Comparing impact and cost-effectiveness of primary prevention strategies for lipid-lowering.

BACKGROUND: Lipid-lowering therapy is costly but effective at reducing coronary heart disease (CHD) risk. OBJECTIVE: To assess the cost-effectiveness and public health impact of Adult Treatment Panel III (ATP III) guidelines and compare with a range of risk- and age-based alternative strategies. DESIGN: The CHD Policy Model, a Markov-type cost-effectiveness model. DATA SOURCES: National surveys (1999 to 2004), vital statistics (2000), the Framingham Heart Study (1948 to 2000), other published data, and a direct survey of statin costs (2008). TARGET POPULATION: U.S. population age 35 to 85 years. Time Horizon: 2010 to 2040. PERSPECTIVE: Health care system. INTERVENTION: Lowering of low-density lipoprotein cholesterol with HMG-CoA reductase inhibitors (statins). OUTCOME MEASURE: Incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Full adherence to ATP III primary prevention guidelines would require starting (9.7 million) or intensifying (1.4 million) statin therapy for 11.1 million adults and would prevent 20,000 myocardial infarctions and 10,000 CHD deaths per year at an annual net cost of $3.6 billion ($42,000/QALY) if low-intensity statins cost $2.11 per pill. The ATP III guidelines would be preferred over alternative strategies if society is willing to pay $50,000/QALY and statins cost $1.54 to $2.21 per pill. At higher statin costs, ATP III is not cost-effective; at lower costs, more liberal statin-prescribing strategies would be preferred; and at costs less than $0.10 per pill, treating all persons with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (>130 mg/dL) would yield net cost savings. RESULTS OF SENSITIVITY ANALYSIS: Results are sensitive to the assumptions that LDL cholesterol becomes less important as a risk factor with increasing age and that little disutility results from taking a pill every day. LIMITATION: Randomized trial evidence for statin effectiveness is not available for all subgroups. CONCLUSION: The ATP III guidelines are relatively cost-effective and would have a large public health impact if implemented fully in the United States. Alternate strategies may be preferred, however, depending on the cost of statins and how much society is willing to pay for better health outcomes. FUNDING: Flight Attendants' Medical Research Institute and the Swanson Family Fund. The Framingham Heart Study and Framingham Offspring Study are conducted and supported by the National Heart, Lung, and Blood Institute.

Assessing the quality of alternative energy sources: Energy Return On the Investment (EROI), the metabolic pattern of societies and energy statistics

This paper presents an initial challenge to tackle the every so "tricky" points encountered when dealing with energy accounting, and thereafter illustrates how such a system of accounting can be used when assessing for the metabolic changes in societies. The paper is divided in four main sections. The first three, present a general discussion on the main issues encountered when conducting energy analyses. The last section, subsequently, combines this heuristic approach to the actual formalization of it, in quantitative terms, for the analysis of possible energy scenarios. Section one covers the broader issue of how to account for the relevant categories used when accounting for Joules of energy; emphasizing on the clear distinction between Primary Energy Sources (PES) (which are the physical exploited entities that are used to derive useable energy forms (energy carriers)) and Energy Carriers (EC) (the actual useful energy that is transmitted for the appropriate end uses within a society). Section two sheds light on the concept of Energy Return on Investment (EROI). Here, it is emphasized that, there must already be a certain amount of energy carriers available to be able to extract/exploit Primary Energy Sources to thereafter generate a net supply of energy carriers. It is pointed out that this current trend of intense energy supply has only been possible to the great use and dependence on fossil energy. Section three follows up on the discussion of EROI, indicating that a single numeric indicator such as an output/input ratio is not sufficient in assessing for the performance of energetic systems. Rather an integrated approach that incorporates (i) how big the net supply of Joules of EC can be, given an amount of extracted PES (the external constraints); (ii) how much EC needs to be invested to extract an amount of PES; and (iii) the power level that it takes for both processes to succeed, is underlined. Section four, ultimately, puts the theoretical concepts at play, assessing for how the metabolic performances of societies can be accounted for within this analytical framework.

Small RNAs as regulators of primary and secondary metabolism in Pseudomonas species.

