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Insomnia is highly prevalent among military veterans but access to cognitive behavioral therapy for insomnia (CBT-I) is limited. Thus, this study examined the feasibility, acceptability, and potential efficacy of Insomnia Coach, a CBT-I-based, free, self-management mobile app. Fifty U.S. veterans, who were mostly male (58%) and mean age 44.5 (range = 28 to 55) years with moderate insomnia symptoms were randomized to Insomnia Coach (n = 25) or a waitlist control condition (n = 25) for 6 weeks. Participants completed self-report measures and sleep diaries at baseline, post-treatment, and follow-up (12 weeks post-randomization), and app participants (n = 15) completed a qualitative interview at post-treatment. Findings suggest that Insomnia Coach is feasible to use, with three-quarters of participants using the app through 6 weeks and engaging with active elements. For acceptability, perceptions of Insomnia Coach were very favorable based on both self-report and qualitative interview responses. Finally, for potential efficacy, at post-treatment, a larger proportion of Insomnia Coach (28%) than waitlist control participants (4%) achieved clinically significant improvement (p = .049) and there was a significant treatment effect on daytime sleep-related impairment (d = -0.6, p = .044). Additional treatment effects emerged at follow-up for insomnia severity (d = -1.1, p = .001), sleep onset latency (d = -0.6, p = .021), global sleep quality (d = -0.9, p = .002), and depression symptoms (d = -0.8, p =.012). These findings provide preliminary evidence that among veterans with moderate insomnia symptoms a CBT-I-based self-management app is feasible, acceptable, and promising for improving insomnia severity and other sleep-related outcomes. Given the vast unmet need for insomnia treatment in the population, Insomnia Coach may provide an easily accessible, convenient public health intervention for individuals not receiving care.

Digital, Background Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. Methods We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. Findings In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65–2·12) than in MICs (1·41, 1·34–1·49) and LICs (1·35, 1·25–1·46; interaction p, Funding Full funding sources are listed at the end of the paper (see Acknowledgments)., Ciencias Médicas y de la Salud

BACKGROUND: Depression hinders obesity treatment; elucidating mechanisms may enable treatment enhancements. OBJECTIVES: The aim was to investigate whether changes in neural targets in the negative affect circuit following psychotherapy mediate subsequent changes in weight and behaviors. METHODS: Adults (n = 108) with obesity and depression were randomly assigned to usual care or an intervention that delivered problem-solving therapy (PST) for depression over 2 mo. fMRI for brain imaging was performed at baseline and 2 mo. BMI, physical activity, and diet were measured at baseline and 12 mo. Mediation analysis assessed between-group differences in neural target changes using t test and correlations between neural target changes and outcome changes (simple and interaction effect) using ordinary least-squares regression. RESULTS: Compared with usual care, PST led to reductions in left amygdala activation (−0.75; 95% CI: −1.49, −0.01) and global scores of the negative affect circuit (−0.43; −0.81, −0.06), engaged by threat stimuli. Increases in amygdala activation and global circuit scores at 2 mo correlated with decreases in physical activity outcomes at 12 mo in the usual-care group; these relations were altered by PST. In relation to change in leisure-time physical activity, standardized β-coefficients were −0.67 in usual care and −0.01 in the intervention (between-group difference: 0.66; 0.02, 1.30) for change in left amygdala activation and −2.02 in usual care and −0.11 in the intervention (difference: 1.92; 0.64, 3.20) for change in global circuit scores. In relation to change in total energy expenditure, standardized β-coefficients were −0.65 in usual care and 0.08 in the intervention (difference: 0.73; 0.29, 1.16) for change in left amygdala activation and −1.65 in usual care and 0.08 in the intervention (difference: 1.74; 0.85, 2.63) for change in global circuit scores. Results were null for BMI and diet. CONCLUSIONS: Short-term changes in the negative affect circuit engaged by threat stimuli following PST for depression mediated longer-term changes in physical activity. This trial was registered at www.clinicaltrials.gov as NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413).

Summary Background To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. Methods The PURE study is a prospective, population-based cohort study of individuals aged 35–70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. Findings This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5–10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. Interpretation Among adults aged 35–70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

The paper deals with the determination of mercury balance for a hard coal-fired circulating fluidized bed boiler operated at various loads (i.e. 100%, 75% and 50% of the Maximum continuous rating, MCR). The research was focused on the determination of the mercury balance by providing data on Hg content in fuel, limestone sorbent, and in the combustion by-products (fly ash and bottom ash). Furthermore, the concentration of mercury in the flue gas in two zones i.e. upstream and downstream the electrostatic precipitator (ESP) were also determined in order to assess the effectiveness of the ESP in mercury reduction. For the calculation of the Hg balance both gaseous mercury species, Hg0, and oxidized mercury, Hg2+, were taken into consideration. The results indicated that over 95% of the mercury was fed into the boiler system with coal and just less than 5% with limestone used for ‘dry’ desulfurization of the flue gas. As for the boiler output, very high mercury content was determined in the fly ashes, while just a minor part (a few percent of the total mercury input) was found in the bottom ashes. The shares of Hg0 and Hg2+ mercury were affected by boiler load.

Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status—wealth and education—differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. Findings Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96–1·58) for high-income countries, 1·59 (1·42–1·78) in middle-income countries, and 2·23 (1·79–2·77) in low-income countries (pinteractionInterpretation Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education. Funding Full funding sources are listed at the end of the paper (see Acknowledgments).

