The nature and treatment of diseases of the ear

by William Kramer. Transl. from the German, with the latest improvements of the author since the last German ed. by James Risdon Bennett

Evaluation of the effectiveness of the Fresh and Healthy Program

Background. Diets high in fat and calories are promoted by the toxic food environment in which high fat, high calorie foods are readily accessible, thus contributing to high rates of overweight and obesity.^ Hypothesis. Changing the food environment to make low-fat, low-calorie foods readily identifiable and accessible while simultaneously offering incentives for choosing those foods will result in increased consumption of targeted foods, thus decreasing caloric and fat intake and ultimately decreasing obesity rates.^ Objective. To conduct an outcome evaluation study on the effectiveness of The Fresh & Healthy Program, a health promotion project designed to promote healthy eating among The Methodist Hospital employees by labeling and promoting low calorie, low fat items in the hospital cafeteria. ^ Program. By promoting healthy eating, this program seeks to address unhealthy dietary behaviors, one of the most widely known and influential behavioral causes of obesity. Food items that are included in the program meet nutritional criteria for calories and fat and are labeled with a special logo. Program participants receive incentives for purchasing Fresh & Healthy items. The program was designed and implemented by a team of registered dietitians, two health education specialists, and retail foodservice managers at The Methodist Hospital in the Texas Medical Center in Houston and has been in existence since April 2006.^ Methods. The evaluation uses a non-randomized, one-group, time series design to evaluate the effect of the program on sales of targeted food items.^ Key words. point-of-purchase, menu labeling, environmental obesity interventions, food pricing interventions ^

A program manual to assist with implementation of a volunteer health and wellness program

Based on the success of a community health and wellness program, Wellness in the City, delivered in Dallas County by trained volunteers, Texas Cooperative Extension (TCE) decided to pilot the program in 16 counties in North and East Texas. Before implementing the program, TCE wanted the Dallas County program to be reviewed and revised as needed to meet the diverse community needs in the pilot counties. TCE also asked for an implementation manual to be developed for the county agents to utilize. ^ To achieve these objectives, I first reviewed literature on other volunteer-implemented health interventions in the U.S. to see how they were planned, disseminated, implemented, and evaluated. Next, I reviewed the Wellness in the City program and materials. I applied all the information I gathered up to that point to the program development committee meetings (committee included seven TCE county agents, a TCE regional program director, and me). The program structure and training materials were revised based on our research and program implementation experience. These changes were made to ensure adequate training for the volunteers and to create a program that is applicable in the communities it will be piloted in. ^ With the program structure and training presentations developed, next I focused on compiling the implementation manual, which includes program details and volunteer recruitment, training, and management materials. The goal was to create a manual with everything the county agents will need to implement the program, so they can focus their efforts on putting the manual to use and recruiting and managing the volunteers. The final step was developing a program evaluation form for the agents to complete. It includes questions to assess the agents' thoughts about the training content, the feasibility of implementing the program using the manual, and the challenges of the program. ^

Analysis of a disaster medical track for the Certificate in Emergency Management and Preparedness Program at the University of Texas at Dallas

Since the tragic events of September 11, 2001, the United States has engaged in building the infrastructure and developing the expertise necessary to protect its borders and its citizens from further attacks against its homeland. One approach has been the development of academic courses to educate individuals on the nature and dangers of subversive attacks and to prepare them to respond to attacks and other large-scale emergencies in their roles as working professionals, participating members of their communities, and collaborators with first responders. An initial review of the literature failed to reveal any university-based emergency management courses or programs with a disaster medical component, despite the public health significance and need for such programs. In the Fall of 2003, The School of Management at The University of Texas at Dallas introduced a continuing education Certificate in Emergency Management and Preparedness Program. This thesis will (1) describe the development and implementation of a new Disaster Medical Track as a component of this Certificate in Emergency Management and Preparedness Program, (2) analyze the need for and effectiveness of this Disaster Medical Track, and (3) propose improvements in the track based on this analysis. ^

Effects of early and late lesion of orbital frontal cortex on visual processing of faces in rhesus macaques (Macaca mulatta)

