Multi-parametric classification of Alzheimer's disease and mild cognitive impairment: the impact of quantitative magnetization transfer MR imaging

Multi-parametric and quantitative magnetic resonance imaging (MRI) techniques have come into the focus of interest, both as a research and diagnostic modality for the evaluation of patients suffering from mild cognitive decline and overt dementia. In this study we address the question, if disease related quantitative magnetization transfer effects (qMT) within the intra- and extracellular matrices of the hippocampus may aid in the differentiation between clinically diagnosed patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI) and healthy controls. We evaluated 22 patients with AD (n=12) and MCI (n=10) and 22 healthy elderly (n=12) and younger (n=10) controls with multi-parametric MRI. Neuropsychological testing was performed in patients and elderly controls (n=34). In order to quantify the qMT effects, the absorption spectrum was sampled at relevant off-resonance frequencies. The qMT-parameters were calculated according to a two-pool spin-bath model including the T1- and T2 relaxation parameters of the free pool, determined in separate experiments. Histograms (fixed bin-size) of the normalized qMT-parameter values (z-scores) within the anterior and posterior hippocampus (hippocampal head and body) were subjected to a fuzzy-c-means classification algorithm with downstreamed PCA projection. The within-cluster sums of point-to-centroid distances were used to examine the effects of qMT- and diffusion anisotropy parameters on the discrimination of healthy volunteers, patients with Alzheimer and MCIs. The qMT-parameters T2(r) (T2 of the restricted pool) and F (fractional pool size) differentiated between the three groups (control, MCI and AD) in the anterior hippocampus. In our cohort, the MT ratio, as proposed in previous reports, did not differentiate between MCI and AD or healthy controls and MCI, but between healthy controls and AD.

[Mitochondrial dysfunction during sepsis, impact and possible regulating role of hypoxia-inducible factor-1alpha]

There is a direct correlation between the development of the multiple organ dysfunction syndrome (MODS) and the elevated mortality associated with sepsis. The mechanisms responsible for MODS development are being studied, however, the main efforts regarding MODS evaluation have focused on oxygen delivery optimization and on the modulation of the characteristic inflammatory cascade of sepsis, all with negative results. Recent studies have shown that there is development of tissue acidosis, even when there are normal oxygen conditions and limited presence of tissue cellular necrosis or apoptosis, which would indicate that cellular energetic dysfunction may be a central element in MODS pathogenesis. Mitochondrias are the main source of cellular energy, central regulators of cell death and the main source for reactive oxygen species. Several mechanisms contribute to mitochondrial dysfunction during sepsis, that is blockage of pyruvate entry into the Krebs cycle, oxidative phosphorylation substrate use in other enzymatic complexes, enzymatic complex inhibition and membrane damage mediated by oxidative stress, and reduction in mitochondrial content. Hypoxia-inducible factor-1alpha (HIF-1alpha) is a nuclear transcription factor with a central role in the regulation of cellular oxygen homeostasis. Its induction under hypoxic conditions is associated to the expression of hundreds of genes that coordinate the optimization of cellular oxygen delivery and the cellular energy metabolism. HIF-1alpha can also be stabilized under normoxic condition during inflammation and this activation seems to be associated with a prominent pro-inflammatory profile, with lymphocytes dysfunction, and to a reduction in cellular oxygen consumption. Further studies should establish a role for HIF-1alpha as a therapeutic target.

Evaluation of physical and mental recovery status after elective liver resection

BACKGROUND AND OBJECTIVE: This prospective, clinical pilot trial compared the Short Form 36 Health Survey (SF-36) and a nine-item quality of recovery [Quality of Recovery 9 (QoR-9)] survey to assess the 1-week outcome after liver resection and prediction of postoperative complications from baseline values before liver resection. METHODS: In 19 patients, the SF-36 was recorded preoperatively (baseline) and on postoperative day (POD) 7. SF-36 z-values (means +/- SD) for the physical component summary (PCS) and mental component summary (MCS) were calculated. QoR-9 (score 0-18) was performed at baseline, POD1, POD3, POD5 and POD7. Descriptive analysis and effect sizes (d) were calculated. RESULTS: From baseline to POD7, PCS decreased from -0.38 +/- 1.30 to -2.10 +/- 0.76 (P = 0.002, d = -1.57) and MCS from -0.71 +/- 1.50 to -1.33 +/- 1.11 (P = 0.061, d = -0.46). QoR-9 was significantly lower at POD1, POD3 and POD5 compared with baseline (P < 0.050, d < -2.0), but not at POD7 (P = 0.060, d = -1.08). Baseline PCS was significantly lower with a high effect size in patients with complications (n = 12) compared with patients without complications (n = 7) (-0.76 +/- 1.46 vs. 0.27 +/- 0.56; P = 0.044, d = -0.84) but not baseline MCS (P = 0.831, d = -0.10) or baseline QoR-9 (P = 0.384, d = -0.44). CONCLUSIONS: The SF-36 indicates that liver resection surgery has a higher impact on physical health than on mental health. QoR-9 determines the feasible time course of recovery with a 1-week return to baseline. Preoperative impaired physical health might predict postoperative complications.

