Rapid diagnostic tests for the home-based management of malaria, in a high-transmission area

Rapid diagnostic tests (RDT) are sometimes recommended to improve the home-based management of malaria. The accuracy of an RDT for the detection of clinical malaria and the presence of malarial parasites has recently been evaluated in a high-transmission area of southern Mali. During the same study, the cost-effectiveness of a 'test-and-treat' strategy for the home-based management of malaria (based on an artemisinin-combination therapy) was compared with that of a 'treat-all' strategy. Overall, 301 patients, of all ages, each of whom had been considered a presumptive case of uncomplicated malaria by a village healthworker, were checked with a commercial RDT (Paracheck-Pf). The sensitivity, specificity, and positive and negative predictive values of this test, compared with the results of microscopy and two different definitions of clinical malaria, were then determined. The RDT was found to be 82.9% sensitive (with a 95% confidence interval of 78.0%-87.1%) and 78.9% (63.9%-89.7%) specific compared with the detection of parasites by microscopy. In the detection of clinical malaria, it was 95.2% (91.3%-97.6%) sensitive and 57.4% (48.2%-66.2%) specific compared with a general practitioner's diagnosis of the disease, and 100.0% (94.5%-100.0%) sensitive but only 30.2% (24.8%-36.2%) specific when compared against the fulfillment of the World Health Organization's (2003) research criteria for uncomplicated malaria. Among children aged 0-5 years, the cost of the 'test-and-treat' strategy, per episode, was about twice that of the 'treat-all' (U.S.$1.0. v. U.S.$0.5). In older subjects, however, the two strategies were equally costly (approximately U.S.$2/episode). In conclusion, for children aged 0-5 years in a high-transmission area of sub-Saharan Africa, use of the RDT was not cost-effective compared with the presumptive treatment of malaria with an ACT. In older patients, use of the RDT did not reduce costs. The question remains whether either of the strategies investigated can be made affordable for the affected population.

Clinical outcomes of patients with low-flow, low-gradient, severe aortic stenosis and either preserved or reduced ejection fraction undergoing transcatheter aortic valve implantation

AIMS Our aim was to evaluate the invasive haemodynamic indices of high-risk symptomatic patients presenting with 'paradoxical' low-flow, low-gradient, severe aortic stenosis (AS) (PLF-LG) and low-flow, low-gradient severe AS (LEF-LG) and to compare clinical outcomes following transcatheter aortic valve implantation (TAVI) among these challenging AS subgroups. METHODS AND RESULTS Of 534 symptomatic patients undergoing TAVI, 385 had a full pre-procedural right and left heart catheterization. A total of 208 patients had high-gradient severe AS [HGAS; mean gradient (MG) ≥40 mmHg], 85 had PLF-LG [MG ≤ 40 mmHg, indexed aortic valve area [iAVA] ≤0.6 cm(2) m(-2), stroke volume index ≤35 mL/m(2), ejection fraction (EF) ≥50%], and 61 had LEF-LG (MG ≤ 40 mmHg, iAVA ≤0.6 cm(2) m(-2), EF ≤40%). Compared with HGAS, PLF-LG and LEF-LG had higher systemic vascular resistances (HGAS: 1912 ± 654 vs. PLF-LG 2006 ± 586 vs. LEF-LG 2216 ± 765 dyne s m(-5), P = 0.007) but lower valvulo-arterial impedances (HGAS: 7.8 ± 2.7 vs. PLF-LG 6.9 ± 1.9 vs. LEF-LG 7.7 ± 2.5 mmHg mL(-1) m(-2), P = 0.027). At 30 days, no differences in cardiac death (6.5 vs. 4.9 vs. 6.6%, P = 0.90) or death (8.4 vs. 6.1 vs. 6.6%, P = 0.88) were observed among HGAS, PLF-LG, and LEF-LG groups, respectively. At 1 year, New York Heart Association functional improvement occurred in most surviving patients (HGAS: 69.2% vs. PLF-LG 71.7% vs. LEF-LG 89.3%, P = 0.09) and no significant differences in overall mortality were observed (17.6 vs. 20.5 vs. 24.5%, P = 0.67). Compared with HGAS, LEF-LG had a higher 1 year cardiac mortality (adjusted hazard ratio 2.45, 95% confidence interval 1.04-5.75, P = 0.04). CONCLUSION TAVI in PLF-LG or LEF-LG patients is associated with overall mortality rates comparable with HGAS patients and all groups profit symptomatically to a similar extent.

