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Recent documents in eScholarship@UMMS
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It's All About Location, Location, Location: A New Perspective on Trauma Transport

Wed, 06/08/2016 - 2:59pm

OBJECTIVE: To determine the effect of aeromedical transport on trauma mortality when accounting for geographic factors.

BACKGROUND: The existing literature on the mortality benefit of aeromedical transport on trauma mortality is controversial. Studies examining patient and injury characteristics find higher mortality, whereas studies measuring injury severity find a protective effect. Previous studies have not adjusted for the time and distance that would have been traveled had a helicopter not been used.

METHODS: Retrospective analysis of an institutional trauma registry. We compared mortality among adult patients ( > /=15 years) transported from the scene of injury to our level I trauma center by air or ground (January 1, 2000-December 31, 2010) using univariate comparisons and multivariable logistic regression. Regression models were constructed to incrementally account for patient demographics and injury mechanism, followed by injury severity, and, finally, by network bands for drive time and roadway distance as predicted by geographic information systems.

RESULTS: Of 4522 eligible patients, 1583 (35%) were transported by air. Patients transported by air had higher unadjusted mortality (4.1% vs 1.9%, P < 0.05). In multivariable modeling, including patient demographics and type of injury, helicopter transport predicted higher mortality than ground transport (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2-4.0). After adding validated injury severity measures to the model, helicopter transport predicted lower mortality (OR 0.7, 95% CI 0.3-0.9). Finally, including geographic covariates found that helicopter transport was not associated with mortality (OR 1.1, 95% CI 0.6-2.3).

CONCLUSIONS: Helicopter transport does not impart a survival benefit for trauma patients when geographic considerations are taken into account.

Cortisol response to the Trier Social Stress Test in pregnant women at risk for postpartum depression

Wed, 06/08/2016 - 2:59pm

Antepartum depression and anxiety are risk factors for postpartum depression (PPD). Postpartum abnormalities in hypothalamic-pituitary-adrenal (HPA) reactivity are associated with PPD. It is not known if antepartum HPA abnormalities exist in women at risk for PPD (AR-PPD). We measured salivary cortisol response to the Trier Social Stress Test (TSST) in 44 (24 AR-PPD, 20 healthy comparison) pregnant women. Depression and anxiety were measured using the Edinburgh Postnatal Depression Scale (EPDS) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). We analyzed longitudinal changes in cortisol using generalized estimating equation methods to control for the correlation within subjects at the six TSST time points. Group differences in area under the curve (AUC) were examined. A majority (70.8 %) of the AR-PPD had prior depression. EPDS total score was higher in AR-PPD vs. comparison women (mean EPDS = 9.8 +/- 4.9 vs. mean EPDS = 2.4 +/- 2.0 respectively, p < 0.001). Mean STAI-S total score was higher in AR-PPD vs. comparison women at all TSST time points and over time (z = 2.71, df = 1, p = 0.007). There was no significant difference in cortisol concentration over time between groups. We observed no detectable difference in cortisol response to psychosocial stress induced by the TSST despite clinically significant between-group differences in current/past depression and current symptomatology.

Patterns of Adult Cross-Racial Friendships: A Context for Understanding Contemporary Race Relations

Wed, 06/08/2016 - 2:59pm

OBJECTIVES: This study examined patterns, characteristics, and predictors of cross-racial friendships as the context for understanding contemporary race relations.

METHOD: A national survey included 1,055 respondents, of whom 55% were white, 32% were black, and 74% were female; ages ranged from 18 to > /=65 years. Focus groups were conducted to assess societal and personal benefits. Participants (n = 31) were racially diverse and aged 20 to 66 years.

RESULTS: After accounting for multiple covariates, regression analysis revealed that Asians, Hispanics, and multiracial individuals are more likely than their white and black counterparts to have cross-racial friends. Females were less likely than males to have 8 or more cross-racial friends. Regression analysis revealed that the depth of cross-racial friendships was greater for women than men and for those who shared more life experiences. Increasing age was associated with lower cross-racial friendship depth. Qualitative analysis of open-ended questions and focus group data established the social context as directly relevant to the number and depth of friendships. Despite the level of depth in cross-racial friendships, respondents described a general reluctance to discuss any racially charged societal events, such as police shootings of unarmed black men.

