Scaling up depot medroxyprogesterone acetate (DMPA): a systematic literature review illustrating the AIDED model

BACKGROUND: Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income countries (LMICs). As a reproductive health technology that has scaled up in diverse contexts, DMPA is an exemplar product innovation with which to illustrate the utility of the AIDED model for scaling up family health innovations. METHODS: We conducted a systematic review of the enabling factors and barriers to scaling up DMPA use in LMICs. We searched 11 electronic databases for academic literature published through January 2013 (n = 284 articles), and grey literature from major health organizations. We applied exclusion criteria to identify relevant articles from peer-reviewed (n = 10) and grey literature (n = 9), extracting data on scale up of DMPA in 13 countries. We then mapped the resulting factors to the five AIDED model components: ASSESS, INNOVATE, DEVELOP, ENGAGE, and DEVOLVE. RESULTS: The final sample of sources included studies representing variation in geographies and methodologies. We identified 15 enabling factors and 10 barriers to dissemination, diffusion, scale up, and/or sustainability of DMPA use. The greatest number of factors were mapped to the ASSESS, DEVELOP, and ENGAGE components. CONCLUSIONS: Findings offer early empirical support for the AIDED model, and provide insights into scale up of DMPA that may be relevant for other family planning product innovations

PENERAPAN METODE RATING FAKTOR DAN MEKANIKA UNTUK PERBAIKAN RANCANGAN GEROBAK BAKSO SEPEDA MOTOR SEBAGAI UPAYA MENJAMIN KESELAMATAN PENGENDARA

Rancangan pada gerobak bakso sepeda motor yang digunakan untuk berjualan keliling belum mempertimbangkan aspek keseimbangan beban, kemudahan mobilitas, tempat penyajian, dan daya tarik pembeli. Penelitian ini bertujuan memperbaiki pada rancangan gerobak bakso sepeda motor berdasarkan kemudahan pelayanan bagi pembeli dan keseimbangan muatan pada sepeda motor. Identifikasi awal dilakukan pada gerobak bakso sepeda motor di wilayah Surakarta dan sekitarnya. Perbaikan  awal  ini  melalui penerapan rating faktor untuk pertimbangan dalam penempatan bagian-bagian dari peletakan beban muatan. Penentuan ukuran pada dimensi rangka dengan memperhatikan aspek anthropometri. Hasil pada penelitian ini memperoleh keseimbangan momen untuk penempatan beban muatan bagian sisi kanan dan sisi kiri dari rancangan gerobak sepeda motor. Keseimbangan momen keseluruhan untuk gerobak bakso sebesar  91,684  Nm. Bagian sisi kanan diseimbangkan pada beban isi kompor 34,0 Nm dan beban isi dandang 46,84 Nm. Keseimbangan momen untuk beban dan rangka di setiap komponen dicapai 162,74 Nm. Hasilnya pada gerobak bakso sepeda motor memiliki tempat penyajian yang menjadi daya tarik pembeli, dan beban muatan lebih seimbang agar memudahkan dalam mobilitas dan keselamatan pengendara. Kata kunci: Gerobak bakso sepeda motor,  faktor rating, anthropometri, mome

Infección por Theileria annae en un perro esplenectomizado

La babesiosis canina es una enfermedad infecciosa de distribución mundial debida a la proliferación en los hematíes del perro de unas babesias específicas transmitidas por garrapatas. Si bien ha sido tradicionalmente asumido que las únicas especies que causan enfermedad en la especie canina son Babesia canis y Babesia gibsoni, publicaciones recientes demuestran que una tercera especie (Theileria annae) también puede causar una enfermedad muy severa. Este trabajo presenta el segundo caso publicado de esta forma de Theileria annae en un perro de 14 años, de raza Basset Hound, esplenectomizado cinco meses antes, que se presentó en la clínica veterinaria con signos de hipertermia, hemoglobinuria, temblores y apatía. El estudio de laboratorio constató una acusada anemia hemolítica regenerativa y una intensa trombocitopenia como datos más característicos. En la extensión de sangre periférica se visualizaron múltiples merozoítos intra (22%) y extraeritrocitarios de pequeño tamaño (1-2 micras), forma anular y presentación única en la mayoría de hematíes. La prontitud del diagnóstico y del tratamiento específico con dipropionato de imidocarb hizo que el cuadro clínico evolucionase con rapidez hacia la curación, en contra de lo que es habitual en los animales esplenectomizados.

