RETINAL LAYER RESPONSE TO RANIBIZUMAB DURING TREATMENT OF DIABETIC MACULAR EDEMA: Thinner is Not Always Better.

PURPOSE To identify individual retinal layer thickness changes associated with visual acuity gain in diabetic macular edema treated with ranibizumab using layer segmentation on high-resolution optical coherence tomography scans. METHODS Retrospective observational case series. Thirty-three treatment-naive eyes with diabetic macular edema were imaged by spectral domain optical coherence tomography at monthly visits while receiving intravitreal ranibizumab treatment as needed, guided by visual acuity. Thickness changes of individual layers after 1 year were quantitatively analyzed and correlated with visual acuity gain. RESULTS The mean best-corrected visual acuity improvement at 1 year was 6.2 (SEM ± 1.5) Early Treatment Diabetic Retinopathy Study letters, and central retinal thickness decreased by 66 ± 18 μm. In the central subfield, there was a significant decrease of thickness for all layers (P < 0.05) except the outer nuclear layer. Multiple linear regression analysis revealed that thickness decrease of the inner retina was associated with better visual acuity, whereas for the outer retina the opposite was true. The best estimate of final visual acuity (R = 0.817, P < 0.001) was obtained, by including baseline visual acuity and thickness change of the inner and outer plexiform layers in the model. CONCLUSION Whereas thickness decrease of the inner retina was positively associated with visual acuity gain, the opposite was found for the outer retina. This might be indirect evidence for recovery of the outer retina during ranibizumab treatment.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

The Adaptation Effect in Bilingual People who Stutter: An Examination of the Oral-Motor Rehearsal Theory

The present study provided further information about stuttering among bilingual populations and attempted to assess the significance of repeated oral-motor movements during an adaptation task in two bilingual adults. This was accomplished by requesting that bilingual people who stutter to complete an adaptation task of the same written passage in two different languages. Explored was the following research question: In bilingual speakers who stutter, what is the effect of altering the oral-motor movements by changing the language of the passage read during an adaptation task? Two bilingual adults were each requested to complete an adaptation task consisting of 10 readings in two separate conditions. Participants 1 and 2 completed two conditions, each of which contained a separate passage. Condition B consisted of an adaptation procedure in which the participants read five successive readings in English followed by five additional successive readings in Language 1 (L1). Following the completion of the first randomly assigned condition, the participant was given a rest period of 30 minutes before beginning the remaining condition and passage. Condition A consisted of an adaptation procedure in which the participants read five successive readings in L1 followed by five additional successive readings in English. Results across participants, conditions, and languages indicated an atypical adaptation curve over 10 readings characterized by a dramatic increase in stuttering following a change of language. Closer examination of individual participants revealed differences in stuttering and adaptation among languages and conditions. Participants 1 and 2 demonstrated differences in adaptation and stuttering among languages. Participant 1 demonstrated an increase in stuttering following a change in language read in Condition B and a decrease in stuttering following a change in language read in Condition A. It is speculated that language proficiency contributed to the observed differences in stuttering following a change of language. Participant 2 demonstrated an increase in stuttering following a change in language read in Condition A and a minimal increase in stuttering following a change in language read in Condition B. It is speculated that a change in the oral-motor plan contributed to the increase in stuttering in Condition A. Collectively, findings from this exploratory study lend support to an interactive effect between language proficiency and a change in the oral-motor plan contributing to increased stuttering following a change of language during an adaptation task.

The Impact of Mobile Technology on the Viewing Experience of the Avid Sports Fan

Viewing sports on television is a very different experience than viewing a game in-person. Sports commentators on television are seemingly able to pull up random statistics as soon as something unexpected happens during a game. Because these statistics are discussed on television, any sports fan who wants to watch a game in-person misses out on the opportunity to hear them during the game. This study identifies what statistics, both common and uncommon, are considered important or interesting by avid sports fans who watch a particular sport at least two times per week. In addition, it considers the rise of mobile technology and the effects that this change of trend will have on business opportunities and experiences. The purpose of the project is to find a way to mimic the television viewing experience for fans who are watching in-person through the use of mobile technology, and in particular through the use of iPhone applications.

