1999-2009 trends in prevalence, unawareness, treatment and control of hypertension in Geneva, Switzerland.

BACKGROUND: There are no time trends in prevalence, unawareness, treatment, and control of hypertension in Switzerland. The objective of this study was to analyze these trends and to determine the associated factors. METHODS/FINDINGS: Population-based study conducted in the Canton of Geneva, Switzerland, between 1999 and 2009. Blood pressure was measured thrice using a standard protocol. Hypertension was defined as mean systolic or diastolic blood pressure ≥140/90 mmHg or self-reported hypertension or anti-hypertensive medication. Unawareness, untreated and uncontrolled hypertension was determined by questionnaires/blood pressure measurements. Yearly age-standardized prevalences and adjusted associations for the 1999-2003 and 2004-2009 survey periods were reported. The 10-year survey included 9,215 participants aged 35 to 74 years. Hypertension remained stable (34.4%). Hypertension unawareness decreased from 35.9% to 17.7% (P<0.001). The decrease in hypertension unawareness was not paralleled by a concomitant absolute increase in hypertension treatment, which remained low (38.2%). A larger proportion of all hypertensive participants were aware but not treated in 2004-2009 (43.7%) compared to 1999-2003 (33.1%). Uncontrolled hypertension improved from 62.2% to 40.6% between 1999 and 2009 (P = 0.02). In 1999-2003 period, factors associated with hypertension unawareness were current smoking (OR = 1.27, 95%CI, 1.02-1.59), male gender (OR = 1.56, 1.27-1.92), hypercholesterolemia (OR = 1.31, 1.20-1.44), and older age (OR 65-74yrs vs 35-49yrs  = 1.56, 1.21-2.02). In 1999-2003 and 2004-2009, obesity and diabetes were negatively associated with hypertension unawareness, high education was associated with untreated hypertension (OR = 1.45, 1.12-1.88 and 1.42, 1.02-1.99, respectively), and male gender with uncontrolled hypertension (OR = 1.49, 1.03-2.17 and 1.65, 1.08-2.50, respectively). Sedentarity was associated with higher risk of hypertension and uncontrolled hypertension in 1999-2003. CONCLUSIONS: Hypertension prevalence remained stable since 1999 in the canton of Geneva. Although hypertension unawareness substantially decreased, more than half of hypertensive subjects still remained untreated or uncontrolled in 2004-2009. This study identified determinants that should guide interventions aimed at improving hypertension treatment and control.

Chimioradiothérapie postopératoire des cancers des voies aérodigestives : vers un nouveau standard [Post-operative radiochemotherapy of the head and neck: Towards new standards?]

Head and neck squamous cell carcinomas are frequently diagnosed at an advanced stage. Their treatment remains controversial, and has to be multidisciplinary. External beam radiotherapy is a recognized treatment option after radical curative surgery in order to improve local control. Different adjuvant treatment options have been studied in order to improve the outcome of these patients. We review in this paper the different prognostic factors indicating an adjuvant treatment and the interest of treatment intensification in bad prognostic patients.

Determination of Vasopressin and Desmopressin in urine by means of liquid chromatography coupled to quadrupole time-of-flight mass spectrometry for doping control purposes.

The anti-diuretic neurohypophysial hormone Vasopressin (Vp) and its synthetic analogue Desmopressin (Dp, 1-desamino-vasopressin) have received considerable attention from doping control authorities due to their impact on physiological blood parameters. Accordingly, the illicit use of Desmopressin in elite sport is sanctioned by the World Anti-Doping Agency (WADA) and the drug is classified as masking agent. Vp and Dp are small (8-9 amino acids) peptides administered orally as well as intranasally. Within the present study a method to determine Dp and Vp in urinary doping control samples by means of liquid chromatography coupled to quadrupole high resolution time-of-flight mass spectrometry was developed. After addition of Lys-Vasopressin as internal standard and efficient sample clean up with a mixed mode solid phase extraction (weak cation exchange), the samples were directly injected into the LC-MS system. The method was validated considering the parameters specificity, linearity, recovery (80-100%), accuracy, robustness, limit of detection/quantification (20/50 pg mL(-1)), precision (inter/intra-day<10%), ion suppression and stability. The analysis of administration study urine samples collected after a single intranasal or oral application of Dp yielded in detection windows for the unchanged target analyte for up to 20 h at concentrations between 50 and 600 pg mL(-1). Endogenous Vp was detected in concentrations of approximately 20-200 pg mL(-1) in spontaneous urine samples obtained from healthy volunteers. The general requirements of the developed method provide the characteristics for an easy transfer to other anti-doping laboratories and support closing another potential gap for cheating athletes.