We have discovered a huge enhancement of the supercapacity (up to 4 times) under sun illumination of electrodes fabricated from cavitated nanoporous carbon being carbonized from an iodine doped β–cyclodexryn. This effect was achieved even without a frequently used KOH treatment and is caused by enhancement of effective activated surfaces. The synthesized cavitated nanoporous carbon exhibits principally different accumulative features at the carbon/electrolyte interface. Relationship between the porous structure, electronic properties of supramolecular nanoporous carbon and enhanced supercapacitance is explored. The impedance spectroscopy measurements (Nyquist diagram) apparently suggest a capacitance mechanism for the energy accumulation. Enhancement of the supercapacity is explained by light-generated carriers in low-dimensional nano-interfaces in relevant mechanism an increasing concentration of delocalized electrons resulting in unlocking of the Helmholtz layer capacity.

It has been demonstrated through the use of both gamma-rays and beam of accelerated electrons (EB) for the radiolytic decomposition of PFOA in diluted aqueous solutions that the most reactive species among the products of water radiolysis are hydrated electrons eaq. The reaction of PFOA with the hydrated electrons takes place with the largest yield in strongly alkaline deaerated solutions. The PFOA decomposition performed at an initial concentration level of 1 mg/L by γ-irradiation requires the use of absorbed doses below 10 kGy, which, depending on the activity of employed 60Co source, requires 2–3 h irradiation time. Similar results were obtained at pH 12 in the presence and also in the absence of t-butanol in the treated solutions. In the case of EB irradiation in a wide range of the absorbed doses (up to 100 kGy), a very pronounced effect of the dose-rate was observed, which can be attributed to various recombination reactions of the products of water radiolysis. A significant improvement in the yield of the PFOA decomposition by EB irradiation can be observed in the presence of trace amounts of nitrate or 100 mM of a formate in the treated solutions. In optimized conditions, about 70–80% decomposition of the initial level of 1 ppm of PFOA can be obtained with an irradiation using 100 kGy absorbed dose, which corresponds to about 5 s treatment with the use of an employed electron accelerator. The acute toxicity measurements and a kinetic modeling are presented, together with a suggestion of the mechanism of radiolytic decomposition of PFOA.

A reference material for virus-like particles traceable to the International System of Units (Système International d'Unités - the SI) is reported. The material addresses the need for developing reference standards to benchmark virus-like gene delivery systems and help harmonize measurement approaches for characterization and testing. The material is a major component of synthetic polypeptide virus-like particles produced by the state-of-the-art synthetic and analytical chemistry methods used to generate gene delivery systems. The purity profile of the material is evaluated to the highest metrological order demonstrating traceability to the SI. The material adds to the emerging toolkit of reference standards for quantitative biology.

Background: There is a need to understand the neural mechanisms targeted by behavioural therapy for depression and how these mechanisms relate to clinical outcomes. We used functional neuroimaging to assess the neural mechanisms that are modified by behavioural therapy and mediate subsequent clinical outcomes in depression. Methods: Participants with depression, co-occurring with obesity, from a parent RAINBOW trial, were randomised to an integrated collaborative care intervention (I-CARE) (n=59) or usual care (n=49). Functional neuroimaging was undertaken at baseline and at 2 months, coinciding with initial 2-months of I-CARE that implemented a 7-step problem-solving therapy process and behavioural activation (for brevity, “PST”). Neural targets were the amygdala, insula, and anterior cingulate cortex (ACC) regions of the negative affect circuit engaged by established tasks presenting threat-related and sad stimuli. Regression models evaluated if early change in neural function mediated the effect of PST on depression severity and problem-solving outcomes at 6- and 12-months post-randomization. Findings: Compared with usual care, PST led to a reduction at 2 months in amygdala activation (Right: b=-0.83, 95% CI -1.55 to -0.11; Left: b=-0.86, -1.63 to -0.10) and amygdala-ACC connectivity (b=0.78, 0.05 to 1.52) engaged by threat stimuli. This PST-dependent reduction in amygdala activation mediated improvement of depression at 6 months relative to usual care. PST also tempered the relationship between insula activation and improved problem solving at 6 and 12 months. Interpretation: PST modifies neural targets within the negative affect circuit to improve symptoms and problem-solving relevant to the clinical and functional recovery of depression. Funding Statement: US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368. Declaration of Interests: LMW is on the Scientific Advisory Board for One Mind Psyberguide and the External Advisory Board for the Laureate Institute for Brain Research. JM is a paid scientific consultant for Health Mentor, Inc. (San Jose, CA). OA is the co-founder of Keywise AI and the servers on the advisory boards of Blueprint Health and Embodied Labs. All other authors do not have anything to declare. Ethics Approval Statement: The Institutional Review Boards for the Stanford University and the University of Illinois at Chicago approved the study.

WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality.The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all50 participants) and cardiovascular disease and mortality in 255 communities (all100 participants), and used individual-level data to adjust for known confounders.95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile5·08 g/day, mean intake 5·75 g/day,5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries.Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.

A new series of tricarbonyl complexes of rhenium(I) in the ‘2 + 1’ system with the bidentate ligand N-methylpyridine-2-carbothioamide (NC5H4-CS-NH-CH3, LH(Me)NS) and a monodentate ligand, being either an anion (Cl, Br, I or SCN) or a neutral molecule (3,5-dimethylpyrazole (Hdmpz) or imidazole (Him)), was synthesized. The use of mixed ligands leads to the formation of neutral or cationic (in the form of PF6− salts) tricarbonylrhenium(I) complexes: [Re(CO)3(LH(Me)NS)X] (X = Cl, Br, I, NCS) (complexes 1–4) and [Re(CO)3(LH(Me)NS)Y]+ (Y = Hdmpz, Him) (5 and 6), respectively. In case of the [Re(CO)3(LH(Me)NS)NCS] complex two polymorphic forms (4a and 4b) have been distinguished. Crystal structure of all complexes was determined by single-crystal X-ray diffraction method and the results were compared with the molecular structures obtained from DFT calculations. The compounds were characterized by FT-IR, NMR, UV-Vis and HPLC techniques. IR and UV-Vis spectra were also simulated by DFT and TD-DFT methods. Cytotoxicity of the complexes was estimated using human ovarian cancer cell line (A2780), its cisplatin resistant cell line (A2780cis) and non-cancerous human embryonic kidney cells (Hek-293). The toxicity of newly synthesized complexes was comparable to cisplatin when tested against both cancerous cell lines (IC50 = 2–49 μM), but lower than cisplatin towards non-cancerous cells (IC50 = 6–63 μM). Among them, the complexes with chloride and iodide anions exhibit remarkable cytotoxicities.