CONCLUSION: This study identified salient characteristics of individuals associated with cross-racial friendships and highlighted the influence of the social, historical, and political context in shaping such friendships. Our findings suggest that contemporary race relations reflect progress as well as polarization.

Sleep Duration and Diet Quality Among Women Within 5 Years of Childbirth in the United States: A Cross-Sectional Study

Wed, 06/08/2016 - 2:59pm

Objective: Only 9 % of women with young children consume a high quality diet. The association between sleep duration and health may be U-shaped. We examined diet quality in relation to sleep duration among US women within 5 years of childbirth.

Methods: Data were from non-pregnant women aged 20-44 years within 5 years of childbirth who completed two 24-h dietary recalls (N = 896) in the National Health and Nutrition Examination Survey 2005-2012. Self-reported weekday/workday sleep duration was categorized as short ( < /=6 h), adequate (7-8 h), or long ( > /=9 h). The Healthy Eating Index (HEI-2010, range 0-100) estimated overall and components of diet quality. Multivariable-adjusted linear regression models estimated the association between sleep duration and diet quality, adjusting for age, race/ethnicity, and education.

Results: Thirty-four percent of women reported short, 57.1 % adequate, and 8.6 % long sleep duration. The average diet quality total score was 47.4 out of 100. Short sleep duration was not associated with diet quality. Long sleep duration was associated with lower quality diet (beta = -4.3; 95 % CI -8.1 to -0.4), lower consumption of total fruit (beta = -0.7; 95 % CI -1.3 to -0.1), whole fruit (beta = -0.9; 95 % CI -1.6 to -0.2), and total protein (beta = -0.7; 95 % CI -1.3 to -0.03), and higher consumption of empty calories (beta = 2.2; 95 % CI -4.3 to -0.1).

Conclusions: for practice Future studies should examine the longitudinal association between sleep duration and diet quality among women following childbirth and whether interventions to improve sleep can enhance diet quality.

The presence of physician champions improved Kangaroo mother care in rural western India

Wed, 06/08/2016 - 2:58pm

AIM: This study determined the effect of physician champions on the two main components of Kangaroo mother care (KMC): skin-to-skin care and breastfeeding.

METHODS: KMC practices among a retrospective cohort of 648 infants admitted to a rural Indian neonatal intensive care unit (NICU) between 5 January 2011 and 7 October 2014 were studied. KMC champions were identified based on their performance evaluation. We examined the effect of withdrawing physician champions on overall use, time to initiation and intensity of skin-to-skin care and breastfeeding, using separate models.

RESULTS: In comparison to when KMC champions were present, their absence was associated with a 45% decrease in the odds of receiving skin-to-skin care, with a 95% Confidence Interval (CI) of 64% to 17%, a 38% decrease in the rate of initiation skin-to-skin care (95% CI 53% to 82%) and an average of 1.47 less hours of skin-to-skin care (95% CI -2.07 to -0.86). Breastfeeding practices were similar across the different champion environments.

CONCLUSION: Withdrawing physician champions from the NICU setting was associated with a decline in skin-to-skin care, but not breastfeeding. Training healthcare workers and community stakeholders to become champions could help to scale up and maintain KMC practices.

eScience Symposium Reflections from Christopher Erdmann: Redefining the Librarian’s Role in eScience

Wed, 06/08/2016 - 2:18pm

Christopher Erdmann, Head Librarian, Wolbach Library, Harvard Smithsonian Center for Astrophysics, shares his multiple experiences at the University of Massachusetts and New England Area Librarian eScience Symposium, as well as current challenges he sees for data science librarians. Christopher presented on a panel at the Eighth Annual eScience Symposium discussing the “future of data science” from a librarian’s perspective. See the video of this panel presentation on the 2016 eScience Symposium website.

