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Deliberate Practice of IV Medication Procedures by Student Nurses: Feasibility, Acceptability, and Preliminary Outcomes: A Dissertation

Thu, 05/26/2016 - 3:25pm

Background: Medication errors continue to be one of the most prevalent problems in healthcare related to patient safety, often resulting in injury or death, with higher incidences of error occurring with intravenous medications. The purpose of this study was to explore the use of deliberate practice (DP) with second-degree nursing students in developing and maintaining fundamental intravenous medication management practices required for safe practice.

Method: This was a feasibility study using a two-arm, single-blind, randomized controlled trial design. Vygotsky’s Zone of Proximal Development model was used to explore the use of a DP teaching intervention to achieve competency in skills associated with safe IV medication management. A convenience sample of first-year, first-semester nursing students enrolled in an accelerated graduate program (N = 32) were invited to participate; 19 enrolled, and 12 completed the study. Students (n = 12) received three 30- minute one-on-one practice sessions at 2-week intervals with an expert nurse (the intervention group focused on IV skills and the control group on skills unrelated to IVs). Pre- and post-intervention instruments tested participants’ confidence with IV management and safety skills. The primary outcome was their ability to safely administer and monitor IV medications during a 20-minute videotaped medication administration scenario.

Results: Low recruitment (19 of 32) and high attrition (37%) were observed. Participants completing the study (5 in the intervention group and 7 in the control group) reported that the time required to attend the sessions was not burdensome (91.7%); time allotted was adequate (100%); 100% reported positive experience; 91.7% found the DP sessions essential to learning. Change in confidence scores for IV skills were not significant (P = 0.210), but were higher in the intervention group (2.97–4.14 = 1.50 change) compared to the control group (2.71–3.77 = 1.04 change). Significant differences were found in overall medication administration skills between the control and intervention groups (t [-2.302], p = 0.044) in favor of the intervention group, particularly with medication preparation skills (p = 0.039). Overall raw scores were low in both groups; only 16–42 (26%–70%) of the total 60 steps required for safe practice were completed. Participants scored lowest in the evaluation phase, with all participants performing less than 50% of the 14 steps.

Conclusion: Even though participant satisfaction was high, significant attrition occurred. Students reported the DP sessions to be beneficial and they felt more confident in performing skills, but three 30-minute sessions (90 minutes) were not adequate to develop, maintain, or refine all the IV-management skills associated with safe medication practices. Determining the length and duration of DP sessions as well as comparing the efficacy of DP sessions between individual and group sessions with varying doses and frequencies is needed to advance our understanding of using DP within nursing education.

Quality Improvement (QI) in Evaluation: Anatomy of a Fishbone (Diagram)

Thu, 05/26/2016 - 2:38pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Evaluating the Full Potential of Your Staff

Thu, 05/26/2016 - 2:38pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Post-Project Debriefings as Part of Performance Improvement

Thu, 05/26/2016 - 2:37pm

Blog post to AEA365, a blog sponsored by the American Evaluation Association (AEA) dedicated to highlighting Hot Tips, Cool Tricks, Rad Resources, and Lessons Learned for evaluators. The American Evaluation Association is an international professional association of evaluators devoted to the application and exploration of program evaluation, personnel evaluation, technology, and many other forms of evaluation. Evaluation involves assessing the strengths and weaknesses of programs, policies, personnel, products, and organizations to improve their effectiveness.

Systematic dissection of roles for chromatin regulators in a yeast stress response

