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Background: Malaria transmission reduction is a goal of many malaria control programmes. Little is known of how much mortality can be reduced by specific reductions in transmission. Verbal autopsy (VA) is widely used for estimating malaria specific mortality rates, but does not reliably distinguish malaria from other febrile illnesses. Overall malaria attributable mortality includes both direct and indirect deaths. It is unclear what proportion of the deaths averted by reducing malaria transmission are classified as malaria in VA., Methods: Both all-cause, and cause-specific mortality reported by VA for children under 5 years of age, were assembled from the KEMRI/CDC health and demographic surveillance system in Siaya county, rural Western Kenya for the years 2002-2004. These were linked to household-specific estimates of the Plasmodium falciparum entomological inoculation rate (EIR) based on high resolution spatio-temporal geostatistical modelling of entomological data. All-cause and malaria specific mortality (by VA), were analysed in relation to EIR, insecticide-treated net use (ITN), socioeconomic status (SES) and parameters describing space-time correlation. Time at risk for each child was analysed using Bayesian geostatistical Cox proportional hazard models, with time-dependent covariates. The outputs were used to estimate the diagnostic performance of VA in measuring mortality that can be attributed to malaria exposure., Results: The overall under-five mortality rate was 80 per 1000 person-years during the study period. Eighty-one percent of the total deaths were assigned causes of death by VA, with malaria assigned as the main cause of death except in the neonatal period. Although no trend was observed in malaria-specific mortality assessed by VA, ITN use was associated with reduced all-cause mortality in infants (hazard ratio 0.15, 95% CI 0.02, 0.63) and the EIR was strongly associated with both all-cause and malaria-specific mortality. 48.2% of the deaths could be attributed to malaria by analysing the exposure-response relationship, though only 20.5% of VAs assigned malaria as the cause and the sensitivity of VAs was estimated to be only 26%. Although VAs assigned some deaths to malaria even in areas where there was estimated to be no exposure, the specificity of the VAs was estimated to be 85%., Conclusion: Interventions that reduce P. falciparum transmission intensity will not only significantly reduce malaria-diagnosed mortality, but also mortality assigned to other causes in under-5 year old children in endemic areas. In this setting, the VA tool based on clinician review substantially underestimates the number of deaths that could be averted by reducing malaria exposure in childhood, but has a reasonably high specificity. This suggests that malaria transmission-reducing interventions such as ITNs can potentially reduce overall child mortality by as much as twice the total direct malaria burden estimated from VAs.

Joint kinematics can be assessed using orientation estimates from Attitude and Heading Reference Systems (AHRS). However, magnetically-perturbed environments affect the accuracy of the estimated orientations. This study investigates, both in controlled and human mobility conditions, a trial calibration technic based on a 2D photograph with a pose estimation algorithm to correct initial difference in AHRS Inertial reference frames and improve joint angle accuracy. In controlled conditions, two AHRS were solidly affixed onto a wooden stick and a series of static and dynamic trials were performed in varying environments. Mean accuracy of relative orientation between the two AHRS was improved from 24.4° to 2.9° using the proposed correction method. In human conditions, AHRS were placed on the shank and the foot of a participant who performed repeated trials of straight walking and walking while turning, varying the level of magnetic perturbation in the starting environment and the walking speed. Mean joint orientation accuracy went from 6.7° to 2.8° using the correction algorithm. The impact of starting environment was also greatly reduced, up to a point where one could consider it as non-significant from a clinical point of view (maximum mean difference went from 8° to 0.6°). The results obtained demonstrate that the proposed method improves significantly the mean accuracy of AHRS joint orientation estimations in magnetically-perturbed environments and can be implemented in post processing of AHRS data collected during biomechanical evaluation of motion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We report on the benefits of changing the bridging group X of bis-pyridyl ligands, that is, Py-X-Py where X is NH, CH 2 , C(CH 3 ) 2 , or PPh, on the photo- and electroluminescent properties of a new family of luminescent cationic H-heterocyclic carbene (NHC) copper(I) complexes. A joint experimental and theoretical study demonstrates that the bridging group affects the molecular conformation from a planar-like structure (X is NH and CH 2 ) to a boat-like structure (X is C(CH 3 ) 2 and PPh), leading to i) four-fold enhancement of the photoluminescence quantum yield (ϕ em ) without affecting the thermally activated delayed fluorescence mechanism, and ii) one order of magnitude reduction of the ionic conductivity (σ) of thin films. This leads to an overall enhancement of the device efficacy and luminance owing to the increased ϕ em and the use of low applied driving currents., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We have converted our Titan one-dimensional photochemical model to simulate the photo- chemistry of Pluto's atmosphere and include condensation and aerosol trapping in the model. We find that condensation and aerosol trapping are important processes in producing the HCN altitude profile observed by the Atacama Large Millimeter Array (ALMA). The nitrogen iso- tope chemistry in Pluto's atmosphere does not appear to significantly fractionate the isotope ratio between N 2 and HCN as occurs at Titan. However, our simulations only cover a brief period of time in a Pluto year, and thus only a brief portion of the solar forcing conditions that Pluto's atmosphere experiences. More work is needed to evaluate photochemical fractionation over a Pluto year. Condensation and aerosol trapping appear to have a major impact on the altitude profile of the isotope ratio in HCN. Since ALMA did not detect HC 15 N in Pluto's atmosphere, we conclude that condensation and aerosol trapping must be much more efficient for HC 15 N compared to HC 14 N. The large uncertainty in photochemical fractionation makes it difficult to use any potential current measurement of 14 N/ 15 N in N 2 to determine the origin of Pluto's nitrogen. More work is needed to understand photochemical fractionation and to evaluate how condensation, sublimation and aerosol trapping will fractionate N 2 and HCN.

