Therapeutic nanoparticles in clinics and under clinical evaluation.

This article reviews nanoparticulate-chemotherapeutic systems that have been developed for human therapy, considering the components of the nanoparticles, the therapeutic agents associated with the nanoparticles and the clinical indications these therapeutic nanoparticles have been developed for. In this evaluation we have put into perspective the types of nanomaterials and their therapeutic indications. We have reviewed the nanoparticulate-chemotherapeutic systems that have been published, approved and marketed and that are currently in clinical use. We have also analyzed the nanoparticulate-chemotherapeutic systems that are in clinical trials and under preclinical development.

EFNS guidelines on cognitive rehabilitation: report of an EFNS task force.

Disorders of language, spatial perception, attention, memory, calculation and praxis are a frequent consequence of acquired brain damage [in particular, stroke and traumatic brain injury (TBI)] and a major determinant of disability. The rehabilitation of aphasia and, more recently, of other cognitive disorders is an important area of neurological rehabilitation. We report here a review of the available evidence about effectiveness of cognitive rehabilitation. Given the limited number and generally low quality of randomized clinical trials (RCTs) in this area of therapeutic intervention, the Task Force considered, besides the available Cochrane reviews, evidence of lower classes which was critically analysed until a consensus was reached. In particular, we considered evidence from small group or single cases studies including an appropriate statistical evaluation of effect sizes. The general conclusion is that there is evidence to award a grade A, B or C recommendation to some forms of cognitive rehabilitation in patients with neuropsychological deficits in the post-acute stage after a focal brain lesion (stroke, TBI). These include aphasia therapy, rehabilitation of unilateral spatial neglect (ULN), attentional training in the post-acute stage after TBI, the use of electronic memory aids in memory disorders, and the treatment of apraxia with compensatory strategies. There is clearly a need for adequately designed studies in this area, which should take into account specific problems such as patient heterogeneity and treatment standardization.

Place de la clinique en médecine ambulatoire--les enseignements de l'etude TOPIC [The place of the clinic in primary case--the TOPIC study].

We know very little about the importance of history and physical examination compared to the importance of paraclinical tests in the diagnostic process in primary care. To answer this question, we examined prospectively 672 consecutive patients with chest pain in primary care. We recorded the timing and the clinical characteristics of the most frequent diagnosis. The resort to laboratory or other clinical tests and reference to specialist were influenced by: emergency consultation, potentially life-threatening aetiology, personal characteristics of the general practitioners' (GP) and patients' anxiety. GPs attributed the diagnosis to history and physical examination alone in 66% and to the association of history, physical examination and tests in 31% cases. This, clinical strategy remains the most important factor in the diagnostic process; even when they are insufficient, they allowed to generate hypotheses and guide investigations.

Therapeutic monitoring of antidepressants in the era of pharmacogenetics studies.

As for other drugs, there is a large interindividual variability of the plasma concentrations of antidepressants for a given dose. Within the last 2 decades, a very large number of pharmacogenetic studies have made it possible to understand the importance of genetic factors on the disposition of drugs in the organism, many of them at the levels of drug metabolism. Polymorphism of CYP2D6 and of other drug-metabolizing enzymes may thus lead to very large differences in drug exposure between patients and possibly also to toxicity or ineffective drug concentrations in some subjects. In consequence, dose recommendations of antidepressants based on genotypes, justified by the principle of administering bioequivalent individualized drug doses, are now proposed. However, blood (and thus possibly brain) concentrations also depend on other factors than the genetic makeup of the patients. Therapeutic drug monitoring of antidepressants allows us to take into account the influence of factors such as comedications, diet, smoking habit, impaired organ function, and compliance. Therapeutic drug monitoring and genotyping are thus complementary, and their combined use contributes to improve pharmacotherapy with antidepressants and other drugs.

Preoperative percutaneous portal vein embolization: evaluation of adverse events in 188 patients.

