Policy and Institutional Support for CA Development (Examples from Europe, Africa, Asia)

Policy and Institutional Support for CA Development (Examples from Europe, Africa, Asia

A Link between Meiotic Prophase Progression and Crossover Control

During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealed that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4) and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors

Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient's tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

The effective action of D-branes in Calabi-Yau orientifold compactifications

In this review article we study type IIB superstring compactifications in the presence of space-time filling D-branes while preserving N=1 supersymmetry in the effective four-dimensional theory. This amount of unbroken supersymmetry and the requirement to fulfill the consistency conditions imposed by the space-time filling D-branes lead to Calabi-Yau orientifold compactifications. For a generic Calabi-Yau orientifold theory with space-time filling D3- or D7-branes we derive the low-energy spectrum. In a second step we compute the effective N=1 supergravity action which describes in the low-energy regime the massless open and closed string modes of the underlying type IIB Calabi-Yau orientifold string theory. These N=1 supergravity theories are analyzed and in particular spontaneous supersymmetry breaking induced by non-trivial background fluxes is studied. For D3-brane scenarios we compute soft-supersymmetry breaking terms resulting from bulk background fluxes whereas for D7-brane systems we investigate the structure of D- and F-terms originating from worldvolume D7-brane background fluxes. Finally we relate the geometric structure of D7-brane Calabi-Yau orientifold compactifications to N=1 special geometry.Comment: LaTeX, 133 pages, Ph.D. Thesis (Advisor: Jan Louis); v2: references adde

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

BACKGROUND & AIMS: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarkerdriven therapeutic strategy targeting DDR and replication stress in PC. METHODS: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. RESULTS: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. CONCLUSIONS: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.Stephan B. Dreyer ... Karin S. Kassahn ... et al

Genomic and molecular analyses identify molecular subtypes of pancreatic cancer recurrence

Pancreatic cancer (PC) remains a highly lethal malignancy, and most patients with localized disease that undergo surgical resection still succumb to recurrent disease. Pattern of recurrence after pancreatectomy is heterogenous, with some studies illustrating that site of recurrence can be associated with prognosis.1 Another study suggested that tumors that develop local and distant recurrence can be regarded as a homogenous disease with similar outcomes.2 Here we investigate novel molecular determinants of recurrence pattern after pancreatectomy for PC

Household Factors Influencing Participation in Bird Feeding Activity: A National Scale Analysis

Ameliorating pressures on the ecological condition of the wider landscape outside of protected areas is a key focus of conservation initiatives in the developed world. In highly urbanized nations, domestic gardens can play a significant role in maintaining biodiversity and facilitating human-wildlife interactions, which benefit personal and societal health and well-being. The extent to which sociodemographic and socioeconomic factors are associated with engagement in wildlife gardening activities remain largely unresolved. Using two household-level survey datasets gathered from across Britain, we determine whether and how the socioeconomic background of a household influences participation in food provision for wild birds, the most popular and widespread form of human-wildlife interaction. A majority of households feed birds (64% across rural and urban areas in England, and 53% within five British study cities). House type, household size and the age of the head of the household were all important predictors of bird feeding, whereas gross annual household income, the occupation of the head of the household, and whether the house is owned or rented were not. In both surveys, the prevalence of bird feeding rose as house type became more detached and as the age of the head of the household increased. A clear, consistent pattern between households of varying size was less evident. When regularity of food provision was examined in the study cities, just 29% of households provided food at least once a week. The proportion of households regularly feeding birds was positively related to the age of the head of the household, but declined with gross annual income. As concerns grow about the lack of engagement between people and the natural environment, such findings are important if conservation organizations are successfully to promote public participation in wildlife gardening specifically and environmentally beneficial behaviour in society more generally