Depression and disease severity in patients with premature acute coronary syndrome

OBJECTIVES The association between depression and cardiovascular disease severity in younger patients has not been assessed, and sex differences are unknown. We assessed whether major depression and depressive symptoms were associated with worse cardiovascular disease severity in patients with premature acute coronary syndrome, and we assessed sex differences in these relationships. METHODS We enrolled 1023 patients (aged ≤ 55 years) hospitalized with acute coronary syndrome from 26 centers in Canada, the United States, and Switzerland, through the GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome study. Left ventricular ejection fraction, Killip class, cardiac troponin I, and Global Registry of Acute Coronary Events score data were collected through chart review. RESULTS The sample comprised 248 patients with major depression and 302 women. In univariate analyses, major depression was associated with a lower likelihood of having an abnormal left ventricular ejection fraction (odds ratio, 0.70; 95% confidence interval, 0.51-0.97; P = .03) and lower troponin I levels (estimate, -4.04; 95% confidence interval, -8.01 to -0.06; P = .05). After adjustment for sociodemographic and clinical characteristics, neither major depression nor depressive symptoms were associated with disease severity indices, and there were no sex differences. CONCLUSION The increased risk of adverse events in depressed patients with premature acute coronary syndrome is not explained by disease severity.

Demographic model of the Swiss cattle population for the years 2009-2011 stratified by gender, age and production type

Demographic composition and dynamics of animal and human populations are important determinants for the transmission dynamics of infectious disease and for the effect of infectious disease or environmental disasters on productivity. In many circumstances, demographic data are not available or of poor quality. Since 1999 Switzerland has been recording cattle movements, births, deaths and slaughter in an animal movement database (AMD). The data present in the AMD offers the opportunity for analysing and understanding the dynamic of the Swiss cattle population. A dynamic population model can serve as a building block for future disease transmission models and help policy makers in developing strategies regarding animal health, animal welfare, livestock management and productivity. The Swiss cattle population was therefore modelled using a system of ordinary differential equations. The model was stratified by production type (dairy or beef), age and gender (male and female calves: 0-1 year, heifers and young bulls: 1-2 years, cows and bulls: older than 2 years). The simulation of the Swiss cattle population reflects the observed pattern accurately. Parameters were optimized on the basis of the goodness-of-fit (using the Powell algorithm). The fitted rates were compared with calculated rates from the AMD and differed only marginally. This gives confidence in the fitted rates of parameters that are not directly deductible from the AMD (e.g. the proportion of calves that are moved from the dairy system to fattening plants).

Short-term functional versus patient-reported outcome of the bicruciate stabilized total knee arthroplasty: prospective consecutive case series

BACKGROUND The main goals of the standard treatment for advanced symptomatic knee osteoarthritis, total knee arthroplasty (TKA), are pain reduction and restoration of knee motion.The aim of this study was to analyse the outcome of the patient-based Knee Injury and Osteoarthritis Outcome Score (KOOS), and the surgeon-based Knee Society Score (KSS) and its Knee Score (KS) and Knee Functional Score (KFS) components after (TKA) using the Journey knee prosthesis, and to assess the correlation of these scores with range of motion (ROM). METHODS In a prospective case series study between August 1st 2008 and May 31st 2011, 99 patients, all operated by a single surgeon, received Journey bicruciate stabilized total knee prostheses. The female/male ratio was 53/34, the mean patient age at surgery was 68 years (range 41-83 years), and the left/right knee ratio was 55/44. The KOOS, range of motion, and KS and KFS were obtained preoperatively and at 1-year follow-up. The pre- and postoperative levels of the outcome measures were compared using the Wilcoxon signed-rank test. Correlation between ROM and patient outcomes was analysed with the Spearman coefficient. RESULTS All KOOS subscores improved significantly. Ninety percent of patients improved by at least the minimum clinically relevant difference of 10 points in stiffness and other symptoms, 94.5% in pain, 94.5% in activities of daily living, 84.9% in sports and recreation, and 90% in knee-related quality of life. The mean passive and active ROM improved from 122.4° (range 90-145°) and 120.4° (range 80-145°) preoperatively to 129.4° (range 90-145°) and 127.1° (range 100-145°) postoperatively. The highest correlation coefficients for ROM and KOOS were observed for the activity and pain subscores. Very low or no correlation was seen for the sport subscore.There was a significant and clinically relevant improvement of KSS (preop/postop 112.2/174.5 points), and its KS (preop/postop 45.6/86.8 points) and KFS (preop/postop 66.6/87.8 points) components. CONCLUSIONS The Journey bicruciate stabilized knee prosthesis showed good 1-year postoperative results in terms of both functional and patient-based outcome. However, higher knee ROM correlates only moderately with patient-based outcome, implying that functionality afforded by the Journey bicruciate TKA is not equivalent to patient satisfaction.