Protein phosphatase 2a (PP2A) binds within the oligomerization domain of striatin and regulates the phosphorylation and activation of the mammalian Ste20-Like kinase Mst3

<p>Abstract</p> <p>Background</p> <p>Striatin, a putative protein phosphatase 2A (PP2A) B-type regulatory subunit, is a multi-domain scaffolding protein that has recently been linked to several diseases including cerebral cavernous malformation (CCM), which causes symptoms ranging from headaches to stroke. Striatin association with the PP2A A/C (structural subunit/catalytic subunit) heterodimer alters PP2A substrate specificity, but targets and roles of striatin-associated PP2A are not known. In addition to binding the PP2A A/C heterodimer to form a PP2A holoenzyme, striatin associates with cerebral cavernous malformation 3 (CCM3) protein, the mammalian Mps one binder (MOB) homolog, Mob3/phocein, the mammalian sterile 20-like (Mst) kinases, Mst3, Mst4 and STK25, and several other proteins to form a large signaling complex. Little is known about the molecular architecture of the striatin complex and the regulation of these sterile 20-like kinases.</p> <p>Results</p> <p>To help define the molecular organization of striatin complexes and to determine whether Mst3 might be negatively regulated by striatin-associated PP2A, a structure-function analysis of striatin was performed. Two distinct regions of striatin are capable of stably binding directly or indirectly to Mob3--one N-terminal, including the coiled-coil domain, and another more C-terminal, including the WD-repeat domain. In addition, striatin residues 191-344 contain determinants necessary for efficient association of Mst3, Mst4, and CCM3. PP2A associates with the coiled-coil domain of striatin, but unlike Mob3 and Mst3, its binding appears to require striatin oligomerization. Deletion of the caveolin-binding domain on striatin abolishes striatin family oligomerization and PP2A binding. Point mutations in striatin that disrupt PP2A association cause hyperphosphorylation and activation of striatin-associated Mst3.</p> <p>Conclusions</p> <p>Striatin orchestrates the regulation of Mst3 by PP2A. It binds Mst3 likely as a dimer with CCM3 via residues lying between striatin's calmodulin-binding and WD-domains and recruits the PP2A A/C heterodimer to its coiled-coil/oligomerization domain. Residues outside the previously reported coiled-coil domain of striatin are necessary for its oligomerization. Striatin-associated PP2A is critical for Mst3 dephosphorylation and inactivation. Upon inhibition of PP2A, Mst3 activation appears to involve autophosphorylation of multiple activation loop phosphorylation sites. Mob3 can associate with striatin sequences C-terminal to the Mst3 binding site but also with sequences proximal to striatin-associated PP2A, consistent with a possible role for Mob 3 in the regulation of Mst3 by PP2A.</p

Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus

Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication

Differentiated function and localisation of SPO11-1 and PRD3 on the chromosome axis during meiotic DSB formation in Arabidopsis thaliana

During meiosis, DNA double-strand breaks (DSBs) occur throughout the genome, a subset of which are repaired to form reciprocal crossovers between chromosomes. Crossovers are essential to ensure balanced chromosome segregation and to create new combinations of genetic variation. Meiotic DSBs are formed by a topoisomerase-VI-like complex, containing catalytic (e.g. SPO11) proteins and auxiliary (e.g. PRD3) proteins. Meiotic DSBs are formed in chromatin loops tethered to a linear chromosome axis, but the interrelationship between DSB-promoting factors and the axis is not fully understood. Here, we study the localisation of SPO11-1 and PRD3 during meiosis, and investigate their respective functions in relation to the chromosome axis. Using immunocytogenetics, we observed that the localisation of SPO11-1 overlaps relatively weakly with the chromosome axis and RAD51, a marker of meiotic DSBs, and that SPO11-1 recruitment to chromatin is genetically independent of the axis. In contrast, PRD3 localisation correlates more strongly with RAD51 and the chromosome axis. This indicates that PRD3 likely forms a functional link between SPO11-1 and the chromosome axis to promote meiotic DSB formation. We also uncovered a new function of SPO11-1 in the nucleation of the synaptonemal complex protein ZYP1. We demonstrate that chromosome co-alignment associated with ZYP1 deposition can occur in the absence of DSBs, and is dependent on SPO11-1, but not PRD3. Lastly, we show that the progression of meiosis is influenced by the presence of aberrant chromosomal connections, but not by the absence of DSBs or synapsis. Altogether, our study provides mechanistic insights into the control of meiotic DSB formation and reveals diverse functional interactions between SPO11-1, PRD3 and the chromosome axis

Temporal Experiment for Storms and Tropical Systems Technology Demonstration (TEMPEST-D) Mission: Enabling Time-Resolved Cloud and Precipitation Observations from 6U-Class Satellite Constellations

