Over-diagnosis of malaria is not a lost cause.

BACKGROUND: Recent studies have highlighted the over-diagnosis of malaria in clinical settings in Africa. This study assessed the impact of a training programme implemented as part of an intervention trial on diagnostic behaviour of clinicians in a rural district hospital in a low-moderate malaria transmission setting. METHODS: From the beginning of 2005, a randomized controlled trial (RCT) of intermittent preventive treatment for malaria in infants (IPTi) has been conducted at the study hospital. As part of the RCT, the study team offered laboratory quality assurance, and supervision and training of paediatric ward staff using information on malaria epidemiology in the community. Data on clinical and blood slide confirmed cases of malaria from 2001 to 2005 were extracted from the hospital records. RESULTS: The proportion of blood slides positive for malaria parasites had decreased from 21% in 2001 to 7% in 2005 (p < .01). The proportion of outpatient and inpatient cases diagnosed as malaria ranged between 34% and 28% from 2001 to 2004 and this decreased substantially to 17% after the introduction of the package of training and support in 2005 (p < .01). There was no clear trend in the ratio of blood slide examined versus total diagnosis of malaria. CONCLUSION: It may be possible to change the diagnostic behaviour of clinicians by rigorous training using local malaria epidemiology data and supportive supervision

3D printing the future: scenarios for supply chains reviewed

Purpose: The aim of this paper is to evaluate existing scenarios for 3D Printing in order to identify the “white space” where future opportunities have not been proposed or developed to date. Based around aspects of order penetration points, geographical scope and type of manufacturing, these gaps are identified. Design/methodology/approach: A structured literature review has been carried out on both academic and trade publications. As of the end of May 2016, this identified 128 relevant articles containing 201 future scenarios. Coding these against aspects of existing manufacturing and supply chain theory has led to the development of a framework for identify “white space” in existing thinking. Findings: The coding shows that existing future scenarios are particularly concentrated on job shop applications and pull based supply chain processes, although there are fewer constraints on geographical scope. Five distinct areas of “white space” are proposed, reflecting various opportunities for future 3DP supply chain development. Research limitations: Being a structured literature review, there are potentially articles not identified through the search criteria used. The nature of the findings is also dependent upon the coding criteria selected. However, these are theoretically derived and reflect important aspect of strategic supply chain management. Practical implications: Practitioners may wish to explore the development of business models within the “white space” areas. Originality/value: Currently, existing future 3DP scenarios are scattered over a wide, multi-disciplinary literature base. By providing a consolidated view of these scenarios, it is possible to identify gaps in current thinking. These gaps are multidisciplinary in nature and represent opportunities for both academics and practitioners to exploit

Properties of High-Latitude CME-Driven Disturbances During Ulysses Second Northern Polar Passage

Ulysses observed five coronal mass ejections (CMEs) and their associated disturbances while the spacecraft was immersed in the polar coronal hole (CH) flow above 70° N in late 2001. Of these CMEs, two were very fast (\u3e850 km s−1) driving strong shocks in the wind ahead, and two others were over-expanding. The two fast CMEs were observed leaving the Sun by LASCO/SOHO, and were observed in the ecliptic by Genesis and ACE. These were large events, spanning at least from the northern heliospheric pole to the ecliptic. One-dimensional hydrodynamic simulations indicate that these could be described as overpressured CMEs launched from the Sun at speeds initially faster than ambient, but then decelerating to the ambient solar wind speed as they propagated outward. The two over-expanding CMEs mark their first occurrence since Ulysses’ first orbit when such CMEs were only observed in polar CH flow

Helium Energetics in the High-Latitude Solar Wind: Ulysses Observations

We present a study of the interplanetary evolution of solar wind helium (alpha particle) energetics. The analysis of Ulysses observations of the fast high-latitude solar wind concentrates on the radial evolution of the alpha-proton differential streaming vαp, the alpha temperature, and the alpha temperature anisotropy. Ulysses observations show that the average vαp steadily decreases with radius, ranging from ∼40 km s−1 at 1.5 AU to ∼15 km s−1 at 4.2 AU. In addition, observations indicate that the alphas cool more slowly than what would be expected from adiabatic expansion. The radial increase in the nonadiabatic heat content of the alphas matches the free energy liberated as vαp decreases with distance, suggesting that the dissipated energy acts to heat the alpha particles. The alphas also exhibit a temperature anisotropy of T⊥α/T‖α = 0.87, which is essentially constant with distance. These and other observations reported here place stringent constraints on recent plasma microinstability models that attempt to explain the evolution of alpha-proton differential streaming and ion heating in the heliosphere

Refining Our Understanding of the Flow Through Coronary Artery Branches; Revisiting Murray's Law in Human Epicardial Coronary Arteries

Background: Quantification of coronary blood flow is used to evaluate coronary artery disease, but our understanding of flow through branched systems is poor. Murray’s law defines coronary morphometric scaling, the relationship between flow (Q) and vessel diameter (D) and is the basis for minimum lumen area targets when intervening on bifurcation lesions. Murray’s original law (Q α D(P)) dictates that the exponent (P) is 3.0, whilst constant blood velocity throughout the system would suggest an exponent of 2.0. In human coronary arteries, the value of Murray’s exponent remains unknown. Aim: To establish the exponent in Murray’s power law relationship that best reproduces coronary blood flows (Q) and microvascular resistances (Rmicro) in a bifurcating coronary tree. Methods and Results: We screened 48 cases, and were able to evaluate inlet Q and Rmicro in 27 branched coronary arteries, taken from 20 patients, using a novel computational fluid dynamics (CFD) model which reconstructs 3D coronary anatomy from angiography and uses pressure-wire measurements to compute Q and Rmicro distribution in the main- and side-branches. Outputs were validated against invasive measurements using a Rayflow™ catheter. A Murray’s power law exponent of 2.15 produced the strongest correlation and closest agreement with inlet Q (zero bias, r = 0.47, p = 0.006) and an exponent of 2.38 produced the strongest correlation and closest agreement with Rmicro (zero bias, r = 0.66, p = 0.0001). Conclusions: The optimal power law exponents for Q and Rmicro were not 3.0, as dictated by Murray’s Law, but 2.15 and 2.38 respectively. These data will be useful in assessing patient-specific coronary physiology and tailoring revascularisation decisions