Response to neoadjuvant treatment of invasive ductal breast carcinomas including outcome evaluation: MRI analysis by an automatic CAD system in comparison to visual evaluation

BACKGROUND The aim of this study was to evaluate imaging-based response to standardized neoadjuvant chemotherapy (NACT) regimen by dynamic contrast-enhanced magnetic resonance mammography (DCE-MRM), whereas MR images were analyzed by an automatic computer-assisted diagnosis (CAD) system in comparison to visual evaluation. MRI findings were correlated with histopathologic response to NACT and also with the occurrence of metastases in a follow-up analysis. PATIENTS AND METHODS Fifty-four patients with invasive ductal breast carcinomas received two identical MRI examinations (before and after NACT; 1.5T, contrast medium gadoteric acid). Pre-therapeutic images were compared with post-therapeutic examinations by CAD and two blinded human observers, considering morphologic and dynamic MRI parameters as well as tumor size measurements. Imaging-assessed response to NACT was compared with histopathologically verified response. All clinical, histopathologic, and DCE-MRM parameters were correlated with the occurrence of distant metastases. RESULTS Initial and post-initial dynamic parameters significantly changed between pre- and post-therapeutic DCE-MRM. Visually evaluated DCE-MRM revealed sensitivity of 85.7%, specificity of 91.7%, and diagnostic accuracy of 87.0% in evaluating the response to NACT compared to histopathology. CAD analysis led to more false-negative findings (37.0%) compared to visual evaluation (11.1%), resulting in sensitivity of 52.4%, specificity of 100.0%, and diagnostic accuracy of 63.0%. The following dynamic MRI parameters showed significant associations to occurring metastases: Post-initial curve type before NACT (entire lesions, calculated by CAD) and post-initial curve type of the most enhancing tumor parts after NACT (calculated by CAD and manually). CONCLUSIONS In the accurate evaluation of response to neoadjuvant treatment, CAD systems can provide useful additional information due to the high specificity; however, they cannot replace visual imaging evaluation. Besides traditional prognostic factors, contrast medium-induced dynamic MRI parameters reveal significant associations to patient outcome, i.e. occurrence of distant metastases.

Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9)

Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9). INTRODUCTION: Pre-eclampsia, a pregnancy-specific disease, contributes substantially to perinatal morbidity and mortality of both the mother and her child. Pre-eclampsia is often associated with high maternal urate serum levels, which in turn has been shown to play a role in the pathogenesis of this disease. The aim of this study was to investigate the glucose transporter GLUT9-mediated placental uric acid transport system. METHODS: In this study western blot, immunofluorescence techniques as well as a transepithelial transport (Transwell) model were used to assess GLUT9 protein expression and, respectively, uric acid transport activity. Electrophysiological techniques and transmission electron microscopy (TEM) were used to characterize the properties and the structure of GLUT9. RESULTS: Uric acid is transported across a BeWo choriocarcinoma cell monolayer with 530 pmol/min. We could successfully overexpress and for the first time purify the GLUT9b isoform using the Xenopus laevis oocytes expression system. Chloride seems to modulate the urate transport system. TEM revealed that GLUT9b isoform is present as monomer and dimmer in the Xenopus laevis overexpression model. A class average of all the particles allowed us to develop a first model of human GLUT9b structure, which was derived from the published crystal structure of the bacterial homologue of GLUT1-4. CONCLUSIONS: In vitro the “materno-fetal” transport of uric acid is slow indicating that in vivo the fetus might be protected from short-term fluctuations of maternal urate serum levels. The low-resolution structure obtained from TEM validates the proposed homology model regarding the structure of human GLUT9b. In ongoing studies this model is used to perform virtual screening to identify novel modulators of the urate transport system enabling the development of novel therapies in pregnancy complications.

