A Weakly Supervised Deep Learning Approach for Detecting Malaria and Sickle Cells in Blood Films

Machine vision analysis of blood films imaged under a brightfield microscope could provide scalable malaria diagnosis solutions in resource constrained endemic urban settings. The major bottleneck in successfully analyzing blood films with deep learning vision techniques is a lack of object-level annotations of disease markers such as parasites or abnormal red blood cells. To overcome this challenge, this work proposes a novel deep learning supervised approach that leverages weak labels readily available from routine clinical microscopy to diagnose malaria in thick blood film microscopy. This approach is based on aggregating the convolutional features of multiple objects present in one hundred high resolution image fields. We show that this method not only achieves expert-level malaria diagnostic accuracy without any hard object-level labels but can also identify individual malaria parasites in digitized thick blood films, which is useful in assessing disease severity and response to treatment. We demonstrate another application scenario where our approach is able to detect sickle cells in thin blood films. We discuss the wider applicability of the approach in automated analysis of thick blood films for the diagnosis of other blood disorders

Cooling a nanomechanical resonator with quantum back-action

Quantum mechanics demands that the act of measurement must affect the measured object. When a linear amplifier is used to continuously monitor the position of an object, the Heisenberg uncertainty relationship requires that the object be driven by force impulses, called back-action. Here we measure the back-action of a superconducting single-electron transistor (SSET) on a radiofrequency nanomechanical resonator. The conductance of the SSET, which is capacitively coupled to the resonator, provides a sensitive probe of the latter's position;back-action effects manifest themselves as an effective thermal bath, the properties of which depend sensitively on SSET bias conditions. Surprisingly, when the SSET is biased near a transport resonance, we observe cooling of the nanomechanical mode from 550mK to 300mK-- an effect that is analogous to laser cooling in atomic physics. Our measurements have implications for nanomechanical readout of quantum information devices and the limits of ultrasensitive force microscopy (such as single-nuclear-spin magnetic resonance force microscopy). Furthermore, we anticipate the use of these backaction effects to prepare ultracold and quantum states of mechanical structures, which would not be accessible with existing technology.Comment: 28 pages, 7 figures; accepted for publication in Natur

Cost-Effectiveness of a Chemoprophylactic Intervention with Single Dose Rifampicin in Contacts of New Leprosy Patients

In 2008, 249,007 new leprosy patients were detected in the world. It therefore remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy. The study is based on a large trial including 21,711 contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to contacts and followed them up for four years. The main outcome measure was the development of clinical leprosy. The cost effectiveness was expressed in US dollars per prevented leprosy case. Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total $6,009 was invested and 38 leprosy cases were prevented after 2 years, costing$158 per prevented leprosy case. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world

Tunable bipolar optical interactions between guided lightwaves

The optical binding forces between guided lightwaves in dielectric waveguides can be either repulsive or attractive. So far only attractive force has been observed. Here we experimentally demonstrate a bipolar optical force between coupled nanomechanical waveguides. Both attractive and repulsive optical forces are obtained. The sign of the force can be switched reversibly by tuning the relative phase of the interacting lightwaves. This tunable, bipolar interaction forms the foundation for the operation of a new class of light force devices and circuits.Comment: 4 figure

X-Linked thrombocytopenia causing mutations in WASP (L46P and A47D) impair T cell chemotaxis

BACKGROUND: Mutation in the Wiskott-Aldrich syndrome Protein (WASP) causes Wiskott-Aldrich syndrome (WAS), X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN). The majority of missense mutations causing WAS and XLT are found in the WH1 (WASP Homology) domain of WASP, known to mediate interaction with WIP (WASP Interacting Protein) and CIB1 (Calcium and Integrin Binding). RESULTS: We analyzed two WASP missense mutants (L46P and A47D) causing XLT for their effects on T cell chemotaxis. Both mutants, WASP(R)(L46P) and WASP(R)(A47D) (S1-WASP shRNA resistant) expressed well in Jurkat(WASP-KD) T cells (WASP knockdown), however expression of these two mutants did not rescue the chemotaxis defect of Jurkat(WASP-KD) T cells towards SDF-1α. In addition Jurkat(WASP-KD) T cells expressing these two WASP mutants were found to be defective in T cell polarization when stimulated with SDF-1α. WASP exists in a closed conformation in the presence of WIP, however both the mutants (WASP(R)(L46P) and WASP(R)(A47D)) were found to be in an open conformation as determined in the bi-molecular complementation assay. WASP protein undergoes proteolysis upon phosphorylation and this turnover of WASP is critical for T cell migration. Both the WASP mutants were found to be stable and have reduced tyrosine phosphorylation after stimulation with SDF-1α. CONCLUSION: Thus our data suggest that missense mutations WASP(R)(L46P) or WASP(R)(A47D) affect the activity of WASP in T cell chemotaxis probably by affecting the turnover of the protein. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-014-0091-1) contains supplementary material, which is available to authorized users

