The unique ethical challenges of conducting research in the rehabilitation medicine population

BACKGROUND: The broad topic of research ethics is one which has been relatively well-investigated and discussed. Unique ethical issues have been identified for such populations as pediatrics, where the issues of consent and assent have received much attention, and obstetrics, with concerns such as the potential for research to cause harm to the fetus. However, little has been written about ethical concerns which are relatively unique to the population of patients seen by the practitioner of rehabilitation medicine. DISCUSSION: This paper reviews unique ethical concerns in conducting research in this population, including decision-making capacity, communication, the potential for subject overuse, the timing of recruitment, hope for a cure and therapeutic misconception and the nature of the health care provider-research subject relationship. SUMMARY: Researchers in the area of rehabilitation medicine should be aware of some of the unique ethical challenges posed by this patient population and should take steps to address any potential concerns in order to optimize subject safety and ensure that studies meet current ethical guidelines and standards

Fungal Adenylyl Cyclase Acts As a Signal Sensor and Integrator and Plays a Central Role in Interaction with Bacteria

10.1371/journal.ppat.1003612PLoS Pathogens910

Statistical Signatures of Photon Localization

The realization that electron localization in disordered systems (Anderson localization) is ultimately a wave phenomenon has led to the suggestion that photons could be similarly localized by disorder. This conjecture attracted wide interest because the differences between photons and electrons - in their interactions, spin statistics, and methods of injection and detection - may open a new realm of optical and microwave phenomena, and allow a detailed study of the Anderson localization transition undisturbed by the Coulomb interaction. To date, claims of three-dimensional photon localization have been based on observations of the exponential decay of the electromagnetic wave as it propagates through the disordered medium. But these reports have come under close scrutiny because of the possibility that the decay observed may be due to residual absorption, and because absorption itself may suppress localization. Here we show that the extent of photon localization can be determined by a different approach - measurement of the relative size of fluctuations of certain transmission quantities. The variance of relative fluctuations accurately reflects the extent of localization, even in the presence of absorption. Using this approach, we demonstrate photon localization in both weakly and strongly scattering quasi-one-dimensional dielectric samples and in periodic metallic wire meshes containing metallic scatterers, while ruling it out in three-dimensional mixtures of aluminum spheres.Comment: 5 pages, including 4 figure

Pulmonary Hypertension in Elderly Patients with Diastolic Dysfunction and Preserved Ejection Fraction

Abstract: Purpose: Patients with diastolic dysfunction may have a disproportionate degree of elevation in pulmonary pressure, particularly in the elderly. Higher pulmonary vascular resistance in the elderly patients with heart failure but preserved ejection fraction suggests that beyond the post-capillary contribution of pulmonary venous congestion, a pre-capillary component of pulmonary arterial hypertension occurs. We aim to identify if pulmonary vascular resistance in elderly patients with diastolic dysfunction is disproportionately higher than patients with systolic dysfunction independent of filling pressures. Methods: 389 patients identified retrospectively between 2003- 2010; elderly with preserved ejection fraction, elderly with depressed ejection fraction, and primary arterial hypertension who underwent right-heart catheterization at Rush University. Results: No significant difference in pulmonary vascular resistance between systolic and diastolic dysfunction. The mean difference in pulmonary vascular resistance was not statistically significant at 0.40 mmHg·min/l (95 % CI-3.03 to 3.83) with similar left ventricular filling pressures with mean difference of 3.38 mmHg (95 % CI,-1.27 to 8.02). When adjusted for filling pressures, there remained no difference in pulmonary vascular resistance for systolic and diastolic dysfunction. The mean pulmonary vascular resistance is more elevated in systolic heart failure compared to diastolic heart failure with means 3.13 mmHg·min/l and 3.52 mmHg·min/l, respectively

Differential effects of exogenous and endogenous cueing in multi-stream RSVP: implications for theories of attentional blink

The attentional blink (AB) refers to the finding that performance on the second of two targets (T1 and T2) in a rapid serial visual presentation (RSVP) stream is impaired when the targets are presented within 200–500 ms. To explore the possible interaction between spatial attentional orienting and temporary attentional deficits, this study used central (endogenous) and peripheral (exogenous) cues in a multi-stream RSVP task and compared the endogenous and exogenous cueing effects inside and outside of the AB period. While the endogenous cueing effect was constant in magnitude over time, the exogenous cueing effect was significantly larger inside than outside of the AB period. Theoretical implications of these findings for the interaction between attention mechanisms in spatial and temporal domains are discussed

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

RNAmute: RNA secondary structure mutation analysis tool

BACKGROUND: RNAMute is an interactive Java application that calculates the secondary structure of all single point mutations, given an RNA sequence, and organizes them into categories according to their similarity with respect to the wild type predicted structure. The secondary structure predictions are performed using the Vienna RNA package. Several alternatives are used for the categorization of single point mutations: Vienna's RNAdistance based on dot-bracket representation, as well as tree edit distance and second eigenvalue of the Laplacian matrix based on Shapiro's coarse grain tree graph representation. RESULTS: Selecting a category in each one of the processed tables lists all single point mutations belonging to that category. Selecting a mutation displays a graphical drawing of the single point mutation and the wild type, and includes basic information such as associated energies, representations and distances. RNAMute can be used successfully with very little previous experience and without choosing any parameter value alongside the initial RNA sequence. The package runs under LINUX operating system. CONCLUSION: RNAMute is a user friendly tool that can be used to predict single point mutations leading to conformational rearrangements in the secondary structure of RNAs. In several cases of substantial interest, notably in virology, a point mutation may lead to a loss of important functionality such as the RNA virus replication and translation initiation because of a conformational rearrangement in the secondary structure

The kSORT Assay to Detect Renal Transplant Patients at High Risk for Acute Rejection: Results of the Multicenter AART Study

Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR. We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART) study. Gene expression was assessed by quantitative real-time PCR (QPCR) in one center. A 17-gene set—the Kidney Solid Organ Response Test (kSORT)—was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91–0.98), validated in 124 independent samples (AUC = 0.95; 95% CI 0.88–1.0) and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy). A novel reference-based algorithm (using 13 12-gene models) was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86–0.99). Further validation of kSORT is planned in prospective clinical observational and interventional trials. The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants

Evaluation of a communication skills program for first-year medical students at the University of Toronto

Abstract Background Effective doctor-patient communication has been linked to numerous benefits for both patient and physician. The purpose of this study was to evaluate the effectiveness of the University of Toronto's Therapeutic Communication Program (TCom) at improving first-year medical students' communication skills. Methods Data were collected during the 1996/97, 1997/98, 1998/99 and 1999/00 academic years. The study used a repeated measures design with a waiting list control group: students were randomly assigned to groups starting the educational intervention in either September (N = 38) or February (N = 41), with the latter being used as a control for the former. Communication skills were assessed at the pre- and post-intervention times and at the end of the academic year from the perspectives of student, standardized patient and external rater. Results Only the external rater, using an instrument designed to assess the students' empathy based on their written responses, showed a time × group interaction effect (p = 0.039), thereby partially supporting the hypothesis that TCom improved the students' communication skills. Students rated themselves less positively after participation in the program (p = 0.038), suggesting that self-evaluation was an ineffective measure of actual performance or that the program helped them learn to more accurately assess their abilities. Conclusion The lack of strong findings may be partly due to the study's small sample sizes. Further research at other medical or professional schools could assess the effectiveness of similar courses on students' communication skills and on other capacities that were not measured in this study, such as their understanding of and comfort with patients, their management of the doctor-patient relationship, and their ability to give and receive feedback