Validation of a novel numerical model to predict regionalized blood flow in the coronary arteries

Aims: Ischaemic heart disease results from insufficient coronary blood flow. Direct measurement of absolute flow (mL/min) is feasible, but has not entered routine clinical practice in most catheterization laboratories. Interventional cardiologists, therefore, rely on surrogate markers of flow. Recently, we described a computational fluid dynamics (CFD) method for predicting flow that differentiates inlet, side branch, and outlet flows during angiography. In the current study, we evaluate a new method that regionalizes flow along the length of the artery. Methods and results: Three-dimensional coronary anatomy was reconstructed from angiograms from 20 patients with chronic coronary syndrome. All flows were computed using CFD by applying the pressure gradient to the reconstructed geometry. Side branch flow was modelled as a porous wall boundary. Side branch flow magnitude was based on morphometric scaling laws with two models: a homogeneous model with flow loss along the entire arterial length; and a regionalized model with flow proportional to local taper. Flow results were validated against invasive measurements of flow by continuous infusion thermodilution (Coroventis™, Abbott). Both methods quantified flow relative to the invasive measures: homogeneous (r 0.47, P 0.006; zero bias; 95% CI -168 to +168 mL/min); regionalized method (r 0.43, P 0.013; zero bias; 95% CI -175 to +175 mL/min). Conclusion: During angiography and pressure wire assessment, coronary flow can now be regionalized and differentiated at the inlet, outlet, and side branches. The effect of epicardial disease on agreement suggests the model may be best targeted at cases with a stenosis close to side branches.</p

CMEs at High Northern Latitudes During Solar Maximum : Ulysses and SOHO Correlated Observations.

From September through November 2001, Ulysses was almost continuously immersed in polar coronal hole (CH) flow during its northern polar pass of the Sun. For much of this time, the flow was fast (&gt; 700 km/s) and steady, quite similar to the steady unstructured flow observed during Ulysses first polar orbit near solar minimum. During the three months Ulysses transited the northern polar CH it observed 5 coronal mass ejections (CMEs). Of these, two were clearly over-expanding and two were at least partially driven by overexpansion. The phenomenon of over-expansion was frequently observed at high latitudes during Ulysses first orbit. The recurrence of over-expanding CMEs during the second orbit at high latitudes indicates that this is a phenomenon apparently unique to and typical of CMEs embedded in polar CH flow. Ulysses was nearly above the solar limb during this three-month interval, providing an opportunity to use LASCO/SOHO observations to study the initial velocity profiles of the CMEs observed further out by Ulysses. These initial conditions were used as inputs into a hydrodynamic code, the results of which are reported here

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

Presumptive treatment of fever cases as malaria: help or hindrance for malaria control?

BACKGROUND: Malaria incidence has been reported to be falling in several countries in sub-Saharan Africa in recent years. This fall appears to have started before the widespread introduction of insecticide-treated nets. In the new era of calls to eliminate and eradicate malaria in sub-Saharan Africa, exploring possible causes for this fall seem pertinent. PRESENTATION OF THE HYPOTHESIS: The authors explore an argument that presumptive treatment of fever cases as malaria may have played a role in reducing transmission of malaria by the prophylactic effect of antimalarials and their widespread use. This strategy, which is already in practise is termed Opportunistic Presumptive Treatment (OPT). TESTING THE HYPOTHESIS: Further comparison of epidemiological indicators between areas with OPT and more targeted treatment is required. If data suggest a benefit of OPT, combining long acting antimalarials that have an anti-gametocyticidal activity component plus using high levels of vector control measures may reduce transmission, prevent resistant strains spreading and be easily implemented. IMPLICATIONS OF THE HYPOTHESIS: OPT is practised widely by presumptive treatment of fever in health facilities and home management of fever. Improving diagnosis using rapid diagnostic tests and thus reducing the number of doses of antimalarials given may have counter intuitive effects on transmission in the context of elimination of malaria in high to moderate transmission settings

Sex differences in coronary microvascular resistance measured by a computational fluid dynamics model

BackgroundIncreased coronary microvascular resistance (CMVR) is associated with coronary microvascular dysfunction (CMD). Although CMD is more common in women, sex-specific differences in CMVR have not been demonstrated previously.AimTo compare CMVR between men and women being investigated for chest pain.Methods and resultsWe used a computational fluid dynamics (CFD) model of human coronary physiology to calculate absolute CMVR based on invasive coronary angiographic images and pressures in 203 coronary arteries from 144 individual patients. CMVR was significantly higher in women than men (860 [650–1,205] vs. 680 [520–865] WU, Z = −2.24, p = 0.025). None of the other major subgroup comparisons yielded any differences in CMVR.ConclusionCMVR was significantly higher in women compared with men. These sex-specific differences may help to explain the increased prevalence of CMD in women