Mon, 05/23/2016 - 10:50am

Packaging of eukaryotic genomes into chromatin has wide-ranging effects on gene transcription. Curiously, it is commonly observed that deletion of a global chromatin regulator affects expression of only a limited subset of genes bound to or modified by the regulator in question. However, in many single-gene studies it has become clear that chromatin regulators often do not affect steady-state transcription, but instead are required for normal transcriptional reprogramming by environmental cues. We therefore have systematically investigated the effects of 83 histone mutants, and 119 gene deletion mutants, on induction/repression dynamics of 170 transcripts in response to diamide stress in yeast. Importantly, we find that chromatin regulators play far more pronounced roles during gene induction/repression than they do in steady-state expression. Furthermore, by jointly analyzing the substrates (histone mutants) and enzymes (chromatin modifier deletions) we identify specific interactions between histone modifications and their regulators. Combining these functional results with genome-wide mapping of several histone marks in the same time course, we systematically investigated the correspondence between histone modification occurrence and function. We followed up on one pathway, finding that Set1-dependent H3K4 methylation primarily acts as a gene repressor during multiple stresses, specifically at genes involved in ribosome biosynthesis. Set1-dependent repression of ribosomal genes occurs via distinct pathways for ribosomal protein genes and ribosomal biogenesis genes, which can be separated based on genetic requirements for repression and based on chromatin changes during gene repression. Together, our dynamic studies provide a rich resource for investigating chromatin regulation, and identify a significant role for the "activating" mark H3K4me3 in gene repression.

Agenda: 2016 UMass Center for Clinical and Translational Science Research Retreat

Fri, 05/20/2016 - 10:30am

Agenda for the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Developing an Adeno-Associated Viral Vector (AAV) Toolbox for CNS Gene Therapy: A Dissertation

Thu, 05/19/2016 - 4:08pm

Neurological disorders – disorders of the brain, spine and associated nerves – are a leading contributor to global disease burden with a sizable economic cost. Adeno-associated viral (AAV) vectors have emerged as an effective platform for CNS gene therapy and have shown early promise in clinical trials. These trials involve direct infusion into brain parenchyma, an approach that may be suboptimal for treatment of neurodegenerative disorders, which often involve more than a single structure in the CNS. However, overall neuronal transduction efficiency of vectors derived from naturally occurring AAV capsids after systemic administration is relatively low. We have developed novel capsids AAV-AS and AAV-B1 that lead to widespread gene delivery throughout the brain and spinal cord, particularly to neuronal populations. Both transduce the adult mouse brain >10-fold more efficiently than the clinical gold standard AAV9 upon intravascular infusion, with gene transfer to multiple neuronal sub-populations. These vectors are also capable of neuronal transduction in a normal cat. We have demonstrated the efficacy of AAV-AS in the context of Huntington's disease by knocking down huntingtin mRNA 33-50% after a single intravenous injection, which is better than what can be achieved by AAV9 at the particular dose. AAVB1 additionally transduces muscle, beta cells, pulmonary alveoli and retinal vasculature at high efficiency, and has reduced sensitivity to neutralizing antibodies in human sera. Generation of this vector toolbox represents a major step towards gaining genetic access to the entire CNS, and provides a platform to develop new gene therapies for neurodegenerative disorders.

Systematic Dissection of Roles for Chromatin Regulators in Dynamics of Transcriptional Response to Stress in Yeast: A Dissertation

Thu, 05/19/2016 - 4:08pm

The following work demonstrates that chromatin regulators play far more pronounced roles in dynamic gene expression than they do in steady-state. Histone modifications have been associated with transcription activity. However, previous analyses of gene expression in mutants affecting histone modifications show limited alteration. I systematically dissected the effects of 83 histone mutants and 119 gene deletion mutants on gene induction/repression in response to diamide stress in yeast. Importantly, I observed far more changes in gene induction/repression than changes in steady-state gene expression. The extensive dynamic gene expression profile of histone mutants and gene deletion mutants also allowed me to identify specific interactions between histone modifications and chromatin modifiers. Furthermore, by combining these functional results with genome-wide mapping of several histone modifications in the same time course, I was able to investigate the correspondence between histone modification occurrence and function. One such observation was the role of Set1-dependent H3K4 methylation in the repression of ribosomal protein genes (RPGs) during multiple stresses. I found that proper repression of RPGs in stress required the presence, but not the specific sequence, of an intron, an element which is almost unique to this gene class in Saccharomyces cerevisiae. This repression may be related to Set1’s role in antisense RNA-mediated gene silencing. Finally, I found a potential role for Set1 in producing or maintaining uncapped mRNAs in cells through a mechanism that does not involved nuclear exoribonucleases. Thus, deletion of Set1 in xrn1Δ suppresses the accumulation of uncapped transcripts observed in xrn1Δ. These findings reveal that Set1, along with other chromatin regulators, plays important roles in dynamic gene expression through diverse mechanisms and thus provides a coherent means of responding to environmental cues.

