Differential impact of severe drought on infant mortality in two sympatric neotropical primates

Extreme climate events can have important consequences for the dynamics of natural populations, and severe droughts are predicted to become more common and intense due to climate change. We analysed infant mortality in relation to drought in two primate species (white-faced capuchins, Cebus capucinus imitator, and Geoffroy's spider monkeys, Ateles geoffroyi) in a tropical dry forest in northwestern Costa Rica. Our survival analyses combine several rare and valuable long-term datasets, including long-term primate life-history, landscape-scale fruit abundance, food-tree mortality, and climate conditions. Infant capuchins showed a threshold mortality response to drought, with exceptionally high mortality during a period of intense drought, but not during periods of moderate water shortage. By contrast, spider monkey females stopped reproducing during severe drought, and the mortality of infant spider monkeys peaked later during a period of low fruit abundance and high food-tree mortality linked to the drought. These divergent patterns implicate differing physiology, behaviour or associated factors in shaping species-specific drought responses. Our findings link predictions about the Earth's changing climate to environmental influences on primate mortality risk and thereby improve our understanding of how the increasing severity and frequency of droughts will affect the dynamics and conservation of wild primates

Pathway-Specific Polygenic Risk Scores as Predictors of Amyloid-beta Deposition and Cognitive Function in a Sample at Increased Risk for Alzheimer's Disease

Polygenic risk scores (PRSs) have been used to combine the effects of variants with small effects identified by genome-wide association studies. We explore the potential for using pathway-specific PRSs as predictors of early changes in Alzheimer’s disease (AD)-related biomarkers and cognitive function. Participants were from the Wisconsin Registry for Alzheimer’s Prevention, a longitudinal study of adults who were cognitively asymptomatic at enrollment and enriched for a parental history of AD. Using genes associated with AD in the International Genomics of Alzheimer’s Project’s meta-analysis, we identified clusters of genes that grouped into pathways involved in amyloid-β (Aβ) deposition and neurodegeneration: Aβ clearance, cholesterol metabolism, and immune response. Weighted pathway-specific and overall PRSs were developed and compared to APOE alone. Mixed models were used to assess whether each PRS was associated with cognition in 1,200 individuals, cerebral Aβ deposition measured using amyloid ligand (Pittsburgh compound B) positron emission imaging in 168 individuals, and cerebrospinal fluid Aβ deposition, neurodegeneration, and tau pathology in 111 individuals, with replication performed in an independent sample. We found that PRSs including APOE appeared to be driven by the inclusion of APOE, suggesting that the pathway-specific PRSs used here were not more predictive than an overall PRS or APOE alone. However, pathway-specific PRSs could prove to be useful as more knowledge is gained on the genetic variants involved in specific biological pathways of AD

The use of telehealth for diabetes management: a qualitative study of telehealth provider perceptions

BACKGROUND: Monitoring and Messaging Devices (MMDs) are telehealth systems used by patients in their homes, and are designed to promote patient self-management, patient education, and clinical monitoring and follow-up activities. Although these systems have been widely promoted by health care systems, including the Veterans Health Administration, very little information is available on factors that facilitate use of the MMD system, or on barriers to use. METHODS: We conducted in-depth qualitative interviews with clinicians using MMD-based telehealth programs at two Veterans Affairs Medical Centers in the Midwestern United States. RESULTS: Findings suggest that MMD program enrollment is limited by both clinical and non-clinical factors, and that patients have varying levels of program participation and system use. Telehealth providers see MMDs as a useful tool for monitoring patients who are interested in working on management of their disease, but are concerned with technical challenges and the time commitment required to use MMDs. CONCLUSION: Telehealth includes a rapidly evolving and potentially promising range of technologies for meeting the growing number of patients and clinicians who face the challenges of diabetes care, and future research should explore the most effective means of ensuring successful program implementation

Escherichia coli induces apoptosis and proliferation of mammary cells

Mammary cell apoptosis and proliferation were assessed after injection of Escherichia coli into the left mammary quarters of six cows. Bacteriological analysis of foremilk samples revealed coliform infection in the injected quarters of four cows. Milk somatic cell counts increased in these quarters and peaked at 24 h after bacterial injection. Body temperature also increased, peaking at 12 h postinjection, The number of apoptotic cells was significantly higher in the mastitic tissue than in the uninfected control. Expression of Bax and interleukin-1 beta converting enzyme increased in the mastitic tissue at 24 h and 72 h postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ significantly from the control at 72 h postinfection, Induction of matrix metalloproteinase-g, stromelysin-1 and urokinase-type plasminogen activator was also observed in the mastitic tissue. Moreover, cell proliferation increased in the infected tissue, These results demonstrate that Escherichia coli-induced mastitis promotes apoptosis and cell proliferation

Managerial Work in a Practice-Embodying Institution - The role of calling, the virtue of constancy

What can be learned from a small scale study of managerial work in a highly marginal and under-researched working community? This paper uses the ‘goods-virtues-practices-institutions’ framework to examine the managerial work of owner-directors of traditional circuses. Inspired by MacIntyre’s arguments for the necessity of a narrative understanding of the virtues, interviews explored how British and Irish circus directors accounted for their working lives. A purposive sample was used to select subjects who had owned and managed traditional touring circuses for at least 15 years, a period in which the economic and reputational fortunes of traditional circuses have suffered badly. This sample enabled the research to examine the self-understanding of people who had, at least on the face of it, exhibited the virtue of constancy. The research contributes to our understanding of the role of the virtues in organizations by presenting evidence of an intimate relationship between the virtue of constancy and a ‘calling’ work orientation. This enhances our understanding of the virtues that are required if management is exercised as a domain-related practice

A novel potent Fas agonist for selective depletion of tumor cells in hematopoietic transplants

There remains a clear need for effective tumor cell purging in autologous stem cell transplantation (ASCT) where residual malignant cells within the autograft contribute to disease relapse. Here we propose the use of a novel Fas agonist with potent pro-apoptotic activity, termed MegaFasL, as an effective ex-vivo purging agent. MegaFasL selectively kills hematological cancer cells from lymphomas and leukemias and prevents tumor development at concentrations that do not reduce the functional capacity of human hematopoietic stem/progenitor cells both in in vitro and in in vivo transplantation models. These findings highlight the potential use of MegaFasL as an ex-vivo purging agent in ASCT

The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p