In light of the recent New Horizons flyby measurements, we present a coupled ion-neutral-photochemistry model developed for simulating the atmosphere of Pluto. Our model results closely match the observed density profiles of CH 4 , N 2 and the C 2 hydrocarbons in the altitude range where available New Horizons measurements are most accurate (above ~ 100-200 km). We found a high eddy coefficient of 10 6 cm 2 s -1 from the surface to an altitude of 150 km, and 3 × 10 6 cm 2 s -1 above 150 km for Pluto's atmosphere. Our results demonstrate that C 2 hydrocarbons must stick to and be removed by aerosol particles in order to reproduce the C2 profiles observed by New Horizons. Incorporation into aerosols in Pluto's atmosphere is a significantly more effective process than condensation, and we found that condensation alone cannot account for the observed shape of the vertical profiles. We empirically determined the sticking efficiency of C2 hydrocarbons to aerosol particles as a function of altitude, and found that the sticking efficiency of C 2 hydrocarbons is inversely related to the aerosol surface area. Aerosols must harden and become less sticky as they age in Pluto's atmosphere. Such hardening with ageing is both necessary and sufficient to explain the vertical profiles of C 2 hydrocarbons in Pluto's atmosphere. This result is in agreement with the fundamental idea of aerosols hardening as they age, as proposed for Titan's aerosols.

When new materials appear as potential alternatives for radiation detection, several criteria have to be fulfilled. The one presented herein is the response variation to large irradiation doses of neutron/gamma discriminating plastic scintillators. Thus, several samples were exposed to high gamma doses reaching 10 kGy. They were characterized in terms of gamma spectrometry and fast neutron/gamma discrimination, prior to and after irradiation. Results show an unexpected increase of the figure of merit (FoM), which is the numerical value for n/γ discrimination performances. An in-depth investigation evaluates the physicochemical impact of such large doses within the material. The characterization includes photophysics, radiation/matter interaction and chemical analyses (EPR, 1 H NMR, fluorescence spectroscopy and HRMS).

Salmonella is a leading cause of bacterial foodborne illness. We report the collaborative investigative efforts of US and Canadian public health officials during the 2013-2014 international outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder. The investigation included open-ended interviews of ill persons, traceback, product testing, facility inspections, and trace forward. Ninety-four persons infected with outbreak strains from 16 states and four provinces were identified; 21% were hospitalized and none died. Fifty-four (96%) of 56 persons who consumed chia seed powder, reported 13 different brands that traced back to a single Canadian firm, distributed by four US and eight Canadian companies. Laboratory testing yielded outbreak strains from leftover and intact product. Contaminated product was recalled. Although chia seed powder is a novel outbreak vehicle, sprouted seeds are recognized as an important cause of foodborne illness; firms should follow available guidance to reduce the risk of bacterial contamination during sprouting.

In September 2015, PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified a cluster of Listeria monocytogenes (Listeria) clinical isolates indistinguishable by two-enzyme pulsed-field gel electrophoresis (PFGE) pattern combination and highly related by whole-genome multilocus sequence typing (wgMLST). A case was defined as isolation of Listeria with the outbreak PFGE pattern and highly related by wgMLST with an isolation date on or after July 5, 2015, the isolate date of the earliest case in this cluster.

The synthesis, photophysical properties, and applications in scintillation counting of N-(2-ethylhexyl)carbazole (EHCz) are reported. This molecule displays all of the required characteristics for an efficient liquid scintillator (emission wavelength, scintillation yield), and can be used without any extra fluorophores. Thus, its scintillation properties are discussed, as well as its fast neutron/gamma discrimination. For the latter application, the material is compared with the traditional liquid scintillator BC-501 A, and other liquid fluorescent molecules classically used as scintillation solvents, such as xylene, pseudocumene (PC), linear alkylbenzenes (LAB), diisopropylnaphthalene (DIN), 1-methylnaphthalene (1-MeNapht), and 4-isopropylbiphenyl (iPrBiph). For the first time, an excimeric form of a molecule has been advantageously used in scintillation counting. A moderate discrimination between fast neutrons and gamma rays was observed in bulk EHCz, with an apparent neutron/gamma discrimination potential half of that of BC-501 A., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Stroke is one of the leading causes of disability worldwide. Consequently, many stroke survivors exhibit difficulties undergoing voluntary movement in their affected upper limb, compromising their functional performance and level of independence. To minimize the negative impact of stroke disabilities, exercises are recognized as a key element in post-stroke rehabilitation. In order to provide the practice of exercises in a uniform and controlled manner as well as increasing the efficiency of therapists' interventions, robotic training has been found, and continues to prove itself, as an innovative intervention for post-stroke rehabilitation. However, the complexity as well as the limited degrees of freedom and workspace of currently commercially available robots can limit their use in clinical settings. Up to now, user-friendly robots covering a sufficiently large workspace for training of the upper limb in its full range of motion are lacking. This paper presents the design and implementation of ERA, an upper-limb 3-DOF force-controlled exerciser robot, which presents a workspace covering the entire range of motion of the upper limb. The ERA robot provides 3D reaching movements in a haptic virtual environment. A description of the hardware and software components of the ERA robot is also presented along with a demonstration of its capabilities in one of the three operational modes that were developed.

Over the last few years, the number of remote patient monitoring (RPM) products and of videoconferencing systems has exploded. There is also a significant number of research initiatives addressing the use of service robots for assistance in daily living activities. From a technological standpoint, providing telehomecare services is certainly feasible. However, one technological barrier is to have access to a telecommunication platform that can be adapted to address the broad range of specifications and requirements of clinical and telehealth applications. Handling the full spectrum of possibilities requires a telecommunication framework that can transmit vital sign data from patients to clinicians, bidirectional audio-video from a standard computing device, and also multiple video streams and bidirectional transmission of control data. This paper presents a framework that integrates such capabilities. It also illustrates the versatility of the framework by presenting custom-designed devices allowing integration of capabilities ranging from RPM to video visits and robot telepresence.

This study presents the influence of various substituents on the photophysical features of heteroleptic copper(I) complexes bearing both N-heterocyclic carbene (NHC) and dipyridylamine (dpa = dipyridylamine skeleton corresponding to ligand L1) ligands. The luminescent properties have been compared to our recently reported archetypal blue emitting [Cu(IPr)(dpa)][PF6] complex. The choice of the substituents on both ligands has been guided to explore the effect of the electron donor/acceptor and "push-pull" on the emission wavelengths and photoluminescence quantum yields. A selection of the best candidates in terms of their photophysical features were applied for developing the first blue light-emitting electrochemical cells (LECs) based on copper(I) complexes. The device analysis suggests that the main concern is the moderate redox stability of the complexes under high applied driving currents, leading to devices with moderate stabilities pointing to a proof-of-concept for further development. Nevertheless, under low applied driving currents the blue emission is stable, showing performance levels competitive to those reported for blue LECs based on iridium(III) complexes. Overall, this work provides valuable guidelines to tackle the design of enhanced NHC copper complexes for lighting applications in the near future.