Distracted Practice and Patient Safety: The Healthcare Team Experience: A Dissertation

Thu, 05/19/2016 - 3:20pm

Purpose: The purpose of this study was to explore the experiences of distracted practice across the healthcare team.

Definition: Distracted practice is the diversion of a portion of available cognitive resources that may be needed to effectively perform/carry out the current activity.

Background: Distracted practice is the result of individuals interacting with the healthcare team, the environment and technology in the performance of their jobs. The resultant behaviors can lead to error and affect patient safety.

Methods: A qualitative descriptive (QD) approach was used that integrated observations with semi-structured interviews. The conceptual framework was based on the distracted driving model and a completed concept analysis.

Results: There were 22 observation sessions and 32 interviews (12 RNs, 11 MDs, and 9 Pharmacists) completed between December, 2014 and July 2015. Results suggested that distracted practice is based on the main theme of cognitive resources which varies by the subthemes of individual differences; environmental disruptions; team awareness; and “rush mode”/time pressure.

Conclusions and Implications: Distracted practice is an individual human experience that occurs when there are not enough cognitive resources available to effectively complete the task at hand. In that moment an individual shifts from thinking critically, being able to complete their current task without error, to not thinking critically and working in an automatic mode. This is when errors occur. Additional research is needed to evaluate intervention strategies to reduce and prevent distracted practice.

Techniques in distal access of wide-necked giant intracranial aneurysms during treatment with flow diversion

Tue, 05/17/2016 - 12:38pm

BACKGROUND: Accessing the normal distal vessel in treatment of wide-necked giant intracranial aneurysms with flow diversion can be difficult.

CASE DESCRIPTION: Through illustrative cases, the authors present several useful techniques in distal access of wide-necked giant aneurysms during flow diversion treatment. Obtaining an optimal projection that separates the outflow limb from the aneurysm is most critical. Each of the three techniques described enabled the distal access to giant intracranial aneurysms during treatment with flow diversion.

CONCLUSION: The looped-around technique, balloon-assisted technique, and retrograde access are valuable strategies in crossing the aneurysm if direct distal access cannot be obtained.

Biosimilars in rheumatology: what the clinician should know

Tue, 05/17/2016 - 12:37pm

Biosimilars are now a reality in rheumatology. Although analytical and non-clinical procedures to establish similarity have evolved significantly, clinical trials demonstrating equivalent efficacy and safety are absolutely required for all biosimilars. The design of such trials, including equivalence and non-inferiority statistical approaches, are discussed. Clinical evidence on biosimilars that have been approved recently or are presently being developed for use in rheumatology is also reviewed and contrasted with that available for biomimics (or intended copies), which are non-innovator biologics that are marketed in several countries but have not undergone review according to a regulatory pathway for biosimilars.

Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy

Tue, 05/17/2016 - 12:37pm

IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-kappaB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-kappaB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.

Endometriosis and ovarian cancer: links, risks, and challenges faced

Tue, 05/17/2016 - 12:37pm

Endometriosis is a benign gynecological condition characterized by specific histological, molecular, and clinical findings. It affects 5%-10% of premenopausal women, is a cause of infertility, and has been implicated as a precursor for certain types of ovarian cancer. Advances in technology, primarily the ability for whole genome sequencing, have led to the discovery of new mutations and a better understanding of the function of previously identified genes and pathways associated with endometriosis associated ovarian cancers (EAOCs) that include PTEN, CTNNB1 (beta-catenin), KRAS, microsatellite instability, ARID1A, and the unique role of inflammation in the development of EAOC. Clinically, EAOCs are associated with a younger age at diagnosis, lower stage and grade of tumor, and are more likely to occur in premenopausal women when compared with other ovarian cancers. A shift from screening strategies adopted to prevent EAOCs has resulted in new recommendations for clinical practice by national and international governing bodies. In this paper, we review the common histologic and molecular characteristics of endometriosis and ovarian cancer, risks associated with EAOCs, clinical challenges and give recommendations for providers.