Controlled dynamic generation of standard 1,6-hexamethylene diisocyanate aerosols

A procedure for the dynamic generation of 1,6-hexamethylene diisocyanate (HDI) aerosol atmospheres of 70 micrograms m-3 (0.01 ppm) to 1.75 mg m-3 (0.25 ppm), based on the precise control of the evaporation of pure liquid HDI and subsequent dilution with air, was developed. The apparatus consisted of a home-made glass nebulizer coupled with a separation stage to exclude non-respirable droplets (greater than 10 microns). The aerosol concentrations were achieved by passing air through the nebulizer at 1.5-4.5 l. min-1 to generate dynamically 0.01-0.25 ppm of diisocyanate in an experimental chamber of 8.55 m3. The distribution of the liquid aerosol was established with an optical counter and the diisocyanate concentration was determined from samples collected in impingers by a high-pressure liquid chromatographic method. The atmospheres generated were suitable for the evaluation both of sampling procedures full scale, and of analytical methods: at 140 micrograms m-3 (0.02 ppm) they remained stable for 15-min provocation tests in clinical asthma, as verified by breath-zone sampling of exposed patients.

Design Guide and Construction Specifications for National Pollutant Discharge Elimination System (NPDES) Site Runoff Control, 2006

According to the 1972 Clean Water Act, the Environmental Protection Agency (EPA) established a set of regulations for the National Pollutant Discharge Elimination System (NPDES). The purpose of these regulations is to reduce pollution of the nation’s waterways. In addition to other pollutants, the NPDES regulates stormwater discharges associated with industrial activities, municipal storm sewer systems, and construction sites. Phase II of the NPDES stormwater regulations, which went into effect in Iowa in 2003, applies to construction activities that disturb more than one acre of ground. The regulations also require certain communities with Municipal Separate Storm Sewer Systems (MS4) to perform education, inspection, and regulation activities to reduce stormwater pollution within their communities. Iowa does not currently have a resource to provide guidance on the stormwater regulations to contractors, designers, engineers, and municipal staff. The Statewide Urban Design and Specifications (SUDAS) manuals are widely accepted as the statewide standard for public improvements. The SUDAS Design manual currently contains a brief chapter (Chapter 7) on erosion and sediment control; however, it is outdated, and Phase II of the NPDES stormwater regulations is not discussed. In response to the need for guidance, this chapter was completely rewritten. It now escribes the need for erosion and sediment control and explains the NPDES stormwater regulations. It provides information for the development and completion of Stormwater Pollution Prevention Plans (SWPPPs) that comply with the stormwater regulations, as well as the proper design and implementation of 28 different erosion and sediment control practices. In addition to the design chapter, this project also updated a section in the SUDAS Specifications manual (Section 9040), which describes the proper materials and methods of construction for the erosion and sediment control practices.

Factors influencing adherence to standard precautions among nursing professionals in psychiatric hospitals

OBJECTIVE Evaluate and correlate individual, work-related and organizational factors that influence adherence to standard precautions among nursing professionals of psychiatric hospitals in São Paulo. METHOD An exploratory cross-sectional study conducted with 35 nursing professionals, using the assessment tool for adherence to standard precautions through the Likert scale, ranging from 1 to 5. RESULTS Knowledge of the precautions received a high score (4.69); adherence received (3.86) and obstacles (3.78), while intermediaries and the scales of organizational factors received low scores (2.61). There was a strong correlation between the magnitude adherence scale and the personal protective equipment availability (r = 0.643; p = 0.000). The training scale for prevention of HIV exposure (p = 0.007) was statistically different between the nurses and nursing assistants. CONCLUSION The organizational factors negatively contributed to adherence to standard precautions, indicating that psychiatric institutions lack safe working conditions, ongoing training and management actions to control infections.

Degradation of pathogen quorum-sensing molecules by soil bacteria: a preventive and curative biological control mechanism.

Abstract The plasmid pME6863, carrying the aiiA gene from the soil bacterium Bacillus sp. A24 that encodes a lactonase enzyme able to degrade N-acyl-homoserine lactones (AHLs), was introduced into the rhizosphere isolate Pseudomonas fluorescens P3. This strain is not an effective biological control agent against plant pathogens. The transformant P. fluorescens P3/pME6863 acquired the ability to degrade AHLs. In planta, P. fluorescens P3/pME6863 significantly reduced potato soft rot caused by Erwinia carotovora and crown gall of tomato caused by Agrobacterium tumefaciens to a similar level as Bacillus sp. A24. Little or no disease reduction was observed for the wild-type strain P3 carrying the vector plasmid without aiiA. Suppression of potato soft rot was observed even when the AHL-degrading P. fluorescens P3/pME6863 was applied to tubers 2 days after the pathogen, indicating that biocontrol was not only preventive but also curative. When antagonists were applied individually with the bacterial plant pathogens, biocontrol activity of the AHL degraders was greater than that observed with several Pseudomonas 2,4-diacetylphloroglucinol-producing strains and with Pseudomonas chlororaphis PCL1391, which relies on production of phenazine antibiotic for disease suppression. Phenazine production by this well characterized biological control strain P. chlororaphis PCL1391 is regulated by AHL-mediated quorum sensing. When P. chlororaphis PCL1391 was co-inoculated with P. fluorescens P3/pME6863 in a strain mixture, the AHL degrader interfered with the normally excellent ability of the antibiotic producer to suppress tomato vascular wilt caused by Fusarium oxysporum f. sp. lycopersici. Our results demonstrate AHL degradation as a novel biocontrol mechanism, but also demonstrate the potential for non-target interactions that can interfere with the biocontrol efficacy of other strains.