A transcript of this interview is available for download via the Download button above.

eScience Symposium Reflections from Jian Qin: Finding Inspiration for Librarians in Data Science

Wed, 06/08/2016 - 2:18pm

Jian Qin, Professor, School of Information Studies, Syracuse University shares her multiple experiences at the University of Massachusetts and New England Area Librarian eScience Symposium, as well as her current efforts in library science and data science education. Jian presented on a panel at the Eighth Annual eScience Symposium discussing the “future of data science” from an educator’s perspective. See the video of this panel presentation on the 2016 eScience Symposium website.

A transcript of this interview is available for download via the Download button above.

Thinking Like A Scientist ... And An Engineer: Training future leaders and innovators in health care systems and delivery

Tue, 06/07/2016 - 3:25pm

Health care is increasingly becoming more complex with the advancement of accountable organizations, expansion of hospital systems, and major insurance and government reforms. As leaders of care teams, physicians are often expected to have a hybrid set of skills extending beyond clinical expertise. Examples of leadership knowledge and skill sets include organizational thinking, health quality improvement, health policy, financial literacy, health innovation, and many more. The number of MD/MBA programs has risen significantly since the 1990s and more recently, leadership pipelines for both medical residents and students have also emerged. These trends support a rising demand for well-rounded physician leaders. This project sets out to answer two questions: will a health care leadership program add value to undergraduate medical training for University of Massachusetts medical students? If so, what would such a leadership program look like?

We used the Lean management framework and “A3” Plan Do Study Analyze cycle (PDSA) to identify the challenges and appropriateness of developing a leadership program, and then to highlight ideas for promoting leadership. Key components of the framework include a root cause analysis and development of counter measures. As a platform for analysis, we examined the experiences of the “Quality Improvement Health Care Elective,” a student led series of lectures on health care process, Lean management, and health care leadership. We tested our counter measures as well as other ideas in a student opinion survey that focused on level of interest in leadership, career aspirations, desired deliverables, and the option of a training certificate.

An estimated 20% of the student population at UMass Medical School completed our survey (n=125). Our study discovered strong interest in the topic of leadership, with 20% of students stating they are very likely to take an elective on leadership, and 54% somewhat likely. Students were especially interested in career aspirations that included management and administration responsibilities, general career exploration, and opportunities for mentorship. These findings can be core features of developing a health care leadership option for medical students at UMass Medical School.

A Review of "Library Analytics and Metrics"

Tue, 06/07/2016 - 8:13am

This is a review of the book, Library Analytics and Metrics, edited by Ben Showers. Published by Facet Publishing, 2015.

Albanian Immigrants' Experience and Attitude toward Health Care in Albania versus the USA

Mon, 06/06/2016 - 9:00am

Purpose: To describe the experiences and attitudes of Albanian immigrants toward health care in Albania versus the United Stated (USA).

Method: A cross-sectional descriptive survey using venue sampling was administered at the Albanian Festival in Worcester on June 5-7, 2015. The data was entered and analyzed using SPSS.

Results: There were a total of 146 subjects eligible for analysis. Most subjects were female (52.7%) and the mean subject age was 41.6 with a range of 18-77 years old. Subjects moved to the USA at a mean age of 28.8 years with a range of 1-66 years old. Subjects have lived in the USA for a mean of 12.9 years, with a range of 3 months to 28 years. Categorical response items comparing health care in Albania versus the USA were statistically significant in favor of the USA health care system regarding comfort seeking care, care worth money, receiving preventative care, and having good communication with the doctor. Subgroup analysis of males vs. females showed a significant finding only on females receiving more preventative care. Continuous response items comparing health care in Albania versus the USA were statistically significant in favor of the USA health care system regarding the patient liking care received and trusting the doctors. Content analysis of the open-ended comments showed positive and negative perceptions of both health care systems.

Conclusions: Our results show that Albanian Immigrants have an overwhelming positive experience and attitude toward the USA health care system in all categories including comfort seeking care, care being worth the money, having good communication with the doctor, trusting the doctors, receiving preventative care, and liking care received. These finding are important because they show that even though Albanian immigrants are exposed to under-funded and corrupt medical care in Albania, the majority does not allow this experience to influence the interaction with USA health care professionals. The findings from this study are applicable to the clinical setting in the USA and some recommendations can be made to USA health care providers about how to best approach Albanian immigrant patients.

