58 research outputs found
Demand for nursing competencies: an exploratory study in Taiwan's hospital system
• Along with increasing complexity of nursing services, hospital employers are demanding qualified and competent staff nurses for high quality clinical care. In Taiwan, disparities in the demand for competent nurses by employers and the supply produced by nursing educators still exist and require attention. A comprehensive understanding of the specific needs of Taiwan's medical care system for nursing services would help bridge the current gap between demand for and supply of competently trained nurses. • This exploratory study investigated hospital employers' perceptions of the extent to which the nursing skills identified by Cleary et al . [Image: Journal of Nursing Scholarship (1998) 20 (4):39–42] were needed for staff nurses in Taiwan's medical care system. There were a total of 21 nursing competencies and classification on these items was also implemented. • A cross-sectional, quantitative, survey design was conducted. Subjects' participation was voluntary, an information leaflet and an informed consent form was included in the questionnaire. A total of 89 nursing employers (nursing directors, associate directors, supervisor, or head nurse) participated, resulting in a 42.6% response rate. • Factor analysis grouped these skills into three factors: basic-level patient care, intermediate-level patient care and basic management, and advanced-level patient care and supervision. This study confirmed that levels of nursing competencies needed differed by type of hospital accreditation. These levels also varied depending on types of services provided, employers' professional titles and tenure of currently employed nurses. • The questionnaire developed for this study could be used as one of the tools to communicate demand and supply of nursing competencies between nurse educators and employers. These competencies could be used to develop a checklist for evaluating adequacy of nursing programmes in order to meet nurses' new roles and responsibilities and improve nursing care quality in the fast-changing health care environment in Taiwan.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75133/1/j.1365-2702.2003.00738.x.pd
Cdk1-Dependent Phosphorylation of Cdc13 Coordinates Telomere Elongation during Cell-Cycle Progression
SummaryElongation of telomeres by telomerase replenishes the loss of terminal telomeric DNA repeats during each cell cycle. In budding yeast, Cdc13 plays an essential role in telomere length homeostasis, partly through its interactions with both the telomerase complex and the competing Stn1-Ten1 complex. Previous studies in yeast have shown that telomere elongation by telomerase is cell cycle dependent, but the mechanism underlying this dependence is unclear. In S. cerevisiae, a single cyclin-dependent kinase Cdk1 (Cdc28) coordinates the serial events required for the cell division cycle, but no Cdk1 substrate has been identified among telomerase and telomere-associated factors. Here we show that Cdk1-dependent phosphorylation of Cdc13 is essential for efficient recruitment of the yeast telomerase complex to telomeres by favoring the interaction of Cdc13 with Est1 rather than the competing Stn1-Ten1 complex. These results provide a direct mechanistic link between coordination of telomere elongation and cell-cycle progression in vivo
Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses
The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
Extensive DNA End Processing by Exo1 and Sgs1 Inhibits Break-Induced Replication
Homology-dependent repair of DNA double-strand breaks (DSBs) by gene conversion involves short tracts of DNA synthesis and limited loss of heterozygosity (LOH). For DSBs that present only one end, repair occurs by invasion into a homologous sequence followed by replication to the end of the chromosome resulting in extensive LOH, a process called break-induced replication (BIR). We developed a BIR assay in Saccharomyces cerevisiae consisting of a plasmid with a telomere seeding sequence separated from sequence homologous to chromosome III by an I-SceI endonuclease recognition site. Following cleavage of the plasmid by I-SceI in vivo, de novo telomere synthesis occurs at one end of the vector, and the other end invades at the homologous sequence on chromosome III and initiates replication to the end of the chromosome to generate a stable chromosome fragment (CF). BIR was infrequent in wild-type cells due to degradation of the linearized vector. However, in the exo1Δ sgs1Δ mutant, which is defective in the 5′-3′ resection of DSBs, the frequency of BIR was increased by 39-fold. Extension of the invading end of the plasmid was detected by physical analysis two hours after induction of the I-SceI endonuclease in the wild-type exo1Δ, sgs1Δ, and exo1Δ sgs1Δ mutants, but fully repaired products were only visible in the exo1Δ sgs1Δ mutant. The inhibitory effect of resection was less in a plasmid-chromosome gene conversion assay, compared to BIR, and products were detected by physical assay in the wild-type strain. The rare chromosome rearrangements due to BIR template switching at repeated sequences were increased in the exo1Δ sgs1Δ mutant, suggesting that reduced resection can decrease the fidelity of homologous recombination
Histone H4 Lysine 12 Acetylation Regulates Telomeric Heterochromatin Plasticity in Saccharomyces cerevisiae
Recent studies have established that the highly condensed and transcriptionally silent heterochromatic domains in budding yeast are virtually dynamic structures. The underlying mechanisms for heterochromatin dynamics, however, remain obscure. In this study, we show that histones are dynamically acetylated on H4K12 at telomeric heterochromatin, and this acetylation regulates several of the dynamic telomere properties. Using a de novo heterochromatin formation assay, we surprisingly found that acetylated H4K12 survived the formation of telomeric heterochromatin. Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12. H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination. Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Baking injera in Addis Ababa, Ethiopia: Women's invisible labor in the teff value chain
Women play an important role in food value chain development, but their labor is often invisible in related policies. Female injera bakers in Addis Ababa, Ethiopia, have suffered a similar fate: their labor has been neglected in policies on improving the teff value chain. Teff is a cereal grown in Ethiopia which is used to make the countries' biggest food staple: injera. In this article we describe and analyze the labor of female injera bakers in Addis Ababa in the teff value chain, and the differences in their visibility along the lines of various identity markers. Based on mixed method research, we found that the effect of the changes in the teff value chain on female injera bakers' labor (in)visibility were most negative where certain identity markers intersect. The negative effects run along the lines of the formality of the labor, gender, class, age and health. We conclude that the Ethiopian government's neglect of female stakeholders in the teff value chain has led to the increase of existing inequalities and further marginalization of the most vulnerable women
Influence of vasoconstriction, temperature, and flow on the kinetics of serotonin uptake in rabbit lungs
Reference file in fasta format to which individual reads were aligned
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