PURPOSE: To retrospectively assess the frequency of adverse events related to percutaneous preoperative portal vein embolization (PPVE). MATERIALS AND METHODS: Institutional review board did not require its approval or patient informed consent for this study. The adverse events that occurred during PPVE or until planned hepatic surgery was performed or cancelled were retrospectively obtained from clinical, imaging, and laboratory data files in 188 patients (109 male and 79 female patients; mean age, 60 years; range, 16-78 years). Liver resection was planned for metastases (n = 137), hepatocarcinoma (n = 31), cholangiocarcinoma (n = 15), fibrolamellar hepatoma (n = 1), and benign disease (n = 4). PPVE was performed with a single-lumen 5-F catheter and a contralateral approach with n-butyl cyanoacrylate mixed with iodized oil as the main embolic agent. The rate of complications in patients with cirrhosis was compared with that in patients without cirrhosis by using the chi(2) test. RESULTS: Adverse events occurred in 24 (12.8%) of 188 patients, including 12 complications and 12 incidental imaging findings. Complications included thrombosis of the portal vein feeding the future remnant liver (n = 1); migration of emboli in the portal vein feeding the future remnant liver, which necessitated angioplasty (n = 2); hemoperitoneum (n = 1); rupture of a metastasis in the gallbladder (n = 1); transitory hemobilia (n = 1); and transient liver failure (n = 6). Incidental findings were migration of small emboli in nontargeted portal branches (n = 10) and subcapsular hematoma (n = 2). Among the 187 patients in whom PPVE was technically successful, there was a significant difference (P < .001) between the occurrence of liver failure after PPVE in patients with cirrhosis (five of 30) and those without (one of 157). Sixteen liver resections were cancelled due to cancer progression (n = 12), insufficient hypertrophy of the nonembolized liver (n = 3), and complete portal thrombosis (n = 1). CONCLUSION: PPVE is a safe adjuvant technique for hypertrophy of the initially insufficient liver reserve. Post-PPVE transient liver failure is more common in patients with cirrhosis than in those without cirrhosis.

Physical activity level and health-related quality of life in the general adult population: a systematic review.

OBJECTIVE: Little is known regarding health-related quality of life and its relation with physical activity level in the general population. Our primary objective was to systematically review data examining this relationship. METHODS: We systematically searched MEDLINE, EMBASE, CINAHL, and PsycINFO for health-related quality of life and physical activity related keywords in titles, abstracts, or indexing fields. RESULTS: From 1426 retrieved references, 55 citations were judged to require further evaluation. Fourteen studies were retained for data extraction and analysis; seven were cross-sectional studies, two were cohort studies, four were randomized controlled trials and one used a combined cross sectional and longitudinal design. Thirteen different methods of physical activity assessment were used. Most health-related quality of life instruments related to the Medical Outcome Study SF-36 questionnaire. Cross-sectional studies showed a consistently positive association between self-reported physical activity and health-related quality of life. The largest cross-sectional study reported an adjusted odds ratio of "having 14 or more unhealthy days" during the previous month to be 0.40 (95% Confidence Interval 0.36-0.45) for those meeting recommended levels of physical activity compared to inactive subjects. Cohort studies and randomized controlled trials tended to show a positive effect of physical activity on health-related quality of life, but similar to the cross-sectional studies, had methodological limitations. CONCLUSION: Cross-sectional data showed a consistently positive association between physical activity level and health-related quality of life. Limited evidence from randomized controlled trials and cohort studies precludes a definitive statement about the nature of this association.

Beyond the 'dyad': a qualitative re-evaluation of the changing clinical consultation.

OBJECTIVE: To identify characteristics of consultations that do not conform to the traditionally understood communication 'dyad', in order to highlight implications for medical education and develop a reflective 'toolkit' for use by medical practitioners and educators in the analysis of consultations. DESIGN: A series of interdisciplinary research workshops spanning 12 months explored the social impact of globalisation and computerisation on the clinical consultation, focusing specifically on contemporary challenges to the clinician-patient dyad. Researchers presented detailed case studies of consultations, taken from their recent research projects. Drawing on concepts from applied sociolinguistics, further analysis of selected case studies prompted the identification of key emergent themes. SETTING: University departments in the UK and Switzerland. PARTICIPANTS: Six researchers with backgrounds in medicine, applied linguistics, sociolinguistics and medical education. One workshop was also attended by PhD students conducting research on healthcare interactions. RESULTS: The contemporary consultation is characterised by a multiplicity of voices. Incorporation of additional voices in the consultation creates new forms of order (and disorder) in the interaction. The roles 'clinician' and 'patient' are blurred as they become increasingly distributed between different participants. These new consultation arrangements make new demands on clinicians, which lie beyond the scope of most educational programmes for clinical communication. CONCLUSIONS: The consultation is changing. Traditional consultation models that assume a 'dyadic' consultation do not adequately incorporate the realities of many contemporary consultations. A paradox emerges between the need to manage consultations in a 'super-diverse' multilingual society, while also attending to increasing requirements for standardised protocol-driven approaches to care prompted by computer use. The tension between standardisation and flexibility requires addressing in educational contexts. Drawing on concepts from applied sociolinguistics and the findings of these research observations, the authors offer a reflective 'toolkit' of questions to ask of the consultation in the context of enquiry-based learning.