Flow-R, a model for susceptibility mapping of debris flows and other gravitational hazards at a regional scale

The development of susceptibility maps for debris flows is of primary importance due to population pressure in hazardous zones. However, hazard assessment by process-based modelling at a regional scale is difficult due to the complex nature of the phenomenon, the variability of local controlling factors, and the uncertainty in modelling parameters. A regional assessment must consider a simplified approach that is not highly parameter dependant and that can provide zonation with minimum data requirements. A distributed empirical model has thus been developed for regional susceptibility assessments using essentially a digital elevation model (DEM). The model is called Flow-R for Flow path assessment of gravitational hazards at a Regional scale (available free of charge under http://www.flow-r.org) and has been successfully applied to different case studies in various countries with variable data quality. It provides a substantial basis for a preliminary susceptibility assessment at a regional scale. The model was also found relevant to assess other natural hazards such as rockfall, snow avalanches and floods. The model allows for automatic source area delineation, given user criteria, and for the assessment of the propagation extent based on various spreading algorithms and simple frictional laws. We developed a new spreading algorithm, an improved version of Holmgren's direction algorithm, that is less sensitive to small variations of the DEM and that is avoiding over-channelization, and so produces more realistic extents. The choices of the datasets and the algorithms are open to the user, which makes it compliant for various applications and dataset availability. Amongst the possible datasets, the DEM is the only one that is really needed for both the source area delineation and the propagation assessment; its quality is of major importance for the results accuracy. We consider a 10 m DEM resolution as a good compromise between processing time and quality of results. However, valuable results have still been obtained on the basis of lower quality DEMs with 25 m resolution.

Assessing the effectiveness of a long-standing rocky intertidal protected area and its contribution to the regional conservation of species, habitats and assemblages

1. The acceptance of reserves as a useful management strategy relies on evidence of their effectiveness in preserving stocks of harvested species and conserving biodiversity. A history of ad hoc decisions in terrestrial and marine protected area planning has meant that many of these areas are contributing inefficiently to conservation goals. The conservation value of existing protected areas should be assessed when planning the placement of additional areas in a reserve network. 2. This study tested (1) the effectiveness of protection for intertidal molluscs of a marine reserve (Bouddi Marine Extension, NSW, Australia) established in 1971, and (2) the contribution of the protected area to the conservation of regional species, assemblages, and habitats. 3. The shell length and population density of one harvested (Cellana tramoserica), and three non-harvested species (Bembicium nanum, Morula marginalba, Nerita atramentosa) of intertidal molluscs were examined in the protected area and two reference locations over two seasons. 4. The heavily collected limpet C. tramoserica was significantly larger in the protected area and was the only species to exhibit a significant difference. No species significantly differed in population density between the protected area and reference locations. 5. Temporally replicated surveys of macro-molluscs at 21 locations over 75km of coastline identified that the existing protected area included 50% of species, two of five assemblage types and 19 of 20 intertidal rocky shore habitats surveyed in the study region. Reservation of a further three rocky reefs would protect a large proportion of species (71%), a representative of each assemblage and all habitat types. 6. Despite originally being selected in the absence of information on regional biodiversity, the protected area is today an effective starting point for expansion to a regional network of intertidal protected areas.

Effect of pressure-controlled intermittent coronary sinus occlusion (PICSO) on myocardial ischaemia and reperfusion in a closed-chest porcine model

AIMS To investigate a pressure-controlled intermittent coronary sinus occlusion (PICSO) system in an ischaemia/reperfusion model. METHODS AND RESULTS We randomly assigned 18 pigs subjected to 60 minutes ischaemia by left anterior descending (LAD) coronary artery balloon occlusion to PICSO (n=12, groups A and B) or to controls (n=6, group C). PICSO started 10 minutes before (group A), or 10 minutes after (group B) reperfusion and was maintained for 180 minutes. A continuous drop of distal LAD pressure was observed in group C. At 180 minutes of reperfusion, LAD diastolic pressure was significantly lower in group C compared to groups A and B (p=0.02). LAD mean pressure was significantly less than the systemic arterial mean pressure in group C (p=0.02), and the diastolic flow slope was flat, compared to groups A and B (p=0.03). IgG and IgM antibody deposition was significantly higher in ischaemic compared to non-ischaemic tissue in group C (p<0.05). Significantly more haemorrhagic lesions were seen in the ischaemic myocardium of group C, compared to groups A and B (p=0.002). The necrotic area differed non-significantly among groups. CONCLUSIONS PICSO was safe and effective in improving coronary perfusion pressure and reducing antibody deposition consistent with reduced microvascular obstruction and ischaemia/reperfusion injury.