Accurate diagnosis, monitoring and treatment are cornerstones of a healthcare system and require reliable measurements. The traceability of measurement results to stated references, and the development of Reference Measurement Systems (RMS), provide mechanisms to achieve the required consistency of results. The primary standards within such an RMS are of pure substance certified reference materials. Developments in modern measurement and mass spectrometric techniques have opened up the possibility to characterize and quantify more complex large molecules such as peptides, enabling RMS to be developed for these analytes. The prohormone angiotensin I is a hypertension biomarker and was selected as a model peptide. The full mass balance approach, the peptide impurity corrected amino acid analysis, elemental analysis and quantitative nuclear magnetic resonance approaches have been investigated and optimized to compare the performance of these different methodologies for the purity mass fraction value assignment of an ANG I calibrator material.

Introduction The purposes of the present work were to label substance P (5–11) with 211 At using a rhodium(III) complex with a bifunctional ligand–2-(1,5,9,13-tetrathiacyclohexadecan-3-yloxy)acetic acid ([16aneS 4 ]-COOH) and to assess the in vitro stability and toxicity of the obtained radiobioconjugate. Methods Two approaches were evaluated to obtain 131 I/ 211 At-Rh[16aneS 4 ]-SP 5–11 radiobioconjugates, based on 2-step and 1-step syntheses. In the first method 131 I/ 211 At-Rh[16aneS 4 ]-COOH complexes were obtained that required further coupling to a biomolecule. In the second approach, the bioconjugate [16aneS 4 ]-SP 5–11 was synthesized and further labeled with 131 I and 211 At through the utilization of a Rh(III) metal cation bridge. The synthesized compounds were analyzed by HPLC, TLC and paper electrophoresis. Results The 131 I/ 211 At-Rh[16aneS 4 ]-COOH complexes were obtained in high yield and possessed good stability in PBS and CSF. Preliminary studies on coupling of 131 I-Rh[16aneS 4 ]-COOH to substance P (5–11) in 2-step synthesis showed that this procedure was too long with respect to 211 At half-life, prompting us to improve it by finally using a 1-step synthesis. This strategy not only shortened the labeling time, but also increased final yield of 131 I/ 211 At-Rh[16aneS 4 ]-SP 5–11 radiobioconjugates. The stability of both compounds in PBS and CSF was high. Toxicity studies with the 211 At-Rh[16aneS 4 ]-SP 5–11 demonstrated that radiobioconjugate significantly reduced T98G cell viability in a dose dependent manner reaching 20% of survival at the highest radioactivity 1200kBq/mL. Conclusions The radiobioconjugate 211 At-Rh[16aneS 4 ]-SP 5–11 revealed its potential in killing glioma T98G cells during in vitro studies; therefore further animal studies to are required to determine its in vivo stability and treatment potential in normal and xenografted mice.

Introduction Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Among the many α emitters, 223 Ra exhibits very attractive nuclear properties for application in radionuclide therapy. The decay of this radioisotope and its daughters is accompanied by the emission of four α -particles, releasing 27.9MeV of cumulative energy. Unfortunately the lack of an appropriate bifunctional ligand for radium has so far been a main obstacle for the application of 223 Ra in receptor targeted therapy. In our studies we investigated the use of nanozeolite–Substance P bioconjugates as vehicles for 223 Ra radionuclides for targeted α therapy. Methods The sodium form of an A-type of nanozeolite (NaA) was synthesized using the template method. Next, the nanozeolite particles were conjugated to the Substance P (5–11) peptide fragment, which targets NK-1 receptors on glioma cells. The obtained bioconjugate was characterized by transmission emission spectroscopy, thermogravimetric analysis and dynamic light scattering analysis. The NaA–silane–PEG–SP(5–11) bioconjugates were labeled with 223 Ra by exchange of the Na + cation and the stability, receptor affinity and cytotoxicity of the obtained radiobioconjugates were tested. Results The 223 Ra-labeled nanozeolite bioconjugate almost quantitatively retains 223 Ra in vitro after 6days, while the retention of decay products varies from 90 to 95%. The synthesized 223 RaA–silane–PEG–SP(5–11) showed high receptor affinity toward NK-1 receptor expressing glioma cells and exhibited a high cytotoxic effect in vitro . Conclusions Substance P functionalized nanozeolite-A represents a viable solution for the use of the 223 Ra in vivo generator as a therapeutic construct for targeting glioma cells.

Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. While use of viral transcriptional promoters may increase the risk of insertional mutagenesis, cellular promoters may not achieve WASp expression levels necessary for optimal therapeutic effect. Here we evaluate a self-inactivating (SIN) lentiviral vector combining a chromatin insulator upstream of a viral MND (MPSV LTR, NCR deleted, dl587 PBS) promoter driving WASp expression. Used as a gene therapeutic in Was−/− mice, this vector resulted in stable WASp+ cells in all hematopoietic lineages and rescue of T and B cell defects with a low number of viral integrations per cell, without evidence of insertional mutagenesis in serial bone marrow transplants. In a gene transfer experiment in non-human primates, the insulated MND promoter (driving GFP expression) demonstrated long-term polyclonal engraftment of GFP+ cells. These observations demonstrate that the insulated MND promoter safely and efficiently reconstitutes clinically effective WASp expression and should be considered for future WAS therapy.