Patients with oral tumors. Part 2: Quality of life after treatment with resection prostheses. Resection prosthetics: evaluation of quality of life

In the present study, the oral health-related quality of life of 18 patients (13 men and 5 women) was evaluated using validated questionnaires as proposed by the European Organization of Research and Treatment of Cancer (EORTC). The patients belonged to a cohort of 48 patients, whose prosthetic treatment was performed during the years 2004-2007. In the course of tumor resection, 12 patients underwent graft surgery and 14 patients radiotherapy. One patient required a nasal epithesis since resection of the nose became necessary. Five patients underwent a full block resection of the mandible, and tumor resection in 3 patients resulted in a large oronasal communication. Prosthetic rehabilitation was performed in all patients, and the follow-up period with regular care covered a minimum of 3 years. Eleven patients received dental implants for better support and retention of the prostheses. In spite of compromised oral conditions, functional restrictions, and some difficulties with the prostheses, the answers to the questionnaire were quite positive. The majority judged their general health as good or even excellent. The subjective perception of the patients may contradict the objective view by the dentist. In fact, the individual patient's history and experience provide a better understanding of the impact of oral tumors on daily life. The overall assessment identified 4 items that were perceived as major problems by all patients: swallowing solid food, dry mouth, limited mouth opening, and appearance. Prosthetic rehabilitation has only a limited influence on such problems.

Evaluation of control and surveillance strategies for classical swine fever using a simulation model

Classical swine fever (CSF) outbreaks can cause enormous losses in naïve pig populations. How to best minimize the economic damage and number of culled animals caused by CSF is therefore an important research area. The baseline CSF control strategy in the European Union and Switzerland consists of culling all animals in infected herds, movement restrictions for animals, material and people within a given distance to the infected herd and epidemiological tracing of transmission contacts. Additional disease control measures such as pre-emptive culling or vaccination have been recommended based on the results from several simulation models; however, these models were parameterized for areas with high animal densities. The objective of this study was to explore whether pre-emptive culling and emergency vaccination should also be recommended in low- to moderate-density areas such as Switzerland. Additionally, we studied the influence of initial outbreak conditions on outbreak severity to improve the efficiency of disease prevention and surveillance. A spatial, stochastic, individual-animal-based simulation model using all registered Swiss pig premises in 2009 (n=9770) was implemented to quantify these relationships. The model simulates within-herd and between-herd transmission (direct and indirect contacts and local area spread). By varying the four parameters (a) control measures, (b) index herd type (breeding, fattening, weaning or mixed herd), (c) detection delay for secondary cases during an outbreak and (d) contact tracing probability, 112 distinct scenarios were simulated. To assess the impact of scenarios on outbreak severity, daily transmission rates were compared between scenarios. Compared with the baseline strategy (stamping out and movement restrictions) vaccination and pre-emptive culling neither reduced outbreak size nor duration. Outbreaks starting in a herd with weaning piglets or fattening pigs caused higher losses regarding to the number of culled premises and were longer lasting than those starting in the two other index herd types. Similarly, larger transmission rates were estimated for these index herd type outbreaks. A longer detection delay resulted in more culled premises and longer duration and better transmission tracing increased the number of short outbreaks. Based on the simulation results, baseline control strategies seem sufficient to control CSF in low-medium animal-dense areas. Early detection of outbreaks is crucial and risk-based surveillance should be focused on weaning piglet and fattening pig premises.