Botulinum toxin A and B raise blood flow and increase survival of critically ischemic skin flaps

BACKGROUND Botulinum toxin (BTX) A and B are commonly used for aesthetic indications and in neuromuscular disorders. New concepts seek to prove efficacy of BTX for critical tissue perfusion. Our aim was to evaluate BTX A and B in a mouse model of critical flap ischemia for preoperative and intraoperative application. METHODS BTX A and B were applied on the vascular pedicle of an axial pattern flap in mice preoperatively or intraoperatively. Blood flow, tissue oxygenation, tissue metabolism, flap necrosis rate, apoptosis assay, and RhoA and eNOS expression were endpoints. RESULTS Blood-flow measurements 1 d after the flap operation revealed a significant reduction to 53% in the control group, while flow was maintained or increased in all BTX groups (103%-129%). Over 5 d all BTX groups showed significant increase in blood flow to 166-187% (P < 0.01). Microdialysis revealed an increase of glucose and reduced lactate/pyruvate ratio and glycerol levels in the flap tissue of all BTX groups. This resulted in significantly improved tissue survival in all BTX groups compared with the control group (62% ± 10%; all P < 0.01): BTX A preconditioning (84% ± 5%), BTX A application intraoperatively (88% ± 4%), BTX B preconditioning (91% ± 4%), and intraoperative BTX B treatment (92% ± 5%). This was confirmed by TUNEL assay. Immunofluorescence demonstrated RhoA and eNOS expression in BTX groups. All BTX applications were similarly effective, despite pharmacologic dissimilarities and different timing. CONCLUSIONS In conclusion, we were able to show on a vascular, tissue, cell, and molecular level that BTX injection to the feeding arteries supports flap survival through ameliorated blood flow and oxygen delivery.

Flux and resident injection in gaseous advection experiments

The occurrence of gaseous pollutants in soils has stimulated many experimental activities, including forced ventilation in the field as well as laboratory transport experiments with gases. The dispersion coefficient in advective-dispersive gas phase transport is often dominated by molecular diffusion, which leads to a large overall dispersivity gamma. Under such conditions it is important to distinguish between flux and resident modes of solute injection and detection. The influence of the inlet type oil the macroscopic injection mode was tested in two series of column experiments with gases at different mean flow velocities nu. First we compared infinite resident and flux injections, and second, semi-infinite resident and flux injections. It is shown that the macroscopically apparent injection condition depends on the geometry of the inlet section. A reduction of the cross-sectional area of the inlet relative to that of the column is very effective in excluding the diffusive solute input, thus allowing us to use the solutions for a flux Injection also at rather low mean flow velocities nu. If the whole cross section of a column is exposed to a large reservoir like that of ambient air, a semi-infinite resident injection is established, which can be distinguished from a flux injection even at relatively high velocities nu, depending on the mechanical dispersivity of the porous medium.

Combined effect of heterogeneity, anisotropy and saturation on steady state flow and transport: Structure recognition and numerical simulation

1 Natural soil profiles may be interpreted as an arrangement of parts which are characterized by properties like hydraulic conductivity and water retention function. These parts form a complicated structure. Characterizing the soil structure is fundamental in subsurface hydrology because it has a crucial influence on flow and transport and defines the patterns of many ecological processes. We applied an image analysis method for recognition and classification of visual soil attributes in order to model flow and transport through a man-made soil profile. Modeled and measured saturation-dependent effective parameters were compared. We found that characterizing and describing conductivity patterns in soils with sharp conductivity contrasts is feasible. Differently, solving flow and transport on the basis of these conductivity maps is difficult and, in general, requires special care for representation of small-scale processes.

Combined effects of heterogeneity, anisotropy, and saturation on steady state flow and transport: A laboratory sand tank experiment

Field soils show rather different spreading behavior at different water saturations, frequently caused by layering of the soil material. We performed tracer experiments in a laboratory sand tank. Such experiments complement and help comprehension of field investigations. We estimated, by image analysis, the first two moments of small plumes traveling through a two-dimensional, heterogeneous medium with strongly anisotropic correlation structure. Three steady state regimes were analyzed. Two main conclusions were drawn. First, low saturation led to very large heterogeneity and to strong preferential flow. Thus the description of the flow paths and the prediction of the solute arrival times require, in this case, more accurate knowledge about the topological structure. Second, saturation-dependent macroscopic anisotropy is an essential element of transport in unsaturated media. For this reason, small structural soil features should be properly upscaled to give appropriate effective soil parameters to be input in transport models.