Despite the large number of heparin and heparan sulfate binding proteins, the molecular mechanism(s) by which heparin alters vascular cell physiology is not well understood. Studies with vascular smooth muscle cells (VSMCs) indicate a role for induction of dual specificity phosphatase 1 (DUSP1) that decreases ERK activity and results in decreased cell proliferation, which depends on specific heparin binding. The hypothesis that unfractionated heparin functions to decrease inflammatory signal transduction in endothelial cells (ECs) through heparin-induced expression of DUSP1 was tested. In addition, the expectation that the heparin response includes a decrease in cytokine-induced cytoskeletal changes was examined. Heparin pretreatment of ECs resulted in decreased TNFα-induced JNK and p38 activity and downstream target phosphorylation, as identified through Western blotting and immunofluorescence microscopy. Through knockdown strategies, the importance of heparin-induced DUSP1 expression in these effects was confirmed. Quantitative fluorescence microscopy indicated that heparin treatment of ECs reduced TNFα-induced increases in stress fibers. Monoclonal antibodies that mimic heparin-induced changes in VSMCs were employed to support the hypothesis that heparin was functioning through interactions with a receptor. Knockdown of transmembrane protein 184A (TMEM184A) confirmed its involvement in heparin-induced signaling as seen in VSMCs. Therefore, TMEM184A functions as a heparin receptor and mediates anti-inflammatory responses of ECs involving decreased JNK and p38 activity., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus., Methods: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination., Results: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy., Conclusions: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

Little is known about how immobilization of the right lower limb might affect driving. The purpose of the present study was to evaluate the effect of 2 types of immobilization on the emergency braking time of healthy subjects during actual driving conditions. The emergency braking times of 14 healthy volunteers were assessed in a closed circuit under 3 conditions: wearing running shoes, wearing an Aircast Walker(®), or wearing a walking cast on their right lower limb. An instrumented car was used to measure the emergency braking times during braking tests with and without a distractor. The foot movement times were significantly increased with both immobilization devices compared with the running shoe (p < .01). The median total braking time with the running shoe during emergency braking without a distractor was 0.452 (interquartile range, 25th to 75th [IQR], 0.413 to 0.472) second. The results obtained with the Aircast Walker(®) or the walking cast were significantly longer (p < .01), at 0.480 (IQR, 0.431 to 0.537) second and 0.512 (IQR, 0.451 to 0.535) second, respectively. When a distractor was added, the total braking time with the running shoe, Aircast Walker(®), and walking cast was 0.489 (IQR, 0.429 to 0.575), 0.516 (IQR, 0.459 to 0.586), and 0.510 (IQR, 0.469 to 0.570) second, respectively, with no statistically significant differences among these 3 conditions. Wearing an immobilization device on the right lower limb minimally lengthens the emergency braking time in healthy drivers under actual driving conditions. Clinicians must nonetheless exercise caution when advising a driver wearing an orthopedic immobilization, because driving a motor vehicle is a complex psychomotor task that goes well beyond the emergency braking time., (Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Continuous monitoring in health and demographic surveillance sites (HDSS) allows for collection of longitudinal demographic data, health related, and socio-economic indicators of the site population. We sought to use household survey data collected between 2002 and 2006 in the Kenya Medical Research Institute in collaboration with Centers for Disease Control and prevention (KEMRI/CDC) HDSS site in Asembo and Gem Western Kenya to estimate socio-economic status (SES) and assess changes of SES over time and space. Data on household assets and characteristics, mainly source of drinking water, cooking fuel, and occupation of household head was annually collected from 44,313 unique households during the study period. An SES index was calculated as a weighted average of assets using weights generated via Principal Component Analysis (PCA), Polychoric PCA, and Multiple Correspondence Analysis (MCA) methods applied to the pooled data. The index from the best method was used to rank households into SES quintiles and assess their transition over time across SES categories. Kriging was employed to produce SES maps at the start and the end of the study period. First component of PCA, Polychoric PCA, and MCA accounted for 13.7%, 31.8%, and 47.3%, respectively of the total variance of all variables. The gap between the poorest and the least poor increased from 1% at the start to 6% at the end of the study period. Spatial analysis revealed that the increase in least poor households was centered in the lower part of study area (Asembo) over time. No significant changes were observed in Gem. The HDSS sites can provide a platform to assess spatial-temporal changes in the SES status of the population. Evidence on how SES varied over time and space within the same geographical area may provide a useful tool to design interventions in health and other areas that have a close bearing to the SES of the population., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Interest in 3D inertial motion tracking devices (AHRS) has been growing rapidly among the biomechanical community. Although the convenience of such tracking devices seems to open a whole new world of possibilities for evaluation in clinical biomechanics, its limitations haven't been extensively documented. The objectives of this study are: 1) to assess the change in absolute and relative accuracy of multiple units of 3 commercially available AHRS over time; and 2) to identify different sources of errors affecting AHRS accuracy and to document how they may affect the measurements over time., Methods: This study used an instrumented Gimbal table on which AHRS modules were carefully attached and put through a series of velocity-controlled sustained motions including 2 minutes motion trials (2MT) and 12 minutes multiple dynamic phases motion trials (12MDP). Absolute accuracy was assessed by comparison of the AHRS orientation measurements to those of an optical gold standard. Relative accuracy was evaluated using the variation in relative orientation between modules during the trials., Findings: Both absolute and relative accuracy decreased over time during 2MT. 12MDP trials showed a significant decrease in accuracy over multiple phases, but accuracy could be enhanced significantly by resetting the reference point and/or compensating for initial Inertial frame estimation reference for each phase., Interpretation: The variation in AHRS accuracy observed between the different systems and with time can be attributed in part to the dynamic estimation error, but also and foremost, to the ability of AHRS units to locate the same Inertial frame., Conclusions: Mean accuracies obtained under the Gimbal table sustained conditions of motion suggest that AHRS are promising tools for clinical mobility assessment under constrained conditions of use. However, improvement in magnetic compensation and alignment between AHRS modules are desirable in order for AHRS to reach their full potential in capturing clinical outcomes.

