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\"Alice C. Fletcher (1838-1923), one of the few women who became anthropologists in the United States during the nineteenth century, was a pioneer in the practice of participant-observation ethnography. She focused her studies over many years among the Native tribes in Nebraska and South Dakota. Life among the Indians, Fletcher's popularized autobiographical memoir written in 1886-87 about her first fieldwork among the Sioux and the Omahas during 1881-82, remained unpublished in Fletcher's archives at the Smithsonian Institution for more than one hundred years. In it Fletcher depicts the humor and hardships of her field experiences as a middle-aged woman undertaking anthropological fieldwork alone, while showing genuine respect and compassion for Native ways and beliefs that was far ahead of her time. What emerges is a complex and fascinating picture of a woman questioning the cultural and gender expectations of nineteenth-century America while insightfully portraying rapidly changing reservation life. Fletcher's account of her early fieldwork is available here for the first time, accompanied by an essay by the editors that sheds light on Fletcher's place in the development of anthropology and the role of women in the discipline. \"-- Provided by publisher.

Introduction Angiogenesis is an early event in the pathogenesis of both psoriatic arthritis (PsA) and rheumatoid arthritis (RA); however, there are striking differences in blood vessel morphology and activation between the two arthropathies. The aim of this study was to assess if the PsA and RA joint microenvironments differentially regulate endothelial cell function. Methods PsA and RA primary synovial fibroblasts (SFC) were isolated from synovial biopsies, grown to confluence, and supernatants harvested and termed ‘conditioned media’ (CM). Human umbilical vein endothelial cells (HUVEC) were cultured with PsA SFC or RA SFC-CM (20%). HUVEC tube formation, migration, and PBMC adhesion were assessed by matrigel tube formation, wound repair, and PBMC adhesion assays. HUVEC cell surface expression of ICAM, VCAM, and E-Selectin was assessed by flow cytometry. Transcriptome analysis of genes promoting angiogenesis was performed by real-time PCR. Finally, a MSD multiplex angiogenic assay was performed on PsA SFC and RA SFC supernatants. Results Macroscopic synovitis and vascularity were similar in PsA and RA patients; however, significant differences in vascular morphological pattern were recorded with tortuous, elongated vessels observed in PsA compared to straight regular branching vessels observed in RA. Transcriptome analysis showed strong upregulation of the pro-angiogenic signature in HUVEC primed with PsA SFC-CM compared to RA SFC-CM and basal control. In parallel, paired PsA SFC-CM significantly induced HUVEC tube formation compared to that of RA SFC-CM. Furthermore, PsA SFC-CM induced HUVEC migration was paralleled by a significant induction in VEGFA, PFKFB3, ICAM-1, and MMP3 mRNA expression. A significant increase in PBMC adhesion and cell surface expression of VCAM-1, ICAM-1, and E-Selectin expression was also demonstrated in PsA SFC-CM-primed HUVEC compared to RA SFC-CM. Finally, VEGF, TSLP, Flt-1, and Tie-2 expression was elevated in PsA SFC-CM compared to RA SFC-CM, with no significant difference in other pro-angiogenic mediators including MIP-3, bFGF, PIGF, and MCP-1. Conclusion PsA SFC and RA SFC secreted factors differentially regulate endothelial cell function, with soluble mediators in the PsA joint microenvironment inducing a more pro-angiogenic phenotype compared to the RA.

Hillary Clinton is arguably one of the most polarizing political figures in American history. She burst into the national spotlight during her husband s presidential campaign, when she managed to both impress and offend the American public. Since then, Clinton has proven herself a capable public servant, with successful terms in the US Senate and as secretary of state. But controversy continually threatens to undermine her accomplishments, and it often seems that her ambitions get the best of her. This biography tells the story of the rise of remarkable woman, from her humble Midwestern beginnings to a historic run for the White House.

Background Bridges, brokers and boundary spanners facilitate transactions and the flow of information between people or groups who either have no physical or cognitive access to one another, or alternatively, who have no basis on which to trust each other. The health care sector is a context that is rich in isolated clusters, such as silos and professional “tribes,” in need of connectivity. It is a key challenge in health service management to understand, analyse and exploit the role of key agents who have the capacity to connect disparate groupings in larger systems. Methods The empirical, peer reviewed, network theory literature on brokerage roles was reviewed for the years 1994 to 2011 following PRISMA guidelines. Results The 24 articles that made up the final literature set were from a wide range of settings and contexts not just healthcare. Methods of data collection, analysis, and the ways in which brokers were identified varied greatly. We found four main themes addressed in the literature: identifying brokers and brokerage opportunities, generation and integration of innovation, knowledge brokerage, and trust. The benefits as well as the costs of brokerage roles were examined. Conclusions Collaborative networks by definition, seek to bring disparate groups together so that they can work effectively and synergistically together. Brokers can support the controlled transfer of specialised knowledge between groups, increase cooperation by liaising with people from both sides of the gap, and improve efficiency by introducing “good ideas” from one isolated setting into another. There are significant costs to brokerage. Densely linked networks are more efficient at diffusing information to all their members when compared to sparsely linked groups. This means that while a bridge across a structural hole allows information to reach actors that were previously isolated, it is not the most efficient way to transfer information. Brokers who become the holders of, or the gatekeepers to, specialised knowledge or resources can become overwhelmed by the role and so need support in order to function optimally.