Role of phosphatidylethanolamine in the function and assembly of phenylalanine-specific permease of Escherichia coli

Transmembrane segments of polytopic membrane proteins once inserted are generally considered stably oriented due to the large free energy barrier for topological reorientation of adjacent extra-membrane domains. However, proper topology and function of the polytopic membrane protein lactose permease (LacY) of Escherichia coli is dependent on the membrane phospholipid composition revealing topological dynamics of transmembrane domains (Bogdanov, M., Heacock, P. N., and Dowhan, W. (2002) EMBO J. 21, 2107–2116). The high affinity phenylalanine permease PheP shares many topological similarities with LacY. In this study, mutant E. coli cells lacking phosphatidylethanolamine (PE) as a membrane component were used to evaluate the role of PE in the function and assembly of PheP. Active transport of phenylalanine by cells lacking PE was severely inhibited (both Vmax and Km were altered), whereas the PheP protein level in membranes was unaffected. Cysteine residues were introduced into predicted periplasmic or cytoplasmic segments of cysteine-less PheP, and the topology of the protein was explored using a membrane-impermeable thiol-specific biotinylated probe. Based on the biotinylation patterns of PheP in whole cells, the N-terminus and adjoining transmembrane hairpin of PheP adopted an inverted topological orientation in PE-lacking cells. Introduction of PE following the assembly of PheP triggered a reorientation of the N-terminus and adjacent hairpin to their native orientation associated with regain of wild type transport function. These results coupled with the results for LacY support a specific role for membrane lipid composition in determining topological organization and function of membrane proteins. Several other secondary symporters are compromised for activity in PE-lacking cells suggesting that lipid-assisted topogenesis is a general property of such transporters. The reversible orientation of these secondary transport proteins in response to a change of phospholipid composition might be a result of inherent conformational flexibility necessary for transport function or during protein assembly. ^

Effects of Estrogen on Muscle Damage in Response to an Acute Resistance Exercise Protocol

Creatine Kinase (CK) is used as a measure of exercise-induced muscle membrane damage. During acute eccentric (muscle lengthening) exercise, muscle sarcolemma, sarcoplasmic reticulum, and Z-lines are damaged, thus causing muscle proteins and enzymes to leak into the interstitial fluid. Strenuous eccentric exercise produces an elevation of oxygen free radicals, which further increases muscle damage. Muscle soreness and fatigue can be attributed to this membrane damage. Estradiol, however, may preserve membrane stability post-exercise (Brancaccio, Maffulli, & Limongelli, 2007; Carter, Dobridge, & Hackney, 2001; Tiidus, 2001). Because estradiol has a similar structure to Vitamin E, which is known to have antioxidant properties, and both are known to affect membrane structure, researchers have proposed that estrogen acts as an antioxidant to provide a protective effect on the post-exercise muscle of women (Sandoval & Matt, 2002). As a result, it has been postulated that muscles in women incur less damage in response to an acute strenuous exercise as compared to men. PURPOSE: To determine if circulating estrogen concentrations are related to muscle damage, as measured by creatine kinase activity and to determine gender differences in creatine kinase as a marker of muscle damage in response to an acute heavy resistance exercise protocol. METHODS: 7 healthy, resistance-trained, eumenhorrheic women (23±3 y, 169±9.1 cm, 66.4±10.5 kg) and 8 healthy, resistance-trained men (25±5 y, 178±6.7 cm, 82.3±9.33 kg) volunteered to participate in the study. Subjects performed an Acute Resistance Exercise Test (ARET) consisting of 6 sets of 5 repetitions Smith machine squats at 90% of their previously determined 1-RM. Blood samples were taken pre-, mid-, post-, 1 hour post-, 6 hours post-, and 24 hours post-exercise. Samples were stored at -80ºC until analyzed. Serum creatine kinase was measured using an assay kit from Genzyme (Framingham, MA). Serum estradiol was measured by an ELISA from GenWay (San Diego, CA). Estradiol b-receptor presence on granulocytes was measured via flow cytometry using primary antibodies from Abcam (Cambridge, MA) and PeCy7 antibodies (secondary) from Santa Cruz (Santa Cruz, CA). RESULTS: No significant correlations between estrogen and CK response were found after an acute resistant exercise protocol. Moreover, no significant change in estradiol receptors were expressed on granulocytes after exercise. Creatine Kinase response, however, differed significantly between genders. Men had higher resting CK concentrations throughout all time points. Creatine Kinase response increased significantly after exercise in both men and women (p=0.008, F=9.798). Men had a significantly higher CK response at 24 hours post exercise than women. A significant condition/sex/time interaction was exhibited in CK response (p=0.02, F=4.547). Perceived general soreness presented a significant condition, sex interaction (p=0.01, F=9.532). DISCUSSION: Although no estradiol and CK response correlations were found in response to exercise, a significant difference in creatine kinase activity was present between men and women. This discrepancy of our results and findings in the literature may be due to the high variability between subjects in creatine kinase activity as well as estrogen concentrations. The lack of significance in change of estradiol receptor expression on granulocytes in response to exercise may be due to intracellular estradiol receptor staining and non-specific gating for granulocytes rather than additional staining for neutrophil markers. Because neutrophils are the initial cells present in the inflammatory response after strenuous exercise, staining for estrogen receptors on this cell type may allow for a better understanding of the effect of estrogen and its hypothesized protective effect against muscle damage. Furthermore, the mechanism of action may include estradiol receptor expression on the muscle fiber itself may play a role in the protective effects of estradiol rather than or in addition to expression on neutrophils. We have shown here that gender differences occur in CK activity as a marker of muscle damage in response to strenuous eccentric exercise, but may not be the result of estradiol concentration or estradiol receptor expression on granulocytes. Other variables should be examined in order to determine the mechanism involved in the difference in creatine kinase as a marker of muscle damage between men and women after heavy resistance exercise.