Many mental disorders disrupt social skills, yet few studies have examined how the brain processes social information. Functional neuroimaging, neuroconnectivity and electrophysiological studies suggest that orbital frontal cortex plays important roles in social cognition, including the analysis of information from faces, which are important cues in social interactions. Studies in humans and non-human primates show that damage to orbital frontal cortex produces social behavior impairments, including abnormal aggression, but these studies have failed to determine whether damage to this area impairs face processing. In addition, it is not known whether damage early in life is more detrimental than damage in adulthood. This study examined whether orbital frontal cortex is necessary for the discrimination of face identity and facial expressions, and for appropriate behavioral responses to aggressive (threatening) facial expressions. Rhesus monkeys (Macaca mulatta) received selective lesions of orbital frontal cortex as newborns or adults. As adults, these animals were compared with sham-operated controls on their ability to discriminate between faces of individual monkeys and between different facial expressions of emotion. A passive visual paired-comparison task with standardized rhesus monkey face stimuli was designed and used to assess discrimination. In addition, looking behavior toward aggressive expressions was assessed and compared with that of normal control animals. The results showed that lesion of orbital frontal cortex (1) may impair discrimination between faces of individual monkeys, (2) does not impair facial expression discrimination, and (3) changes the amount of time spent looking at aggressive (threatening) facial expressions depending on the context. The effects of early and late lesions did not differ. Thus, orbital frontal cortex appears to be part of the neural circuitry for recognizing individuals and for modulating the response to aggression in faces, and the plasticity of the immature brain does not allow for recovery of these functions when the damage occurs early in life. This study opens new avenues for the assessment of rhesus monkey face processing and the neural basis of social cognition, and allows a better understanding of the nature of the neuropathology in patients with mental disorders that disrupt social behavior, such as autism. ^

A path analysis of an after-school health and exercise program for elementary school children in El Paso, Texas

As schools are pressured to perform on academics and standardized examinations, schools are reluctant to dedicate increased time to physical activity. After-school exercise and health programs may provide an opportunity to engage in more physical activity without taking time away from coursework during the day. The current study is a secondary data analysis of data from a randomized trial of a 10-week after-school program (six schools, n = 903) that implemented an exercise component based on the CATCH physical activity component and health modules based on the culturally-tailored Bienestar health education program. Outcome variables included BMI and aerobic capacity, health knowledge and healthy food intentions as assessed through path analysis techniques. Both the baseline model (χ2 (df = 8) = 16.90, p = .031; RMSEA = .035 (90% CI of .010–.058), NNFI = 0.983 and the CFI = 0.995) and the model incorporating intervention participation proved to be a good fit to the data (χ2 (df = 10) = 11.59, p = .314. RMSEA = .013 (90% CI of .010–.039); NNFI = 0.996 and CFI = 0.999). Experimental group participation was not predictive of changes in health knowledge, intentions to eat healthy foods or changes in Body Mass Index, but it was associated with increased aerobic capacity, β = .067, p < .05. School characteristics including SES and Language proficiency proved to be significantly associated with changes in knowledge and physical indicators. Further effects of school level variables on intervention outcomes are recommended so that tailored interventions can be developed aimed at the specific characteristics of each participating school. ^

Nonpurging binge eaters versus nonbinge eaters and treatment retention for adult obesity

Dropout from obesity treatment has been a major factor associated with weight control failure, with few reliable predictors of dropouts or completers. Previous studies have tended to treat obese people as a homogeneous group with standard behavior modification-based interventions. Current research indicates there may be subgroups within the obese population, binge eaters and nonbinge eaters, who have different dropout rates. Current studies also recommend focusing on the subset of this subgroup that does not engage in purging (vomiting, laxative abuse, or excessive exercise) to compensate for binge eating. This research uses a secondary dataset (N = 156) from a prospective study in which participants were randomized to a Food Dependency (FD) and a Behavioral Self-Management (BSM) group for weight reduction. Criteria for subjects in the original study included (1) scoring higher on the existing Binge Eating Scale (BES) in order to ensure enrollment of more binge eaters and (2) no compensatory purging behavior for binge eating. Subjects were then reclassified in this study as binge eaters or nonbinge eaters using the more stringent proposed 1994 DSM-IV criteria for Binge Eating Disorder (BED). Subjects were followed for dropout. Variables studied were binge status, age at obesity onset, age at study baseline, class instructor, number of previous weight loss attempts, race, marital status, body mass index (BMI kg/m$\sp2$), type of intervention, work status, educational level, and social support. Stepwise backward regression Cox survival analysis indicated binge status had a consistent, statistically significant protective effect on dropout in which binge eaters were half as likely to dropout versus nonbinge eaters (p = 0.04). Cox proportional hazards analysis indicated no statistical difference in dropout by type of intervention (FD, p = 0.13; BSM, p = 0.80) when controlling for binge status. All other variables did not reach significance, which is consistent with the literature. Implications of these findings suggest that (1) the proposed 1994 DSM-IV criteria for BED is a more useful classification that the existing DSM-III-R criteria, and (2) the identification of subgroups among obese subjects is an important step in dropout and weight loss intervention research. Future research can confirm this finding. ^