Dynamics of the control of Aedes (Stegomyia) aegypti Linnaeus (Diptera, Culicidae) by Bacillus thuringiensis var israelensis, related with temperature, density and concentration of insecticide

The dynamics of the control of Aedes (Stegomyia) aegypti Linnaeus, (Diptera, Culicidae) by Bacillus thuringiensis var israelensis has been related with the temperature, density and concentration of the insecticide. A mathematical model for biological control of Aedes aegypti with Bacillus thuringiensis var israelensis (Bti) was constructed by using data from the literature regarding the biology of the vector. The life cycle was described by differential equations. Lethal concentrations (LC50 and LC95) of Bti were determined in the laboratory under different experimental conditions. Temperature, colony, larvae density and bioinsecticide concentration presented marked differences in the analysis of the whole set of variables; although when analyzed individually, only the temperature and concentration showed changes. The simulations indicated an inverse relationship between temperature and mosquito population, nonetheless, faster growth of populations is reached at higher temperatures. As conclusion, the model suggests the use of integrated control strategies for immature and adult mosquitoes in order to achieve a reduction of Aedes aegypti.

Solving higher-dimensional continuous time stochastic control problems by value function regression

The paper develops a method to solve higher-dimensional stochasticcontrol problems in continuous time. A finite difference typeapproximation scheme is used on a coarse grid of low discrepancypoints, while the value function at intermediate points is obtainedby regression. The stability properties of the method are discussed,and applications are given to test problems of up to 10 dimensions.Accurate solutions to these problems can be obtained on a personalcomputer.

Validation of methane measurement using headspace-GC-MS and quantification by a stable isotope-labeled internal standard generated in situ.

A previous study has shown the possibility to identify methane (CH4 ) using headspace-GC-MS and quantify it with a stable isotope as internal standard. The main drawback of the GC-MS methods discussed in literature for CH4 measurement is the absence of a specific internal standard necessary to perform quantification. However, it becomes essential to develop a safer method to limit the manipulation of gaseous CH4 and to precisely control the injected amount of gas for spiking and calibration by comparison with external calibration. To avoid the manipulation of a stable isotope-labeled gas, we have chosen to generate a labeled gas as an internal standard in a vial on the basis of the formation of CH4 by the reaction of Grignard reagent methylmagnesium chloride with deuterated water. This method allows precise measurement of CH4 concentrations in gaseous sample as well as in a solid or a liquid sample after a thermodesorption step in a headspace vial. A full accuracy profile validation of this method is then presented.

Training in flexible intensive insulin therapy improves quality of life, decreases the risk of hypoglycaemia and ameliorates poor metabolic control in patients with type 1 diabetes.

AIM: Intensified insulin therapy has evolved to be the standard treatment of type 1 diabetes. However, it has been reported to increase significantly the risk of hypoglycaemia. We studied the effect of structured group teaching courses in flexible insulin therapy (FIT) on psychological and metabolic parameters in patients with type 1 diabetes. METHODS: We prospectively followed 45 type 1 diabetic patients of our outpatient clinic participating in 5 consecutive FIT teaching courses at the University Hospital of Basel. These courses consist of 7 weekly ambulatory evening group sessions. Patients were studied before and 1, 6, and 18 months after the course. Main outcome measures were glycated haemoglobin (HbA1c), severe hypoglycaemic events, quality of life (DQoL), diabetes self-control (IPC-9) and diabetes knowledge (DWT). RESULTS: Quality of life, self-control and diabetes knowledge improved after the FIT courses (all p<0.001). The frequency of severe hypoglycaemic events decreased ten-fold from 0.33 episodes/6 months at baseline to 0.03 episodes/6 months after 18 months (p<0.05). Baseline HbA1c was 7.2+/-1.1% and decreased in the subgroup with HbA1c > or = 8% from 8.4% to 7.8% (p<0.05). CONCLUSIONS: In an unselected, but relatively well-controlled population of type 1 diabetes, a structured, but not very time consuming FIT teaching programme in the outpatient setting improves psychological well-being and metabolic parameters.