Background: Although it is well known that drug pressure selects for drug-resistant parasites, the role of transmission reduction by insecticide-treated bed nets (ITNs) on drug resistance remains unclear. In this study, the drug resistance profile of current and previous first-line anti-malarials in Kenya was assessed within the context of drug policy change and scale-up of ITNs. National first-line treatment changed from chloroquine (CQ) to sulphadoxine-pyrimethamine (SP) in 1998 and to artemether-lumefantrine (AL) in 2004. ITN use was scaled-up in the Asembo, Gem and Karemo areas of western Kenya in 1997, 1999 and 2006, respectively., Methods: Smear-positive samples (N = 253) collected from a 2007 cross-sectional survey among children in Asembo, Gem and Karemo were genotyped for mutations in pfcrt and pfmdr1 (CQ), dhfr and dhps (SP), and at pfmdr-N86 and the gene copy number in pfmdr1 (lumefantrine). Results were compared among the three geographic areas in 2007 and to retrospective molecular data from children in Asembo in 2001., Results: In 2007, 69 and 85% of samples harboured the pfmdr1-86Y mutation and dhfr/dhps quintuple mutant, respectively, with no significant differences by study area. However, the prevalence of the pfcrt-76T mutation differed significantly among areas (p <0.02), between 76 and 94%, with the highest prevalence in Asembo. Several 2007 samples carried mutations at dhfr-164L, dhps-436A, or dhps-613T. From 2001 to 2007, there were significant increases in the pfcrt-76T mutation from 82 to 94% (p <0.03), dhfr/dhps quintuple mutant from 62 to 82% (p <0.03), and an increase in the septuple CQ and SP combined mutant haplotype, K 76 Y 86 I 51 R 59 N 108 G 437 E 540 , from 28 to 39%. The prevalence of the pfmdr1-86Y mutation remained unchanged. All samples were single copy for pfmdr1., Conclusions: Molecular markers associated with lumefantrine resistance were not detected in 2007. More recent samples will be needed to detect any selective effects by AL. The prevalence of CQ and SP resistance markers increased from 2001 to 2007 in the absence of changes in transmission intensity. In 2007, only the prevalence of pfcrt-76T mutation differed among study areas of varying transmission intensity. Resistant parasites were most likely selected by sustained drug pressure from the continued use of CQ, SP, and mechanistically similar drugs, such as amodiaquine and cotrimoxazole. There was no clear evidence that differences in transmission intensity, as a result of ITN scale-up, influenced the prevalence of drug resistance molecular markers.

Malaria is among the leading causes of mortality in the younger under-five group of children zero to four years of age. This study aims at describing the relationship between rainfall and temperature on under-five malaria or anaemia mortality in Kenya Medical Research Institute and United States Centers for Disease Control (KEMRI/CDC) Health and Demographic Surveillance System (HDSS). This study was conducted through the ongoing KEMRI and CDC collaboration. A general additive model with a Poisson link function was fit to model the weekly association of lagged cumulative rainfall and average temperature on malaria/anemia mortality in KEMRI/CDC HDSS for the period 2003 to 2008. A trend function was included in the model to control for time trends and seasonality not explained by weather fluctuations. 95% confidence intervals was presented with estimates. Malaria or anemia mortality was found to be associated with changes in temperature and rainfall in the KEMRI HDSS, with a delay up to 16 weeks. The empirical estimates of associations describe established biological relationships well. This information, and particularly, the strength of the relationships over longer lead times can highlight the possibility of developing a predictive forecast with lead times up to 16 weeks in order to enhance preparedness to high transmission episodes.

Cyclospora cayetanensis was identified in 176 returned travellers from the Riviera Maya region of Mexico between 1 June and 22 September 2015; 79 in the United Kingdom (UK) and 97 in Canada. UK cases completed a food exposure questionnaire. This increase in reported Cyclospora cases highlights risks of gastrointestinal infections through travelling, limitations in Cyclospora surveillance and the need for improved hygiene in the production of food consumed in holiday resorts.

Recent developments of plastic scintillators are reviewed, from 2000 to March 2014, distributed in two different chapters. First chapter deals with the chemical modifications of the polymer backbone, whereas modifications of the fluorescent probe are presented in the second chapter. All examples are provided with the scope of detection of various radiation particles. The main characteristics of these newly created scintillators and their detection properties are given., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

By combining the sensitivity of fluorescent units with the response of "smart" polymers to environmental changes, we propose a new approach for chemical detection applications. The system proved to be sensitive to 12 ppb of diethyl chlorophosphate (DCP), a Sarin surrogate, and to discriminate between the interfering molecules.

We describe the synthesis of new cationic tricoordinated copper complexes bearing bidentate pyridine-type ligands and N-heterocyclic carbene as ancillary ligands. These cationic copper complexes were fully characterized by NMR, electrochemistry, X-ray analysis, and photophysical studies in different environments. Density functional theory calculations were also undertaken to rationalize the assignment of the electronic structure and the photophysical properties. These tricoordinated cationic copper complexes possess a stabilizing CH-π interaction leading to high stability in both solid and liquid states. In addition, these copper complexes, bearing dipyridylamine ligands having a central nitrogen atom as potential anchoring point, exhibit very interesting luminescent properties that render them potential candidates for organic light-emitting diode applications.

This article presents a retrospective analysis of enteric disease outbreak investigations led by or conducted in collaboration with provincial health authorities in the Province of Quebec from 2002 through 2012. Objectives were to characterize enteric disease outbreaks, quantify and describe those for which a source was identified (including the control measures implemented), identify factors that contributed to or impeded identification of the source, and recommend areas for improvement in outbreak investigations (including establishment of criteria to initiate investigations). A descriptive analysis of enteric disease outbreak summaries recorded in a provincial database since 2002 was conducted, and corresponding outbreak reports were reviewed. Among 61 enteric disease outbreaks investigated, primary pathogens involved were Salmonella (46%), Escherichia coli O157:H7 (25%), and Listeria monocytogenes (13%). Sources were identified for 37 (61%) of 61 of the outbreaks, and descriptive studies were sufficient to identify the source for 26 (70%) of these. During the descriptive phase of the investigation, the causes of 21 (81%) of 26 outbreaks were identified by promptly collecting samples of suspected foods based on case interviews. Causes of outbreaks were more likely to be detected by weekly surveillance or alert systems (odds ratio = 6.0, P = 0.04) than by serotyping or molecular typing surveillance and were more likely to be associated with a common event or location (odds ratio = 11.0, P = 0.023). Among the 37 outbreaks for which causes were identified, 24 (65%) were associated with contaminated food, and recalls were the primary control measure implemented (54%). Review of enteric outbreaks investigated at the provincial level in Québec has increased the province's ability to quantify success and identify factors that can promote success. Multiple criteria should be taken into account to identify case clusters that are more likely to be resolved.

