284 research outputs found
FAK-inhibition opens the door to checkpoint immunotherapy in Pancreatic Cancer
Immunotherapy has had remarkable success in the treatment of some cancer types. However, pancreatic cancer has remained largely refractory to immunotherapy, including immune checkpoint inhibitors. Recently, Jiang and colleagues identified a key role for FAK in regulating the composition of the fibrotic and immuno-suppressive pancreatic tumour niche, and showed that FAK inhibitors can be used in combination with immune checkpoint blockade and gemcitabine chemotherapy to significantly delay pancreatic tumour progression. This study further supports the use of FAK inhibitors in combination with immunotherapy
Why do women not use antenatal services in low and middle income countries? A metasynthesis of qualitative studies
Background:
Almost 50% of women in low & middle income countries (LMICβs) donβt receive adequate antenatal care. Womenβs views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies.
Methods and Findings:
Using a pre-determined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMICβs who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line of argument synthesis. We derived policy relevant hypotheses from the findings.
We included 21 papers representing the views of more than 1230 women from 15 countries. Three key themes were identified: βPregnancy as socially risky and physiologically healthyβ; βResource use and survival in conditions of extreme povertyβand βNot getting it right first timeβ. The line of argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralized, risk-focused antenatal care programmes may be at odds with the resources, beliefs and experiences of pregnant women who underuse antenatal services.
Conclusions:
Our findings suggest that there may be a mis-alignment between current antenatal provision and the social and cultural context of some women in LMICβs. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences are likely to be underused, especially when attendance generates increased personal risks of lost family resource or physical danger during travel; when the promised care is not delivered due to resource constraints; and when women experience covert or overt abuse in care settings
The Worldvolume Action of Kink Solitons in AdS Spacetime
A formalism is presented for computing the higher-order corrections to the
worldvolume action of co-dimension one solitons. By modifying its potential, an
explicit "kink" solution of a real scalar field in AdS spacetime is found. The
formalism is then applied to explicitly compute the kink worldvolume action to
quadratic order in two expansion parameters--associated with the hypersurface
fluctuation length and the radius of AdS spacetime respectively. Two
alternative methods are given for doing this. The results are expressed in
terms of the trace of the extrinsic curvature and the intrinsic scalar
curvature. In addition to conformal Galileon interactions, we find a
non-Galileon term which is never sub-dominant. This method can be extended to
any conformally flat bulk spacetime.Comment: 32 pages, 3 figures, typos corrected and additional comments adde
The breadth of primary care: a systematic literature review of its core dimensions
Background: Even though there is general agreement that primary care is the linchpin of effective health care delivery, to date no efforts have been made to systematically review the scientific evidence supporting this supposition. The aim of this study was to examine the breadth of primary care by identifying its core dimensions and to assess the evidence for their interrelations and their relevance to outcomes at (primary) health system level.
Methods: A systematic review of the primary care literature was carried out, restricted to English language journals reporting original research or systematic reviews. Studies published between 2003 and July 2008 were searched in MEDLINE, Embase, Cochrane Library, CINAHL, King's Fund Database, IDEAS Database, and EconLit.
Results: Eighty-five studies were identified. This review was able to provide insight in the complexity of primary care as a multidimensional system, by identifying ten core dimensions that constitute a primary care system. The structure of a primary care system consists of three dimensions: 1. governance; 2. economic conditions; and 3. workforce development. The primary care process is determined by four dimensions: 4. access; 5. continuity of care; 6. coordination of care; and 7. comprehensiveness of care. The outcome of a primary care system includes three dimensions: 8. quality of care; 9. efficiency care; and 10. equity in health. There is a considerable evidence base showing that primary care contributes through its dimensions to overall health system performance and health.
Conclusions: A primary care system can be defined and approached as a multidimensional system contributing to overall health system performance and health
Effects of sample handling and storage on quantitative lipid analysis in human serum
There is sparse information about specific storage and handling protocols that minimize analytical error and variability in samples evaluated by targeted metabolomics. Variance components that affect quantitative lipid analysis in a set of human serum samples were determined. The effects of freeze-thaw, extraction state, storage temperature, and freeze-thaw prior to density-based lipoprotein fractionation were quantified. The quantification of high abundance metabolites, representing the biologically relevant lipid species in humans, was highly repeatable (with coefficients of variation as low as 0.01 and 0.02) and largely unaffected by 1β3 freeze-thaw cycles (with 0β8% of metabolites affected in each lipid class). Extraction state had effects on total lipid class amounts, including decreased diacylglycerol and increased phosphatidylethanolamine in thawed compared with frozen samples. The effects of storage temperature over 1Β week were minimal, with 0β4% of metabolites affected by storage at 4Β°C, β20Β°C, or β80Β°C in most lipid classes, and 19% of metabolites in diacylglycerol affected by storage at β20Β°C. Freezing prior to lipoprotein fractionation by density ultracentrifugation decreased HDL free cholesterol by 37% and VLDL free fatty acid by 36%, and increased LDL cholesterol ester by 35% compared with fresh samples. These findings suggest that density-based fractionation should preferably be undertaken in fresh serum samples because up to 37% variability in HDL and LDL cholesterol could result from a single freeze-thaw cycle. Conversely, quantitative lipid analysis within unfractionated serum is minimally affected even with repeated freeze-thaw cycles
EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.
Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease
The Interplay Between Post-Critical Beliefs and Anxiety: An Exploratory Study in a Polish Sample
The present research investigates the relationship between anxiety and the religiosity dimensions that Wulff (Psychology of religion: classic and contemporary views, Wiley, New York, 1991; Psychology of religion. Classic and contemporary views, Wiley, New York, 1997; Psychologia religii. Klasyczna i wspΓ³Εczesna, Wydawnictwo Szkolne i Pedagogiczne, Warszawa, 1999) described as Exclusion vs. Inclusion of Transcendence and Literal vs. Symbolic. The researchers used the Post-Critical Belief scale (Hutsebaut in J Empir Theol 9(2):48β66, 1996; J Empir Theol 10(1):39β54, 1997) to measure Wulffβs religiosity dimensions and the IPAT scale (Krug et al. 1967) to measure anxiety. Results from an adult sample (NΒ =Β 83) suggest that three dimensions show significant relations with anxiety. Orthodoxy correlated negatively with suspiciousness (L) and positively with guilt proneness (O) factorβin the whole sample. Among women, Historical Relativism negatively correlated with suspiciousness (L), lack of integration (Q3), general anxiety and covert anxiety. Among men, Historical Relativism positively correlated with tension (Q4) and emotional instability (C), general anxiety, covert anxiety and overt anxiety. External Critique was correlated with suspiciousness (L) by men
Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever
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Restricting Microbial Exposure in Early Life Negates the Immune Benefits Associated with Gut Colonization in Environments of High Microbial Diversity
Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity.
Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the
immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological
development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared
animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires
maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolatorreared
animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were
increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in
pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent
later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals.
This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in
indoor-reared animals.
Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number
of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require
sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively
impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune
homeostasis
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