The effectiveness of a promotora-led intervention for Mexican Americans with type 2 diabetes

Purpose. The purpose of this randomized control repeated measures trial was to determine the effectiveness of a self-management intervention led by community lay workers called promotoras on the health outcomes of Mexican Americans with type 2 diabetes living in a major city on the Texas - Mexico border. The specific aims of this study, in relation to the intervention group participants, were to: (1) decrease the glycosylated hemoglobin (A1c) blood levels at the six-month assessment, (2) increase diabetes knowledge at the three and six-month assessments, and (3) strengthen the participants' beliefs in their ability to manage diabetes at the three and six-month assessments.^ Methods. One hundred and fifty Mexican American participants were recruited at a Catholic faith-based clinic and randomized into an intervention group and a usual-care control group. Personal characteristics, acculturation and baseline A1c, diabetes knowledge and diabetes health beliefs were measured. The six-month, two-phase intervention was culturally specific and it was delivered entirely by promotoras. Phase One of the intervention consisted of sixteen hours of participative group education and bi-weekly telephone contact follow-up. Phase Two consisted of bi-weekly follow-up using inspirational faith-based health behavior change postcards. The A1c levels, diabetes knowledge and diabetes health beliefs were measured at baseline, and three and six months post-baseline. The mean changes between the groups were analyzed using analysis of covariance. ^ Results. The 80% female sample, with a mean age of 58 years, demonstrated very low: acculturation, income, education, health insurance coverage, and strong Catholicism. No significant changes were noted at the three-month assessment, but the mean change of the A1c levels (F (1, 148 = 10.28, p < .001) and the diabetes knowledge scores (F (1, 148 = 9.0, p < .002) of the intervention group improved significantly at six months, adjusting for health insurance coverage. The diabetes health belief scores decreased in both groups.^ Conclusions. This study demonstrated that an intervention led by promotoras could result in decreased A1c levels and increased diabetes knowledge in spite of the very low acculturation, educational level and insurance coverage of the intervention group participants. Clinical implications and recommendations for future research are suggested. ^

Identification and functional characterization of novel phosphotyrosine and phosphoserine residues in the interleukin-2 receptor complex