Rapid drop in the reproduction number during the Ebola outbreak in the Democratic Republic of Congo.

The Democratic Republic of Congo (DRC) experienced a confined rural outbreak of Ebola virus disease (EVD) with 69 reported cases from July to October 2014. Understanding the transmission dynamics during the outbreak can provide important information for anticipating and controlling future EVD epidemics. I fitted an EVD transmission model to previously published data of this outbreak and estimated the basic reproduction number R 0 = 5.2 (95% CI [4.0-6.7]). The model suggests that the net reproduction number Rt fell below unity 28 days (95% CI [25-34] days) after the onset of symptoms in the index case. This study adds to previous epidemiological descriptions of the 2014 EVD outbreak in DRC, and is consistent with the notion that a rapid implementation of control interventions helped reduce further spread.

A Lentiviral Vector Expressing Japanese Encephalitis Virus-like Particles Elicits Broad Neutralizing Antibody Response in Pigs.

BACKGROUND Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in Southeast Asia. Vaccination of domestic pigs has been suggested as a "one health" strategy to reduce viral disease transmission to humans. The efficiency of two lentiviral TRIP/JEV vectors expressing the JEV envelope prM and E glycoproteins at eliciting protective humoral response was assessed in a mouse model and piglets. METHODOLOGY/PRINCIPAL FINDINGS A gene encoding the envelope proteins prM and E from a genotype 3 JEV strain was inserted into a lentiviral TRIP vector. Two lentiviral vectors TRIP/JEV were generated, each expressing the prM signal peptide followed by the prM protein and the E glycoprotein, the latter being expressed either in its native form or lacking its two C-terminal transmembrane domains. In vitro transduction of cells with the TRIP/JEV vector expressing the native prM and E resulted in the efficient secretion of virus-like particles of Japanese encephalitis virus. Immunization of BALB/c mice with TRIP/JEV vectors resulted in the production of IgGs against Japanese encephalitis virus, and the injection of a second dose one month after the prime injection greatly boosted antibody titers. The TRIP/JEV vectors elicited neutralizing antibodies against JEV strains belonging to genotypes 1, 3, and 5. Immunization of piglets with two doses of the lentiviral vector expressing JEV virus-like particles led to high titers of anti-JEV antibodies, that had efficient neutralizing activity regardless of the JEV genotype tested. CONCLUSIONS/SIGNIFICANCE Immunization of pigs with the lentiviral vector expressing JEV virus-like particles is particularly efficient to prime antigen-specific humoral immunity and trigger neutralizing antibody responses against JEV genotypes 1, 3, and 5. The titers of neutralizing antibodies elicited by the TRIP/JEV vector are sufficient to confer protection in domestic pigs against different genotypes of JEV and this could be of a great utility in endemic regions where more than one genotype is circulating.

Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts

IMPORTANCE Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). OBJECTIVE To assess the association between differences in thyroid function within the reference range and CHD risk. DESIGN, SETTING, AND PARTICIPANTS Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. EXPOSURES Thyroid function as expressed by serum thyrotropin levels at baseline. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. RESULTS Among 55,412 individuals, 1813 people (3.3%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. CONCLUSIONS AND RELEVANCE Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer.

Anticancer therapies currently used in the clinic often can neither eradicate the tumor nor prevent disease recurrence due to tumor resistance. In this study, we showed that chemoresistance to pemetrexed, a multi-target anti-folate (MTA) chemotherapeutic agent for non-small cell lung cancer (NSCLC), is associated with a stem cell-like phenotype characterized by an enriched stem cell gene signature, augmented aldehyde dehydrogenase activity and greater clonogenic potential. Mechanistically, chemoresistance to MTA requires activation of epithelial-to-mesenchymal transition (EMT) pathway in that an experimentally induced EMT per se promotes chemoresistance in NSCLC and inhibition of EMT signaling by kaempferol renders the otherwise chemoresistant cancer cells susceptible to MTA. Relevant to the clinical setting, human primary NSCLC cells with an elevated EMT signaling feature a significantly enhanced potential to resist MTA, whereas concomitant administration of kaempferol abrogates MTA chemoresistance, regardless of whether it is due to an intrinsic or induced activation of the EMT pathway. Collectively, our findings reveal that a bona fide activation of EMT pathway is required and sufficient for chemoresistance to MTA and that kaempferol potently regresses this chemotherapy refractory phenotype, highlighting the potential of EMT pathway inhibition to enhance chemotherapeutic response of lung cancer.