It is clear that we can benefit from multi-constellation GNSS in precise relative positioning. On the other hand, it is still an open problem how to combine multi-GNSS signals in a single functional model. This study presents methodology and quality assessment of selected methods allowing for multi-GNSS observations combining in relative kinematic positioning using baselines up to tens of kilometers. In specific, this paper characterizes loose and tight integration strategies applied to the ionosphere and troposphere weighted model. Performance assessment of the established strategies was based on the analyses of the integer ambiguity resolution and rover coordinates’ repeatability obtained in the medium range instantaneous RTK positioning with the use of full constellation dual frequency GPS and Galileo signals. Since full constellation of Galileo satellites is not yet available, the observational data were obtained from a hardware GNSS signal simulator using regular geodetic GNSS receivers. The results indicate on similar and high performance of the loose, and tight integration with calibrated receiver ISBs strategies. These approaches have undeniable advantage over single system positioning in terms of reliability of the integer ambiguity resolution as well as rover coordinate repeatability.

BACKGROUND: Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. METHODS: In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. FINDINGS: Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. INTERPRETATION: Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

The source of the residues of anthropogenic endocrine disruptor known as bisphenol A (BPA) in the natural environment and foods is both production and very wide use of several classes of polymers. Because of the documented inefficiency of BPA removal from waters and wastewaters using conventional treatment methods, several advanced oxidation processes (AOPs) employing hydroxyl radicals ( OH) were developed for this purpose in the recent decade. In this work, especially efficient removal of BPA was performed with the use of OH radicals, which are formed from water radiolysis by irradiation with γ-rays. For the initial BPA level 10 mg L-1 (43.9 μM) the pseudo first order rate-constant for the reaction of OH with BPA in neutral, aerated solutions was evaluated to be 0.392 min−1 (6.23 kGy−1), which can be also much higher for lower initial BPA concentration. The possibility to predict the yield of radiolytic BPA decomposition based on Total Organic Carbon content of irradiated natural environmental samples was demonstrated. A detailed mechanism of radical reactions involving OH radicals and superoxide radical anions (O2 −) was proposed leading to the formation of decomposition products which were identified by LC/MS analysis. Moreover, the changes in the cytotoxicity of γ-irradiated BPA solutions were examined for two cell lines of human origin, namely liver carcinoma cells HepG2, and breast cancer cells MDA-MB-231.

The ship domain is a concept commonly proposed as a safety assessment criterion in planning collision avoidance manoeuvres of a ship or its safe route. The work presents authors’ methods for determining an effective ship domain based on tests using Electronic Chart Display and Information System (ECDIS) simulator. The tests were conducted on non-autonomous real time models of ships steered by expert navigators. Domains were determined for ships of different sizes and speeds. The ship domain was approximated to an ellipse. The study covered absolute and relative domains, the latter defined in ship length units. The dependence of the domain shape and size on ship size and speed has been analysed and described. The formulated analytical relationships enable us to determine the domain of a ship varying in size and speed.

The continuous progress in GNSS (Global Navigation Satellite System) has led to considering this measurement technique as a powerful tool for the detection of the displacement response on seismic events and a source of comprehensive information on seismic wave propagation. Hence, as a natural consequence of the significant performance of high-rate GNSS measurements, a lot of effort has been made to develop dedicated algorithms for the GNSS-seismology. At present, the relative positioning mode is considered as the most accurate method for coordinate displacement determination with GNSS measurements. This holds true providing that all errors are carefully modelled or significantly reduced, which is not a trivial task in a wide area scenario. In this paper we validate the algorithms and the system developed for an automatic Galileo and GPS (Global Positioning System) high-rate signals processing over medium-length baselines. The system aims at the characterisation of the displacement response to seismic events, which are induced by mining exploitation. Addressing the requirements of the monitoring network, the system takes advantage of a ionosphere-weighted positioning model and a multi-baseline solution, which may be considered as superior with respect to the commonly employed single-baseline mode. The validation of the system feasibility was performed in two manners: by processing the data collected during actual MW 3.8 seismic event and with the use of single-axis shake table. The results of the former experiment showed a high agreement between the GNSS and accelerometer-derived results in a frequency domain. The latter proved that the system is capable of detecting the dynamic displacements with a millimetre-level precision at distances of over 30 km from the reference stations.

The study compared the slaughter value and meat quality of heifers and once-calved heifers slaughtered at the age of 18 and 28months, respectively. The once-calved heifers at the age of 15months, were bred with semen of Limousine bulls and following the calving they fed their offspring and then they were slaughtered. There were no differences in the carcass conformation and fatness between the treatments. Once-calved heifers' carcasses had a higher proportion (P

Although salt intake derived from data on urinary sodium excretion in free-living populations has been used in public policy, a population study on urinary sodium excretion has not been done in Canada. We assessed dietary sodium and potassium intake using a 24-hour urine collection in a large survey of urban and rural communities from 4 Canadian cities and determined the association of these electrolytes with blood pressure (BP).One thousand seven hundred consecutive individuals, aged 37-72 years, attending their annual follow-up visits of the ongoing Prospective and Urban Rural Epidemiology (PURE) study in Vancouver, Hamilton, Ottawa, and Quebec City, Canada, collected a 24-hour urine sample using standardized procedures.Mean sodium excretion was 3325 mg/d and mean potassium excretion was 2935 mg/d. Sodium excretion ranged from 3093 mg/d in Vancouver to 3642 mg/d in Quebec City, after adjusting for covariates. Potassium excretion ranged from 2844 mg/d in Ottawa to 3082 mg/d in Quebec City. Both electrolytes were higher in men than in women and in rural populations than in urban settings (P0.001 for all). Sodium excretion was between 3000 and 6000 mg/d in 48.3% of the participants,3000 mg/d in 46.7%, and6000 mg/d in only 5%. No significant association between sodium or potassium excretion and BP was found.Sodium consumption in these Canadians is within a range comparable to other Western countries, and intake in most individuals is6000 mg/d, with only 5% at higher levels. Within this range, sodium or potassium levels were not associated with BP.

