537 research outputs found

    Impact of Marginal Exciton-Charge-Transfer State Offset on Charge Generation and Recombination in Polymer:Fullerene Solar Cells

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    The energetic offset between the initial photoexcited state and charge-transfer (CT) state in organic heterojunction solar cells influences both charge generation and open-circuit voltage (Voc). Here, we use time-resolved spectroscopy and voltage loss measurements to analyze the effect of the exciton–CT state offset on charge transfer, separation, and recombination processes in blends of a low-band-gap polymer (INDT-S) with fullerene derivatives of different electron affinity (PCBM and KL). For the lower exciton–CT state offset blend (INDT-S:PCBM), both photocurrent generation and nonradiative voltage losses are lower. The INDT-S:PCBM blend shows different excited-state dynamics depending on whether the donor or acceptor is photoexcited. Surprisingly, the charge recombination dynamics in INDT-S:PCBM are distinctly faster than those in INDT-S:KL upon excitation of the donor. We reconcile these observations using a kinetic model and by considering hybridization between the lowest excitonic and CT states. The modeling results show that this hybridization can significantly reduce Voc losses while still allowing reasonable charge generation efficiency

    Ten steps or climbing a mountain: A study of Australian health professionals' perceptions of implementing the baby friendly health initiative to protect, promote and support breastfeeding

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    Background: The Baby Friendly Hospital (Health) Initiative (BFHI) is a global initiative aimed at protecting, promoting and supporting breastfeeding and is based on the ten steps to successful breastfeeding. Worldwide, over 20,000 health facilities have attained BFHI accreditation but only 77 Australian hospitals (approximately 23%) have received accreditation. Few studies have investigated the factors that facilitate or hinder implementation of BFHI but it is acknowledged this is a major undertaking requiring strategic planning and change management throughout an institution. This paper examines the perceptions of BFHI held by midwives and nurses working in one Area Health Service in NSW, Australia. Methods: The study used an interpretive, qualitative approach. A total of 132 health professionals, working across four maternity units, two neonatal intensive care units and related community services, participated in 10 focus groups. Data were analysed using thematic analysis. Results: Three main themes were identified: ‘Belief and Commitment’; ‘Interpreting BFHI’ and ‘Climbing a Mountain’. Participants considered the BFHI implementation a high priority; an essential set of practices that would have positive benefits for babies and mothers both locally and globally as well as for health professionals. It was considered achievable but would take commitment and hard work to overcome the numerous challenges including a number of organisational constraints. There were, however, differing interpretations of what was required to attain BFHI accreditation with the potential that misinterpretation could hinder implementation. A model described by Greenhalgh and colleagues on adoption of innovation is drawn on to interpret the findings. Conclusion: Despite strong support for BFHI, the principles of this global strategy are interpreted differently by health professionals and further education and accurate information is required. It may be that the current processes used to disseminate and implement BFHI need to be reviewed. The findings suggest that there is a contradiction between the broad philosophical stance and best practice approach of this global strategy and the tendency for health professionals to focus on the ten steps as a set of tasks or a checklist to be accomplished. The perceived procedural approach to implementation may be contributing to lower rates of breastfeeding continuation

    IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth infection.

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    Type 2 immune responses are essential in protection against intestinal helminth infections. In this study we show that IL-22, a cytokine important in defence against bacterial infections in the intestinal tract, is also a critical mediator of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite normal levels of type 2 cytokine production. The impaired worm expulsion correlated with reduced goblet cell hyperplasia and reduced expression of goblet cell markers. We further confirmed our findings in a second nematode model, the murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a similar phenotype to that seen in N.brasiliensis infection, with impaired worm expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis demonstrated that IL-22 is able to directly induce the expression of several goblet cell markers, including mucins. Taken together, our findings reveal that IL-22 plays an important role in goblet cell activation, and thus, a key role in anti-helminth immunity