The surface relief gratings (SRGs) can be generated when azo-polymer films are exposed to laser beam interference as a result of mass migration. Despite considerable research effort over the past two decades this complex phenomenon remains incompletely understood. Here we show, for the first time, the athermal photofluidisation of azo-polysiloxane films exposed to 488 nm light, directly monitored by optical microscopy. A process of surface relief erasure occurring in parallel with its inscription was also observed during laser irradiation. We therefore propose a new mechanism of SRG formation, based on three different processes: (1) the polymer photo-fluidization in illuminated regions, (2) the mass displacement from illuminated to dark regions and (3) the inverse mass displacement, from dark to illuminated regions. The mechanical properties of the films during UV light irradiation were investigated by classical rheology and, for the first time, by using amplitude modulation-frequency modulation atomic force microscopy (AM-FM AFM).

Introduction: In this study, we optimize pharmacotherapy in children who failed anticholinergic monotherapy by simultaneous administration of 2 anticholinergics (oxybutynin and/or tolterodine and/or solifenacin)., Methods: This report is an update of our previously published study on double anticholinergic regimen in children with refractory incontinence due to neurogenic (NDO) and non-neurogenic (DO) detrusor overactivity. Patients with an insufficient response (clinically/urodynamically) to an optimized dose of a single anticholinergic (oxybutynin or tolterodine) received a second anticholinergic (tolterodine or solifenacin), in addition to the pre-existing medication. The primary end-point was efficacy (continence) and the secondary end-points were tolerability and safety. The Patient Perception of Bladder Condition (PPBC) scale was used to rate subjective improvement of patients., Results: In total, 56 patients with DO (n = 31) or NDO (n = 25) were enrolled at a mean age of 11.4 ± 3.5 years and were followed for a minimum of 3 months. The duration of double treatment was 36 ± 23 months. Our results found that 23 patients became dry, 18 improved significantly and 15 improved moderately. Urodynamic capacity improved from 158 ± 87 mL to 359 ± 148 mL and maximal pressure of contractions decreased from 76 ± 24 to 22 ± 22 cmH2O (p < 0.0001). The overall success rate was 82%, since 10 patients discontinued treatment for unsatisfactory clinical response or bothersome side effects. No side effects were reported by 28 patients, mild side effects by 20, moderate side effects by 8; 2 patients withdrew from the study due to their side effects. Of the 35 patients who voided spontaneously, 8 developed post-void residuals (>20%)., Conclusions: With a larger cohort and prospective follow-up, we reiterated that double anticholinergic regimen in children with DO or NDO refractory to anticholinergic monotherapy is a feasible and efficient approach.

Introduction: We evaluate the efficacy and safety of solifenacin to treat incontinence in children with non-neurogenic (DO) or neurogenic detrusor overactivity (NDO) refractory to oxybutinin or tolterodine., Methods: We updated and extended our previously published non-randomized uncontrolled study on open-label use of adjusted-dose regimens of solifenacin (1.25-10 mg) in children with refractory incontinence. The follow-up included voiding diaries, post-void residuals, urine cultures, ultrasounds and urodynamic studies. Clinical data were updated as of September 2012. Subjective improvement was assessed with the Patient Perception of Bladder Condition (PPBC) scale. The primary end point was efficacy toward continence and secondary end points were tolerability and safety., Results: Overall, 244 patients (112 girls, 132 boys) were enrolled; 53 with NDO and 191 with DO. Minimal follow-up was 5 months, the mean duration of treatment was 21.0 months and the mean age at initiation was 9.2 years. Urodynamic capacity improved from 145 ± 76 mL to 339 ± 152 mL and the amplitude of uninhibited contractions decreased from 66 ± 26 to 20 ± 20 cmH2O (p < 0.0001). The overall success rate is 91%, and more specifically 94% for non-neurogenic and 79% for neurogenic, which is significantly different (p = 0.013). Twenty-three patients discontinued treatment for unsatisfactory clinical response or bothersome side effects. No side effects were reported by 175 patients, mild by 46, moderate by 9, and 14 withdrew due to their side effects. Ten patients developed post-void residuals of ≥20 mL., Conclusion: Although higher in the non-neurogenic group, high subjective and objective success rates were maintained over a longer follow-up with an adjusted-dose regimen of solifenacin to treat pediatric NDO or DO refractory to oxybutynin or tolterodine. Moreover, we found acceptable tolerability and safety profiles.

Background: Bariatric surgery is one of few obesity treatments to produce substantial weight loss but only a small proportion of medically-eligible patients, especially men and racial minorities, undergo bariatric surgery., Objective: To describe primary care patients' consideration of bariatric surgery, potential variation by sex and race, and factors that underlie any variation., Design, Setting, and Patients: Telephone interview of 337 patients with a body mass index or BMI > 35 kg/m(2) seen at four diverse primary care practices in Greater-Boston., Measurements: Patients' consideration of bariatric surgery., Results: Of 325 patients who had heard of bariatric surgery, 34 % had seriously considered surgery. Men were less likely than women and African Americans were less likely than Caucasian patients to have considered surgery after adjustment for sociodemographics and BMI. Comorbid conditions did not explain sex and racial differences but racial differences dissipated after adjustment for quality of life (QOL), which tended to be higher among African American than Caucasian patients. Physician recommendation of bariatric surgery was independently associated with serious consideration for surgery [OR 4.95 (95 % CI 2.81-8.70)], but did not explain variation in consideration of surgery across sex and race. However, if recommended by their doctor, men were as willing and African American and Hispanic patients were more willing to consider bariatric surgery than their respective counterparts after adjustment. Nevertheless, only 20 % of patients reported being recommended bariatric surgery by their doctor and African Americans and men were less likely to receive this recommendation; racial differences in being recommended surgery were also largely explained by differences in QOL. High perceived risk to bariatric surgery was the most commonly cited barrier; financial concerns were uncommonly cited., Limitations: Single geographic region; examined consideration and not who eventually proceeded with bariatric surgery., Conclusion: African Americans and men were less likely to have considered bariatric surgery and were less likely to have been recommended surgery by their doctors. Differences in how obesity affects QOL appear to account for some of these variations. High perceived risk rather than financial barrier was the major deterrent for patients.