The provenance of marbles used for ancient statuary and architecture is of utmost importance for archaeologists, art historians and archaeometrists. The aim of this paper is to provide a comprehensive characterisation of the white marble exploited in antiquity in Goktepe (Mugla Province, Turkey) to increase the reliability for identifying this marble in ancient artefacts. A campaign of interdisciplinary archaeological and geological fieldwork undertaken by the Marmora Asiatica project is based on a multi-method approach and on a representative set of samples used for the archaeometric analyses. Petrographic investigation showed that the Goktepe marble is more variable with regard to fabrics and grain size than previously suggested, whereas it is generally non-luminescent and dolomite-free. Stable C and O isotope and elemental analyses confirmed the results reported so far. We also report, for the first time for Goktepe white marble, the results of Sr isotope measurements, which in combination with elemental ratios, e.g. Sr/Mg and Mn/Sr, and δ18O values, greatly improve the discrimination among Goktepe, Carrara and other fine-grained white marbles. Applicability of these proxies was tested on artefacts from Hadrian's Villa, for which Carrara and Goktepe provenance had been proposed. The paper also reports new archaeological findings and results of estimates of stone extracted from the quarries, which allowed for a recontextualization of the significance of quarries at Goktepe. High-resolution topographic measurements, performed for the first time with the use of a 3-D laser scanner, combined with geological field study, allowed for precise calculation of the volume of the white variety extracted in antiquity. Estimates of 17000 m3 is almost a half less than previously suggested. Moreover, a careful study of the existing literature showed that in some instances assignment of white marble artefacts to the Goktepe quarries may not be accurate. Verification of provenance for those problematic artefacts and a more reliable identification of Goktepe marbles in the future can be achieved by application of the set of analyses proposed in this work, which has a higher discrimination potential.

The authors’ approach to stepwise transient plane source method for measuring specific heat, thermal diffusivity and thermal conductivity of chosen materials: foams, polymers and metals has been presented. The dynamic temperature field is generated by the passage of the constant current through a plane electrical resistance made of thin nichrome foil in the form of disk sandwiched between two identical pieces of sample material. The sample material must completely cover the heater. A step-wise heating power is applied to this heater, resulting in a transient temperature response that is recorded by the two thermocouples mounted on the samples on the both sides of the heater. To determine thermal properties of materials it is sufficient to measure the temperature as a function of time by only one thermocouple. However, if it is possible a better way is to take the average of both signals, i.e. from the both thermocouples. From temperature response in this sandwich-sample setup configuration the thermal properties are obtained by plotting the temperature increase at the center of the sample’s surfaces along the axis symmetry of the measuring stack as a function of square root of time Δ T ( t ) . The initial part of this plot is used to determine the thermal conductivity from the slope of the best line-fit. The second part of dependence Δ T ( t ) is used to determine the thermal diffusivity by an iterative procedure giving the best model fit to the experimental data points. The paper presents the study design of determining thermophysical parameters of solid states and metrological conditions of the step-wise transient method. The proposed method is easy to implement as an academic research tool. Part 1 concerns theoretical considerations of the method, while Part 2 contains the results of experimental research.

The subject of the paper which is a continuation of part 1 are issues related to the implementation of the stepwise transient plane source method. Both the measuring device and the testing methodology were developed. Measurements of thermophysical properties k, a and cp of selected materials from the group of thermal insulating foams (polyurethanes, polystyrenes), organic glass polymers and metals, including high thermal conductivity ones, i.e. duralumin at one measurement, were carried out. The measurement time was on the order of a few to several hundred seconds. Procedures for calculating thermal effusivity b and thermal diffusivity a were illustrated. Parameters of the thin-layer heater used in the measurement system were studied, i.e. measurements of the resistance change of the heater in the function of the voltage of the power supply and examination of the heater homogeneity were performed using a thermal imaging camera. The method requires that the thermocouples should be mounted on the faces of the samples. According to authors, this is an advantage of the method, because it allows to limit the applied pressure of the measuring stack on the accuracy of materials thermophysical properties measurements, especially metals. The measurements confirmed the suitability of the method for testing the thermophysical parameters of different groups of materials. The obtained experimentally accuracy of thermophysical parameters of testing materials in relation to reference values did not exceed 10%. The usefulness of the analytical solution of 2D transient heat conduction problem in the considered measuring stack has been confirmed by the results of numerical simulation, which includes heat transfer in a sample and in a flexible thin layer Kapton-nichrome heater.

RAFT (ang. Reversible Addition–Fragmentation chain Transfer) polymerization has been considered as one of the most successful techniques for the preparation of polymers with predetermined molecular weights, narrow molecular weight distributions and high degree of chain end functionalities. This method was used for grafting of N-isopropylacrylamide onto polyurethane (PUR) surface to improve biocompability of the matrix surface. The pristine and grafted samples were investigated by the following surface characterization techniques: ATR-FTIR spectroscopy and scanning electron microscopy (SEM). The analysis of paramagnetic species was performed by EPR spectroscopy in order to evaluate the ability of PUR to form covalent bonds with monomer molecules. Grafting of PNIPAAm onto PUR surface in controlled manner was confirmed by GPC. The wettability of PUR and PUR-g-PNIPAAm surfaces was evaluated by contact angle (CA) measurements. Preliminary in vitro cytotoxicity experiments were carried out to study biocompability of pristine and modified samples using MTT assay. Attachment and proliferation of MG-63 osteosarcoma cells on polyurethane films before and after radiation grafting was investigated to assess the potential use of this material for biomedical applications. The applied modification resulted in surface changes of poly(ester-urethane). Polyurethane matrix coated by poly(N-isopropylacrylamide), the polymer classified to the group of thermosensitive polymers, exhibited hydrophilic properties in water at 25 °C, while at 35 °C the surface properties change into hydrophobic. Additionally, narrow molecular weight distribution of the grafted chains was obtained, uniformly covering the surface of the matrix. In vitro studies confirmed that the modified matrices are not cytotoxic when degree of NIPAAm grafting is 14% and number-average molecular weight of the grafted chains (Mn) is about 40,000 g/mol.