Perceptions of hypertension treatment among patients with and without diabetes

<p>Abstract</p> <p>Background</p> <p>Despite the availability of a wide selection of effective antihypertensive treatments and the existence of clear treatment guidelines, many patients with hypertension do not have controlled blood pressure. We conducted a qualitative study to explore beliefs and perceptions regarding hypertension and gain an understanding of barriers to treatment among patients with and without diabetes.</p> <p>Methods</p> <p>Ten focus groups were held for patients with hypertension in three age ranges, with and without diabetes. The topic guides for the groups were: What will determine your future health status? What do you understand by "raised blood pressure"? How should one go about treating raised blood pressure?</p> <p>Results</p> <p>People with hypertension tend to see hypertension not as a disease but as a risk factor for myocardial infarction or stroke. They do not view it as a continuous, degenerative process of damage to the vascular system, but rather as a binary risk process, within which you can either be a winner (not become ill) or a loser. This makes non-adherence to treatment a gamble with a potential positive outcome. Patients with diabetes are more likely to accept hypertension as a chronic illness with minor impact on their routine, and less important than their diabetes. Most participants overestimated the effect of stress as a causative factor believing that a reduction in levels of stress is the most important treatment modality. Many believe they "know their bodies" and are able to control their blood pressure. Patients without diabetes were most likely to adopt a treatment which is a compromise between their physician's suggestions and their own understanding of hypertension.</p> <p>Conclusion</p> <p>Patient denial and non-adherence to hypertension treatment is a prevalent phenomenon reflecting a conscious choice made by the patient, based on his knowledge and perceptions regarding the medical condition and its treatment. There is a need to change perception of hypertension from a gamble to a disease process. Changing the message from the existing one of "silent killer" to one that depicts hypertension as a manageable disease process may have the potential to significantly increase adherence rates.</p

Immunomodulatory role of Keratin 76 in oral and gastric cancer

Keratin 76 (Krt76) is an epithelial differentiation marker that is downregulated in oral squamous cell carcinomas, correlating with poor prognosis. Here the authors show that genetic ablation of Krt76 in a mouse model results in increased susceptibility to carcinogenesis via enhanced accumulation of Tregs

Synthesis and characterization of BaTiO3/-Fe2O3 core/shell structure

Multiferroic materials attracted a lot of attention in recent years because of their significant scientific interest and technological applications. The multiferroic core/shell powders have a better connectivity between the phases, resulting in superior dielectric and magneto electric properties. In this study, the influence of preparation condition on structure and properties of BaTiO3/-Fe2O3 core/shell composite materials was examined. The five samples were obtained by varying synthesis conditions, such as synthesized method (co-precipitation and sonochemical method) and pH values of solution. XRD and Raman spectroscopy analyses were performed in order to determine phase composition and structural changes within samples. Morphology modifications were examined by SEM and EDS analyses. Finally, effect of structural and microstructural changes on magnetic and electrical properties was detected and explained

Estimates of CO2 from fires in the United States: implications for carbon management

<p>Abstract</p> <p>Background</p> <p>Fires emit significant amounts of CO₂to the atmosphere. These emissions, however, are highly variable in both space and time. Additionally, CO₂emissions estimates from fires are very uncertain. The combination of high spatial and temporal variability and substantial uncertainty associated with fire CO₂emissions can be problematic to efforts to develop remote sensing, monitoring, and inverse modeling techniques to quantify carbon fluxes at the continental scale. Policy and carbon management decisions based on atmospheric sampling/modeling techniques must account for the impact of fire CO₂emissions; a task that may prove very difficult for the foreseeable future. This paper addresses the variability of CO₂emissions from fires across the US, how these emissions compare to anthropogenic emissions of CO₂and Net Primary Productivity, and the potential implications for monitoring programs and policy development.</p> <p>Results</p> <p>Average annual CO₂emissions from fires in the lower 48 (LOWER48) states from 2002–2006 are estimated to be 213 (± 50 std. dev.) Tg CO₂yr^-1and 80 (± 89 std. dev.) Tg CO₂yr^-1in Alaska. These estimates have significant interannual and spatial variability. Needleleaf forests in the Southeastern US and the Western US are the dominant source regions for US fire CO₂emissions. Very high emission years typically coincide with droughts, and climatic variability is a major driver of the high interannual and spatial variation in fire emissions. The amount of CO₂emitted from fires in the US is equivalent to 4–6% of anthropogenic emissions at the continental scale and, at the state-level, fire emissions of CO₂can, in some cases, exceed annual emissions of CO₂from fossil fuel usage.</p> <p>Conclusion</p> <p>The CO₂released from fires, overall, is a small fraction of the estimated average annual Net Primary Productivity and, unlike fossil fuel CO₂emissions, the pulsed emissions of CO₂during fires are partially counterbalanced by uptake of CO₂by regrowing vegetation in the decades following fire. Changes in fire severity and frequency can, however, lead to net changes in atmospheric CO₂and the short-term impacts of fire emissions on monitoring, modeling, and carbon management policy are substantial.</p

Ligand-Induced Tyrosine Phosphorylation of Cysteinyl Leukotriene Receptor 1 Triggers Internalization and Signaling in Intestinal Epithelial Cells

Leukotriene D(4) (LTD(4)) belongs to the bioactive lipid group known as eicosanoids and has implications in pathological processes such as inflammation and cancer. Leukotriene D(4) exerts its effects mainly through two different G-protein-coupled receptors, CysLT(1) and CysLT(2). The high affinity LTD(4) receptor CysLT(1)R exhibits tumor-promoting properties by triggering cell proliferation, survival, and migration in intestinal epithelial cells. In addition, increased expression and nuclear localization of CysLT(1)R correlates with a poorer prognosis for patients with colon cancer