It is shown that lasing can be achieved in commercial organic liquid scintillators. Using a dynamic grating induced by an interference pattern in the scintillator volume, distributed feedback lasing is shown to occur in four out of five commercial liquid scintillators that have been investigated. Although these scintillators are not designed for lasing application, their purpose being to measure radioactivity, induction of a laser effect, furthermore with a tuning range of approximately 30 nm, has been attained.

Background: Inertial measurement of motion with Attitude and Heading Reference Systems (AHRS) is emerging as an alternative to 3D motion capture systems in biomechanics. The objectives of this study are: 1) to describe the absolute and relative accuracy of multiple units of commercially available AHRS under various types of motion; and 2) to evaluate the effect of motion velocity on the accuracy of these measurements., Methods: The criterion validity of accuracy was established under controlled conditions using an instrumented Gimbal table. AHRS modules were carefully attached to the center plate of the Gimbal table and put through experimental static and dynamic conditions. Static and absolute accuracy was assessed by comparing the AHRS orientation measurement to those obtained using an optical gold standard. Relative accuracy was assessed by measuring the variation in relative orientation between modules during trials., Findings: Evaluated AHRS systems demonstrated good absolute static accuracy (mean error < 0.5(o)) and clinically acceptable absolute accuracy under condition of slow motions (mean error between 0.5(o) and 3.1(o)). In slow motions, relative accuracy varied from 2(o) to 7(o) depending on the type of AHRS and the type of rotation. Absolute and relative accuracy were significantly affected (p<0.05) by velocity during sustained motions. The extent of that effect varied across AHRS., Interpretation: Absolute and relative accuracy of AHRS are affected by environmental magnetic perturbations and conditions of motions. Relative accuracy of AHRS is mostly affected by the ability of all modules to locate the same global reference coordinate system at all time., Conclusions: Existing AHRS systems can be considered for use in clinical biomechanics under constrained conditions of use. While their individual capacity to track absolute motion is relatively consistent, the use of multiple AHRS modules to compute relative motion between rigid bodies needs to be optimized according to the conditions of operation.

The paper introduces a new class of materials with azo-polysiloxanic structure bearing the property to generate nano-structured surfaces by laser irradiation. The ability to modulate the optical response of the film, through a modification of the polymer chemical structure, has been investigated. The azo-materials were tested for their ability to support cell adhesion and growth, with very promising results. A future use of these materials as growth support in cell cultures is of great interest, due to an easy, one step-method to generate the surface relief grating and to the possibility to introduce a large range of chemical modifications due to the presence of the chlorobenzyl groups in the polymeric side-chain., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background. Primary healthcare (PHC) renewal gives rise to important challenges for policy makers, managers, and researchers in most countries. Evaluating new emerging forms of organizations is therefore of prime importance in assessing the impact of these policies. This paper presents a set of methods related to the configurational approach and an organizational taxonomy derived from our analysis. Methods. In 2005, we carried out a study on PHC in two health and social services regions of Quebec that included urban, suburban, and rural areas. An organizational survey was conducted in 473 PHC practices. We used multidimensional nonparametric statistical methods, namely, multiple correspondence and principal component analyses, and an ascending hierarchical classification method to construct a taxonomy of organizations. Results. PHC organizations were classified into five distinct models: four professional and one community. Study findings indicate that the professional integrated coordination and the community model have great potential for organizational development since they are closest to the ideal type promoted by current reforms. Conclusion. Results showed that the configurational approach is useful to assess complex phenomena such as the organization of PHC. The analysis highlights the most promising organizational models. Our study enhances our understanding of organizational change in health services organizations.

By studying the number and method of homicidal poisoning in Miami-Dade County, Florida; New York City, NY; Oakland County, Michigan; and Sweden, we have confirmed that this is an infrequently established crime.Several difficulties come with the detection of homicidal poisonings. Presenting symptoms and signs are often misdiagnosed as natural disease, especially if the crime is committed in a hospital environment, suggesting that an unknown number of homicides go undetected.In the reported cases analyzed, the lethal agent of choice has changed over the years. In earlier years, traditional poisons such as arsenic, cyanide, and parathion were frequently used. Such poisonings are nowadays rare, and instead, narcotics are more commonly detected in victims of this crime.

Previous research reports examining the relationship between attitudes toward dying, death, and involvement in death-related occupations have provided mixed findings as no clear pattern has been identified. Examination of the relationship between attitudes toward dying, death, and recreational activity has not received much attention. The current study examined attitudes toward dying and death of older men categorized into four groups defined by recreational activities. The groups included skydivers (high death risk), nursing home residents (high death exposure), volunteer firefighters (high death risk and high death exposure), and a control group. The analyses found that skydivers reported the least fear of death, while nursing home residents reported the highest level. In addition, skydivers and firefighters had higher death acceptance scores than nursing home residents and the control group for the confrontation dimension, whereas skydivers had higher death acceptance scores than all groups, and firefighters were more accepting of death than nursing home residents for the integration dimension.

Background: Reform of primary healthcare (PHC) organisations is underway in Canada. The capacity of various types of PHC organizations to respond to populations' needs remains to be assessed. The main objective of this study was to evaluate the association of PHC affiliation with unmet needs for care., Methods: Population-based survey of 9205 randomly selected adults in two regions of Quebec, Canada. Outcomes Self-reported unmet needs for care and identification of the usual source of PHC., Results: Among eligible adults, 18% reported unmet needs for care in the last six months. Reasons reported for unmet needs were: waiting times (59% of cases); unavailability of usual doctor (42%); impossibility to obtain an appointment (36%); doctors not accepting new patients (31%). Regression models showed that unmet needs were decreasing with age and was lower among males, the least educated, and unemployed or retired. Controlling for other factors, unmet needs were higher among the poor and those with worse health status. Having a family doctor was associated with fewer unmet needs. People reporting a usual source of care in the last two-years were more likely to report unmet need for care. There were no differences in unmet needs for care across types of PHC organisations when controlling for affiliation with a family physician., Conclusion: Reform models of primary healthcare consistent with the medical home concept did not differ from other types of organisations in our study. Further research looking at primary healthcare reform models at other levels of implementation should be done.