Background Access to a primary care physician (PCP) improves health outcomes among patients with hypertension. The study objective was to compare PCP use among patients with incident hypertension with and without comorbidities. Methods Hypertensive patients newly diagnosed between April 1, 1998 and March 31, 2009 were identified using Alberta administrative databases. Three comorbidity subgroups were defined: (1) none, (2) vascular risk related, and (3) unrelated. The number of PCP visits was calculated using zero-inflation Poisson regression, with time trends compared using the χ 2 test. A Cox model was used to assess the association between PCP use and clinical outcomes. Results Of 456,263 newly diagnosed hypertensive patients (mean age, 57.6 years; 50.6% men; 62.5% no comorbidity), 88% had seen a PCP in the year before diagnosis, and 94% had seen a PCP in the year after being diagnosed. Compared with before diagnosis, the mean number of PCP visits increased after diagnosis (none, 3.95 vs 6.15; vascular risk related, 6.45 vs 7.99; and unrelated, 6.76 vs 8.24). Over the study period, the frequency of PCP visits before diagnosis was constant, and there was a statistically significant decline in the adjusted mean number of visits after diagnosis. Those with higher PCP use were less likely to die but more likely to be hospitalized regardless of comorbidity. Conclusions The frequency of PCP visits was high before and after diagnosis. Increased PCP use was associated with a lower risk of death; however, it does increase the costs of caring for patients with hypertension. Therefore, future studies are necessary to determine the optimal level required to achieve cost-effective use of PCP resources.

The objective of the study was the estimation of the effect of polycyclic aromatic hydrocarbons (PAH) on the biological properties of soils in the vicinity of biochar production sites. Assays performed in the soils included the content of PAHs, as well as the microbiological (counts of bacteria and fungi), biochemical (enzymatic activity: dehydrogenases, acidic and alkalic phosphatase, protease and urease) and ecotoxicological properties of the soils (phytotoxicity to Lepidium sativum , Microtox®— Vibrio fischeri , MARA—11 different microorganisms, Daphtoxkit F™— Daphnia magna ). In spite of the low level of industrialisation of the area studied, the content of PAHs in the soils was very high. Depending on the soil sampling site, the content of total PAHs varied from 1796.8 to 101,282.7 μg/kg. The highest levels in the soils studied were characteristic of fluoranthene and pyrene. The counts of bacteria and fungi, as well as the enzymatic activity, were clearly related with the sampling sites. In most of the objects studied those parameters had high values, which indicated correct runs of the biological processes in most of the soils studied. Depending on the ecotoxicological assay applied, and on the sampling sites, the toxicity of the soils was varied, but only in a few cases the phytotoxicity was correlated with the content of PAHs.

Smallholder irrigation may considerably contribute to agricultural productivity growth in Sub-Saharan Africa. However, the full potential of expanding smallholder irrigation under alternative irrigation technologies is not known. This paper presents a study to assess the irrigation expansion potential for four smallholder irrigation technologies: motor pumps, treadle pumps, communal river diversion, and small reservoirs. An integrated modeling system that combines GIS data analysis, biophysical and economic predictive modeling, and crop mix optimization techniques was developed for the assessment. The study revealed a large potential for profitable smallholder irrigation expansion in Sub-Sahara Africa. Area expansion potential is 30 million ha for motor pumps, 24 million ha for treadle pumps, 22 million ha for small reservoirs and 20 million ha for communal river diversions. The technologies can benefit between 113 and 369 million rural people in the region generating net revenues of US $ 14–22 billion/yr, depending on technology. Final expansion potential depends on irrigation technology cost and commodity price developments.

Background This population-based study assessed rates of all-cause mortality, myocardial infarction, heart failure, and stroke for up to 12 years of follow-up in 3.5 million Canadian adults newly diagnosed with hypertension. Methods Hypertension cohort, outcomes, and covariates were defined using validated case definitions applied to inpatient and outpatient administrative health databases. Factors associated with each outcome were identified using Cox proportional hazards models. Results Of 3,531,089 adults newly diagnosed with hypertension and without a previous history of cardiovascular disease, 29.4% were younger than 50 years of age; 48.2% were male, and 17.2% resided in a rural area. Over a median follow-up length of 6.1 years, the crude all-cause mortality rate was 22.4 per 1000 person-years. The incidence of hospitalized myocardial infarction (8.4 per 1000 person-years) and hospitalized heart failure (8.5 per 1000 person-years) was higher than stroke (6.9 per 1000 person-years). The incidence rate for any cardiovascular hospitalization was 19.3 per 1000 person-years. Older age, male sex, lower income, rural residence, and a higher number of Charlson comorbidities were each independently associated with a higher risk of mortality and incident cardiovascular disease hospitalizations. Conclusions In a nationally-representative incident cohort of hypertensive adults we have demonstrated higher mortality rates and poorer outcomes for the elderly, males, and those living in rural or low income locations. Innovative approaches to the provision of care for these high-risk individuals will lead to improved patient outcomes.

