Getting antimalarials on target: impact of national roll-out of malaria rapid diagnostic tests on health facility treatment in three regions of Tanzania.

OBJECTIVES: Parasitological confirmation of malaria prior to treatment is recommended for patients of all ages, with malaria rapid diagnostic tests (mRDTs) an important tool to target artemisinin-based combination therapies (ACTs) to patients with malaria. To evaluate the impact on case management practices of routine government implementation of mRDTs, we conducted large-scale health facility surveys in three regions of Tanzania before and after mRDT roll-out. METHODS: Febrile patients at randomly selected health facilities were interviewed about care received at the facility, and blood samples were collected for reference blood smears. Health facility staff were interviewed about their qualifications and availability of malaria diagnostics and drugs. RESULTS: The percentage of febrile patients tested for malaria at the facility increased from 15.8% in 2010 to 54.9% in 2012. ACTs were obtained by 65.8% of patients positive by reference blood smear in 2010 and by 50.2% in 2012 (P = 0.0675); no antimalarial was obtained by 57.8% of malaria-negative patients in 2010 and by 82.3% in 2012 (P < 0.0001). Overall, ACT use decreased (39.9-21.3%, P < 0.0001) and antibiotic use increased (31.2-48.5%, P < 0.0001). CONCLUSION: Roll-out of mRDTs in Tanzania dramatically improved diagnostic testing for malaria and reduced overuse of ACTs for patients without parasitemia. However, post-roll-out almost 50% of febrile patients did not receive a diagnostic test, and almost 50% of patients testing positive did not receive ACTs. Stock-outs of ACTs and mRDTs were important problems. Further investigation is needed to determine reasons for not providing ACTs to patients with malaria and potential for inappropriate antibiotic use

Low Porosity Metallic Periodic Structures with Negative Poisson's Ratio

Auxetic behavior in low porosity metallic structures is demonstrated via a simple system of orthogonal elliptical voids. In this minimal 2D system, the Poisson's ratio can be effectively controlled by changing the aspect ratio of the voids. In this way, large negative values of Poisson's ratio can be achieved, indicating an effective strategy for designing auxetic structures with desired porosity.Engineering and Applied Science

A comparative analysis of numerical approaches to the mechanics of elastic sheets

Numerically simulating deformations in thin elastic sheets is a challenging problem in computational mechanics due to destabilizing compressive stresses that result in wrinkling. Determining the location, structure, and evolution of wrinkles in these problems has important implications in design and is an area of increasing interest in the fields of physics and engineering. In this work, several numerical approaches previously proposed to model equilibrium deformations in thin elastic sheets are compared. These include standard finite element-based static post-buckling approaches as well as a recently proposed method based on dynamic relaxation, which are applied to the problem of an annular sheet with opposed tractions where wrinkling is a key feature. Numerical solutions are compared to analytic predictions of the ground state, enabling a quantitative evaluation of the predictive power of the various methods. Results indicate that static finite element approaches produce local minima that are highly sensitive to initial imperfections, relying on a priori knowledge of the equilibrium wrinkling pattern to generate optimal results. In contrast, dynamic relaxation is much less sensitive to initial imperfections and can generate low-energy solutions for a wide variety of loading conditions without requiring knowledge of the equilibrium solution beforehand.Engineering and Applied Science

Measuring magnetism in the Milky Way with the Square Kilometre Array

Magnetic fields in the Milky Way are present on a wide variety of sizes and strengths, influencing many processes in the Galactic ecosystem such as star formation, gas dynamics, jets, and evolution of supernova remnants or pulsar wind nebulae. Observation methods are complex and indirect; the most used of these are a grid of rotation measures of unresolved polarized extragalactic sources, and broadband polarimetry of diffuse emission. Current studies of magnetic fields in the Milky Way reveal a global spiral magnetic field with a significant turbulent component; the limited sample of magnetic field measurements in discrete objects such as supernova remnants and HII regions shows a wide variety in field configurations; a few detections of magnetic fields in Young Stellar Object jets have been published; and the magnetic field structure in the Galactic Center is still under debate. The SKA will unravel the 3D structure and configurations of magnetic fields in the Milky Way on sub-parsec to galaxy scales, including field structure in the Galactic Center. The global configuration of the Milky Way disk magnetic field, probed through pulsar RMs, will resolve controversy about reversals in the Galactic plane. Characteristics of interstellar turbulence can be determined from the grid of background RMs. We expect to learn to understand magnetic field structures in protostellar jets, supernova remnants, and other discrete sources, due to the vast increase in sample sizes possible with the SKA. This knowledge of magnetic fields in the Milky Way will not only be crucial in understanding of the evolution and interaction of Galactic structures, but will also help to define and remove Galactic foregrounds for a multitude of extragalactic and cosmological studies.Comment: 19 pages, 2 figures; to appear as part of 'Cosmic Magnetism' in Proceedings 'Advancing Astrophysics with the SKA (AASKA14)', PoS(AASKA14)09