Mycoplasma-induced minimally conscious state

Mycoplasma pneumoniae (M. pneumoniae) frequently causes community-acquired respiratory tract infection and often presents as atypical pneumonia. Following airborne infection and a long incubation period, affected patients mostly suffer from mild or even asymptomatic and self-limiting disease. In particular in school-aged children, M. pneumoniae is associated with a wide range of extrapulmonary manifestations including central nervous system (CNS) disease. In contrast to children, severe CNS manifestations are rarely observed in adults. We report a case of a 37 year-old previously healthy immunocompetent adult with fulminant M. pneumoniae-induced progressive encephalomyelitis who was initially able to walk to the emergency department. A few hours later, she required controlled mechanical ventilation for ascending transverse spinal cord syndrome, including complete lower extremity paraplegia. Severe M. pneumoniae-induced encephalomyelitis was postulated, and antimicrobial, anti-inflammatory and immunosuppressive therapy was applied on the intensive care unit. Despite early and targeted therapy using four different immunosuppressive strategies, clinical success was limited. In our patient, locked-in syndrome developed followed by persistent minimally conscious state. The neurological status was unchanged until day 230 of follow-up. Our case underlines that severe M. pneumoniae- related encephalomyelitis must not only be considered in children, but also in adults. Moreover, it can be fulminant and fatal in adults. Our case enhances the debate for an optimal antimicrobial agent with activity beyond the blood-brain barrier. Furthermore, it may underline the difficulty in clinical decision making regarding early antimicrobial treatment in M. pneumoniae disease, which is commonly self-limited.

Comparison of Routine Brain Imaging at 3 T and 7 T.

OBJECTIVE The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], image quality, diagnostic confidence) from a standard brain magnetic resonance imaging examination encompassing common neurological disorders such as demyelinating disease, gliomas, cerebrovascular disease, and epilepsy, with comparable sequence protocols and acquisition times at 3 T and at 7 T. MATERIALS AND METHODS Ten healthy volunteers and 4 subgroups of 40 patients in total underwent comparable magnetic resonance protocols with standard diffusion-weighted imaging, 2D and 3D turbo spin echo, 2D and 3D gradient echo and susceptibility-weighted imaging of the brain (10 sequences) at 3 T and 7 T. The subgroups comprised patients with either lesional (n = 5) or nonlesional (n = 4) epilepsy, intracerebral tumors (n = 11), demyelinating disease (n = 11) (relapsing-remitting multiple sclerosis [MS, n = 9], secondary progressive MS [n = 1], demyelinating disease not further specified [n = 1]), or chronic cerebrovascular disorders [n = 9]). For quantitative analysis, SNR and CNR were determined. For a semiquantitative assessment of the diagnostic confidence, a 10-point scale diagnostic confidence score (DCS) was applied. Two experienced radiologists with additional qualification in neuroradiology independently assessed, blinded to the field strength, 3 pathology-specific imaging criteria in each of the 4 disease groups and rated their diagnostic confidence. The overall image quality was semiquantitatively assessed using a 4-point scale taking into account whether diagnostic decision making was hampered by artifacts or not. RESULTS Without correction for spatial resolution, SNR was higher at 3 T except in the T2 SPACE 3D, DWI single shot, and DIR SPACE 3D sequences. The SNR corrected by the ratio of 3 T/7 T voxel sizes was higher at 7 T than at 3 T in 10 of 11 sequences (all except for T1 MP2RAGE 3D).In CNR, there was a wide variation between sequences and patient cohorts, but average CNR values were broadly similar at 3 T and 7 T.DCS values for all 4 pathologic entities were higher at 7 T than at 3 T. The DCS was significantly higher at 7 T for diagnosis and exclusion of cortical lesions in vascular disease. A tendency to higher DCS at 7 T for cortical lesions in MS was observed, and for the depiction of a central vein and iron deposits within MS lesions. Despite motion artifacts, DCS values were higher at 7 T for the diagnosis and exclusion of hippocampal sclerosis in mesial temporal lobe epilepsy (improved detection of the hippocampal subunits). Interrater agreement was 69.7% at 3 T and 93.3% at 7 T. There was no significant difference in the overall image quality score between 3 T and 7 T taking into account whether diagnostic decision making was hampered by artifacts or not. CONCLUSIONS Ultra-high-field magnetic resonance imaging at 7 T compared with 3 T yielded an improved diagnostic confidence in the most frequently encountered neurologic disorders. Higher spatial resolution and contrast were identified as the main contributory factors.