Decade-long trends (1999-2009) in the characteristics, management, and hospital outcomes of patients hospitalized with acute myocardial infarction with prior diabetes and chronic kidney disease

Tue, 05/17/2016 - 12:37pm

BACKGROUND: Despite the increasing magnitude and impact, there are limited data available on the clinical management and in-hospital outcomes of patients who have diabetes mellitus (DM) and chronic kidney disease (CKD) at the time of hospitalization for acute myocardial infarction (AMI). The objectives of our population-based observational study in residents of central Massachusetts were to describe decade-long trends (1999-2009) in the characteristics, in-hospital management, and hospital outcomes of AMI patients with and without these comorbidities.

METHODS: We reviewed the medical records of 6,018 persons who were hospitalized for AMI on a biennial basis between 1999 and 2009 at all eleven medical centers in central Massachusetts. Our sample consisted of the following four groups: DM with CKD (n=587), CKD without DM (n=524), DM without CKD (n=1,442), and non-DM/non-CKD (n=3,465).

RESULTS: Diabetic patients with CKD were more likely to have a higher prevalence of previously diagnosed comorbidities, to have developed heart failure acutely, and to have a longer hospital stay compared with non-DM/non-CKD patients. Between 1999 and 2009, there were marked increases in the prescribing of beta-blockers, statins, and aspirin for patients with CKD and DM as compared to those without these comorbidities. In-hospital death rates remained unchanged in patients with DM and CKD, while they declined markedly in patients with CKD without DM (20.2% dying in 1999; 11.3% dying in 2009).

CONCLUSION: Despite increases in the prescribing of effective cardiac medications, AMI patients with DM and CKD continue to experience high in-hospital death rates.

The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens

Tue, 05/17/2016 - 12:37pm

It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different information (e.g., spatial, emotional and cognitive). Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD) and long-term potentiation (LTP) and long-term potentiation (tLTP) and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute Ethyl Alcohol (EtOH) has little effects on higher order information coming from the PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons

Tue, 05/17/2016 - 12:36pm

The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM) and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM) allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs) in mice. 3D reconstruction of dendritic spines in GCs aged 3-4 and 8-9 weeks revealed two different stages of dendritic spine development and unexpected features of synapse formation, including vacant and branched dendritic spines and presynaptic terminals establishing synapses with up to 10 dendritic spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner.

eIF2alpha Confers Cellular Tolerance to S. aureus alpha-Toxin

Tue, 05/17/2016 - 12:36pm

We report on the role of conserved stress-response pathways for cellular tolerance to a pore forming toxin. First, we observed that small molecular weight inhibitors including of eIF2alpha-phosphatase, jun-N-terminal kinase (JNK), and PI3-kinase sensitized normal mouse embryonal fibroblasts (MEFs) to the small pore forming S. aureus alpha-toxin. Sensitization depended on expression of mADAM10, the murine ortholog of a proposed high-affinity receptor for alpha-toxin in human cells. Similarly, eIF2alpha (S51A/S51A) MEFs, which harbor an Ala knock-in mutation at the regulated Ser51 phosphorylation site of eukaryotic translation initiation factor 2alpha, were hyper-sensitive to alpha-toxin. Inhibition of translation with cycloheximide did not mimic the tolerogenic effect of eIF2alpha-phosphorylation. Notably, eIF2alpha-dependent tolerance of MEFs was toxin-selective, as wild-type MEFs and eIF2alpha (S51A/S51A) MEFs exhibited virtually equal sensitivity to Vibrio cholerae cytolysin. Binding of S. aureus alpha-toxin to eIF2alpha (S51A/S51A) MEFs and toxicity in these cells were enhanced as compared to wild-type cells. This led to the unexpected finding that the mutant cells carried more ADAM10. Because basal phosphorylation of eIF2alpha in MEFs required amino acid deprivation-activated eIF2alpha-kinase 4/GCN2, the data reveal that basal activity of this kinase mediates tolerance of MEFs to alpha-toxin. Further, they suggest that modulation of ADAM10 is involved. During infection, bacterial growth may cause nutrient shortage in tissues, which might activate this response. Tolerance to alpha-toxin was robust in macrophages and did not depend on GCN2. However, JNKs appeared to play a role, suggesting differential cell type and toxin selectivity of tolerogenic stress responses. Understanding their function or failure will be important to comprehend anti-bacterial immune responses.