Analysis of Pressure Head-Flow Loops of Pulsatile Rotodynamic Blood Pumps

The clinical importance of pulsatility is a recurring topic of debate in mechanical circulatory support. Lack of pulsatility has been identified as a possible factor responsible for adverse events and has also demonstrated a role in myocardial perfusion and cardiac recovery. A commonly used method for restoring pulsatility with rotodynamic blood pumps (RBPs) is to modulate the speed profile, synchronized to the cardiac cycle. This introduces additional parameters that influence the (un)loading of the heart, including the timing (phase shift) between the native cardiac cycle and the pump pulses, and the amplitude of speed modulation. In this study, the impact of these parameters upon the heart-RBP interaction was examined in terms of the pressure head-flow (HQ) diagram. The measurements were conducted using a rotodynamic Deltastream DP2 pump in a validated hybrid mock circulation with baroreflex function. The pump was operated with a sinusoidal speed profile, synchronized to the native cardiac cycle. The simulated ventriculo-aortic cannulation showed that the level of (un)loading and the shape of the HQ loops strongly depend on the phase shift. The HQ loops displayed characteristic shapes depending on the phase shift. Increased contribution of native contraction (increased ventricular stroke work [WS ]) resulted in a broadening of the loops. It was found that the previously described linear relationship between WS and the area of the HQ loop for constant pump speeds becomes a family of linear relationships, whose slope depends on the phase shift.

Interhemispheric cerebral blood flow balance during recovery of motor hand function after ischemic stroke - a longitudinal MRI study using arterial spin labeling perfusion

BACKGROUND Unilateral ischemic stroke disrupts the well balanced interactions within bilateral cortical networks. Restitution of interhemispheric balance is thought to contribute to post-stroke recovery. Longitudinal measurements of cerebral blood flow (CBF) changes might act as surrogate marker for this process. OBJECTIVE To quantify longitudinal CBF changes using arterial spin labeling MRI (ASL) and interhemispheric balance within the cortical sensorimotor network and to assess their relationship with motor hand function recovery. METHODS Longitudinal CBF data were acquired in 23 patients at 3 and 9 months after cortical sensorimotor stroke and in 20 healthy controls using pulsed ASL. Recovery of grip force and manual dexterity was assessed with tasks requiring power and precision grips. Voxel-based analysis was performed to identify areas of significant CBF change. Region-of-interest analyses were used to quantify the interhemispheric balance across nodes of the cortical sensorimotor network. RESULTS Dexterity was more affected, and recovered at a slower pace than grip force. In patients with successful recovery of dexterous hand function, CBF decreased over time in the contralesional supplementary motor area, paralimbic anterior cingulate cortex and superior precuneus, and interhemispheric balance returned to healthy control levels. In contrast, patients with poor recovery presented with sustained hypoperfusion in the sensorimotor cortices encompassing the ischemic tissue, and CBF remained lateralized to the contralesional hemisphere. CONCLUSIONS Sustained perfusion imbalance within the cortical sensorimotor network, as measured with task-unrelated ASL, is associated with poor recovery of dexterous hand function after stroke. CBF at rest might be used to monitor recovery and gain prognostic information.

Assessment of low-flow, low-gradient, severe aortic stenosis: an invasive evaluation is required for decision making.

Low-flow, low-gradient severe aortic stenosis (AS) is characterised by a small aortic valve area (AVA) and low mean gradient (MG) secondary to a low cardiac output and may occur in patients with either a preserved or reduced left ventricular ejection fraction (LVEF). Symptomatic patients presenting with low-flow, low-gradient severe AS have a dismal prognosis independent of baseline LVEF if managed conservatively and should therefore undergo aortic valve replacement if feasible. Transthoracic echocardiography (TTE) is the first-line investigation for the assessment of AS haemodynamic severity. However, when confronted with guideline-discordant AVA (small) and MG (low) values, there are several reasons other than severe AS combined with a low cardiac output which may lead to such a situation, including erroneous measurements, small body size, inherent inconsistencies in the guidelines' criteria, prolonged ejection time and aortic pseudostenosis. The distinction between these various entities poses a diagnostic challenge. However, it is important to make a distinction because each has very different implications in terms of risk stratification and therapeutic management. In such instances, cardiac catheterisation forms an integral part of the work-up of these patients in order to confirm or refute the echocardiographic findings to guide management decisions appropriately.