Small RNAs (sRNAs) exert important functions in pseudomonads. Classical sRNAs comprise the 4.5S, 6S, 10Sa and 10Sb RNAs, which are known in enteric bacteria as part of the signal recognition particle, a regulatory component of RNA polymerase, transfer-messenger RNA (tmRNA) and the RNA component of RNase P, respectively. Their homologues in pseudomonads are presumed to have analogous functions. Other sRNAs of pseudomonads generally have little or no sequence similarity with sRNAs of enteric bacteria. Numerous sRNAs repress or activate the translation of target mRNAs by a base-pairing mechanism. Examples of this group in Pseudomonas aeruginosa are the iron-repressible PrrF1 and PrrF2 sRNAs, which repress the translation of genes encoding iron-containing proteins, and PhrS, an anaerobically inducible sRNA, which activates the expression of PqsR, a regulator of the Pseudomonas quinolone signal. Other sRNAs sequester RNA-binding proteins that act as translational repressors. Examples of this group in P. aeruginosa include RsmY and RsmZ, which are central regulatory elements in the GacS/GacA signal transduction pathway, and CrcZ, which is a key regulator in the CbrA/CbrB signal transduction pathway. These pathways largely control the extracellular activities (including virulence traits) and the selection of the energetically most favourable carbon sources, respectively, in pseudomonads.

Reduction of alcohol consumption by brief alcohol intervention in primary care: systematic review and meta-analysis.

BACKGROUND: Numerous trials of the efficacy of brief alcohol intervention have been conducted in various settings among individuals with a wide range of alcohol disorders. Nevertheless, the efficacy of the intervention is likely to be influenced by the context. We evaluated the evidence of efficacy of brief alcohol interventions aimed at reducing long-term alcohol use and related harm in individuals attending primary care facilities but not seeking help for alcohol-related problems. METHODS: We selected randomized trials reporting at least 1 outcome related to alcohol consumption conducted in outpatients who were actively attending primary care centers or seeing providers. Data sources were the Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of retrieved references and previous reviews. Study selection and data abstraction were performed independently and in duplicate. We assessed the validity of the studies and performed a meta-analysis of studies reporting alcohol consumption at 6 or 12 months of follow-up. RESULTS: We examined 19 trials that included 5639 individuals. Seventeen trials reported a measure of alcohol consumption, of which 8 reported a significant effect of intervention. The adjusted intention-to-treat analysis showed a mean pooled difference of -38 g of ethanol (approximately 4 drinks) per week (95% confidence interval, -51 to -24 g/wk) in favor of the brief alcohol intervention group. Evidence of other outcome measures was inconclusive. CONCLUSION: Focusing on patients in primary care, our systematic review and meta-analysis indicated that brief alcohol intervention is effective in reducing alcohol consumption at 6 and 12 months.

Dengue-2 infection and the induction of apoptosis in human primary monocytes

Monocytes/macrophages are important targets for dengue virus (DENV) replication; they induce inflammatory mediators and are sources of viral dissemination in the initial phase of the disease. Apoptosis is an active process of cellular destruction genetically regulated, in which a complex enzymatic pathway is activated and may be trigged by many viral infections. Since the mechanisms of apoptotic induction in DENV-infected target cells are not yet defined, we investigated the virus-cell interaction using a model of primary human monocyte infection with DENV-2 with the aim of identifying apoptotic markers. Cultures analyzed by flow cytometry and confocal microscopy yielded DENV antigen positive cells with rates that peaked at the second day post infection (p.i.), decayed afterwards and produced the apoptosis-related cytokines TNF-α and IL-10. Phosphatidylserine, an early marker for apoptosis, was increased at the cell surface and the Fas death receptor was upregulated at the second day p.i. at significantly higher rates in DENV infected cell cultures than controls. However, no detectable changes were observed in the expression of the anti-apoptotic protein Bcl-2 in infected cultures. Our data support virus modulation of extrinsic apoptotic factors in the in vitro model of human monocyte DENV-2 infection. DENV may be interfering in activation and death mechanisms by inducing apoptosis in target cells.

Auditory-visual multisensory interactions in humans: timing, topography, directionality, and sources.

Current models of brain organization include multisensory interactions at early processing stages and within low-level, including primary, cortices. Embracing this model with regard to auditory-visual (AV) interactions in humans remains problematic. Controversy surrounds the application of an additive model to the analysis of event-related potentials (ERPs), and conventional ERP analysis methods have yielded discordant latencies of effects and permitted limited neurophysiologic interpretability. While hemodynamic imaging and transcranial magnetic stimulation studies provide general support for the above model, the precise timing, superadditive/subadditive directionality, topographic stability, and sources remain unresolved. We recorded ERPs in humans to attended, but task-irrelevant stimuli that did not require an overt motor response, thereby circumventing paradigmatic caveats. We applied novel ERP signal analysis methods to provide details concerning the likely bases of AV interactions. First, nonlinear interactions occur at 60-95 ms after stimulus and are the consequence of topographic, rather than pure strength, modulations in the ERP. AV stimuli engage distinct configurations of intracranial generators, rather than simply modulating the amplitude of unisensory responses. Second, source estimations (and statistical analyses thereof) identified primary visual, primary auditory, and posterior superior temporal regions as mediating these effects. Finally, scalar values of current densities in all of these regions exhibited functionally coupled, subadditive nonlinear effects, a pattern increasingly consistent with the mounting evidence in nonhuman primates. In these ways, we demonstrate how neurophysiologic bases of multisensory interactions can be noninvasively identified in humans, allowing for a synthesis across imaging methods on the one hand and species on the other.

