Although the returns of customer participation on new product development (NPD) performance can vary substantially, the current literature lacks a systematic conceptual and empirical integration ...showing when customer participation is valuable in enhancing NPD performance. Building on knowledge management theory, the authors present a conceptual framework that synthesizes a variety of contingency factors. A meta-analysis empirically examines the moderating effects of contextual factors between customer participation and NPD performance. The analysis reveals that involving customers in the ideation and launch stages of NPD improves new product financial performance directly as well as indirectly through acceleration of time to market, whereas customer participation in the development phase slows down time to market, deteriorating new product financial performance. Furthermore, the benefits of customer participation on NPD performance are greater in technologically turbulent NPD projects, in emerging countries, in low-tech industries, for business customers, and for small firms. The authors discuss several theoretical and managerial implications about when to engage customers in the innovation process.
In a study of fluid resuscitation, patients received 6% hydroxyethyl starch (HES; 130/0.4) or saline until ICU discharge or death or for 90 days. There was no significant difference in 90-day ...mortality, although more patients in the HES group received renal-replacement therapy.
The administration of intravenous fluids to increase intravascular volume is a frequent intervention in the intensive care unit (ICU), but the choice of resuscitation fluid remains controversial.
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Globally, 0.9% sodium chloride (saline) is the most commonly used fluid, although colloids are administered as often as crystalloids, and hydroxyethyl starch (HES) is the most frequently used colloid.
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Several studies have questioned the safety of HES in critically ill patients, with particular concern that its use increases the risk of acute kidney injury.
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Most concern has focused on the use of concentrated HES solutions (10%) with a molecular weight of . . .
Radio tracking of the MESSENGER spacecraft has provided a model of Mercury's gravity field. In the northern hemisphere, several large gravity anomalies, including candidate mass concentrations ...(mascons), exceed 100 mi Hi-Galileos (mgal). Mercury's northern hemisphere crust is thicker at low latitudes and thinner in the polar region and shows evidence for thinning beneath some impact basins. The low-degree gravity field, combined with planetary spin parameters, yields the moment of inertia CIMR² = 0.353 ± 0.017, where M and R are Mercury's mass and radius, and a ratio of the moment of inertia of Mercury's solid outer shell to that of the planet of CJC = 0.452 ± 0.035. A model for Mercury's radial density distribution consistent with these results includes a solid silicate crust and mantle overlying a solid iron-sulfide layer and an iron-rich liquid outer core and perhaps a solid inner core.
Gay and bisexual men and other men who have sex with men (MSM) account for more than two thirds of new HIV infections in the U.S., with Black MSM experiencing the greatest burden. Antiretroviral ...pre-exposure prophylaxis (PrEP) can reduce MSM's vulnerability to HIV infection. Uptake of PrEP has been limited, particularly among racial and ethnic minority MSM. Four semi-structured focus groups with gay and bisexual men and other MSM at risk for HIV infection were convened in Boston and Jackson in late 2013. The analysis plan utilized a within-case, across-case approach to code and analyze emerging themes, and to compare results across the two cities. Participants recruited in Jackson were primarily Black gay men, while Boston participants were mostly non-Hispanic White gay men. Participants in both sites shared concerns about medication side effects and culturally insensitive health care for gay men. Jackson participants described stronger medical mistrust, and more frequently described experiences of anti-gay and HIV related stigma. Multiple addressable barriers to PrEP uptake were described. Information about side effects should be explicitly addressed in PrEP education campaigns. Providers and health departments should address medical mistrust, especially among Black gay and bisexual men and other MSM, in part by training providers in how to provide affirming, culturally competent care. Medicaid should be expanded in Mississippi to cover low-income young Black gay and bisexual men and other MSM.
Full-length RNA sequencing (RNA-Seq) has been applied to bulk tissue, cell lines and sorted cells to characterize transcriptomes, but applying this technology to single cells has proven to be ...difficult, with less than ten single-cell transcriptomes having been analyzed thus far. Although single splicing events have been described for ≤200 single cells with statistical confidence, full-length mRNA analyses for hundreds of cells have not been reported. Single-cell short-read 3' sequencing enables the identification of cellular subtypes, but full-length mRNA isoforms for these cell types cannot be profiled. We developed a method that starts with bulk tissue and identifies single-cell types and their full-length RNA isoforms without fluorescence-activated cell sorting. Using single-cell isoform RNA-Seq (ScISOr-Seq), we identified RNA isoforms in neurons, astrocytes, microglia, and cell subtypes such as Purkinje and Granule cells, and cell-type-specific combination patterns of distant splice sites. We used ScISOr-Seq to improve genome annotation in mouse Gencode version 10 by determining the cell-type-specific expression of 18,173 known and 16,872 novel isoforms.