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.

Rapid Diagnostics for Infectious Disease using Noble Metal Nanoparticles

Fri, 05/20/2016 - 3:30pm

Rapid point-of-care (POC) diagnostic devices are needed for field-forward screening of severe acute systemic febrile illnesses such as dengue, Ebola, chikungunya, and others. Multiplexed rapid lateral flow diagnostics have the potential to distinguish among multiple pathogens, thereby facilitating diagnosis and improving patient care. We present a platform for multiplexed pathogen detection which uses gold or silver nanoparticles conjugated to antibodies to sense the presence of biomarkers for different infectious diseases. We exploit the size-dependent optical properties of Ag NPs to construct a multiplexed paperfluidic lateral flow POC sensor. AgNPs of different sizes were conjugated to antibodies that bind to specific biomarkers. Red AgNPs were conjugated to antibodies that could recognize the glycoprotein for Ebola virus, green AgNPs to those that could recognize nonstructural protein 1 for dengue virus, and orange AgNPs for non structural protein 1 for yellow fever virus. Presence of each of the biomarkers resulted in a different colored band on the test line in the lateral flow test. Thus, we were able to use NP color to distinguish among three pathogens that cause a febrile illness. Because positive test lines can be imaged by eye or a mobile phone camera, the approach is adaptable to low-resource, widely deployable settings. This design requires no external excitation source and permits multiplexed analysis in a single channel, facilitating integration and manufacturing. We will also discuss engineering the nanoparticle physical properties and surface chemistry for improving detection and also optimizing device properties, and expansion of the device to detect other diseases.

Older women’s muscle and gait response to a bout of exercise differs by physical activity level

Fri, 05/20/2016 - 3:30pm

Changes in gait are a consequence of aging and likely contribute to knee osteoarthritis (OA) incidence. Decrements in muscle function with age, including muscle power and fatigue resistance, may contribute to changes in gait and, subsequently, knee OA. Examining the impact of habitual physical activity (PA) on gait mechanics and muscle function may provide insight for interventions to modify knee OA risk. As knee OA affects women at greater rates than men, the current study focused on older women. The aim of this study was to determine if older women with different levels of habitual PA experienced the same effect, in terms of muscle function and gait biomechanics, in response to 30 minutes of treadmill walking (30MTW). We hypothesized that sedentary women (SED) would display greater decreases in knee extensor strength and power and larger changes in gait biomechanics compared to highly active women (ACT). Twelve women (6 SED, 6 ACT) aged 61.3±3.9 years with BMI 22.3±2.2 participated in this study. Gait mechanics and knee extensor strength and power were collected pre- and post-30MTW. Unpaired t-tests were used to compare changes in knee extensor function and gait mechanics between SED and ACT with significance set at p<0.1. In response to the 30MTW, there was a larger decrease in high-velocity knee extensor power for SED vs. ACT (-26.3±12.2 vs. -12.9±13.7%). In addition, SED compared to ACT had a larger increase in sagittal hip range of motion during stance (+1.9±2.5 vs. +0.3±0.7°), a larger increase in dorsiflexion at heel strike (+2.2±1.7 vs. +0.3±2.3°), a larger decrease in plantarflexion at toe-off (-1.6±2.5 vs. +0.9±1.9°), and a larger decrease in anterior position of the femur relative to the tibia during loading response (-2.6±4.0 vs. +0.5±2.9 mm). These findings suggest PA level may affect biomechanical health in older women, especially with regard to exercise-induced fatigue.