Chromosome Conformation Capture (3C) technology was used to identify physical interactions between the proximal Wiskott-Aldrich Syndrome protein (WASp) promoter and its distant DNA segments in Jurkat-T cells. We found that two hematopoietic specific DNase I hypersensitive (DHS) sites (proximal DHS-A, and distal DHS-B) which had high interaction frequencies with the proximal WASp promoter indicating potential regulatory activity for these DHS sites. Subsequently, we cloned several DNA fragments around the proximal DHS-A site into a luciferase reporter vector. Interestingly, no fragments showed enhancer activity, but two fragments exhibited strong silencing activity in Jurkat-T cells. After aligning the chromatin state profiling for hematopoietic and nonhematopoietic cells using the human genome browser (UCSC), we found a 5 kb putative hematopoietic specific enhancer region located 250 kb downstream of the WAS gene. This putative enhancer region contains two hematopoietic cell specific DHS sites. Subsequently, the hematopoietic specific DHS sites enhanced luciferase expression from the proximal WASp promoter in all hematopoietic cells we tested. Finally, using a lentiviral vector stable expression system, the hematopoietic specific-enhancer(s) increased GFP reporter gene expression in hematopoietic cells, and increased WASp gene expression in WASp deficient cells. This enhancer may have the potential to be used in gene therapy for hematological diseases.

International audience; Glycolipids of Myrmekioderma sponges contain Myrmekiosides, a new family of glycolipids with a unique structure of mono-O-alkyl-diglycosylglycerols. This report deals with the identification and biological activity of the new Myrmekioside E from Myrmekioderma dendyi. Its structure has been elucidated from spectroscopic data and chemical degradation studies. It contained a glycerol backbone linked to xylose and N-acetylglucosamine, and an alkyl long-chain with a terminal alcohol group. A related glycolipid, Trikentroside, known in the sponge Trikentrion laeve, was subjected to a comparative biological evaluation. Both glycolipids inhibit proliferation of two human non-small cell lung cancer cell lines (NSCLC-N6 and A549).

Nanoparticles (NPs) occurring in the environment rapidly agglomerate and form particles of larger diameters. The extent to which this abates the effects of NPs has not been clarified. The motivation of this study was to examine how the agglomeration/aggregation state of silver (20nm and 200nm) and titanium dioxide (21nm) nanoparticles may affect the kinetics of cellular binding/uptake and ability to induce cytotoxic responses in THP1, HepG2 and A549 cells. Cellular binding/uptake, metabolic activation and cell death were assessed by the SSC flow cytometry measurements, the MTT-test and the propidium iodide assay. The three types of particles were efficiently taken up by the cells, decreasing metabolic activation and increasing cell death in all the cell lines. The magnitude of the studied endpoints depended on the agglomeration/aggregation state of particles, their size, time-point and cell type. Among the three cell lines tested, A549 cells were the most sensitive to these particles in relation to cellular binding/uptake. HepG2 cells showed a tendency to be more sensitive in relation to metabolic activation. THP-1 cells were the most resistant to all three types of particles in relation to all endpoints tested. Our findings suggest that particle features such as size and agglomeration status as well as the type of cells may contribute to nanoparticles biological impact.

Background Heart failure (HF) is a leading morbid cause of hospitalization and death. HF is often accompanied by comorbid conditions, increasing the health care burden. This study describes hospital mortality and identifies comorbid conditions associated with HF. Methods Acute care hospital separations in 2005-2006, with a diagnosis of HF I50, I500, I501, I509 ( The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Canada [ICD-10-CA]) were identified from all Canadian jurisdictions except Quebec. Results A total of 2,457,527 hospital separations among 1,812,923 individuals, identifying 8,212,869 diagnoses were reported. Among those, a total of 33,693 (1.9%) of all hospitalized individuals had a most responsible diagnosis of HF, accounting for 42,399 hospital separations. Further, HF was coded 77,049 times as a comorbid diagnosis, altogether occurring in 4.9% of all hospitalizations. The most common primary diagnoses associated with comorbid HF were acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD), and pneumonia. Seniors had a much higher hospitalization rate due to HF. Hospitalized individuals with a primary diagnosis of HF had an almost 3-fold higher 30-day in-hospital mortality rate and nearly double the mean hospital stay than that for all causes. On average, hospitalizations with a primary diagnosis of HF had 3.9 comorbidities, most commonly chronic ischemic heart disease (IHD), atrial fibrillation and flutter, diabetes, renal failure, etc.; 1.7 times greater for HF than for all causes. Conclusions HF has a high in-hospital mortality rate particularly among the elderly and is associated with many cardiac and noncardiac conditions. HF necessitates long hospital stays, which increases the burden on the health care system in Canada.

In the past 150 years, roughly half of the countries in the world eliminated malaria. Nowadays, there are 99 endemic countries - 67 are controlling malaria and 32 are pursuing an elimination strategy. This four-part Series presents evidence about the technical, operational, and financial dimensions of malaria elimination. The first paper in this Series reviews definitions of elimination and the state that precedes it: controlled low-endemic malaria. Feasibility assessments are described as a crucial step for a country transitioning from controlled low-endemic malaria to elimination. Characteristics of the 32 malaria-eliminating countries are presented, and contrasted with countries that pursued elimination in the past. Challenges and risks of elimination are presented, including Plasmodium vivax, resistance in the parasite and mosquito populations, and potential resurgence if investment and vigilance decrease. The benefits of elimination are outlined, specifically elimination as a regional and global public good. Priorities for the next decade are described. © 2010 Elsevier Ltd.