Formative Evaluation of the "Time Twisters": A Comic Book Based Obesity Prevention Curriculum for Elementary School Students

Introduction: Obesity is a public health problem, particularly in Hispanic children. Alternative media channels may offer the potential to motivate children to engage in health promoting behaviors. A comic book, “Time Twisters”, was developed to impact screen time use, physical activity, and dietary behavior for elementary school children and evaluated for acceptability and feasibility prior to implementation in a multi-component physical activity intervention. [See PDF for complete abstract]

COGNITIVE IMPACT OF INTERACTIVE MULTIMEDIA

Technology has been gradually introduced in heath education. One of the most attractive features of this technology-based education is the use of multimedia. In this article we explore the research evidence about the role that multimedia is playing in education. From that analysis we describe the most relevant features of this technology to prepare a common ground of discussion about the evaluation of its impact on educational outcomes. As part of this analysis, we organize current research evidence on the use of technology in medical education, distinguishing diverse variables involved in the process, like knowledge (declarative, procedural), learner characteristics, curricular scenario, etc. This article presents an overview of the Distributed Representations theory and its relationship with research on educational outcomes and multimedia. Next we discuss the relationship between media and diverse learning theories, proposing a theory based taxonomy for educational multimedia.

Evaluation of deformable image registration for improved 4D CT-derived ventilation for image guided radiotherapy

Recent treatment planning studies have demonstrated the use of physiologic images in radiation therapy treatment planning to identify regions for functional avoidance. This image-guided radiotherapy (IGRT) strategy may reduce the injury and/or functional loss following thoracic radiotherapy. 4D computed tomography (CT), developed for radiotherapy treatment planning, is a relatively new imaging technique that allows the acquisition of a time-varying sequence of 3D CT images of the patient's lungs through the respiratory cycle. Guerrero et al. developed a method to calculate ventilation imaging from 4D CT, which is potentially better suited and more broadly available for IGRT than the current standard imaging methods. The key to extracting function information from 4D CT is the construction of a volumetric deformation field that accurately tracks the motion of the patient's lungs during the respiratory cycle. The spatial accuracy of the displacement field directly impacts the ventilation images; higher spatial registration accuracy will result in less ventilation image artifacts and physiologic inaccuracies. Presently, a consistent methodology for spatial accuracy evaluation of the DIR transformation is lacking. Evaluation of the 4D CT-derived ventilation images will be performed to assess correlation with global measurements of lung ventilation, as well as regional correlation of the distribution of ventilation with the current clinical standard SPECT. This requires a novel framework for both the detailed assessment of an image registration algorithm's performance characteristics as well as quality assurance for spatial accuracy assessment in routine application. Finally, we hypothesize that hypo-ventilated regions, identified on 4D CT ventilation images, will correlate with hypo-perfused regions in lung cancer patients who have obstructive lesions. A prospective imaging trial of patients with locally advanced non-small-cell lung cancer will allow this hypothesis to be tested. These advances are intended to contribute to the validation and clinical implementation of CT-based ventilation imaging in prospective clinical trials, in which the impact of this imaging method on patient outcomes may be tested.

Intensive Family Preservation Services: Do They Have Any Impact on Family Functioning?

Tills article presents a review of the intensive family preservation evaluation literature, the prepost test rnethology employed to evaluate three models in one state and the findings which have informed policymakers and program designers as the service expands. After intensive family preservation services, significant changes were found in parent-centered risk, parental disposition, and child-centered and child performance. No changes were found in economic risk and household adequacy.

Skills training and social influences for violence prevention in middle schools: A curriculum evaluation

This pilot study evaluated the effect of skills training and of social influences on self-reported aggressive behavior in a sample of 239 sixth-grade students. The effect of two intervention groups and one control group were compared. In the first intervention group, a 15-session, violence-prevention curriculum was taught by the teacher. In the second intervention group, the same curriculum was taught by the teacher with the assistance of peer leaders trained to modify social norms about violence. The control group was evaluated but did not receive any training. The design included four schools. In two schools, three classes were assigned to one of the two interventions or to the control group. In the other two schools, two classes were assigned to either intervention (teacher only) or control. Students were evaluated before and after the implementation of the curriculum using a standardized questionnaire.^ The primary outcome was the effect of the curriculum and peer leaders on self-reported aggressive behaviors. The secondary outcome was their impact on intervening variables: knowledge about violence, conflict-resolution skills, self-efficacy, and attitudes.^ The intervention had a moderate effect on reducing self-reported aggressive behaviors among boys in two of the six classes that received the curriculum. Both classes with peer leaders reduced their aggressive behavior, but this reduction was significant in only one. A peer leader selection problem could probably explain this lack of effect.^ In three of the four schools, both interventions had an overall significant effect on increasing knowledge about violence and skills to reduce violence. Students also developed a more negative attitude toward violence after the intervention. As hypothesized, attitude change was stronger among students from the teacher plus peer leader group. No intervention effect was observed on self-efficacy nor on attitudes toward skills to reduce violence. Limitations of the study and implications for violence prevention in schools are discussed. ^