    Health care costs, utilization and patterns of care following Lyme disease

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    BACKGROUND:Lyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome - a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Little is known about the impact of Lyme disease or post-treatment Lyme disease symptoms (PTLDS) on health care costs and utilization in the United States. OBJECTIVES:1) to examine the impact of Lyme disease on health care costs and utilization, 2) to understand the relationship between Lyme disease and the probability of developing PTLDS, 3) to understand how PTLDS may impact health care costs and utilization. METHODS:This study utilizes retrospective data on medical claims and member enrollment for persons aged 0-64 years who were enrolled in commercial health insurance plans in the United States between 2006-2010. 52,795 individuals treated for Lyme disease were compared to 263,975 matched controls with no evidence of Lyme disease exposure. RESULTS:Lyme disease is associated with 2,968highertotalhealthcarecosts(952,968 higher total health care costs (95% CI: 2,807-3,128, p<.001) and 87% more outpatient visits (95% CI: 86%-89%, p<.001) over a 12-month period, and is associated with 4.77 times greater odds of having any PTLDS-related diagnosis, as compared to controls (95% CI: 4.67-4.87, p<.001). Among those with Lyme disease, having one or more PTLDS-related diagnosis is associated with 3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses. CONCLUSIONS:Lyme disease is associated with increased costs above what would be expected for an easy to treat infection. The presence of PTLDS-related diagnoses after treatment is associated with significant health care costs and utilization

    Efficacy of praziquantel and artemisinin derivatives for the treatment and prevention of human schistosomiasis: a systematic review and meta-analysis

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    <p>Abstract</p> <p>Background</p> <p>Praziquantel has been used as first-line drug for chemotherapy of schistosomiasis since 1984. Besides praziquantel, artemether and artesunate have also been used for the control of this infectious disease since late 1990s. In this article, we conducted a systematic review and meta-analysis to evaluate the antischistosomal efficacy of different medication strategies including monotherapy or combination therapies of these drugs.</p> <p>Results</p> <p>A number of 52 trials from 38 articles published in peer-reviewed journals before July 2011 were selected for analysis after searching the following literature databases: the Cochrane Library, PubMed/Medline, ISI Web of Science, Chinese Biomedicine Literature Database, and China National Knowledge Infrastructure. Our meta-analyses showed that a dosage of 30-60 mg/kg praziquantel compared with placebo produced a protection rate of about 76% (95% CI: 67%-83%) for treating human schistosomiasis, which varied from 70% to 76% with no significant differences among the subspecies <it>S. haematobium</it>, <it>S. japonicum </it>or <it>S. mansoni</it>. Protection rates were higher when praziquantel doses were elevated, as concluded from the nRCTs results: the protection rate of praziquantel at 40 mg/kg was 52% (95% CI: 49%-55%), and it increased to 91% (95% CI: 88%-92%) when the dosages were elevated to 60/80/100 mg/kg divided two or more doses. Multiple doses of artemether or artesunate over 1- or 2-week intervals resulted in protection rates of 65% to 97% for preventing schistosomiasis, and increased doses and shorter medication intervals improved their efficacies. Praziquantel and artemisinin derivatives (artemether or artesunate) in combination resulted in a higher protection rate of 84% (95% CI: 64%-91%) than praziquantel monotherapy for treatment. praziquantel and artesunate in combination had a great protection rate of 96% (95% CI: 78%-99%) for preventing schistosomes infection.</p> <p>Conclusions</p> <p>According to the results, praziquantel remains effective in schistosomiasis treatment, and multiple doses would improve its efficacy; meanwhile, praziquantel is also a good drug for preventing acute schistosomiasis morbidity. It's better to use multiple doses of artemether or artesunate with 1- or 2-week intervals for prevention against schistosome infection. Praziquantel and artemether or artesunate in combination perform better in treatment than praziquantel monotherapy, and they are especially suitable for treating the patients with repeated exposure to infected water.</p

    Incidence and prevalence of patellofemoral pain: a systematic review and meta-analysis

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    Background: Patellofemoral pain is considered one of the most common forms of knee pain, affecting adults, adolescents, and physically active populations. Inconsistencies in reported incidence and prevalence exist and in relation to the allocation of healthcare and research funding, there is a clear need to accurately understand the epidemiology of patellofemoral pain. Methods: An electronic database search was conducted, as well as grey literature databases, from inception to June 2017. Two authors independently selected studies, extracted data and appraised methodological quality. If heterogeneous, data were analysed descriptively. Where studies were homogeneous, data were pooled through a meta-analysis. Results: 23 studies were included. Annual prevalence for patellofemoral pain in the general population was reported as 22.7%, and adolescents as 28.9%. Incidence rates in military recruits ranged from 9.7 – 571.4/1,000 person-years, amateur runners in the general population at 1080.5/1,000 person-years and adolescents amateur athletes 5.1% - 14.9% over 1 season. One study reported point prevalence within military populations as 13.5%. The pooled estimate for point prevalence in adolescents was 7.2% (95% Confidence Interval: 6.3% - 8.3%), and in female only adolescent athletes was 22.7% (95% Confidence Interval 17.4% - 28.0%). Conclusion: This review demonstrates high incidence and prevalence levels for patellofemoral pain. Within the context of this, and poor long term prognosis and high disability levels, PFP should be an urgent research priority

