Measuring Coverage in MNCH:A Validation Study Linking Population Survey Derived Coverage to Maternal, Newborn, and Child Health Care Records in Rural China

Accurate data on coverage of key maternal, newborn, and child health (MNCH) interventions are crucial for monitoring progress toward the Millennium Development Goals 4 and 5. Coverage estimates are primarily obtained from routine population surveys through self-reporting, the validity of which is not well understood. We aimed to examine the validity of the coverage of selected MNCH interventions in Gongcheng County, China.We conducted a validation study by comparing women's self-reported coverage of MNCH interventions relating to antenatal and postnatal care, mode of delivery, and child vaccinations in a community survey with their paper- and electronic-based health care records, treating the health care records as the reference standard. Of 936 women recruited, 914 (97.6%) completed the survey. Results show that self-reported coverage of these interventions had moderate to high sensitivity (0.57 [95% confidence interval (CI): 0.50-0.63] to 0.99 [95% CI: 0.98-1.00]) and low to high specificity (0 to 0.83 [95% CI: 0.80-0.86]). Despite varying overall validity, with the area under the receiver operating characteristic curve (AUC) ranging between 0.49 [95% CI: 0.39-0.57] and 0.90 [95% CI: 0.88-0.92], bias in the coverage estimates at the population level was small to moderate, with the test to actual positive (TAP) ratio ranging between 0.8 and 1.5 for 24 of the 28 indicators examined. Our ability to accurately estimate validity was affected by several caveats associated with the reference standard. Caution should be exercised when generalizing the results to other settings.The overall validity of self-reported coverage was moderate across selected MNCH indicators. However, at the population level, self-reported coverage appears to have small to moderate degree of bias. Accuracy of the coverage was particularly high for indicators with high recorded coverage or low recorded coverage but high specificity. The study provides insights into the accuracy of self-reports based on a population survey in low- and middle-income countries. Similar studies applying an improved reference standard are warranted in the future

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma

BACKGROUND: Through negative regulation of gene expression, microRNAs (miRNAs) can function in cancers as oncosuppressors, and they can show altered expression in various tumor types. Here we have investigated medulloblastoma tumors (MBs), which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many cell-fate-determining stages. MBs occur bimodally, with the peak incidence seen between 3-4 years and 8-9 years of age, although it can also occur in adults. Notch regulates a subset of the MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulated these phenomena, and can be used in anti-cancer therapies. METHODOLOGY/PRINCIPAL FINDINGS: In a screening of MB cell lines, the miRNA miR-199b-5p was seen to be a regulator of the Notch pathway through its targeting of the transcription factor HES1. Down-regulation of HES1 expression by miR-199b-5p negatively regulates the proliferation rate and anchorage-independent growth of MB cells. MiR-199b-5p over-expression blocks expression of several cancer stem-cell genes, impairs the engrafting potential of MB cells in the cerebellum of athymic/nude mice, and of particular interest, decreases the MB stem-cell-like (CD133+) subpopulation of cells. In our analysis of 61 patients with MB, the expression of miR-199b-5p in the non-metastatic cases was significantly higher than in the metastatic cases (P = 0.001). Correlation with survival for these patients with high levels of miR-199b expression showed a positive trend to better overall survival than for the low-expressing patients. These data showing the down-regulation of miR-199b-5p in metastatic MBs suggest a potential silencing mechanism through epigenetic or genetic alterations. Upon induction of de-methylation using 5-aza-deoxycytidine, lower miR-199b-5p expression was seen in a panel of MB cell lines, supported an epigenetic mechanism of regulation. Furthermore, two cell lines (Med8a and UW228) showed significant up-regulation of miR-199b-5p upon treatment. Infection with MB cells in an induced xenograft model in the mouse cerebellum and the use of an adenovirus carrying miR-199b-5p indicate a clinical benefit through this negative influence of miR-199b-5p on tumor growth and on the subset of MB stem-cell-like cells, providing further proof of concept. CONCLUSIONS/SIGNIFICANCE: Despite advances in our understanding of the pathogenesis of MB, one-third of these patients remain incurable and current treatments can significantly damage long-term survivors. Here we show that miR-199b-5p expression correlates with metastasis spread, identifying a new molecular marker for a poor-risk class in patients with MB. We further show that in a xenograft model, MB tumor burden can be reduced, indicating the use of miR199b-5p as an adjuvant therapy after surgery, in combination with radiation and chemotherapy, for the improvement of anti-cancer MB therapies and patient quality of life. To date, this is the first report that expression of a miRNA can deplete the tumor stem cells, indicating an interesting therapeutic approach for the targeting of these cells in brain tumors