Primary activity measurements with a 4πβ-4πγ coincidence counting system.

The radioactive concentrations of (166m)Ho, (134)Cs and (133)Ba solutions have been standardised using a 4πβ-4πγ coincidence counting system we have recently set up. The detection in the beta channel is performed using various geometries of a UPS-89 plastic scintillator optically coupled to a selected low-noise 1in. diameter photomultiplier tube. The light-tight thin capsule that encloses this beta detector is housed within the well of a 5in.×5in. NaI(Tl) monocrystal detector. The beta detection efficiency can be varied either by optical filtering or electronic discrimination when the electrons loose all their energy in the plastic scintillator. This 4πβ-4πγ coincidence system improves on our 4πβ(PC)-γ system in that its sample preparation is less labour intensive, it yields larger beta- and gamma-counting efficiencies thus enabling the standardisation of low activity sources with good statistics in reasonable time, and it makes standardising short-lived radionuclides easier. The resulting radioactive concentrations of (166m)Ho, (134)Cs and (133)Ba are found to agree with those measured with other primary measurement methods thus validating our 4πβ-4πγ coincidence counting system.

Structural characterization of rockfall sources in Yosemite Valley from remote sensing data and field surveys

Yosemite Valley poses significant rockfall hazard and related risk due to its glacially steepened walls and approximately 4 million visitors annually. To assess rockfall hazard, it is necessary to evaluate the geologic structure that contributes to the destabilization of rockfall sources and locate the most probable future source areas. Coupling new remote sensing techniques (Terrestrial Laser Scanning, Aerial Laser Scanning) and traditional field surveys, we investigated the regional geologic and structural setting, the orientation of the primary discontinuity sets for large areas of Yosemite Valley, and the specific discontinuity sets present at active rockfall sources. This information, combined with better understanding of the geologic processes that contribute to the progressive destabilization and triggering of granitic rock slabs, contributes to a more accurate rockfall susceptibility assessment for Yosemite Valley and elsewhere.

Role of complementary therapies in the understanding of primary healthcare professionals: a systematic review

Objective To identify the understanding of the healthcare professionals in relation to the role of complementary therapies in primary health care. Method Systematic review by way of the following information sources: PubMed, CINAHL, PeriEnf, AMED, EMBASE, Web of Science, Psicoinfo and Psicodoc, using the keyword Primary Health Care alone, and associated with the following keywords: Medicinal Plants, Herbal Medicine, Homeopathy, Traditional Chinese Medicine, Acupuncture, Anthroposophical Medicine. Results Twenty-two studies from 1986 to 2011 were included. We identified three styles of practice: conventional medicine, complementary therapies and integrative medicine. Positioning professional practices within these three styles may facilitate discussion of concepts of health care, enhancing the health care provided as a result. Conclusion The work process in primary care presents difficulties for conducting integrative and holistic health care, but this practice has been introduced over time by professionals who integrate conventional medicine and complementary therapies, concerned with the care and well-being of patients.


Geochemistry and stable isotope composition of fresh alkaline porphyry copper tailings: Implications on sources and mobility of elements during transport and early stages of deposition

