The concept for innovative Comprehensive Assessment of Lowland Rivers.

Current river assessment methods focus on evaluating a single aspect (e.g. the physical and chemical quality of the water or its hydromorphological state) and usually do not integrate various factors.

Is lymphangitic streaking associated with different pathogens?

Objectives: Little is known regarding the differences in microbiology associated with cellulitis or abscess with or without lymphangitic streaking. The objective of our study is to assess whether there are differences in the pathogens identified from wound cultures of patients with paronychia with and without associated lymphangitis.

Methods: Retrospective cross-sectional study at a tertiary pediatric emergency department over 25 years.

Assessment of the impact of land use in an agricultural catchment area on water quality of lowland rivers.

In several countries around the world, agricultural land area exceeds 70% (Uruguay 82.6%, Kazakhstan 80.4%, Turkmenistan 72.

Linking world bank development indicators and outcomes of congenital heart surgery in low-income and middle-income countries: retrospective analysis of quality improvement data.

Objective: Many low-income and middle-income countries (LMICs) struggle to provide the health services investment required for life-saving congenital heart disease (CHD) surgery. We explored associations between risk-adjusted CHD surgical mortality from 17 LMICs and global development indices to identify patterns that might inform investment strategies.

Design: Retrospective analysis: country-specific standardised mortality ratios were graphed against global development indices reflective of wealth and healthcare investment.

A Phase 2 clinical trial of PF-05212377 (SAM-760) in subjects with mild to moderate Alzheimer's disease with existing neuropsychiatric symptoms on a stable daily dose of donepezil.

Background: Symptomatic benefits have been reported for 5-HT receptor antagonists in Alzheimer's disease (AD) trials. SAM-760 is a potent and selective 5-HT receptor antagonist that has demonstrated central 5-HT receptor saturation in humans at a dose of 30 mg.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial evaluating the efficacy and safety of SAM-760 30 mg once daily (QD) for 12 weeks in subjects with AD on a stable regimen of donepezil 5 to 10 mg QD.

Postoperative Infection in Developing World Congenital Heart Surgery Programs: Data From the International Quality Improvement Collaborative.

Background: Postoperative infections contribute substantially to morbidity and mortality after congenital heart disease surgery and are often preventable. We sought to identify risk factors for postoperative infection and the impact on outcomes after congenital heart surgery, using data from the International Quality Improvement Collaborative for Congenital Heart Surgery in Developing World Countries.

Methods And Results: Pediatric cardiac surgical cases performed between 2010 and 2012 at 27 participating sites in 16 developing countries were included.

Single-Cell-Based Analysis Highlights a Surge in Cell-to-Cell Molecular Variability Preceding Irreversible Commitment in a Differentiation Process.

In some recent studies, a view emerged that stochastic dynamics governing the switching of cells from one differentiation state to another could be characterized by a peak in gene expression variability at the point of fate commitment. We have tested this hypothesis at the single-cell level by analyzing primary chicken erythroid progenitors through their differentiation process and measuring the expression of selected genes at six sequential time-points after induction of differentiation. In contrast to population-based expression data, single-cell gene expression data revealed a high cell-to-cell variability, which was masked by averaging.

Development and psychometric characteristics of the pediatric inpatient experience survey (PIES).

Objective: To study the psychometric properties of the Pediatric Inpatient Experience Survey (PIES), a mail and phone survey for parent reporting of family-centered aspects of inpatient care experiences.

Design: Two waves of cross-sectional survey data were collected by mail and phone in 2009 to design a measurement instrument with good psychometric characteristics. Additional cross-sectional data from a mail administration in 2011 confirmed the measurement domains.

Stochastic fluctuations and distributed control of gene expression impact cellular memory.

Despite the stochastic noise that characterizes all cellular processes the cells are able to maintain and transmit to their daughter cells the stable level of gene expression. In order to better understand this phenomenon, we investigated the temporal dynamics of gene expression variation using a double reporter gene model. We compared cell clones with transgenes coding for highly stable mRNA and fluorescent proteins with clones expressing destabilized mRNA-s and proteins.

Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease.

Objective: To examine safety, tolerability, and efficacy of PF-04494700, an inhibitor of the receptor for advanced glycation end products (RAGE), in mild to moderate Alzheimer disease (AD).