Impact of medical practice guidelines on the assessment of patients with acute coronary syndrome without persistent ST segment elevation.

OBJECTIVE: To assess the impact of introducing clinical practice guidelines on acute coronary syndrome without persistent ST segment elevation (ACS) on patient initial assessment. DESIGN: Prospective before-after evaluation over a 3-month period. SETTING: The emergency ward of a tertiary teaching hospital. PATIENTS: All consecutive patients with ACS evaluated in the emergency ward over the two 3-month periods. INTERVENTION: Implementation of the practice guidelines, and the addition of a cardiology consultant to the emergency team. MAIN OUTCOME MEASURES: Diagnosis, electrocardiogram interpretation, and risk stratification after the initial evaluation. RESULTS: The clinical characteristics of the 328 and 364 patients evaluated in the emergency ward for suspicion of ACS before and after guideline implementation were similar. Significantly more patients were classified as suffering from atypical chest pain (39.6% versus 47.0%; P = 0.006) after guideline implementation. Guidelines availability was associated with significantly more formal diagnoses (79.9% versus 92.9%; P < 0.0001) and risk stratification (53.7% versus 65.4%, P < 0.0001) at the end of initial assessment. CONCLUSION: Guidelines implementation, along with availability of a cardiology consultant in the emergency room had a positive impact on initial assessment of patients evaluated for suspicion of ACS. It led to increased confidence in diagnosis and stratification by risk, which are the first steps in initiating effective treatment for this common condition.

Correlation between subjective evaluation of symptoms and objective findings in early recurrent head and neck squamous cell carcinoma.

IMPORTANCE: This study addresses the value of patients' reported symptoms as markers of tumor recurrence after definitive therapy for head and neck squamous cell carcinoma. OBJECTIVE: To evaluate the correlation between patients' symptoms and objective findings in the diagnosis of local and/or regional recurrences of head and neck squamous cell carcinomas in the first 2 years of follow-up. DESIGN: Retrospective single-institution study of a prospectively collected database. SETTING: Regional hospital. PARTICIPANTS: We reviewed the clinical records of patients treated for oral cavity, oropharyngeal, laryngeal, and hypopharyngeal carcinomas between January 1, 2008, and December 31, 2009, with a minimum follow-up of 2 years. MAIN OUTCOMES AND MEASURES: Correlation between symptoms and oncologic status (recurrence vs remission) in the posttreatment period. RESULTS: Of the 101 patients included, 30 had recurrences. Pain, odynophagia, and dysphonia were independently correlated with recurrence (odds ratios, 16.07, 11.20, and 5.90, respectively; P < .001). New-onset symptoms had the best correlation with recurrences. Correlation was better between 6 to 12 and 18 to 21 months after therapy and in patients initially treated unimodally (P < .05). Primary stage and tumor site had no effect. CONCLUSIONS AND RELEVANCE: The correlation between symptoms and oncologic status is low during substantial periods within the first 2 years of follow-up. New-onset symptoms, especially pain, odynophagia, or dysphonia, better correlate with tumor recurrence, especially in patients treated unimodally.