We report herein the design, synthesis, and biological screening of a series of 15 disulfide prodrugs as precursors of albitiazolium bromide (T3/SAR97276, compound 1), a choline analogue which is currently being evaluated in clinical trials (phase II) for severe malaria. The corresponding prodrugs are expected to revert back to the active bis-thiazolium salt through an enzymatic reduction of the disulfide bond. To enhance aqueous solubility of these prodrugs, an amino acid residue (valine or lysine) or a phosphate group was introduced on the thiazolium side chain. Most of the novel derivatives exhibited potent in vitro antimalarial activity against P. falciparum. After oral administration, the cyclic disulfide prodrug 8 showed the best improvement of oral efficacy in comparison to the parent drug.

Background: Understanding the relationship between Plasmodium falciparum malaria transmission and health outcomes requires accurate estimates of exposure to infectious mosquitoes. However, measures of exposure such as mosquito density and entomological inoculation rate (EIR) are generally aggregated over large areas and time periods, biasing the outcome-exposure relationship. There are few studies examining the extent and drivers of local variation in malaria exposure in endemic areas., Methods: We describe the spatio-temporal dynamics of malaria transmission intensity measured by mosquito density and EIR in the KEMRI/CDC health and demographic surveillance system using entomological data collected during 2002-2004. Geostatistical zero inflated binomial and negative binomial models were applied to obtain location specific (house) estimates of sporozoite rates and mosquito densities respectively. Model-based predictions were multiplied to estimate the spatial pattern of annual entomological inoculation rate, a measure of the number of infective bites a person receive per unit of time. The models included environmental and climatic predictors extracted from satellite data, harmonic seasonal trends and parameters describing space-time correlation., Results: Anopheles gambiae s.l was the main vector species accounting for 86% (n=2309) of the total mosquitoes collected with the remainder being Anopheles funestus. Sixty eight percent (757/1110) of the surveyed houses had no mosquitoes. Distance to water bodies, vegetation and day temperature were strongly associated with mosquito density. Overall annual point estimates of EIR were 6.7, 9.3 and 9.6 infectious bites per annum for 2002, 2003 and 2004 respectively. Monthly mosquito density and EIR varied over the study period peaking in May during the wet season each year. The predicted and observed densities of mosquitoes and EIR showed a strong seasonal and spatial pattern over the study area., Conclusions: Spatio-temporal maps of malaria transmission intensity obtained in this study are not only useful in understanding variability in malaria epidemiology over small areas but also provide a high resolution exposure surface that can be used to analyse the impact of transmission on malaria related and all-cause morbidity and mortality.

Background: Targeted global efforts to improve survival of young adults need information on mortality trends; contributions from health and demographic surveillance system (HDSS) are required., Methods and Findings: This study aimed to explore changing trends in deaths among adolescents (15-19 years) and young adults (20-24 years), using census and verbal autopsy data in rural western Kenya using a HDSS. Mid-year population estimates were used to generate all-cause mortality rates per 100,000 population by age and gender, by communicable (CD) and non-communicable disease (NCD) causes. Linear trends from 2003 to 2009 were examined. In 2003, all-cause mortality rates of adolescents and young adults were 403 and 1,613 per 100,000 population, respectively, among females; and 217 and 716 per 100,000, respectively, among males. CD mortality rates among females and males 15-24 years were 500 and 191 per 100,000 (relative risk [RR] 2.6; 95% confidence intervals [CI] 1.7-4.0; p<0.001). NCD mortality rates in same aged females and males were similar (141 and 128 per 100,000, respectively; p = 0.76). By 2009, young adult female all-cause mortality rates fell 53% (χ(2) for linear trend 30.4; p<0.001) and 61.5% among adolescent females (χ(2) for linear trend 11.9; p<0.001). No significant CD mortality reductions occurred among males or for NCD mortality in either gender. By 2009, all-cause, CD, and NCD mortality rates were not significantly different between males and females, and among males, injuries equalled HIV as the top cause of death., Conclusions: This study found significant reductions in adolescent and young adult female mortality rates, evidencing the effects of targeted public health programmes, however, all-cause and CD mortality rates among females remain alarmingly high. These data underscore the need to strengthen programmes and target strategies to reach both males and females, and to promote NCD as well as CD initiatives to reduce the mortality burden amongst both gender.

This pilot study explored the feasibility of in-home teletreatment for patients with post-stroke anomia. Three participants over 65 years of age suffering from post-stroke anomia were treated in this pre/post-intervention case study. They received 12 speech therapy teletreatments (two sessions/week for 6 weeks) aimed at improving confrontation naming skills. Half of the failed items from a set of 120 preselected stimuli were trained during treatment (Block A-trained stimuli) while the other half served as controls (Block B-untrained stimuli). Variables measured were: 1) efficacy of treatment (performance on Block-A vs. Block B Stimuli), and 2) participants' satisfaction with teletreatment (using a French adaptation of the Telemedicine satisfaction questionnaire). All participants showed a clinically relevant improvement on confrontation naming of trained items and less improvement for untrained items. The researchers also obtained high satisfaction scores on the questionnaire (above 57/60). This pilot study supports the feasibility of speech therapy teletreatments applied to neurological language disorders.

The proportion of malaria vectors harboring the infectious stage of the parasite (the sporozoite rates) is an important component of measures of malaria transmission. Variation in time and/or space in sporozoite rates contribute substantially to spatio-temporal variation in transmission. However, because most vectors test negative for sporozoites, sporozoite rate data are sparse with large number of observed zeros across locations or over time in the case of longitudinal data. Rarely are appropriate methods and models used in analyzing such data. In this study, Bayesian zero inflated binomial (ZIB) geostatistical models were developed and compared with standard binomial analogues to analyze sporozoite data obtained from the KEMRI/CDC health and demographic surveillance system (HDSS) site in rural Western Kenya during 2002-2004. ZIB models showed a better predictive ability, identified more significant covariates and obtained narrower credible intervals for all parameters compared to standard geostatistical binomial model., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The goal of this project is to evaluate the implementation of an integrated and interdisciplinary program for prevention and management of cardiometabolic risk (PCMR). The intervention is based on the Chronic Care Model. The study will evaluate the implementation of the PCMR in 6 of the 12 health and social services centres (CSSS) in Montréal, and the effects of the PCMR on patients and the practice of their primary care physicians up to 40 months following implementation, as well as the sustainability of the program. Objectives are: 1-to evaluate the effects of the PCMR and their persistence on patients registered in the program and the practice of their primary care physicians, by implementation site and degree of exposure to the program; 2-to assess the degree of implementation of PCMR in each CSSS territory and identify related contextual factors; 3-to establish the relationships between the effects observed, the degree of PCMR implementation and the related contextual factors; 4-to assess the impact of the PCMR on strengthening local services networks., Methods/design: The evaluation will use a mixed design that includes two complementary research strategies. The first strategy is similar to a quasi-experimental "before-after" design, based on a quantitative approach; it will look at the program's effects and their variations among the six territories. The effects analysis will use data from a clinical database and from questionnaires completed by participating patients and physicians. Over 3000 patients will be recruited. The second strategy corresponds to a multiple case study approach, where each of the six CSSS constitutes a case. With this strategy, qualitative methods will set out the context of implementation using data from semi-structured interviews with program managers. The quantitative data will be analyzed using linear or multilevel models complemented with an interpretive approach to qualitative data analysis., Discussion: Our study will identify contextual factors associated with the effectiveness, successful implementation and sustainability of such a program. The contextual information will enable us to extrapolate our results to other contexts with similar conditions., Trial Registration: ClinicalTrials.gov: NCT01326130.