There is compelling evidence that epithelial cells (ECs) at mucosal surfaces, beyond their role in creating a physical barrier, are integral components of innate and adaptive immunity. The capacity ...of these cells to license the functions of specific immune cell populations in the airway and gastrointestinal tract offers the prospect of novel therapeutic strategies to target multiple inflammatory diseases in which barrier immunity is dysregulated. In this review, we discuss the critical functions of EC-derived thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and IL-33 in the development and regulation of T-helper 2 (Th2) cytokine-dependent immune responses. We first highlight recent data that have provided new insights into the factors that control expression of this triad of cytokines and their receptors. In addition, we review their proinflammatory and immunoregulatory functions in models of mucosal infection and inflammation. Lastly, we discuss new findings indicating that despite their diverse structural features and differential expression of their receptors, TSLP, IL-25, and IL-33 cross-regulate one another and share overlapping properties that influence Th2 cytokine-dependent responses at mucosal sites.
Human health impacts of ecosystem alteration Myers, Samuel S.; Gaffikin, Lynne; Golden, Christopher D. ...
Proceedings of the National Academy of Sciences - PNAS,
11/2013, Letnik:
110, Številka:
47
Journal Article
Recenzirano
Odprti dostop
Human activity is rapidly transforming most of Earth’s natural systems. How this transformation is impacting human health, whose health is at greatest risk, and the magnitude of the associated ...disease burden are relatively new subjects within the field of environmental health. We discuss what is known about the human health implications of changes in the structure and function of natural systems and propose that these changes are affecting human health in a variety of important ways. We identify several gaps and limitations in the research that has been done to date and propose a more systematic and comprehensive approach to applied research in this field. Such efforts could lead to a more robust understanding of the human health impacts of accelerating environmental change and inform decision making in the land-use planning, environmental conservation, and public health policy realms.
Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant ...studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we report a genome-wide association study of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 36,041 UK Biobank participants, with replication in 2184 participants from the Multi-Ethnic Study of Atherosclerosis. We identify 45 previously unreported loci associated with cardiac structure and function, many near well-established genes for Mendelian cardiomyopathies. A polygenic score of MRI-derived left ventricular end systolic volume strongly associates with incident DCM in the general population. Even among carriers of TTN truncating mutations, this polygenic score influences the size and function of the human heart. These results further implicate common genetic polymorphisms in the pathogenesis of DCM.
Antiretroviral pre-exposure prophylaxis (PrEP) has been demonstrated to decrease HIV acquisition in multiple efficacy trials, but medication adherence is critical, and was suboptimal in several ...studies. Fifty HIV-uninfected at risk men who have sex with men (MSM) were randomized to a cognitive behavioral intervention condition or a time and session-matched comparison counseling intervention. The experimental intervention entailed four nurse-delivered initial and two booster sessions based on Life-Steps, an ART treatment adherence intervention. The comparison condition provided information and supportive counseling. The primary analyses compared adherence (Wisepill and tenofovir plasma levels) at 3 and 6 months. Fifty-eight MSM were screened to enroll 50 participants. Median age was 38.2 years old, 86% were white; 64% had completed college. Wisepill adherence was high in both groups, and not statistically different. Plasma tenofovir levels were significantly higher in the intervention group at 6 months using mean substitution analysis (i.e., computing missing variables) (p = 0.037), however, in the completer analyses (i.e., using only those completing all study visits), there were no statistically significant differences between randomization conditions. Medication adherence was high across a cognitive-behavioral (Life-Steps) and time-matched counseling intervention for PrEP adherence, with some evidence suggesting superiority of Life-Steps in this pilot RCT. Further evaluation in a fully powered efficacy trial is warranted to assess the robustness of this intervention.
Multiple cytokines, including interleukin 6 (IL-6), IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine receptor subunit. In this study, we ...describe a patient with a homozygous mutation of
(encoding GP130 p.N404Y) who presented with recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, and an impaired acute-phase response, as well as skeletal abnormalities including craniosynostosis. The p.N404Y missense substitution is associated with loss of IL-6, IL-11, IL-27, and OSM signaling but a largely intact LIF response. This study identifies a novel immunodeficiency with phenotypic similarities to STAT3 hyper-IgE syndrome caused by loss of function of GP130.
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