An evaluation of the personal response system program for the elderly in Harris County, Texas

The Personal Response System Program at Huffington Center on Aging, Baylor College of Medicine, provides emergency call systems for elderly people living independently in Houston, Texas. The goal of the project was to complete a formative evaluation of the Personal Response System Program. The specific aims of the evaluation were three-fold. One aim was to evaluate participant health status and level of disability. The second aim was to develop a health care cost estimation strategy. Finally, a preliminary cost-effectiveness analysis was completed to evaluate the program's impact on health care costs and health status among the elderly target population. ^ The evaluation was a longitudinal, randomized experimental design. After the screening of 120 volunteers for eligibility, clients were asked to complete a written questionnaire and a monthly health service contact diary. Volunteers were contacted by telephone interviewers to collect health status information from 100 eligible clients (83%) on three occasions during the six months of follow-up. ^ Initially, volunteers were randomized to two experimental groups. The two groups were found to be comparable at the beginning of the study. No significant differences were detected related to health status, level of disability, or history of physician visits at baseline. However, the group with the Personal Response System (PRS) device had more adverse health events, higher IADL scores, more frequent use of walkers, lower average health status scores, and fewer community volunteers hours than the usual care comparison group. ^ The health care costs were estimated based on an algorithm adapted from the American Medical Association guidelines. Average total health care costs for the group with the PRS device ($912) were greater than the usual care group ($464). However, median health care values for the PRS group ($263) were similar to the usual care comparison group ($234). The preliminary findings indicated that the use of the PRS device was not associated with health care cost savings. ^ In the preliminary cost-effectiveness analysis, use of the personal response system was found to be associated with increased mental health status among elderly clients. The cost-effectiveness evaluation indicated that the associated cost for six months was $710 per unit increase in mental component score when the $150 PRS subscription was included. However, clients with the PRS device were found to have a greater decline in physical health status during the six-month follow-up. The beneficial effect on mental health status was found to be in contrast to negative findings associated with changes in physical health status. The implications for future research relate to the need to identify risk factors among geriatric populations to better target groups that would most likely benefit from PRS Program enrollment. ^

Impact of Preindustrial Biomass-Burning Emissions on the Oxidation Pathways of Tropospheric Sulfur and Nitrogen

Ice core measurements (H2O2 and CH4/HCHO) and modeling studies indicate a change in the oxidation capacity of the atmosphere since the onset of the Industrial Revolution due to increases in fossil fuel burning emissions [e. g., Lelieveld et al., 2002; Hauglustaine and Brasseur, 2001; Wang and Jacob, 1998; Staffelbach et al., 1991]. The mass-independent fractionation (MIF) in the oxygen isotopes of sulfate and nitrate from a Greenland ice core reveal that biomass-burning events in North America just prior to the Industrial Revolution significantly impacted the oxidation pathways of sulfur and nitrogen species deposited in Greenland ice. This finding highlights the importance of biomass-burning emissions for atmospheric chemistry in preindustrial North America and warrants the inclusion of this impact in modeling studies estimating changes in atmospheric oxidant chemistry since the Industrial Revolution, particularly when using paleo-oxidant data as a reference for model evaluation.

Systematic reviews published in higher impact clinical journals were of higher quality.

OBJECTIVES To compare the methodological quality of systematic reviews (SRs) published in high- and low-impact factor (IF) Core Clinical Journals. In addition, we aimed to record the implementation of aspects of reporting, including Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram, reasons for study exclusion, and use of recommendations for interventions such as Grading of Recommendations Assessment, Development and Evaluation (GRADE). STUDY DESIGN AND SETTING We searched PubMed for systematic reviews published in Core Clinical Journals between July 1 and December 31, 2012. We evaluated the methodological quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. RESULTS Over the 6-month period, 327 interventional systematic reviews were identified with a mean AMSTAR score of 63.3% (standard deviation, 17.1%), when converted to a percentage scale. We identified deficiencies in relation to a number of quality criteria including delineation of excluded studies and assessment of publication bias. We found that SRs published in higher impact journals were undertaken more rigorously with higher percentage AMSTAR scores (per IF unit: β = 0.68%; 95% confidence interval: 0.32, 1.04; P < 0.001), a discrepancy likely to be particularly relevant when differences in IF are large. CONCLUSION Methodological quality of SRs appears to be better in higher impact journals. The overall quality of SRs published in many Core Clinical Journals remains suboptimal.