CHARACTERIZATION AND TREATMENT OF A NOVEL MOUSE MODEL OF TSC-ASSOCIATED AUTISM

Tuberous sclerosis complex (TSC) is a dominant tumor suppressor disorder caused by mutations in either TSC1 or TSC2. The proteins of these genes form a complex to inhibit the mammalian target of rapamycin complex 1 (mTORC1), which controls protein translation and cell growth. TSC causes substantial neuropathology, often leading to autism spectrum disorders (ASDs) in up to 60% of patients. The anatomic and neurophysiologic links between these two disorders are not well understood. However, both disorders share cerebellar abnormalities. Therefore, we have characterized a novel mouse model in which the Tsc2 gene was selectively deleted from cerebellar Purkinje cells (Tsc2f/-;Cre). These mice exhibit progressive Purkinje cell degeneration. Since loss of Purkinje cells is a well-reported postmortem finding in patients with ASD, we conducted a series of behavior tests to assess if Tsc2f/-;Cre mice displayed autistic-like deficits. Using the three chambered social choice assay, we found that Tsc2f/-;Cre mice showed behavioral deficits, exhibiting no preference between a stranger mouse and an inanimate object, or between a novel and a familiar mouse. Tsc2f/-;Cre mice also demonstrated increased repetitive behavior as assessed with marble burying activity. Altogether, these results demonstrate that loss of Tsc2 in Purkinje cells in a haploinsufficient background lead to behavioral deficits that are characteristic of human autism. Therefore, Purkinje cells loss and/or dysfunction may be an important link between TSC and ASD. Additionally, we have examined some of the cellular mechanisms resulting from mutations in Tsc2 leading to Purkinje cell death. Loss of Tsc2 led to upregulation of mTORC1 and increased cell size. As a consequence of increased protein synthesis, several cellular stress pathways were upregulated. Principally, these included altered calcium signaling, oxidative stress, and ER stress. Likely as a consequence of ER stress, there was also upregulation of ubiquitin and autophagy. Excitingly, treatment with an mTORC1 inhibitor, rapamycin attenuated mTORC1 activity and prevented Purkinje cell death by reducing of calcium signaling, the ER stress response, and ubiquitin. Remarkably, rapamycin treatment also reversed the social behavior deficits, thus providing a promising potential therapy for TSC-associated ASD.

Renal Cryoablation: Investigation of Periprocedural Visualization Tools and Treatment Response Quantification

Cryoablation for small renal tumors has demonstrated sufficient clinical efficacy over the past decade as a non-surgical nephron-sparing approach for treating renal masses for patients who are not surgical candidates. Minimally invasive percutaneous cryoablations have been performed with image guidance from CT, ultrasound, and MRI. During the MRI-guided cryoablation procedure, the interventional radiologist visually compares the iceball size on monitoring images with respect to the original tumor on separate planning images. The comparisons made during the monitoring step are time consuming, inefficient and sometimes lack the precision needed for decision making, requiring the radiologist to make further changes later in the procedure. This study sought to mitigate uncertainty in these visual comparisons by quantifying tissue response to cryoablation and providing visualization of the response during the procedure. Based on retrospective analysis of MR-guided cryoablation patient data, registration and segmentation algorithms were investigated and implemented for periprocedural visualization to deliver iceball position/size with respect to planning images registered within 3.3mm with at least 70% overlap and a quantitative logit model was developed to relate perfusion deficit in renal parenchyma visualized in verification images as a result of iceball size visualized in monitoring images. Through retrospective study of 20 patient cases, the relationship between likelihood of perfusion loss in renal parenchyma and distance within iceball was quantified and iteratively fit to a logit curve. Using the parameters from the logit fit, the margin for 95% perfusion loss likelihood was found to be 4.28 mm within the iceball. The observed margin corresponds well with the clinically accepted margin of 3-5mm within the iceball. In order to display the iceball position and perfusion loss likelihood to the radiologist, algorithms were implemented to create a fast segmentation and registration module which executed in under 2 minutes, within the clinically-relevant 3 minute monitoring period. Using 16 patient cases, the average Hausdorff distance was reduced from 10.1mm to 3.21 mm with average DSC increased from 46.6% to 82.6% before and after registration.