A high performance liquid chromatography–hybrid tandem mass spectrometry (LC–MS n ) method utilising electrospray ionisation has been developed and implemented for the simultaneous determination of several cardiac glycosides (CGs) as well as their corresponding aglycones formed by and extracted from herbaceous plants of the genus Digitalis . The method has been validated in-house and its performance characteristics (linearity, repeatability, limits of detection, etc.) were assessed for use in the quantification of CGs and their corresponding aglycones. LODs from 38 to 936 pg g −1 in solution, corresponding to mass fraction impurity levels from 0.0009 (or 0.00008%) to 0.019 mg g −1 (or 0.0019%) detectable in the pure materials have been realized. Moreover, the method was used to characterize and to determine the inherent CG impurities in batches of the therapeutic monitored drug digoxin which served as candidate reference material for an organic purity assessment inter-laboratory study (CCQM-P20.f) organised by the BIPM Chemistry Section and carried out within the framework of the Organic Analysis Working Group (OAWG) of the Consultative Committee for Amount of Substance – Metrology in Chemistry (CCQM). Digoxin was selected from materials required for the establishment of reference measurement systems for clinical chemistry and laboratory medicine.

Lentiviral vectors are useful for transducing primitive hematopoietic cells. We examined four envelope proteins for their ability to mediate lentiviral transduction of mobilized human CD34(+) peripheral blood cells. Lentiviral particles encoding green fluorescent protein (GFP) were pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G), the amphotropic (AMPHO) murine leukemia virus envelope protein, the endogenous feline leukemia viral envelope protein or the feline leukemia virus type C envelope protein. Because the relative amount of genome RNA per ml was similar for each pseudotype, we transduced CD34(+) cells with a fixed volume of each vector preparation. Following an overnight transduction, CD34(+) cells were transplanted into immunodeficient mice which were sacrificed 12 weeks later. The average percentages of engrafted human CD45(+) cells in total bone marrow were comparable to that of the control, mock-transduced group (37-45%). Lenti-particles pseudotyped with the VSV-G envelope protein transduced engrafting cells two- to tenfold better than particles pseudotyped with any of the gamma-retroviral envelope proteins. There was no correlation between receptor mRNA levels for the gamma-retroviral vectors and transduction efficiency of primitive hematopoietic cells. These results support the use of the VSV-G envelope protein for the development of lentiviral producer cell lines for manufacture of clinical-grade vector.

The chemical composition and its seasonal variation of the red seaweed Grateloupia turuturu, an invasive macroalgae from Brittany, France, were investigated. Size, ash, protein, lipid, dietary fibre (soluble, insoluble and total), protein pigment (R-phycoerythrin, R-phycocyanin), and fatty acid content were measured in G. turuturu samples collected over 1 year (2006). The average size of this seaweed was 32.0 cm long and approximately 5.0 cm wide, while the size of the thallus was maximal in June (in length and width). On the dry weight basis, this alga was constituted of more than 18% ash, about 23% protein, 2.6% lipids, and approximately 60% dietary fibre. The most abundant fatty acids were palmitic acid and eicosapentaenoic acid (52% and 12% of the fatty acid fraction, respectively). The study of seasonal variations showed that the best period to collect the seaweed for food use is between February and June.

To assess the long-term risk of developing cancer among heart transplant recipients compared to the Canadian general population, we carried out a retrospective cohort study of 1703 patients who received a heart transplant between 1981 and 1998, identified from the Canadian Organ Replacement Register database. Vital status and cancer incidence were determined through record linkage to the Canadian Mortality Database and Canadian Cancer Registry. Cancer incidence rates among heart transplant patients were compared to those of the general population. The observed number of incident cancers was 160 with 58.9 expected in the general population (SIR = 2.7, 95% CI = 2.3, 3.2). The highest ratios were for non-Hodgkin's lymphoma (NHL) (SIR = 22.7, 95% CI = 17.3, 29.3), oral cancer (SIR = 4.3, 95% CI = 2.1, 8.0) and lung cancer (SIR = 2.0, 95% CI = 1.2, 3.0). Compared to the general population, SIRs for NHL were particularly elevated in the first year posttransplant during more recent calendar periods, and among younger patients. Within the heart transplant cohort, overall cancer risks increased with age, and the 15-year cumulative incidence of all cancers was estimated to be 17%. There is an excess of incident cases of cancer among heart transplant recipients. The relative excesses are most marked for NHL, oral and lung cancer.

Information plays a key role in monitoring, management, evaluation and policy development related to cardiovascular diseases. Canada currently lacks a comprehensive, integrated pan-Canadian system to address the growing burden of cardiovascular diseases, including reliable and timely data that can be used by policy-makers, health care providers, researchers and the public. Theme Working Group 1 (one of six Theme Working Groups) aimed to address different aspects of the Canadian Heart Health Strategy and Action Plan, with a focus on strengthening information systems. Members of the group, who are experts in the cardiovascular field and/or information systems, defined the scope of the issue, identified gaps and solutions, and discussed priorities. The process is described and suggestions for final recommendations are presented. These suggestions were made taking into consideration the needs of health care providers, patients and consumers, the needs for planning, innovation, evaluation and system improvement, and the needs for information on populations and environments. A sustained integrated system that meets cardiovascular information needs requires a major commitment of expertise, leadership and funding.

The exceptional ability of marine sponges to adapt to often drastic changes of their environments could be due to special structural features in cell membranes, including firstly phospholipids (PL). Thus, PL class composition was investigated in marine sponges (22 species from 19 genera to 15 families) originating from various locations (East Atlantic, North Atlantic, South-West Pacific, Mediterranean Sea, Red Sea, Arabian-Persian Gulf). The quantitative determination of PL class composition was obtained by high-performance thin-layer chromatography (HPTLC) with scanning densitometry of the different spots. Previous reports have shown phosphatidylethanolamine (PE) as the major PL class in marine sponges, followed by phosphatidylcholine (PC), while other papers described PC as a minor class and even lacking. This survey found PE as the major PL class in only two species, while PC was the major class in 13 species including a calcareous one. The great abundance of bacteria in some sponges was evidenced from the relatively high proportions of particular PL classes. Various PL distributions were observed even for the sponge species collected in the same area and belonging to the same genus. Thus, no clear rule on PL composition in marine sponges can be stated to date.