Discovery and Development of Human Monoclonal Antibodies to Block RhD Alloimmunization During Pregnancy

Fri, 05/20/2016 - 3:30pm

Exposure of an Rh negative mother to red blood cells (RBCs) of an Rh positive fetus results in alloimmunization and development of anti-RhD antibodies. The anti-RhD antibodies cause hemolytic disease of the new born babies during subsequent pregnancies. Current prophylactic treatment involves polyclonal anti-RhD IgG purified from plasma of humans and is administered in approximately 20% of pregnancies. While the current prophylaxis is effective, it involves the use of human plasma and non-RhD specific antibodies, thus posing a risk of transmitting infections and undesired antibody reactions. Moreover, there is a serious scarcity of plasma donors to meet the requirement of anti-RhD antibodies. In this study we propose to discover and develop anti-RhD monoclonal human antibodies to replace the current polyclonal prophylaxis. We are using humanized BLT mice (fetal CD34+ stem cells, liver and thymus) reconstituted with RhD negative donor material and were immunized by using adenovirus containing RhD transgene. Serum samples were collected after 4-6 weeks of immunization. Our results show that the RhD immunized mice had considerably higher titer of IgG and IgA antibodies in the serum compared to the control, suggesting an immune response developed upon immunization. Splenocytes from antibody producing mice will be fused with a human fusion partner for the isolation of hybridomas producing human monoclonal antibodies. The immunoreactivity and functional activity of these antibodies will be discussed.

Sustained Expression with Partial Correction of Neutrophil Defects 5 Years After Intramuscular rAAV1 Gene Therapy for Alpha-1 Antitrypsin Deficiency

Fri, 05/20/2016 - 3:30pm

Alpha-1 antitrypsin (AAT) deficiency is a common monogenic disorder resulting in emphysema, which is currently treated with weekly infusions of protein replacement. We previously reported achieving plasma wild-type (M) AAT concentrations at 2.5-3.8% of the therapeutic level at 1 year after intramuscular (IM) administration of 6×1012vg/kg of a recombinant adeno-associated virus serotype 1 (rAAV1)-AAT vector in AAT-deficient patients, with an associated regulatory T cell (Treg) response to AAV1 capsid epitopes in the absence of any exogenous immune suppression. Here, we report sustained expression at greater than 2% of the therapeutic level for 5 years after one-time treatment with rAAV1-AAT in an AAT-deficient patient from that study, with partial correction of neutrophil defects previously reported in AAT-deficient patients. There was also evidence of an active Treg response (FoxP3+, Helios+) and an exhausted cytotoxic T cell response (PD-1+, LAG-3+) to AAV1 capsid. These findings suggest that muscle-based AAT gene replacement is toleragenic and that very stable levels of M AAT may exert beneficial effects at lower concentrations than previously anticipated.

Serum Levels of Alpha-1 Antitrypsin following Vascular Limb or Intra-Muscular Delivery of AAV1 or AAV8 Gene Therapy Vectors in Rhesus Macaques

Fri, 05/20/2016 - 3:30pm

Alpha-one antitrypsin (AAT) deficiency is a genetic disease that results in both lung disease and potentially liver failure in affected patients. In un-affected people AAT is produced in the liver and secreted to act as an anti-protease (primarily counteracting the effects of neutrophil elastase) in the lung. On-going human clinical trials have focused on intra-muscular delivery of adeno-associated virus (AAV1) to patients. The goal of delivery to the muscle is to have the myocytes serve as bio-factories to produce normal AAT protein and secrete it into the blood where it can exert its normal function in the lung. In the last Phase II trial patients in the highest dose cohort were given 100 intra-muscular (IM) injections with serum AAT levels still below therapeutic thresholds.

Previous work has shown that delivering AAV vector to the musculature of the limb via the vasculature, while blood flow is obstructed using a tourniquet, leads to wide-spread gene expression in myocytes. We hypothesize that local delivery via IM injection results in saturated AAT expression within the myocytes surrounding the injection sight and that a more widespread delivery would result in an overall increase in serum AAT levels with the same dose of AAV gene therapy vector due to production by a larger overall number of myocytes. We have been able to show that we can attain similar or slightly higher (573.0 ng/ml versus 562.5 ng/nl) serum AAT levels using a vascular delivery method in rhesus macaques when compared to IM delivery. These results have been obtained using AAV1. Animals receiving either AAV1 or AAV8 show a decrease in muscle immune cell infiltrates following intra-vascular delivery versus IM delivery, which may improve long-term expression. Serum AAT data from animals dosed using AAV8, a serotype shown to better target muscle following vascular delivery, are currently being processed.