P2Y14 is a member of the pyrimidinergic GPCR family. UDP-Glc has been previously shown to activate human P2Y14, whereas UDP was unable to activate the receptor. In this study, the authors used conventional and nonconventional methods to further characterize P2Y14 and its ligands. Conventional calcium mobilization and nonconventional cellular impedance functional assays revealed that UMP and UDP selectively activated HEK cells coexpressing P2Y14 and Gα(qi5). In the impedance assays, the presence of exogenous Gα(qi5) resulted in agonist-induced Gq signaling, whereas in the absence of exogenous Gα(qi5), the signal was indicative of Gi. The authors established the first P2Y14 membrane filtration binding assay using a novel optimized expression vector and [(3)H]UDP as radioligand. UDP-Glc, UMP, and UDP dose dependently inhibited [(3)H]UDP binding in the binding assay, and saturation analysis revealed that UDP bound P2Y14 with a K(D) = 10 nM and a B(max) = 110 pmol/mg. The authors screened a phosphonate library and identified compound A, which inhibited UDP-Glc-mediated calcium signaling in the fluorometric imaging plate reader assay (IC(50) = 2.3 µM) and competed for [(3)H]UDP binding in the novel binding assay with a K(i) = 1280 nM.

Our series of competitive antagonists against the G-protein coupled receptor P2Y(14) were found to be highly shifted in the presence of serum (>99% protein bound). A binding assay using 2% human serum albumin (HSA) was developed to guide further SAR studies and led to the identification of the zwitterion 2, which is substantially less shifted (18-fold) than our previous lead compound 1 (323-fold). However, as the bioavailability of 2 was low, a library of ester pro-drugs was prepared (7a-7j) and assessed in vitro. The most interesting candidates were then profiled in vivo and led to the identification of the pro-drug 7j, which possesses a substantially improved pharmacokinetic profile., (Copyright © 2011. Published by Elsevier Ltd.)

A new series of indole amide acting as hCRTH2 receptor ligands had been explored and are described herein. Several amide derivatives displaying low nanomolar activity in hCRTH2 binding and whole blood assays were identified. They were found to behave as a full antagonists, exhibiting good selectivity over related prostaglandin receptors. Also, prototypical compounds in this novel series which displayed acceptable CYP profiles and were orally bioavailable in rats were identified., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A weak, UDP-competitive antagonist of the pyrimidinergic receptor P2RY(14) with a naphthoic acid core was identified through high-throughput screening. Optimization provided compounds with improved potency but poor pharmacokinetics. Acylglucuronidation was determined to be the major route of metabolism. Increasing the electron-withdrawing nature of the substituents markedly reduced glucuronidation and improved the pharmacokinetic profile. Additional optimization led to the identification of compound 38 which is an 8 nM UDP-competitive antagonist of P2Y(14) with a good pharmacokinetic profile., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A weak antagonist of the pyrimidinergic receptor P2Y(14) containing a dihydropyridopyrimidine core was identified through high-throughput screening. Subsequent optimization led to potent, non-UTP competitive antagonists and represent the first reported non-nucleotide antagonists of this receptor. Compound 18q was identified as a 10 nM P2Y(14) antagonist with good oral bioavailability and provided sufficient exposure in mice to be used as a tool for future in vivo studies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Approximately 2 billion persons worldwide are infected with schistosomiasis and soil-transmitted helminths (STH), many in areas where endemic malaria transmission coexists. Few data exist on associations between these infections. Nested within a larger clinical trial, primigravid and secundigravid women provided blood samples for human immunodeficiency virus (HIV) testing and peripheral malaria films and stool and urine for evaluation of STH and Schistosoma spp. during their initial antenatal clinic visit. The most common parasitic infections were malaria (37.6%), S. haematobium (32.3%), and hookworm (14.4%); 14.2% of women were HIV-infected. S. haematobium infection was associated with lower malarial parasite densities (344 versus 557 parasites/μL blood; P < 0.05). In multivariate analysis, HIV and hookworm infection were independently associated with malaria infection (adjusted odds ratio = 1.9 and 95% confidence interval = 1.2-3.0 for HIV; adjusted odds ratio = 1.9 and 95% confidence interval = 1.03-3.5 for hookworm). Concurrent helminthic infection had both positive and negative effects on malaria parasitemia among pregnant women in Malawi.

Two main avenues are advocated to improve the capability of healthcare systems to satisfy the public's needs and expectations: more resources and better organization. This paper sheds some light on this debate. It assesses the extent to which patients' positive rating of their healthcare experience and the extent to which they use services are related to the availability of healthcare resources. Findings indicate that patients' evaluations of their care experience and use of services were higher when the availability of resources was either limited or average. In no case were positive ratings of services and greater use of them associated with greater resource availability. Thus, simply adding resources runs the risk of diminishing, rather than improving, users' healthcare experience.

A new class of 7-azaindole analogs of MK-7246 as potent and selective CRTH2 antagonists is reported. The SAR leading to the identification of the optimal azaindole regioisomer as well as the pharmacokinetics and off-target activities of the most potent antagonists are disclosed., (Copyright © 2010 Elsevier Ltd. All rights reserved.)