Interleukin-2 (IL-2) is a major T cell growth factor and plays an essential role in the development of normal immune responses. The Janus kinases (Jaks) and Signal transducers and activators of transcription (Stats) are critical for transducing signals from the IL-2 receptors (IL2Rs) to the nucleus to control cell growth and differentiation. In recent years there has been increasing evidence to indicate that the IL-2 activated Jak3/Stat5 pathway provides a new molecular target for immune suppression. Thus, understanding the regulation of this effector cascade has important therapeutic potential.^ One objective of this work was to identify and define the role and molecular mechanism of novel phosphorylation sites in Jak3. Using functional proteomics, three novel Jak3 phosphorylation sites, Y904, Y939 and S574 were identified. Phosphospecific antibodies confirmed that phosphorylation of Y904 and Y939 were mediated by IL-2 and other IL-2 family cytokines in distinct cell types. Biochemical analysis demonstrated that phosphorylation of both Y904 and Y939 positively regulated Jak3 enzymatic activity, while phosphorylation of S574 did not affect Jak3 in vitro kinase activity. However, a gain-of-function mutation of S574 in Jak3 abrogated IL-2 mediated Stat5 activation, suggesting that phosphorylation of this residue might serve a negative role to attenuate IL-2 signaling. Furthermore, mechanistic analysis suggested that phosphorylation of Y904 in Jak3 affects the KmATP of Jak3, while phosphorylation of Y939 in Jak3 was required to bind one of its substrates, Stat5.^ The second objective was to determine the role of serine/threonine phosphatases in the regulation of the IL2R complex. Activation of Jak3 and Stat5 by IL-2 is a transient event mediated by phosphorylation. Using a specific PP1/PP2A inhibitor, we observed that inhibition of PP1/PP2A negatively regulated the IL-2 activated Jak3/Stat5 signaling pathway in a human NK cell line (YT) and primary human T cells. More importantly, coimmunoprecipitation assays indicated that inhibition of PP1/PP2A blocked the formation of an active IL2R complex. Pretreatment of cells with the inhibitor also reduced the electrophoretic mobility of the IL2Rβ and IL2Rγ subunits in YT cells, suggesting that inhibition of PP1/PP2A directly or indirectly regulates undefined serine/threonine kinases which phosphorylate these proteins. Based on these observations, a model has emerged that serine/threonine phosphorylation of the IL2Rβ and IL2Rγ subunits causes a conformational change of these proteins, which disrupts IL2R dimerization and association of Jak3 and Stat5 to these receptors.^

A qualitative analysis of leadership styles and the selection of quality improvement in primary care practice

In the Practice Change Model, physicians act as key stakeholders, people who have both an investment in the practice and the capacity to influence how the practice performs. This leadership role is critical to the development and change of the practice. Leadership roles and effectiveness are an important factor in quality improvement in primary care practices.^ The study conducted involved a comparative case study analysis to identify leadership roles and the relationship between leadership roles and the number and type of quality improvement strategies adopted during a Practice Change Model-based intervention study. The research utilized secondary data from four primary care practices with various leadership styles. The practices are located in the San Antonio region and serve a large Hispanic population. The data was collected by two ABC Project Facilitators from each practice during a 12-month period including Key Informant Interviews (all staff members), MAP (Multi-method Assessment Process), and Practice Facilitation field notes. This data was used to evaluate leadership styles, management within the practice, and intervention tools that were implemented. The chief steps will be (1) to analyze if the leader-member relations contribute to the type of quality improvement strategy or strategies selected (2) to investigate if leader-position power contributes to the number of strategies selected and the type of strategy selected (3) and to explore whether the task structure varies across the four primary care practices.^ The research found that involving more members of the clinic staff in decision-making, building bridges between organizational staff and clinical staff, and task structure are all associated with the direct influence on the number and type of quality improvement strategies implemented in primary care practice.^ Although this research only investigated leadership styles of four different practices, it will offer future guidance on how to establish the priorities and implementation of quality improvement strategies that will have the greatest impact on patient care improvement. ^

Hypertension and cognitive decline among patients of Alzheimer's disease

Objective. The main aim of our study is to assess the effect of hypertension on the decline in cognitive impairment among Alzheimer’s patients. Methods. We analyzed the data of AD patients enrolled in Baylor ADMDC in a prospective study design. We divided AD patients into two groups based on the definition of hypertension. We described a decline in cognitive impairment as a change of 5 points in mini-mental state examination score (MMSE) from the baseline visit. Results. Independent of covariates, AD patients with hypertension did not exhibit a significant decline in cognitive impairment after adjustment of covariates, age, race and education (Hazard Ratio (HR) = 1.07, p value 0.58, 95% confidence interval 0.84-1.39) than AD patients without hypertension. In addition, AD patients with hypertension did not experience decline in cognitive impairment sooner than AD patients without hypertension. (P value 0.83). Conclusions . Hypertension is not associated with cognitive impairment over time among patients with Alzheimer’s disease enrolled in Baylor ADMDC after other potential confounders were taken into account. These findings should not be interpreted as a basis for discouraging appropriate medical treatment of hypertension in AD patients. Greater efforts should be made to improve the recognition of hypertension as a modifiable risk factor for decline in cognitive impairment in AD population. ^