Effects of Externally Applied, Cyclical, Low Magnitude Forces on Orthodontic Tooth Movement in Rats

Orthodontic tooth movement requires external orthodontic forces to be converted to cellular signals that result in the coordinated removal of bone on one side of the tooth (compression side) by osteoclasts, and the formation of new bone by osteoblasts on the other side (tension side). The length of orthodontic treatment can take several years, leading to problems of caries, periodontal disease, root resorption, and patient dissatisfaction. It appears that the velocity of tooth movement is largely dependent on the rate of alveolar bone remodeling. Pharmacological approaches to increase the rate of tooth movement are limited due to patient discomfort, severe root resorption, and drug-induced side effects. Recently, externally applied, cyclical, low magnitude forces (CLMF) have been shown to cause an increase in the bone mineral density of long bones, and in the growth of craniofacial structures in a variety of animal models. In addition, CLMF is well tolerated by the patient and produces no known adverse effects. However, its application in orthodontic tooth movement has not been specifically determined. Since factors that increase alveolar bone remodeling enhance the rate of orthodontic tooth movement, we hypothesized that externally applied, cyclical, low magnitude forces (CLMF) will increase the rate of orthodontic tooth movement. In order to test this hypothesis we used an in vivo rat orthodontic tooth movement model. Our specific aims were: Specific Aim 1: To develop an in vivo rat model for tooth movement. We developed a tooth movement model based upon two established rodent models (Ren and Yoshimatsu et al, See Figure 1.). The amount of variation of tooth movement in rats exposed to 25-60 g of mesial force activated viii from the first molar to the incisor for 4 weeks was calculated. Specific Aim 2: To determine the frequency dose response of externally applied, cyclical, low magnitude forces (CLMF) for maximal tooth movement and osteoclast numbers. Our working hypothesis for this aim was that the amount of tooth movement would be dose dependent on the frequency of application of the CLMF. In order to test this working hypothesis, we varied the frequency of the CLMF from 30, 60, 100, and 200 Hz, 0.4N, two times per week, for 10 minutes for 4 weeks, and measured the amount of tooth movement. We also looked at the number of osteoclasts for the different frequencies; we hypothesized an increase in osteoclasts for the dose respnse of different frequencies. Specific Aim 3: To determine the effects of externally applied, cyclical, low magnitude forces (CLMF) on PDL proliferation. Our working hypothesis for this aim was that PDL proliferation would increase with CLMF. In order to test this hypothesis we compared CLMF (30 Hz, 0.4N, two times per week, for 10 minutes for 4 weeks) performed on the left side (experimental side), to the non-CLMF side, on the right (control side). This was an experimental study with 24 rats in total. The experimental group contained fifteen (15) rats in total, and they all received a spring plus a different frequency of CLMF. Three (3) received a spring and CLMF at 30 Hz, 0.4N for 10 minutes. Six (6) received a spring and CLMF at 60 Hz, 0.4N for 10 minutes. Three (3) received a spring and CLMF at 100 Hz, 0.4N for 10 minutes. Three (3) received a spring and CLMF at 200 Hz, 0.4N for 10 minutes. The control group contained six (6) rats, and received only a spring. An additional ix three (3) rats received CLMF (30 Hz, 0.4N, two times per week, for 10 minutes for 4 weeks) only, with no spring, and were used only for histological purposes. Rats were subjected to the application of orthodontic force from their maxillary left first molar to their left central incisor. In addition some of the rats received externally applied, cyclical, low magnitude force (CLMF) on their maxillary left first molar. micro-CT was used to measure the amount of orthodontic tooth movement. The distance between the maxillary first and second molars, at the most mesial point of the second molar and the most distal point of the first molar (1M-2M distance) were used to evaluate the distance of tooth movement. Immunohistochemistry was performed with TRAP staining and BrdU quantification. Externally applied, cyclical, low magnitude forces (CLMF) do appear to have an effect on the rate, while not significant, of orthodontic tooth movement in rats. It appears that lower CLMF decreases the rate of tooth movement, while higher CLMF increases the rate of tooth movement. Future studies with larger sample sizes are needed to clarify this issue. CLMF does not appear to affect the proliferation in PDL cells, and has no effect on the number of osteoclasts.