    Enhanced Discrimination of Malignant from Benign Pancreatic Disease by Measuring the CA 19-9 Antigen on Specific Protein Carriers

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    The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer), owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67–80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease

    Colorectal Cancer Stem Cells Are Enriched in Xenogeneic Tumors Following Chemotherapy

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    Patients generally die of cancer after the failure of current therapies to eliminate residual disease. A subpopulation of tumor cells, termed cancer stem cells (CSC), appears uniquely able to fuel the growth of phenotypically and histologically diverse tumors. It has been proposed, therefore, that failure to effectively treat cancer may in part be due to preferential resistance of these CSC to chemotherapeutic agents. The subpopulation of human colorectal tumor cells with an ESA(+)CD44(+) phenotype are uniquely responsible for tumorigenesis and have the capacity to generate heterogeneous tumors in a xenograft setting (i.e. CoCSC). We hypothesized that if non-tumorigenic cells are more susceptible to chemotherapeutic agents, then residual tumors might be expected to contain a higher frequency of CoCSC.Xenogeneic tumors initiated with CoCSC were allowed to reach approximately 400 mm(3), at which point mice were randomized and chemotherapeutic regimens involving cyclophosphamide or Irinotecan were initiated. Data from individual tumor phenotypic analysis and serial transplants performed in limiting dilution show that residual tumors are enriched for cells with the CoCSC phenotype and have increased tumorigenic cell frequency. Moreover, the inherent ability of residual CoCSC to generate tumors appears preserved. Aldehyde dehydrogenase 1 gene expression and enzymatic activity are elevated in CoCSC and using an in vitro culture system that maintains CoCSC as demonstrated by serial transplants and lentiviral marking of single cell-derived clones, we further show that ALDH1 enzymatic activity is a major mediator of resistance to cyclophosphamide: a classical chemotherapeutic agent.CoCSC are enriched in colon tumors following chemotherapy and remain capable of rapidly regenerating tumors from which they originated. By focusing on the biology of CoCSC, major resistance mechanisms to specific chemotherapeutic agents can be attributed to specific genes, thereby suggesting avenues for improving cancer therapy

    Chronic Helminth Infections Protect Against Allergic Diseases by Active Regulatory Processes

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    Developed countries are suffering from an epidemic rise in immunologic disorders, such as allergy-related diseases and certain autoimmunities. Several studies have demonstrated a negative association between helminth infections and inflammatory diseases (eg, allergy), providing a strong case for the involvement of helminth infections in this respect. However, some studies point in the opposite direction. The discrepancy may be explained by differences in frequency, dose, time, and type of helminth. In this review, new studies are discussed that may support the concept that chronic helminth infections in particular—but not acute infections—are associated with the expression of regulatory networks necessary for downmodulating allergic immune responses to harmless antigens. Furthermore, different components of regulatory networks are highlighted, such as the role of regulatory T and B cells, modulation of dendritic cells, early innate signals from structural cells (eg, epithelial cells), and their individual contributions to protection against allergic diseases. It is of great interest to define and characterize specific helminth molecules that have profound immunomodulatory capacities as targets for therapeutic application in the treatment or prophylaxis of allergic manifestations

    Drosophila melanogaster as a Model Host for the Burkholderia cepacia Complex

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    Colonization with bacterial species from the Burkholderia cepacia complex (Bcc) is associated with fast health decline among individuals with cystic fibrosis. In order to investigate the virulence of the Bcc, several alternative infection models have been developed. To this end, the fruit fly is increasingly used as surrogate host, and its validity to enhance our understanding of host-pathogen relationships has been demonstrated with a variety of microorganisms. Moreover, its relevance as a suitable alternative to mammalian hosts has been confirmed with vertebrate organisms.The aim of this study was to establish Drosophila melanogaster as a surrogate host for species from the Bcc. While the feeding method proved unsuccessful at killing the flies, the pricking technique did generate mortality within the populations. Results obtained with the fruit fly model are comparable with results obtained using mammalian infection models. Furthermore, validity of the Drosophila infection model was confirmed with B. cenocepacia K56-2 mutants known to be less virulent in murine hosts or in other alternative models. Competitive index (CI) analyses were also performed using the fruit fly as host. Results of CI experiments agree with those obtained with mammalian models.We conclude that Drosophila is a useful alternative infection model for Bcc and that fly pricking assays and competition indices are two complementary methods for virulence testing. Moreover, CI results indicate that this method is more sensitive than mortality tests
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