Determining associations and assessing methodological issues in a case-control study of hazardous air pollutants and neural tube defects

Recent studies have reported positive associations between maternal exposures to air pollutants and several adverse birth outcomes. However, there have been no assessments of the association between environmental hazardous air pollutants (HAPs) such as benzene, toluene, ethylbenzene, and xylene (BTEX) and neural tube defects (NTDs) a common and serious group of congenital malformations. Before examining this association, two important methodological questions must be addressed: (1) is maternal residential movement likely to result in exposure misclassification and (2) is it appropriate to lump defects of the neural tube, such as anencephaly and spina bifida, into a composite disease endpoint (i.e., NTDs). ^ Data from the National Birth Defects Prevention Study and Texas Birth Defects Registry were used to: (1) assess the extent to which change of residence may result in exposure misclassification when exposure is based on the address at delivery; (2) formally assess heterogeneity of the associations between known risk factors for NTDs, using polytomous logistic regression; and (3) conduct a case-control study assessing the association between ambient air levels of BTEX and the risk of NTDs among offspring. ^ Regarding maternal residential mobility, this study suggests address at delivery was not significantly different from using address at conception when assigning quartile of benzene exposure (OR 1.0, 95% CI 0.9, 1.3). On the question of effect heterogeneity among NTDs, the effect estimates for infant sex P = 0.017), maternal body mass index P = 0.016), and folate supplementation P = 0.050) were significantly different for anencephaly and spina bifida, suggesting it is often more appropriate to assess potential risk factors among subgroups of NTDs. For the main study question on the association between environmental HAPs and NTDs, mothers who have offspring with isolated spina bifida are 2.4 times likely to live in areas with the highest benzene levels (95% CI 1.1, 5.0). However, no other significant associations were observed.^ This project is the first to include not only an assessment of the relationship between environmental levels of BTEX and NTDs, but also two separate studies addressing important methodological issues associated with this question. Our results contribute to the growing body of evidence regarding air pollutant exposure and adverse birth outcomes. ^

Determinants of CD4 cell count decline after treatment interruption

Patients who had started HAART (Highly Active Anti-Retroviral Treatment) under previous aggressive DHHS guidelines (1997) underwent a life-long continuous HAART that was associated with many short term as well as long term complications. Many interventions attempted to reduce those complications including intermittent treatment also called pulse therapy. Many studies were done to study the determinants of rate of fall in CD4 count after interruption as this data would help guide treatment interruptions. The data set used here was a part of a cohort study taking place at the Johns Hopkins AIDS service since January 1984, in which the data were collected both prospectively and retrospectively. The patients in this data set consisted of 47 patients receiving via pulse therapy with the aim of reducing the long-term complications. ^ The aim of this project was to study the impact of virologic and immunologic factors on the rate of CD4 loss after treatment interruption. The exposure variables under investigation included CD4 cell count and viral load at treatment initiation. The rates of change of CD4 cell count after treatment interruption was estimated from observed data using advanced longitudinal data analysis methods (i.e., linear mixed model). Using random effects accounted for repeated measures of CD4 per person after treatment interruption. The regression coefficient estimates from the model was then used to produce subject specific rates of CD4 change accounting for group trends in change. The exposure variables of interest were age, race, and gender, CD4 cell counts and HIV RNA levels at HAART initiation. ^ The rate of fall of CD4 count did not depend on CD4 cell count or viral load at initiation of treatment. Thus these factors may not be used to determine who can have a chance of successful treatment interruption. CD4 and viral load were again studied by t-tests and ANOVA test after grouping based on medians and quartiles to see any difference in means of rate of CD4 fall after interruption. There was no significant difference between the groups suggesting that there was no association between rate of fall of CD4 after treatment interruption and above mentioned exposure variables. ^

Hormone therapy and physical activity as predictors of lung cancer risk and survival: The California Teachers Study