The Temporal Experiment for Storms and Tropical Systems Technology Demonstration (TEMPEST-D) mission is to demonstrate the capability of 6U-Class satellite constellations to perform repeat-pass radiometry to measure clouds and precipitation with high temporal resolution on a global basis. The TEMPEST mission concept is to improve understanding of clouds and precipitation by providing critical information on their time evolution in different climatic regimes. Measuring at five frequencies from 89 to 182 GHz, TEMPEST-D millimeter-wave radiometers are capable of penetrating into the cloud to observe changes as precipitation begins or ice accumulates inside the storm. The TEMPEST-D flight model radiometer instrument has been completed, passed functional testing, vibration testing and self-compatibility testing with the XB1 spacecraft bus. The next steps for the TEMPEST-D millimeter-wave radiometer are thermal vacuum testing and antenna pattern measurements. The complete TEMPEST-D flight system will be delivered to NanoRacks for launch integration in the autumn of 2017, in preparation for launch to the ISS in the second quarter of 2018, with deployment shortly thereafter into a nominal orbit at 400-km altitude and 51.6° inclination

Last Men Standing: Chlamydatus Portraits and Public Life in Late Antique Corinth

Notable among the marble sculptures excavated at Corinth are seven portraits of men wearing the long chlamys of Late Antique imperial office. This unusual costume, contemporary portrait heads, and inscribed statue bases all help confirm that new public statuary was created and erected at Corinth during the 4th and 5th centuries. These chlamydatus portraits, published together here for the first time, are likely to represent the Governor of Achaia in his capital city, in the company of local benefactors. Among the last works of the ancient sculptural tradition, they form a valuable source of information on public life in Late Antique Corinth

Protein phosphatase beta, a putative type-2A protein phosphatase from the human malaria parasite Plasmodium falciparum.

Protein phosphatases play a critical role in the regulation of the eukaryotic cell cycle and signal transduction. A putative protein serine/threonine phosphatase gene has been isolated from the human malaria parasite Plasmodium falciparum. The gene has an unusual intron that contains four repeats of 32 nucleotides and displays a high degree of size polymorphism among different strains of P. falciparum. The open reading frame reconstituted by removal of the intron encodes a protein of 466 amino acids with a predicted molecular mass of approximately 53.7 kDa. The encoded protein, termed protein phosphatase beta (PP-beta), is composed of two distinct domains. The C-terminal domain comprises 315 amino acids and exhibits a striking similarity to the catalytic subunits of the type-2A protein phosphatases. Database searches revealed that the catalytic domain has the highest similarity to Schizosaccharomyces pombe Ppa1 (58% identity and 73% similarity). However, it contains a hydrophilic insert consisting of five amino acids. The N-terminal domain comprises 151 amino acid residues and exhibits several striking features, including high levels of charged amino acids and asparagine, and multiple consensus phosphorylation sites for a number of protein kinases. An overall structural comparison of PP-beta with other members of the protein phosphatase 2A group revealed that PP-beta is more closely related to Saccharomyces cerevisiae PPH22. Southern blots of genomic DNA digests and chromosomal separations showed that PP-beta is a single-copy gene and is located on chromosome 9. A 2800-nucleotide transcript of this gene is expressed specifically in the sexual erythrocytic stage (gametocytes). The results indicate that PP-beta may be involved in sexual stage development

Identifying differential exon splicing using linear models and correlation coefficients

Background: With the availability of the Affymetrix exon arrays a number of tools have been developed to enable the analysis. These however can be expensive or have several pre-installation requirements. This led us to develop an analysis workflow for analysing differential splicing using freely available software packages that are already being widely used for gene expression analysis. The workflow uses the packages in the standard installation of R and Bioconductor (BiocLite) to identify differential splicing. We use the splice index method with the LIMMA framework. The main drawback with this approach is that it relies on accurate estimates of gene expression from the probe-level data. Methods such as RMA and PLIER may misestimate when a large proportion of exons are spliced. We therefore present the novel concept of a gene correlation coefficient calculated using only the probeset expression pattern within a gene. We show that genes with lower correlation coefficients are likely to be differentially spliced.Results: The LIMMA approach was used to identify several tissue-specific transcripts and splicing events that are supported by previous experimental studies. Filtering the data is necessary, particularly removing exons and genes that are not expressed in all samples and cross-hybridising probesets, in order to reduce the false positive rate. The LIMMA approach ranked genes containing single or few differentially spliced exons much higher than genes containing several differentially spliced exons. On the other hand we found the gene correlation coefficient approach better for identifying genes with a large number of differentially spliced exons.Conclusion: We show that LIMMA can be used to identify differential exon splicing from Affymetrix exon array data. Though further work would be necessary to develop the use of correlation coefficients into a complete analysis approach, the preliminary results demonstrate their usefulness for identifying differentially spliced genes. The two approaches work complementary as they can potentially identify different subsets of genes (single/few spliced exons vs. large transcript structure differences)