A high-resolution map of direct and indirect connectivity of erosion risk areas to surface waters in Switzerland: A risk assessment tool for planning and policy-making

Off-site effects of soil erosion are becoming increasingly important, particularly the pollution of surface waters. In order to develop environmentally efficient and cost effective mitigation options it is essential to identify areas that bear both a high erosion risk and high connectivity to surface waters. This paper introduces a simple risk assessment tool that allows the delineation of potential critical source areas (CSA) of sediment input into surface waters concerning the agricultural areas of Switzerland. The basis are the erosion risk map with a 2 m resolution (ERM2) and the drainage network, which is extended by drained roads, farm tracks, and slope depressions. The probability of hydrological and sedimentological connectivity is assessed by combining soil erosion risk and extended drainage network with flow distance calculation. A GIS-environment with multiple-flow accumulation algorithms is used for routing runoff generation and flow pathways. The result is a high resolution connectivity map of the agricultural area of Switzerland (888,050 ha). Fifty-five percent of the computed agricultural area is potentially connected with surface waters, 45% is not connected. Surprisingly, the larger part of 34% (62% of the connected area) is indirectly connected with surface waters through drained roads, and only 21% are directly connected. The reason is the topographic complexity and patchiness of the landscape due to a dense road and drainage network. A total of 24% of the connected area and 13% of the computed agricultural area, respectively, are rated with a high connectivity probability. On these CSA an adapted land use is recommended, supported by vegetated buffer strips preventing sediment load. Even areas that are far away from open water bodies can be indirectly connected and need to be included in planning of mitigation measures. Thus, the connectivity map presented is an important decision-making tool for policy-makers and extension services. The map is published on the web and thus available for application.

Gene flow and the maintenance of species boundaries

Hybrid zones are regions where individuals from genetically differentiated populations meet and mate, resulting in at least some offspring of mixed ancestry. Patterns of gene flow (introgression) in hybrid zones vary across the genome, allowing assessment of the role of individual genes or genome regions in reproductive isolation. Here, we document patterns of introgression between two recently diverged species of field crickets. We sampled at a very fine spatial scale and genotyped crickets for 110 highly differentiated single nucleotide polymorphisms (SNPs) identified through transcriptome scans. Using both genomic and geographic cline analysis, we document remarkably abrupt transitions (<100 m) in allele frequencies for 50 loci, despite high levels of gene flow at other loci. These are among the steepest clines documented for any hybridizing taxa. Furthermore, the cricket hybrid zone provides one of the clearest examples of the semi-permeability of species boundaries. Comparisons between data from the fine-scale transect and data (for the same set of markers) from sampling a much larger area in a different region of the cricket hybrid zone reveal consistent patterns of introgression for individual loci. The consistency in patterns of introgression between these two distant and distinct regions of the hybrid zone suggests that strong selection is acting to maintain abrupt discontinuities within the hybrid zone and that genomic regions with restricted introgression likely include genes that contribute to nonecological prezygotic barriers.

Clinical outcomes and revascularization strategies in patients with low-flow, low-gradient severe aortic valve stenosis according to the assigned treatment modality

OBJECTIVES This study compared clinical outcomes and revascularization strategies among patients presenting with low ejection fraction, low-gradient (LEF-LG) severe aortic stenosis (AS) according to the assigned treatment modality. BACKGROUND The optimal treatment modality for patients with LEF-LG severe AS and concomitant coronary artery disease (CAD) requiring revascularization is unknown. METHODS Of 1,551 patients, 204 with LEF-LG severe AS (aortic valve area <1.0 cm(2), ejection fraction <50%, and mean gradient <40 mm Hg) were allocated to medical therapy (MT) (n = 44), surgical aortic valve replacement (SAVR) (n = 52), or transcatheter aortic valve replacement (TAVR) (n = 108). CAD complexity was assessed using the SYNTAX score (SS) in 187 of 204 patients (92%). The primary endpoint was mortality at 1 year. RESULTS LEF-LG severe AS patients undergoing SAVR were more likely to undergo complete revascularization (17 of 52, 35%) compared with TAVR (8 of 108, 8%) and MT (0 of 44, 0%) patients (p < 0.001). Compared with MT, both SAVR (adjusted hazard ratio [adj HR]: 0.16; 95% confidence interval [CI]: 0.07 to 0.38; p < 0.001) and TAVR (adj HR: 0.30; 95% CI: 0.18 to 0.52; p < 0.001) improved survival at 1 year. In TAVR and SAVR patients, CAD severity was associated with higher rates of cardiovascular death (no CAD: 12.2% vs. low SS [0 to 22], 15.3% vs. high SS [>22], 31.5%; p = 0.037) at 1 year. Compared with no CAD/complete revascularization, TAVR and SAVR patients undergoing incomplete revascularization had significantly higher 1-year cardiovascular death rates (adj HR: 2.80; 95% CI: 1.07 to 7.36; p = 0.037). CONCLUSIONS Among LEF-LG severe AS patients, SAVR and TAVR improved survival compared with MT. CAD severity was associated with worse outcomes and incomplete revascularization predicted 1-year cardiovascular mortality among TAVR and SAVR patients.