Cigarette smoking is responsible for the majority of lung cancer cases worldwide; however, a proportion of never smokers still develop lung cancer over their lifetime, prompting investigation into additional factors that may modify lung cancer incidence, as well as mortality. Although hormone therapy (HT), physical activity (PA), and lung cancer have been previously examined, the associations remain unclear. This study investigated exposure to HT and PA that may modulate underlying mechanisms of lung cancer etiology and progression among women by using existing, de-identified data from the California Teachers Study (CTS).^ The CTS cohort, established in 1995–1996, has 133,479 active and retired female teachers and administrators, recruited through the California State Teachers Retirement System, and followed annually for cancer diagnosis, death, and change of address. Each woman enrolled in the CTS returned a questionnaire covering a wide variety of issues related to cancer risk and women's health, including recent and past HT use and physical activity, as well as active and environmental cigarette smoke exposure. Complete data to assess the associations between HT and lung cancer risk and survival were available for 60,592 postmenopausal women. Between 1995 and 2007, 727 of these women were diagnosed with invasive lung cancer; 441 of these died. Complete data to assess the associations between PA and lung cancer risk and survival were available for 118,513 women. Between 1995 and 2007, 853 of these women were diagnosed with invasive lung cancer; 516 of these died.^ After careful adjustment for smoking habits and other potential confounders, no measure of HT use was associated with lung cancer risk; however, any HT use (vs. no use) was associated with a decrease in lung-cancer-specific mortality. Specifically, among women who only used estrogen (E-only), decreases in lung cancer mortality were seen for recent use, but not for former use; no association was observed for estrogen plus progestin (E+P). Furthermore, among former users of HT, a statistically significant decrease in lung cancer mortality was observed for E-only use within 5 years prior to baseline, but not for E-only use >5 years prior to baseline. Neither long-term recreational PA nor recent recreational PA alone were associated with lung cancer risk; however, among women with a BMI<25 and ever smokers, high long-term moderate+strenuous PA was associated with a decrease in lung cancer risk. Women with non-local disease showed a decrease in lung cancer mortality associated with increasing duration of strenuous long-term activity, and 1.50-3.00 h/wk/y of recent moderate or recent strenuous PA. Long-term moderate PA was associated with decreased lung cancer mortality in never smokers, whereas recent moderate PA was associated with increased lung cancer mortality in current smokers. ^ Placing our findings in the context of the current literature, HT does not appear to be associated with lung cancer risk and previous studies reporting a protective effect of HT use on lung cancer risk may be subject to residual confounding by smoking. Looking at our findings regarding PA overall, the evidence still remains inconclusive regarding whether or not physical activity influence lung cancer risk or mortality. Our results suggest that recreational PA may associated with decreased lung cancer risk among women with BMI<25 and ever smoking-women; however, residual confounding by smoking should be strongly considered. To our knowledge, this is the first study to investigate lifetime recreational PA and lung cancer mortality among women. Our results contribute to the growing body of knowledge regarding non-smoking-related risk factors for lung cancer incidence and mortality among women. Given the potential clinical and interventional significance, further study and validation of these findings is warranted.^

A case-comparison study of weight fluctuations during young adulthood and coronary artery disease during middle age

The hypothesis that large fluctuations in weight during young adulthood are associated with the degree of coronary artery disease was investigated by comparing patterns of weight change of patients with angiographically defined diseased or normal arteries. Participants (n = 823) were selected from men and women aged 40-74 years who had undergone angiography at North Carolina Baptist Hospital during 1987-88. Weight history from age 20 to 40 was assessed with a mailed questionnaire. Per cent prevalence of "yo-yo dieting" adjusted for age, race, and coronary disease risk factors in patients who had 0, 1, 2, 3, or more than 3 diseased arteries was 8.6, 8.8, 3.7, 5.6 and 7.1 per cent respectively (p = 0.313). These results do not support the research hypothesis. However, since the results may have been confound by neuroticism, they should not be interpreted as strong evidence against this hypothesis. ^

Development of a standard sign-out procedure for clinicians in a pediatric intensive care unit