Prevention of acid mine drainage (AMD) in sulfide-containing tailings requires the identification of the geochemical processes and element pathways in the early stages of tailing deposition. However, analyses of recently deposited tailings in active tailings impoundments are scarce because mineralogical changes occur near the detection limits of many assays. This study shows that a detailed geochemical study which includes stable isotopes of water (delta H-2, delta O-18), dissolved sulfates (delta S-34, delta O-18) and hydrochernical parameter (pH, Eh, DOC, major and trace elements) from tailings samples taken at different depths in rainy and dry seasons allows the understanding of weathering (oxidation, dissolution, sorption, and desorption), water and element pathways, and mixing processes in active tailings impoundments. Fresh alkaline tailings (pH 9.2-10.2) from the Cu-Mo porphyry deposit in El Teniente, Chile had low carbonate (0.8-1.1 Wt-% CaCO3 equivalent) and sulfide concentrations (0.8-1.3 wt.%, mainly as pyrite). In the alkaline tailings water, Mo and Cu (up to 3.9 mg/L Mo and 0.016 mg/L Cu) were mobile as MoO42- and Cu (OH)(2)(0). During the flotation, tailings water reached equilibrium with gypsum (up to 738 mg/L Ca and 1765 mg/ L SO4). The delta S-34 VS. delta O-18 covariations of dissolved sulfate (2.3 to 4.5% delta S-34 and 4.1 to 6.0 % delta O-18) revealed the sulfate sources: the dissolution of primary sulfates (12.0 to 13.2%. delta S-34, 7.4 to 10.9%.delta O-18) and oxidation of primary sulfides (-6.7 to 1.7%. delta S-34). Sedimented tailings in the tailings impoundment can be divided into three layers with different water sources, element pathways, and geochemical processes. The deeper sediments (> 1 m depth) were infiltrated by catchment water, which partly replaced the original tailings water, especially during the winter season. This may have resulted in the change from alkaline to near-neutral pH and towards lower concentrations of most dissolved elements. The neutral pH and high DOC (up to 99.4 mg/L C) of the catchment water mobilized Cu (up to 0.25 mg/L) due to formation of organic Cu complexes; and Zn (up to 130 mg/L) due to dissolution of Zn oxides and desorption). At I m depth, tailings pore water obtained during the winter season was chemically and isotopically similar to fresh tailings water (pH 9.8-10.6, 26.7-35.5 mg/L Cl, 2.3-6.0 mg/L Mo). During the summer, a vadose zone evolved locally and temporarily up to 1.2 m depth. resulting in a higher concentration of dissolved solids in the pore water due to evaporation. During periodical new deposition of fresh tailings, the geochemistry of the surface layer was geochemically similar to fresh tailings. In periods without deposition, sulfide oxidation was suggested by decreasing pH (7.7-9.5), enrichment of MoO42- and SO42-, and changes in the isotopic composition of dissolved sulfates. Further enrichment for Na, K, Cl, SO4, Mg, Cu, and Mo (up to 23.8 mg/L Mo) resulted from capillary transport towards the surface followed by evaporation and the precipitation of highly soluble efflorescent salts (e.g., mirabilite, syngenite) at the tailing surface during summer. (C) 2008 Elsevier B.V. All rights reserved.

Low density polyethylene (LDPE) passive samplers for the investigation of polychlorinated biphenyl (PCB) point sources in rivers

This study aims to provide a passive sampling approach which can be routinely used to investigate polychlorinated biphenyl (PCB) sources in rivers. The approach consists of deploying low density polyethylene (LDPE) strips downstream and upstream of potential PCB sources as well as in their water discharges. Concentrations of indicator PCBs (iPCBs) absorbed in samplers (Cs) from upstream and downstream sites are compared with each other to reveal increases of PCB levels. Cs measured in water discharges are used to determine if released amounts of PCBs are compatible with increases revealed in the river. As water velocity can greatly vary along a river stretch and influences the uptake at each site in a different way, differences in velocity have to be taken into account to correctly interpret Cs. LDPE strips were exposed to velocities between 1.6 and 37 cm s−1 using a channel system built in the field. Relationships between velocity and Cs were established for each iPCB to determine the expected change in Cs due to velocity variations. For PCBs 28 and 52, this change does not exceed a factor 2 for velocity variations in the range from 1.6 to 100 cm s−1 (extrapolated data above 37 cm s−1). For PCBs 101, 138, 153 and 180, this change only exceeds a factor 2 in the case of large velocity variations. The approach was applied in the Swiss river Venoge to first conduct a primary investigation of potential PCB sources and then conduct thorough investigations of two suspected sources.

Microquasars as high energy gamma-ray sources

Galactic microquasars are certainly one of the most recent additions to the field of high energy astrophysics and have attracted increasing interest over the last decade. However, the high energy part of the spectrum of microquasars is the most poorly known, mainly due the lack of sensitive instrumentation in the past. Microquasars are now primary targets for all of the observatories working in the X-ray and gamma-ray domains. They also appear as the possible counterparts for some of the unidentified sources of high-energy gamma-rays detected by the experiment EGRET on board the satellite COMPTON-GRO. This paper provides a general review of the main observational results obtained up to now as well as a summary of the scenarios for production of high-energy gamma-rays at the present moment.