Guideline for diagnosis and treatment of subacromial pain syndrome

Treatment of "subacromial impingement syndrome" of the shoulder has changed drastically in the past decade. The anatomical explanation as "impingement" of the rotator cuff is not sufficient to cover the pathology. "Subacromial pain syndrome", SAPS, describes the condition better. A working group formed from a number of Dutch specialist societies, joined by the Dutch Orthopedic Association, has produced a guideline based on the available scientific evidence. This resulted in a new outlook for the treatment of subacromial pain syndrome. The important conclusions and advice from this work are as follows: (1) The diagnosis SAPS can only be made using a combination of clinical tests. (2) SAPS should preferably be treated non-operatively. (3) Acute pain should be treated with analgetics if necessary. (4) Subacromial injection with corticosteroids is indicated for persistent or recurrent symptoms. (5) Diagnostic imaging is useful after 6 weeks of symptoms. Ultrasound examination is the recommended imaging, to exclude a rotator cuff rupture. (6) Occupational interventions are useful when complaints persist for longer than 6 weeks. (7) Exercise therapy should be specific and should be of low intensity and high frequency, combining eccentric training, attention to relaxation and posture, and treatment of myofascial trigger points (including stretching of the muscles) may be considered. (8) Strict immobilization and mobilization techniques are not recommended. (9) Tendinosis calcarea can be treated by shockwave (ESWT) or needling under ultrasound guidance (barbotage). (10) Rehabilitation in a specialized unit can be considered in chronic, treatment resistant SAPS, with pain perpetuating behavior. (11) There is no convincing evidence that surgical treatment for SAPS is more effective than conservature management. (12) There is no indication for the surgical treatment of asymptomatic rotator cuff tears

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 96 (FGE.96): Consideration of 88 flavouring substances considered by EFSA for which EU production volumes / anticipated production volumes have been submitted on request by DG SANCO. Addendum to FGE. 51, 52, 53, 54, 56, 58, 61, 62, 63, 64, 68, 69, 70, 71, 73, 76, 77, 79, 80, 83, 84, 85 and 87

Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism1. To identify new causes of human overgrowth, we performed exome sequencing in ten proband-parent trios and detected two de novo DNMT3A mutations. We identified 11 additional de novo mutations by sequencing DNMT3A in a further 142 individuals with overgrowth. The mutations alter residues in functional DNMT3A domains, and protein modeling suggests that they interfere with domain-domain interactions and histone binding. Similar mutations were not present in 1,000 UK population controls (13/152 cases versus 0/1,000 controls; P < 0.0001). Mutation carriers had a distinctive facial appearance, intellectual disability and greater height. DNMT3A encodes a DNA methyltransferase essential for establishing methylation during embryogenesis and is commonly somatically mutated in acute myeloid leukemia2, 3, 4. Thus, DNMT3A joins an emerging group of epigenetic DNA- and histone-modifying genes associated with both developmental growth disorders and hematological malignancie

Seed Germination Strategies of Mediterranean Halophytes Under Saline Condition

The study of the ecological strategies adopted by seed plants to ensure their success in different environments is closely related to germination ecology. This implies a careful knowledge of ecophysiology of seeds and, therefore, also of interaction between plants and the complexity of external factors. In particular, the environmental conditions of the area where a plant grows and produces seeds represent the main factors that influence successful seedling establishment. The physical-chemical features of habitats, and therefore their heterogeneity, affect the behavior of seeds in different ways. In addition to the timing of seed production, they can induce or terminate dormancy and/or germination and influence the germination pattern of different seeds in the same plant and so the composition and dispersal of soil seed banks. Salinity is a major abiotic stress affecting growth and plant productivity worldwide, constituting one of the main topics of study in the field of plant physiology. Halophytes are the plants that have the availability to survive and develop in different types of saline habitats. In this chapter, we consider some examples to illustrate the main adaptive strategies used by the seeds of halophytes on ecophysiological perspectives to survive in habitats affected by high levels of salinity. The focus is on the species that live in the brackish or salt coastal areas of the Mediterranean Basin. On these environments, the salt stress may act synergistically with intense anthropic pressure, generating profound alterations in the ecosystem and threatening the survival of the plant species very sensitive to the effects of climate change also. The results show the main diverse strategies, such as dormancy cycling, seed heteromorphism, and recovery capacity, from saline shock, favoring the chances of seed survival. The interaction between temperature and salinity during germination was also discussed assessing its crucial role as an ecological strategy

Concentration-Dependent, Size-Independent Toxicity of Citrate Capped AuNPs in Drosophila melanogaster

The expected potential benefits promised by nanotechnology in various fields have led to a rapid increase of the presence of engineered nanomaterials in a high number of commercial goods. This is generating increasing questions about possible risks for human health and environment, due to the lack of an in-depth assessment of the physical/chemical factors responsible for their toxic effects. In this work, we evaluated the toxicity of monodisperse citrate-capped gold nanoparticles (AuNPs) of different sizes (5, 15, 40, and 80 nm) in the model organism Drosophila melanogaster, upon ingestion. To properly evaluate and distinguish the possible dose- and/or size-dependent toxicity of the AuNPs, we performed a thorough assessment of their biological effects, using two different dose-metrics. In the first approach, we kept constant the total surface area of the differently sized AuNPs (Total Exposed Surface area approach, TES), while, in the second approach, we used the same number concentration of the four different sizes of AuNPs (Total Number of Nanoparticles approach, TNN). We observed a significant AuNPs-induced toxicity in vivo, namely a strong reduction of Drosophila lifespan and fertility performance, presence of DNA fragmentation, as well as a significant modification in the expression levels of genes involved in stress responses, DNA damage recognition and apoptosis pathway. Interestingly, we found that, within the investigated experimental conditions, the toxic effects in the exposed organisms were directly related to the concentration of the AuNPs administered, irrespective of their size

Calcified Algae for Tissue Engineering.

This book presents the latest advances in marine structures and related biomaterials for applications in both soft- and hard-tissue engineering, as well as controlled drug delivery