Background: Poor communication among health care providers is cited as the most common cause of sentinel events involving patients. Sign-out of patient data at the change of clinician shifts is a component of communication that is especially vulnerable to errors. Sign-outs are particularly extensive and complex in intensive care units (ICUs). There is a paucity of validated tools to assess ICU sign-outs. ^ Objective: To design a valid and reliable survey tool to assess the perceptions of Pediatric ICU (PICU) clinicians about sign-out. ^ Design: Cross-sectional, web-based survey ^ Setting: Academic hospital, 31-bed PICU ^ Subjects: Attending faculty, fellows, nurse practitioners and physician assistants. ^ Interventions: A survey was designed with input from a focus group and administered to PICU clinicians. Test-retest reliability, internal consistency and validity of the survey tool were assessed. ^ Measurements and Main Results: Forty-eight PICU clinicians agreed to participate. We had 42(88%) and 40(83%) responses in the test and retest phases. The mean scores for the ten survey items ranged from 2.79 to 3.67 on a five point Likert scale with no significant test-retest difference and a Pearson correlation between pre and post answers of 0.65. The survey item scores showed internal consistency with a Cronbach's Alpha of 0.85. Exploratory factor analysis revealed three constructs: efficacy of sign-out process, recipient satisfaction and content applicability. Seventy eight % clinicians affirmed the need for improvement of the sign-out process and 83% confirmed the need for face- to-face verbal sign-out. A system-based sign-out format was favored by fellows and advanced level practitioners while attendings preferred a problem-based format (p=0.003). ^ Conclusions: We developed a valid and reliable survey to assess clinician perceptions about the ICU sign-out process. These results can be used to design a verbal template to improve and standardize the sign-out process.^

Comparison of Tumor Shrinkage and Cumulative Dose Distribution for Lung Cancers

Background: The physical characteristic of protons is that they deliver most of their radiation dose to the target volume and deliver no dose to the normal tissue distal to the tumor. Previously, numerous studies have shown unique advantages of proton therapy over intensity-modulated radiation therapy (IMRT) in conforming dose to the tumor and sparing dose to the surrounding normal tissues and the critical structures in many clinical sites. However, proton therapy is known to be more sensitive to treatment uncertainties such as inter- and intra-fractional variations in patient anatomy. To date, no study has clearly demonstrated the effectiveness of proton therapy compared with the conventional IMRT under the consideration of both respiratory motion and tumor shrinkage in non-small cell lung cancer (NSCLC) patients. Purpose: This thesis investigated two questions for establishing a clinically relevant comparison of the two different modalities (IMRT and proton therapy). The first question was whether or not there are any differences in tumor shrinkage between patients randomized to IMRT versus passively scattered proton therapy (PSPT). Tumor shrinkage is considered a standard measure of radiation therapy response that has been widely used to gauge a short-term progression of radiation therapy. The second question was whether or not there are any differences between the planned dose and 5D dose under the influence of inter- and intra-fractional variations in the patient anatomy for both modalities. Methods: A total of 45 patients (25 IMRT patients and 20 PSPT patients) were used to quantify the tumor shrinkage in terms of the change of the primary gross tumor volume (GTVp). All patients were randomized to receive either IMRT or PSPT for NSCLC. Treatment planning goals were identical for both groups. All patients received 5 to 8 weekly repeated 4-dimensional computed tomography (4DCT) scans during the course of radiation treatments. The original GTVp contours were propagated to T50 of weekly 4DCT images using deformable image registration and their absolute volumes were measured. Statistical analysis was performed to compare the distribution of tumor shrinkage between the two population groups. In order to investigate the difference between the planned dose and the 5D dose with consideration of both breathing motion and anatomical change, we re-calculated new dose distributions at every phase of the breathing cycle for all available weekly 4DCT data sets which resulted 50 to 80 individual dose calculations for each of the 7 patients presented in this thesis. The newly calculated dose distributions were then deformed and accumulated to T50 of the planning 4DCT for comparison with the planned dose distribution. Results: At the end of the treatment, both IMRT and PSPT groups showed mean tumor volume reductions of 23.6% ( 19.2%) and 20.9% ( 17.0 %) respectively. Moreover, the mean difference in tumor shrinkage between two groups is 3% along with the corresponding 95% confidence interval, [-8%, 14%]. The rate of tumor shrinkage was highly correlated with the initial tumor volume size. For the planning dose and 5D dose comparison study, all 7 patients showed a mean difference of 1 % in terms of target coverage for both IMRT and PSPT treatment plans. Conclusions: The results of the tumor shrinkage investigation showed no statistically significant difference in tumor shrinkage between the IMRT and PSPT patients, and the tumor shrinkage between the two modalities is similar based on the 95% confidence interval. From the pilot study of comparing the planned dose with the 5D dose, we found the difference to be only 1%. Overall impression of the two modalities in terms of treatment response as measured by the tumor shrinkage and 5D dose under the influence of anatomical change that were designed under the same protocol (i.e. randomized trial) showed similar result.