Patient Safety Net Update

It’s been three months since we’ve gone live with Patient Safety Net, and it has been a great success! Managers and front line staff have been trained on how to input, review, and submit event reports that formerly were detailed on the hard copy “RIR” forms. Utilization of the webbased PSN system has been better than expected. PSN has enabled us to greatly improve the way we document and react to patient safety related events.

The design and evaluation of a 2D dose verification system for intensity modulated radiotherapy

The usage of intensity modulated radiotherapy (IMRT) treatments necessitates a significant amount of patient-specific quality assurance (QA). This research has investigated the precision and accuracy of Kodak EDR2 film measurements for IMRT verifications, the use of comparisons between 2D dose calculations and measurements to improve treatment plan beam models, and the dosimetric impact of delivery errors. New measurement techniques and software were developed and used clinically at M. D. Anderson Cancer Center. The software implemented two new dose comparison parameters, the 2D normalized agreement test (NAT) and the scalar NAT index. A single-film calibration technique using multileaf collimator (MLC) delivery was developed. EDR2 film's optical density response was found to be sensitive to several factors: radiation time, length of time between exposure and processing, and phantom material. Precision of EDR2 film measurements was found to be better than 1%. For IMRT verification, EDR2 film measurements agreed with ion chamber results to 2%/2mm accuracy for single-beam fluence map verifications and to 5%/2mm for transverse plane measurements of complete plan dose distributions. The same system was used to quantitatively optimize the radiation field offset and MLC transmission beam modeling parameters for Varian MLCs. While scalar dose comparison metrics can work well for optimization purposes, the influence of external parameters on the dose discrepancies must be minimized. The ability of 2D verifications to detect delivery errors was tested with simulated data. The dosimetric characteristics of delivery errors were compared to patient-specific clinical IMRT verifications. For the clinical verifications, the NAT index and percent of pixels failing the gamma index were exponentially distributed and dependent upon the measurement phantom but not the treatment site. Delivery errors affecting all beams in the treatment plan were flagged by the NAT index, although delivery errors impacting only one beam could not be differentiated from routine clinical verification discrepancies. Clinical use of this system will flag outliers, allow physicists to examine their causes, and perhaps improve the level of agreement between radiation dose distribution measurements and calculations. The principles used to design and evaluate this system are extensible to future multidimensional dose measurements and comparisons. ^

Predictors of survival in Alzheimer's disease

Alzheimer's disease (AD) is associated with greater mortality and reduced survival among individuals with Alzheimer's disease as compared to those without dementia. It is uncertain how these survival estimates change when the clinical signs and/or symptoms of comorbid conditions are present in individuals' with Alzheimer's disease. Cardiovascular risk factors such as hypertension, hyperlipidemia, congestive heart failure, coronary artery disease, and diabetes mellitus are common conditions in the aged population. Independently, these factors influence mortality and may have an additive effect on reduced survival in an individual with concomitant Alzheimer's disease. The bulk of the evidence from previous research efforts suggests an association between vascular co-morbidities and Alzheimer's disease incidence, but their role in survival remains to be elucidated. The objective of this proposed study was to examine the effects of cardiovascular comorbidities on the survival experience of individuals with probable Alzheimer's disease in order to identify prognostic factors for life expectancy following onset of disease. This study utilized data from the Baylor College of Medicine Alzheimer's Disease Center (ADC) longitudinal study of Alzheimer's disease and other memory disorders. Individuals between the ages of 55-69, 70-79, and ≥80 had a median survival from date of onset of 9.2 years, 8.0 years, and 7.2 years, respectively (p<0.001) and 5.5 years, 4.3 years, and 3.4 years from diagnosis. Sex was the strongest predictor of death from onset of AD, with females having a 30 percent lower risk compared to males. These findings further support the notion that age (both from onset and from diagnosis) and sex are the strongest predictors of survival among those with AD. ^