0.16, p = .049) and N-oleylethanolamide (OEA) levels (b = 0.22, p = .004), as well as high Novelty seeking (b = 0.18, p<.001) and low Harm avoidance (b = -0.16, p<.001). CONCLUSIONS Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.