Evaluation of Temporary Ramp Metering for Work Zones, 2012

Ramp metering has been successfully implemented in many states to improve traffic operations on freeways. Studies have documented the positive mobility and safety benefits of ramp metering. However, there have been no studies on the use of ramp metering for work zones. This report documents the results from the first deployment of temporary ramp meters in work zones in the United States. Temporary ramp meters were deployed at seven urban short-term work zones in Missouri. Safety measures such as driver compliance, merging behavior, and speed differentials were extracted from video-based field data. Mobility analysis was conducted using a calibrated simulation model and the total delays were obtained for under capacity, at capacity, and over capacity conditions. This evaluation suggests that temporary ramp meters should only be deployed at work zone locations where there is potential for congestion and turned on only during above-capacity conditions. The compliance analysis showed that non-compliance could be a major safety issue in the deployment of temporary ramp meters for under-capacity conditions. The use of a three-section instead of a traditional two-section signal head used for permanent ramp metering produced significantly higher compliance rates. Ramp metering decreased ramp platoons by increasing the percentage of single-vehicle merges to over 70% from under 50%. The accepted-merge-headway results were not statistically significant even though a slight shift towards longer headways was found with the use of ramp meters. Mobility analysis revealed that ramp metering produced delay savings for both mainline and ramp vehicles for work zones operating above capacity. On average a 24% decrease in total delay (mainline plus ramp) at low truck percentage and a 19% decrease in delay at high truck percentage conditions resulted from ramp metering.

Evaluation of Variable Advisory Speed Limits in Work Zones, TPF-5(081), 2013

Variable advisory speed limit (VASL) systems could be effective at both urban and rural work zones, at both uncongested and congested sites. At uncongested urban work zones, the average speeds with VASL were lower than without VASL. But the standard deviation of speeds with VASL was higher. The increase in standard deviation may be due to the advisory nature of VASL. The speed limit compliance with VASL was about eight times greater than without VASL. At the congested sites, the VASL were effective in making drivers slow down gradually as they approached the work zone, reducing any sudden changes in speeds. Mobility-wise the use of VASL resulted in a decrease in average queue length, throughput, number of stops, and an increase in travel time. Several surrogate safety measures also demonstrated the benefits of VASL in congested work zones. VASL deployments in rural work zones resulted in reductions in mean speed, speed variance, and 85th percentile speeds downstream of the VASL sign. The study makes the following recommendations based on the case studies investigated: 1. The use of VASL is recommended for uncongested work zones to achieve better speed compliance and lower speeds. Greater enforcement of regulatory speed limits could help to decrease the standard deviation in speeds; 2. The use of VASL to complement the static speed limits in rural work zones is beneficial even if the VASL is only used to display the static speed limits. It leads to safer traffic conditions by encouraging traffic to slow down gradually and by reminding traffic of the reduced speed limit. A well-designed VASL algorithm, like the P5 algorithm developed in this study, can significantly improve the mobility and safety conditions in congested work zones. The use of simulation is recommended for optimizing the VASL algorithms before field deployment.

Non-Destructive Evaluation of Iowa Pavements Phase 2: Development of a Fully Automated Software System for Rapid Analysis/Processing of the Falling Weight Deflectometer Data, 2009

The Office of Special Investigations at Iowa Department of Transportation (DOT) collects FWD data on regular basis to evaluate pavement structural conditions. The primary objective of this study was to develop a fully-automated software system for rapid processing of the FWD data along with a user manual. The software system automatically reads the FWD raw data collected by the JILS-20 type FWD machine that Iowa DOT owns, processes and analyzes the collected data with the rapid prediction algorithms developed during the phase I study. This system smoothly integrates the FWD data analysis algorithms and the computer program being used to collect the pavement deflection data. This system can be used to assess pavement condition, estimate remaining pavement life, and eventually help assess pavement rehabilitation strategies by the Iowa DOT pavement management team. This report describes the developed software in detail and can also be used as a user-manual for conducting simulation studies and detailed analyses. *********************** Large File ***********************

Supporting interdisciplinary case studies: development and implementation of a joint learning environment for students in forensic science and criminal law

Scientific reporting and communication is a challenging topic for which traditional study programs do not offer structured learning activities on a regular basis. This paper reports on the development and implementation of a web application and associated learning activities that intend to raise the awareness of reporting and communication issues among students in forensic science and law. The project covers interdisciplinary case studies based on a library of written reports about forensic examinations. Special features of the web framework, in particular a report annotation tool, support the design of various individual and group learning activities that focus on the development of knowledge and competence in dealing with reporting and communication challenges in the students' future areas of professional activity.