Peridynamic Modeling of Ruptures in Biomembranes

We simulate the formation of spontaneous ruptures in supported phospholipid double bilayer membranes, using peridynamic modeling. Experiments performed on spreading double bilayers typically show two distinct kinds of ruptures, floral and fractal, which form spontaneously in the distal (upper) bilayer at late stages of double bilayer formation on high energy substrates. It is, however, currently unresolved which factors govern the occurrence of either rupture type. Variations in the distance between the two bilayers, and the occurrence of interconnections (“pinning sites”) are suspected of contributing to the process. Our new simulations indicate that the pinned regions which form, presumably due to Ca2+ ions serving as bridging agent between the distal and the proximal bilayer, act as nucleation sites for the ruptures. Moreover, assuming that the pinning sites cause a non-zero shear modulus, our simulations also show that they change the rupture mode from floral to fractal. At zero shear modulus the pores appear to be circular, subsequently evolving into floral pores. With increasing shear modulus the pore edges start to branch, favoring fractal morphologies. We conclude that the pinning sites may indirectly determine the rupture morphology by contributing to shear stress in the distal membrane

Melanoma-restricted genes

Human metastatic cutaneous melanoma has gained a well deserved reputation for its immune responsiveness. The reason(s) remain(s) unknown. We attempted previously to characterize several variables that may affect the relationship between tumor and host immune cells but, taken one at the time, none yielded a convincing explanation. With explorative purposes, high-throughput technology was applied here to portray transcriptional characteristics unique to metastatic cutaneous melanoma that may or may not be relevant to its immunogenic potential. Several functional signatures could be identified descriptive of immune or other biological functions. In addition, the transcriptional profile of metastatic melanoma was compared with that of primary renal cell cancers (RCC) identifying several genes co-coordinately expressed by the two tumor types. Since RCC is another immune responsive tumor, commonalities between RCC and melanoma may help untangle the enigma of their potential immune responsiveness. This purely descriptive study provides, therefore, a map for the investigation of metastatic melanoma in future clinical trials and at the same time may invite consideration of novel therapeutic targets

Diverse peptide hormones affecting root growth identified in the Medicago truncatula secreted peptidome

Multigene families encoding diverse secreted peptide hormones play important roles in plant development. A need exists to efficiently elucidate the structures and post-translational-modifications of these difficult-to-isolate peptide hormones in planta so that their biological functions can be determined. A mass spectrometry and bioinformatics approach was developed to comprehensively analyze the secreted peptidome of Medicago hairy root cultures and xylem sap. We identified 759 spectra corresponding to the secreted products of twelve peptide hormones including four CEP (C-TERMINALLY ENCODED PEPTIDE), two CLE (CLV3/ENDOSPERM SURROUNDING REGION RELATED) and six XAP (XYLEM SAP ASSOCIATED PEPTIDE) peptides. The MtCEP1, MtCEP2, MtCEP5 and MtCEP8 peptides identified differed in post-translational-modifications. Most were hydroxylated at conserved proline residues but some MtCEP1 derivatives were tri-arabinosylated. In addition, many CEP peptides possessed unexpected N- and C-terminal extensions. The pattern of these extensions suggested roles for endo- and exoproteases in CEP peptide maturation. Longer than expected, hydroxylated and homogeneously modified mono- and tri-arabinosylated CEP peptides corresponding to their in vivo structures were chemically synthesized to probe the effect of these post-translational-modifications on function. The ability of CEP peptides to elevate root nodule number was increased by hydroxylation at key positions. MtCEP1 peptides with N-terminal extensions or with tri-arabinosylation modification, however, were unable to impart increased nodulation. The MtCLE5 and MtCLE17 peptides identified were of precise size, and inhibited main root growth and increased lateral root number. Six XAP peptides, each beginning with a conserved DY sulfation motif, were identified including MtXAP1a, MtXAP1b, MtXAP1c, MtXAP3, MtXAP5 and MtXAP7. MtXAP1a and MtXAP5 inhibited lateral root emergence. Transcriptional analyses demonstrated peptide hormone gene expression in the root vasculature and tip. Since hairy roots can be induced on many plants, their corresponding root cultures may represent ideal source materials to efficiently identify diverse peptide hormones in vivo in a broad range of species.This work was supported by ARC grants to MAD: DP150104050 and LP150100826. NP was partly supported by an Endeavor Fellowship. NAMR was supported by an ANU Ph.D. scholarship supported by DP120101893. AI was supported by an Australian Post-graduate Award and an AW Howard Memorial Award. LC was supported by the Bruce-Veness Chandler and the John A. Lamberton research scholarship

Designed glycopeptidomimetics disrupt protein−protein interactions mediating amyloid β‑peptide aggregation and restore neuroblastoma cell viability