Batch effect confounding leads to strong bias in performance estimates obtained by cross-validation.

BACKGROUND: With the large amount of biological data that is currently publicly available, many investigators combine multiple data sets to increase the sample size and potentially also the power of their analyses. However, technical differences ("batch effects") as well as differences in sample composition between the data sets may significantly affect the ability to draw generalizable conclusions from such studies. FOCUS: The current study focuses on the construction of classifiers, and the use of cross-validation to estimate their performance. In particular, we investigate the impact of batch effects and differences in sample composition between batches on the accuracy of the classification performance estimate obtained via cross-validation. The focus on estimation bias is a main difference compared to previous studies, which have mostly focused on the predictive performance and how it relates to the presence of batch effects. DATA: We work on simulated data sets. To have realistic intensity distributions, we use real gene expression data as the basis for our simulation. Random samples from this expression matrix are selected and assigned to group 1 (e.g., 'control') or group 2 (e.g., 'treated'). We introduce batch effects and select some features to be differentially expressed between the two groups. We consider several scenarios for our study, most importantly different levels of confounding between groups and batch effects. METHODS: We focus on well-known classifiers: logistic regression, Support Vector Machines (SVM), k-nearest neighbors (kNN) and Random Forests (RF). Feature selection is performed with the Wilcoxon test or the lasso. Parameter tuning and feature selection, as well as the estimation of the prediction performance of each classifier, is performed within a nested cross-validation scheme. The estimated classification performance is then compared to what is obtained when applying the classifier to independent data.

Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.

PURPOSE: To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU). DESIGN: Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial. PARTICIPANTS: Subjects with unilateral or bilateral NIPU. METHODS: One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (> or =0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (> or =0.1 mg/kg daily). MAIN OUTCOME MEASURES: Time to first recurrence of uveitis. RESULTS: Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P< or =0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group. CONCLUSIONS: The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant.

Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study.

The trabecular bone score (TBS) is a new parameter that is determined from gray-level analysis of dual-energy X-ray absorptiometry (DXA) images. It relies on the mean thickness and volume fraction of trabecular bone microarchitecture. This was a preliminary case-control study to evaluate the potential diagnostic value of TBS as a complement to bone mineral density (BMD), by comparing postmenopausal women with and without fractures. The sample consisted of 45 women with osteoporotic fractures (5 hip fractures, 20 vertebral fractures, and 20 other types of fracture) and 155 women without a fracture. Stratification was performed, taking into account each type of fracture (except hip), and women with and without fractures were matched for age and spine BMD. BMD and TBS were measured at the total spine. TBS measured at the total spine revealed a significant difference between the fracture and age- and spine BMD-matched nonfracture group, when considering all types of fractures and vertebral fractures. In these cases, the diagnostic value of the combination of BMD and TBS likely will be higher compared with that of BMD alone. TBS, as evaluated from standard DXA scans directly, potentially complements BMD in the detection of osteoporotic fractures. Prospective studies are necessary to fully evaluate the potential role of TBS as a complementary risk factor for fracture.

An adenovirus-based fluorescent reporter vector to identify and isolate HIV-infected cells.

A procedure is described that allows the simple identification and sorting of live human cells that transcribe actively the HIV virus, based on the detection of GFP fluorescence in cells. Using adenoviral vectors for gene transfer, an expression cassette including the HIV-1 LTR driving the reporter gene GFP was introduced into cells that expressed stably either the Tat transcriptional activator, or an inactive mutant of Tat. Both northern and fluorescence-activated cell sorting (FACS) analysis indicate that cells containing the functional Tat protein presented levels of GFP mRNA and GFP fluorescence several orders of magnitude higher than control cells. Correspondingly, cells infected with HIV-1 showed similar enhanced reporter gene activation. HIV-1-infected cells of the lymphocytic line Jurkat were easily identified by fluorescence-activated cell sorting (FACS) as they displayed a much higher green fluorescence after transduction with the reporter adenoviral vector. This procedure could also be applied on primary human cells as blood monocyte-derived macrophages exposed to the adenoviral LTR-GFP reporter presented a much higher fluorescence when infected with HIV-1 compared with HIV-uninfected cells. The vector described has the advantages of labelling cells independently of their proliferation status and that analysis can be carried on intact cells which can be isolated subsequently by fluorescence-activated cell sorting (FACS) for further culture. This work suggests that adenoviral vectors carrying a virus-specific transcriptional control element controlling the expressions of a fluorescent protein will be useful in the identification and isolation of cells transcribing actively the viral template, and to be of use for drug screening and susceptibility assays.