Incidence and Imaging Outcomes of Acute Scaffold Disruption and Late Structural Discontinuity After Implantation of the Absorb Everolimus-Eluting Fully Bioresorbable Vascular Scaffold: Optical Coherence Tomography Assessment in the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions).

OBJECTIVES This study sought to describe the frequency and clinical impact of acute scaffold disruption and late strut discontinuity of the second-generation Absorb bioresorbable polymeric vascular scaffolds (Absorb BVS, Abbott Vascular, Santa Clara, California) in the ABSORB (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) cohort B study by optical coherence tomography (OCT) post-procedure and at 6, 12, 24, and 36 months. BACKGROUND Fully bioresorbable scaffolds are a novel approach to treatment for coronary narrowing that provides transient vessel support with drug delivery capability without the long-term limitations of metallic drug-eluting stents. However, a potential drawback of the bioresorbable scaffold is the potential for disruption of the strut network when overexpanded. Conversely, the structural discontinuity of the polymeric struts at a late stage is a biologically programmed fate of the scaffold during the course of bioresorption. METHODS The ABSORB cohort B trial is a multicenter single-arm trial assessing the safety and performance of the Absorb BVS in the treatment of 101 patients with de novo native coronary artery lesions. The current analysis included 51 patients with 143 OCT pullbacks who underwent OCT at baseline and follow-up. The presence of acute disruption or late discontinuities was diagnosed by the presence on OCT of stacked, overhung struts or isolated intraluminal struts disconnected from the expected circularity of the device. RESULTS Of 51 patients with OCT imaging post-procedure, acute scaffold disruption was observed in 2 patients (3.9%), which could be related to overexpansion of the scaffold at the time of implantation. One patient had a target lesion revascularization that was presumably related to the disruption. Of 49 patients without acute disruption, late discontinuities were observed in 21 patients. There were no major adverse cardiac events associated with this finding except for 1 patient who had a non-ischemia-driven target lesion revascularization. CONCLUSIONS Acute scaffold disruption is a rare iatrogenic phenomenon that has been anecdotally associated with anginal symptoms, whereas late strut discontinuity is observed in approximately 40% of patients and could be viewed as a serendipitous OCT finding of a normal bioresorption process without clinical implications. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Post-therapeutic response evaluation by a combination of endoscopy and CT scan in esophagogastric adenocarcinoma after chemotherapy: better than its reputation.

BACKGROUND Neoadjuvant chemotherapy is an accepted standard of care for locally advanced esophagogastric cancer. As only a subgroup benefits, a response-based tailored treatment would be of interest. The aim of our study was the evaluation of the prognostic and predictive value of clinical response in esophagogastric adenocarcinomas. METHODS Clinical response based on a combination of endoscopy and computed tomography (CT) scan was evaluated retrospectively within a prospective database in center A and then transferred to center B. A total of 686/740 (A) and 184/210 (B) patients, staged cT3/4, cN0/1 underwent neoadjuvant chemotherapy and were then re-staged by endoscopy and CT before undergoing tumor resection. Of 184 patients, 118 (B) additionally had an interim response assessment 4-6 weeks after the start of chemotherapy. RESULTS In A, 479 patients (70 %) were defined as clinical nonresponders, 207 (30 %) as responders. Median survival was 38 months (nonresponders: 27 months, responders: 108 months, log-rank, p < 0.001). Clinical and histopathological response correlated significantly (p < 0.001). In multivariate analysis, clinical response was an independent prognostic factor (HR for death 1.4, 95 %CI 1.0-1.8, p = 0.032). In B, 140 patients (76 %) were nonresponders and 44 (24 %) responded. Median survival was 33 months, (nonresponders: 27 months, responders: not reached, p = 0.003). Interim clinical response evaluation (118 patients) also had prognostic impact (p = 0.008). Interim, preoperative clinical response and histopathological response correlated strongly (p < 0.001). CONCLUSION Preoperative clinical response was an independent prognostic factor in center A, while in center B its prognostic value could only be confirmed in univariate analysis. The accordance with histopathological response was good in both centers, and interim clinical response evaluation showed comparable results to preoperative evaluation.