Bad For You presents facts, figures and more to debunk myths about things throughout history, such as comic books, video games, and texting, that have been deemed to cause bad behavior and psychological damage in children.

Despite the considerable injury burden attributable to falls at home among the general population, few effective safety interventions have been identified. We tested the safety benefits of home modifications, including handrails for outside steps and internal stairs, grab rails for bathrooms, outside lighting, edging for outside steps, and slip-resistant surfacing for outside areas such as decks and porches. We did a single-blind, cluster-randomised controlled trial of households from the Taranaki region of New Zealand. To be eligible, participants had to live in an owner-occupied dwelling constructed before 1980 and at least one member of every household had to be in receipt of state benefits or subsidies. We randomly assigned households by electronic coin toss to either immediate home modifications (treatment group) or a 3-year wait before modifications (control group). Household members in the treatment group could not be masked to their assigned status because modifications were made to their homes. The primary outcome was the rate of falls at home per person per year that needed medical treatment, which we derived from administrative data for insurance claims. Coders who were unaware of the random allocation analysed text descriptions of injuries and coded injuries as all falls and injuries most likely to be affected by the home modifications tested. To account for clustering at the household level, we analysed all injuries from falls at home per person-year with a negative binomial generalised linear model with generalised estimating equations. Analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000779279. Of 842 households recruited, 436 (n=950 individual occupants) were randomly assigned to the treatment group and 406 (n=898 occupants) were allocated to the control group. After a median observation period of 1148 days (IQR 1085–1263), the crude rate of fall injuries per person per year was 0·061 in the treatment group and 0·072 in the control group (relative rate 0·86, 95% CI 0·66–1·12). The crude rate of injuries specific to the intervention per person per year was 0·018 in the treatment group and 0·028 in the control group (0·66, 0·43–1·00). A 26% reduction in the rate of injuries caused by falls at home per year exposed to the intervention was estimated in people allocated to the treatment group compared with those assigned to the control group, after adjustment for age, previous falls, sex, and ethnic origin (relative rate 0·74, 95% CI 0·58–0·94). Injuries specific to the home-modification intervention were cut by 39% per year exposed (0·61, 0·41–0·91). Our findings suggest that low-cost home modifications and repairs can be a means to reduce injury in the general population. Further research is needed to identify the effectiveness of particular modifications from the package tested. Health Research Council of New Zealand.

\"Describes climate change, its effects, and the controversy around it\"-- Provided by publisher.

Chimaeric human–murine adeno-associated virus (AAV) capsids are described that transduce human primary hepatocytes more efficiently than currently used AAV vectors; the novel vectors may be good clinical candidates. Models to test gene-vector viruses One of the most promising gene-therapy vectors currently in clinical trials is the rAAV8 (recombinant adeno-associated viral serotype 8) virus. Yet the performance of this, and some other AAV vectors, often fails to live up to expectations raised by the results of animal studies. Here Mark Kay et al . use a mouse model with a chimaeric murine/human liver to compare rAAV transduction efficiency in human and mouse cells. They find that the rAAV2 vector transduces both species equally well, but that AAV8 is about 20-fold less efficient at transducing human cells than mouse cells. The data correlate well with clinical data and may go some way towards explaining why rAAV8 underperforms in human trials. The authors suggest that the use of a human primary cell xenotransplant model may more accurately predict potential transduction efficiency in humans than the commonly used mouse and non-human primate models. Recombinant adeno-associated viral (rAAV) vectors have shown early promise in clinical trials 1 , 2 , 3 . The therapeutic transgene cassette can be packaged in different AAV capsid pseudotypes, each having a unique transduction profile. At present, rAAV capsid serotype selection for a specific clinical trial is based on effectiveness in animal models. However, preclinical animal studies are not always predictive of human outcome 4 , 5 , 6 , 7 , 8 . Here, in an attempt to further our understanding of these discrepancies, we used a chimaeric human–murine liver model to compare directly the relative efficiency of rAAV transduction in human versus mouse hepatocytes in vivo . As predicted from preclinical and clinical studies 4 , 5 , 8 , rAAV2 vectors functionally transduced mouse and human hepatocytes at equivalent but relatively low levels. However, rAAV8 vectors, which are very effective in many animal models, transduced human hepatocytes rather poorly—approximately 20 times less efficiently than mouse hepatocytes. In light of the limitations of the rAAV vectors currently used in clinical studies, we used the same murine chimaeric liver model to perform serial selection using a human-specific replication-competent viral library composed of DNA-shuffled AAV capsids. One chimaeric capsid composed of five different parental AAV capsids was found to transduce human primary hepatocytes at high efficiency in vitro and in vivo, and provided species-selected transduction in primary liver, cultured cells and a hepatocellular carcinoma xenograft model. This vector is an ideal clinical candidate and a reagent for gene modification of human xenotransplants in mouse models of human diseases. More importantly, our results suggest that humanized murine models may represent a more precise approach for both selecting and evaluating clinically relevant rAAV serotypes for gene therapeutic applications.