How anti-Alzheimer’s drug candidates that reduce amyloid 1−42 peptide fibrillization interact with the most neurotoxic species is far from being understood. We report herein the capacity of sugar-based peptidomimetics to inhibit both Aβ1−42 early oligomerization and fibrillization. A wide range of bio- and physicochemical techniques, such as a new capillary electrophoresis method, nuclear magnetic resonance, and surface plasmon resonance, were used to identify how these new molecules can delay the aggregation of Aβ1−42. We demonstrate that these molecules interact with soluble oligomers in order to maintain the presence of nontoxic monomers and to prevent fibrillization. These compounds totally suppress the toxicity of Aβ1−42 toward SH-SY5Y neuroblastoma cells, even at substoichiometric concentrations. Furthermore, demonstration that the best molecule combines hydrophobic moieties, hydrogen bond donors and acceptors, ammonium groups, and a hydrophilic β-sheet breaker element provides valuable insight for the future structure-based design of inhibitors of Aβ1−42 aggregation

Propuesta de Supply Chain Management y Logística para la Empresa Postobón S.A

El presente trabajo es la presentación y desarrollo del Diplomado de profundización Supply Chain Management y Logística del grupo 207115_22 del 2022, como opción de grado en el que se quiere identificar estructuras, procesos logísticos y cadena de suministro. El desarrollo de este proyecto tiene como finalidad la comprensión de conceptos que tienen relación con la Supply Chain Management y la Logística, cuya empresa de estudio escogida fue Postobón S.A. No obstante, la empresa ha dejado huella gracias a su constitución, enfoque empresarial, desplazamiento de ajuste y transformación. La empresa ha adoptado en su estructura organizativa la Gestión de la Cadena de Suministro y la logística con sinónimos o disciplinas complementarias. En el capítulo uno se puede ver la red estructurada que tiene la empresa, estableciendo sus proveedores y clientes. Además, de ello se determinan las operaciones realizadas en su planta de producción y los procesos estratégicos basándose en el enfoque Global Supply Chain fórum los cuales son explicados en el capítulo dos. Así mismo, en el capítulo tres se discriminan el total de los procesos implementados por la compañía basándose en el enfoque APICS-SCO. Por otro lado, en el capítulo cinco se explica que es el LPI y se expone cual es el desempeño de la compañía en términos de logística durante el año en vigencia. Abordando el capítulo seis encontramos una descripción del CONPES 3547, el cual describe medidas para reducir costos y demoras a través del pleno acceso a los mercados globales; la compañía cuenta con centros de distribución, los cuales cuentan con una alta rotación de inventario. En el capítulo siete encontramos un layout de la planta y la forma en la cual se tiene distribuido el inventario, así como una propuesta de mejora en la distribución con el fin de mejorar el flujo de mercancía. Llegando al capítulo ocho se describe específicamente los diferentes modos y medios de transporte utilizados por la compañía en el proceso de aprovisionamiento de materia prima y distribución del producto terminado, en este trabajo se propone una estrategia de aprovisionamiento la cual se detalla en el capítulo nueve y finalmente en el capítulo número diez se identifican las mega tendencias en Supply Chain Management y Logística. Esta es una gran oportunidad para identificar y plantear el plan propuesto aplicando las metodologías de SCM Y Logística, logrando asegurar un buen desempeño con las actividades en la producción y distribución de sus productos.The present work is the presentation and development of the Supply Chain Management and Logistics deepening Diploma of the group 207115_22 of 2022, as a degree option in which you want to identify structures, logistics processes and supply chain. The purpose of developing this project is to understand concepts that are related to Supply Chain Management and Logistics, whose chosen study company was Postobón S.A. However, the company has made its mark thanks to its constitution, entrepreneurial approach, fit shift and transformation. The company has adopted Supply Chain Management and logistics with synonyms or complementary disciplines in its organizational structure. In chapter one you can see the structured network that the company has, establishing its suppliers and customers. In addition, the operations carried out in its production plant and the strategic processes are determined based on the Global Supply Chain forum approach, which are explained in chapter two. Likewise, in chapter three the total of the processes implemented by the company are discriminated based on the APICS-SCO approach. On the other hand, in chapter five it is explained what the LPI is and the performance of the company in terms of logistics during the current year is exposed. Addressing chapter six we find a description of CONPES 3547, which describes measures to reduce costs and delays through full access to global markets; The company has distribution centers, which have a high inventory turnover. In chapter seven we find a layout of the plant and the way in which the inventory is distributed, as well as a proposal to improve the distribution in order to improve the flow of merchandise. Arriving at chapter eight, the different modes and means of transport used by the company in the supply process of raw material and distribution of the finished product are specifically described, in this work a supply strategy is proposed, which is detailed in chapter nine and Finally, in chapter number ten, the mega trends in Supply Chain Management and Logistics are identified. This is a great opportunity to identify and propose the proposed plan by applying the SCM and Logistics methodologies, managing to ensure good performance with the activities in the production and distribution of its products

Document Delivery and Resource Sharing: Global Perspectives

This publication is intended to provide librarians, library practitioners, as well as teachers, researchers, and students of universities and research organizations and other interested parties, a foundation in resource sharing principles, practices and management. This publication provides an overview of where things stand today with resource sharing, including key trends, challenges, opportunities, and priorities. The publication seeks to address international resource sharing, exploring the current state of European and international resource sharing systems and the governing laws and regulations and includes case studies and best practices from various countries