Quantifying polymorphism and divergence from epigenetic data: a framework for inferring the action of selection

Tue, 05/17/2016 - 12:36pm

Epigenetic modifications are alterations that regulate gene expression without modifying the underlying DNA sequence. DNA methylation and histone modifications, for example, are capable of spatial and temporal regulation of expression-with several studies demonstrating that these epigenetic marks are heritable. Thus, like DNA sequence, epigenetic marks are capable of storing information and passing it from one generation to the next. Because the epigenome is dynamic and epigenetic modifications can respond to external environmental stimuli, such changes may play an important role in adaptive evolution. While recent studies provide strong evidence for species-specific signatures of epigenetic marks, little is known about the mechanisms by which such modifications evolve. In order to address this question, we analyze the genome wide distribution of an epigenetic histone mark (H3K4me3) in prefrontal cortex neurons of humans, chimps and rhesus macaques. We develop a novel statistical framework to quantify within- and between-species variation in histone methylation patterns, using an ANOVA-based method and defining an FST -like measure for epigenetics (termed epi- FST), in order to develop a deeper understanding of the evolutionary pressures acting on epigenetic variation. Results demonstrate that genes with high epigenetic FST values are indeed significantly overrepresented among genes that are differentially expressed between species, and we observe only a weak correlation with SNP density.

Role of Energy Metabolism in the Brown Fat Gene Program

Tue, 05/17/2016 - 12:36pm

In murine and human brown adipose tissue (BAT), mitochondria are powerful generators of heat that safely metabolize fat, a feature that has great promise in the fight against obesity and diabetes. Recent studies suggest that the actions of mitochondria extend beyond their conventional role as generators of heat. There is mounting evidence that impaired mitochondrial respiratory capacity is accompanied by attenuated expression of Ucp1 and other BAT-selective genes, implying that mitochondria exert transcriptional control over the brown fat gene program. In this review, we discuss the current understanding of brown fat mitochondria, their potential role in transcriptional control of the brown fat gene program, and potential strategies to treat obesity in humans by leveraging thermogenesis in brown adipocytes.

The Resource Identification Initiative: A cultural shift in publishing

Tue, 05/17/2016 - 12:35pm

A central tenet in support of research reproducibility is the ability to uniquely identify research resources, i.e., reagents, tools, and materials that are used to perform experiments. However, current reporting practices for research resources are insufficient to allow humans and algorithms to identify the exact resources that are reported or answer basic questions such as "What other studies used resource X?" To address this issue, the Resource Identification Initiative was launched as a pilot project to improve the reporting standards for research resources in the methods sections of papers and thereby improve identifiability and reproducibility. The pilot engaged over 25 biomedical journal editors from most major publishers, as well as scientists and funding officials. Authors were asked to include Research Resource Identifiers (RRIDs) in their manuscripts prior to publication for three resource types: antibodies, model organisms, and tools (including software and databases). RRIDs represent accession numbers assigned by an authoritative database, e.g., the model organism databases, for each type of resource. To make it easier for authors to obtain RRIDs, resources were aggregated from the appropriate databases and their RRIDs made available in a central web portal ( RRIDs meet three key criteria: they are machine readable, free to generate and access, and are consistent across publishers and journals. The pilot was launched in February of 2014 and over 300 papers have appeared that report RRIDs. The number of journals participating has expanded from the original 25 to more than 40. Here, we present an overview of the pilot project and its outcomes to date. We show that authors are generally accurate in performing the task of identifying resources and supportive of the goals of the project. We also show that identifiability of the resources pre- and post-pilot showed a dramatic improvement for all three resource types, suggesting that the project has had a significant impact on reproducibility relating to research resources.