Potential roles for bcl-2 in the pathogenesis, progression, and treatment of prostate cancer

The most common molecular alterations observed in prostate cancer are increased bcl-2 protein expression and mutations in p53. Understanding the molecular alterations associated with prostate cancer are critical for successful treatment and designing new therapeutic interventions. Hormone-ablation therapy remains the most effective nonsurgical treatment; however, most patients will relapse with hormone-independent, refractory disease. This study addresses how hormone-ablation therapy may increase bcl-2, develops a transgenic model to elucidate the role of bcl-2 multistep prostate carcinogenesis, and assesses how bcl-2 may confer resistance to cell death induction using adenoviral wild-type p53 gene therapy. ^ Two potential androgen response elements were identified in the bcl-2 promoter. Bcl-2 promoter luciferase constructs were transfected into the hormone- sensitive LNCaP prostate cell line. In the presence of dihydrotestosterone, the activity of one bcl-2 promoter luciferase construct was repressed 40% compared to control cells grown in charcoal-stripped serum. Additionally, it was demonstrated that both bcl-2 mRNA and protein were downregulated in the LNCaP cells grown in the presence DHT. This suggests that DHT represses bcl-2 expression through possible direct and indirect mechanisms and that hormone-ablation therapy may actually increases bcl-2 protein. ^ To determine the role of bcl-2 in prostate cancer progression in vivo, probasin-bcl-2 mice were generated where human bcl-2 was targeted to the prostate. Increased bcl-2 expression rendered the ventral prostate more resistant to apoptosis induction following castration. When the probasin-bcl-2 mice were crossed with TRAMP mice, the latency to tumor formation was decreased. The expression of bcl-2 in the double transgenic mice did not affect the incidence of metastases. The double transgenic model will facilitate the study of in vivo effects of specific genetic lesions during the pathogenesis of prostate cancer. ^ The effects of increased bcl-2 protein on wild-type adenoviral p53-mediated cell death were determined in prostatic cell lines. Increased bcl-2 protected PC3 and DU145 cell lines, which possess mutant p53, from p53-mediated cell death and reductions in cell viability. Bcl-2 did not provide the same protective effect in LNCaP cell line, which expresses wild-type p53. This suggests that the ability of bcl-2 to protect against p53-mediated cell death is dependent upon the endogenous status of p53. ^

Early and Middle Miocene calcareous nannofossil distribution in the North Atlantic Ocean

Deep Sea Drilling Project Site 563, located on the west flank of the northern Mid-Atlantic Ridge, recovered a long Miocene section from which magnetostratigraphic and isotopic stratigraphy are available. Quantitative analyses of calcareous nannofossil assemblages have been performed in the Lower and Middle Miocene sediments from Site 563. The abundance patterns of the identified species allow us to determine several bioevents for this time interval. The recognized biohorizons, related to the available magnetostratigraphy, provide new data on the biostratigraphic value of many species and on the synchroneity of the events over a wide geographic area. Relations with the oxygen isotope stratigraphy are also reported. Sphenolith distribution is examined in particular detail due to their biostratigraphic importance in the Early Miocene. In particular the recently described species Sphenolithus procerus, Sphenolithus tintinnabulum and Sphenolithus multispinatus can be useful to subdivide the Lower Miocene zones NN2 and NN3. A large variety of Reticulofenestra pseudoumbilicus has been identified within zones NN6 and NN7.

Model results in NetCDF format of North African vegetation-precipitation in early and mid-Holocene climate simulated by CCSM3-DGVM//

The present study analyses the sign, strength, and working mechanism of the vegetation-precipitation feedback over North Africa in middle (6 ka BP) and early Holocene (9 ka BP) simulations using the comprehensive coupled climate-vegetation model CCSM3-DGVM (Community Climate System Model version 3 and a dynamic global vegetation model). The coupled model simulates enhanced summer rainfall and a northward migration of the West African monsoon trough along with an expansion of the vegetation cover for the early and middle Holocene compared to the pre-industrial period. It is shown that dynamic vegetation enhances the orbitally triggered summer precipitation anomaly by approximately 20% in the Sahara-Sahel region (10-25° N, 20° W-30° E) in both the early and mid-Holocene experiments compared to their fixed-vegetation counterparts. The primary vegetation-rainfall feedback identified here operates through surface latent heat flux anomalies by canopy evaporation and transpiration and their effect on the mid-tropospheric African easterly jet, whereas the effects of vegetation changes on surface albedo and local water recycling play a negligible role. Even though CCSM3-DGVM simulates a positive vegetation-precipitation feedback in the North African region, this feedback is not strong enough to produce multiple equilibrium climate-ecosystem states on a regional scale.