Radio detections towards unidentified variable EGRET sources

A considerable fraction of the -ray sources discovered with the Energetic Gamma-Ray Experiment Telescope (EGRET) remain unidentified. The EGRET sources that have been properly identified are either pulsars or variable sources at both radio and gamma-ray wavelengths. Most of the variable sources are strong radio blazars. However, some low galactic-latitude EGRET sources, with highly variable -ray emission, lack any evident counterpart according to the radio data available until now. Aims. The primary goal of this paper is to identify and characterise the potential radio counterparts of four highly variable -ray sources in the galactic plane through mapping the radio surroundings of the EGRET confidence contours and determining the variable radio sources in the field whenever possible. Methods. We have carried out a radio exploration of the fields of the selected EGRET sources using the Giant Metrewave Radio Telescope (GMRT) interferometer at 21 cm wavelength, with pointings being separated by months. Results. We detected a total of 151 radio sources. Among them, we identified a few radio sources whose flux density has apparently changed on timescales of months. Despite the limitations of our search, their possible variability makes these objects a top-priority target for multiwavelength studies of the potential counterparts of highly variable, unidentified gamma-ray sources.

Short and long-term effects of tillage systems and nutrient sources on soil physical properties of a Southern Brazilian Hapludox

Soil tillage promotes changes in soil structure. The magnitude of the changes varies with the nature of the soil, tillage system and soil water content and decreases over time after tillage. The objective of this study was to evaluate short-term (one year period) and long-term (nine year period) effects of soil tillage and nutrient sources on some physical properties of a very clayey Hapludox. Five tillage systems were evaluated: no-till (NT), chisel plow + one secondary disking (CP), primary + two (secondary) diskings (CT), CT with burning of crop residues (CTb), and CT with removal of crop residues from the field (CTr), in combination with five nutrient sources: control without nutrient application (C); mineral fertilizers, according to technical recommendations for each crop (MF); 5 Mg ha-1 yr-1 of poultry litter (wetmatter) (PL); 60 m³ ha-1 yr-1 of cattle slurry (CS) and; 40 m³ ha-1 yr-1 of swine slurry (SS). Bulk density (BD), total porosity (TP), and parameters related to the water retention curve (macroporosity, mesoporosity and microporosity) were determined after nine years and at five sampling dates during the tenth year of the experiment. Soil physical properties were tillage and time-dependent. Tilled treatments increased total porosity and macroporosity, and reduced bulk density in the surface layer (0.00-0.05 m), but this effect decreased over time after tillage operations due to natural soil reconsolidation, since no external stress was applied in this period. Changes in pore size distribution were more pronounced in larger and medium pore diameter classes. The bulk density was greatest in intermediate layers in all tillage treatments (0.05-0.10 and 0.12-0.17 m) and decreased down to the deepest layer (0.27-0.32 m), indicating a more compacted layer around 0.05-0.20 m. Nutrient sources did not significantly affect soil physical and hydraulic properties studied.

Aggregate stability as affected by short and long-term tillage systems and nutrient sources of a hapludox in southern Brazil

The ability of a soil to keep its structure under the erosive action of water is usually high in natural conditions and decreases under frequent and intensive cultivation. The effect of five tillage systems (NT = no-till; CP = chisel plowing and one secondary disking; CT = primary and two secondary distings; CTb = CT with crop residue burning; and CTr = CT with removal of crop residues from the field), combined with five nutrient sources (C = control, no nutrient application; MF = mineral fertilizers according to technical recommendations for each crop; PL = 5 Mg ha-1 y-1 fresh matter of poultry litter; CM = 60 m³ ha-1 y-1 slurry cattle manure; and SM = 40 m³ ha-1 y-1 slurry swine manure) on wet-aggregate stability was determined after nine years (four sampled soil layers) and on five sampling dates in the 10th year (two sampled soil layers) of the experiment. The size distribution of the air-dried aggregates was strongly affected by soil bulk density, and greater values of geometric mean diameter (GMD AD) found in some soil tillage or layer may be partly due to the higher compaction degree. After nine years, the GMD AD on the surface was greater in NT and CP compared to conventional tillage systems (CT, CTb and CTr), due to the higher organic matter content, as well as less soil mobilization. Aggregate stability in water, on the other hand, was affected by the low variation in previous gravimetric moisture of aggregates, which contributed to a high coefficient of variation of this attribute. The geometric mean diameter of water-stable aggregates (GMD WS) was highest in the 0.00-0.05 m layer in the NT system, in the layers 0.05-0.10 and 0.12-0.17 m in the CT, and values were intermediate in CP. The stability index (SI) in the surface layers was greater in treatments where crop residues were kept in the field (NT, CP and CT), which is associated with soil organic matter content. No differences were found in the layer 0.27-0.32 m. The effect of nutrient sources on GMD AD and GMD WS was small and did not affect SI.