Methods: Double-blind, placebo-controlled trial at 40 academic centers (United States). Subjects with AD and Mini-Mental State Examination score 14-26 were randomized to PF-04494700 60 mg/day × 6 days, then 20 mg daily (high dose); 15 mg/day × 6 days, then 5 mg daily (low dose); or placebo, for 18 months.

Safety and pharmacokinetics of PF-04360365 following a single-dose intravenous infusion in Japanese subjects with mild-to-moderate Alzheimer's disease: a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study.

Objective: PF-04360365 is a humanized IgG(2)Δa anti-amyloid β (Aβ) antibody designed to improve outcome in Alzheimer's disease (AD). Single doses of 0.1 - 10 mg/kg were safe and well tolerated in Western (mostly Caucasian) subjects with mild-to-moderate AD.

Quantifying the contribution of chromatin dynamics to stochastic gene expression reveals long, locus-dependent periods between transcriptional bursts.

Background: A number of studies have established that stochasticity in gene expression may play an important role in many biological phenomena. This therefore calls for further investigations to identify the molecular mechanisms at stake, in order to understand and manipulate cell-to-cell variability. In this work, we explored the role played by chromatin dynamics in the regulation of stochastic gene expression in higher eukaryotic cells.

Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study.

Objectives: Ponezumab is a humanized antiamyloid beta (Aβ) monoclonal antibody designed to treat Alzheimer disease (AD).

Methods: This randomized, double-blind, single-dose-escalation study evaluated the safety, pharmacokinetics, and pharmacodynamics of 0.1, 0.

Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate Alzheimer disease.

Objective: Ponezumab (PF-04360365) is a humanized anti-amyloid beta (Aβ) monoclonal antibody designed for treatment of Alzheimer disease (AD). A single 2-hour intravenous infusion of 0.1 to 10 mg/kg was previously shown to be safe and well tolerated in subjects with mild to moderate AD, with measurable effects on plasma and cerebrospinal fluid Aβ.

On the lack of specificity of proteins and its consequences for a theory of biological organization.

It is now widely recognized that gene expression and cellular processes include a probabilistic component. However, this does not essentially modify the theory of genetic programming. This stochastic aspect, which is called noise, is usually conceived as a margin of fluctuation in the way the genetic program functions and the latter remains understood as a specific mechanism guided by genetic information.

Modifications of erythrocyte membrane hydration induced by organic tin compounds.

A study on the effects of selected organic chlorides of tin on the extent of hydration of the lipid bilayer of erythrocyte ghosts from pig blood is presented. The following compounds were used, dibutyltin dichloride (DBT), tributyltin chloride (TBT), diphenyltin dichloride (DPhT) and triphenyltin chloride (TPhT). The degree of membrane hydration was measured by the ATR FTIR technique, which makes it possible to estimate the level of carbonyl and phosphate group hydration in lipids of membranes.

Modeling embryogenesis and cancer: an approach based on an equilibrium between the autostabilization of stochastic gene expression and the interdependence of cells for proliferation.

A large amount of data demonstrating the stochastic nature of gene expression and cell differentiation has accumulated during the last 40 years. These data suggest that a gene in a cell always has a certain probability of being activated at any time and that instead of leading to on and off switches in an all-or-nothing fashion, the concentration of transcriptional regulators increases or decreases this probability. In order to integrate these data in an appropriate theoretical frame, we have tested the relevance of the selective model of cell differentiation by computer simulation experiments.

Dynamic CpG and non-CpG methylation of the Peg1/Mest gene in the mouse oocyte and preimplantation embryo.

In somatic tissues, the CpG island of the imprinted Peg1/Mest gene is methylated on the maternal allele. We have examined the methylation of CpG and non-CpG sites of this differentially methylated CpG island in freshly ovulated oocytes, in vitro aged oocytes, and preimplantation embryos. The CpG methylation pattern was heterogeneous in freshly ovulated oocytes, despite the fact that they all were arrested in metaphase II.

Local and spatial factors determining HIV-1 protease substrate recognition.

Insertional mutagenesis of the Escherichia coli thymidylate synthase (TS) was used to address substrate recognition of HIV-1 protease in a well characterized structural context. By modifying the TS conformation while maintaining its enzymic activity, we investigated the influence of protein folding on protease-substrate recognition. A slight destabilization of the TS structure permitted the cleavage of a target site, which was resistant in the native TS.