Functional electrical stimulation for foot drop in multiple sclerosis: a systematic review and meta-analysis of the effect on gait speed

Objective: To review the efficacy of functional electrical stimulation (FES) used for foot drop in people with multiple sclerosis (pwMS) on gait speed in short and long walking performance tests. Data sources: Five databases (Cochrane Library, CINAHL, Embase, MEDLINE, Pubmed) and reference lists were searched. Study selection: Studies of both observational and experimental design where gait speed data in pwMS could be extracted were included. Data extraction: Data were independently extracted and recorded. Methodological quality was assessed using the Effective Public Health Practice Project (EPHPP) tool. Data synthesis: Nineteen studies (described in 20 articles) recruiting 490 pwMS were identified and rated moderate or weak, with none gaining a strong rating. All studies rated weak for blinding. Initial and ongoing orthotic and therapeutic effects were assessed with regards to the impact of FES on gait speed in short and long walking tests. Meta-analyses of the short walk tests revealed a significant initial orthotic effect (t = 2.14, p = 0.016) with a mean increase in gait speed of 0.05 meters per second (m/s) and ongoing orthotic effect (t = 2.81, p = 0.003) with a mean increase of 0.08m/s. There were no initial or ongoing effect on gait speed in long walk tests and no therapeutic effect on gait speed in either short or long walk tests. Conclusions: FES used for foot drop has a positive initial and ongoing effect on gait speed in short walking tests. Further fully-powered randomized controlled trials comparing FES with alternative treatments are required

Covalently interconnected transition metal dichalcogenide networks via defect engineering for high-performance electronic devices.

Solution-processed semiconducting transition metal dichalcogenides are at the centre of an ever-increasing research effort in printed (opto)electronics. However, device performance is limited by structural defects resulting from the exfoliation process and poor inter-flake electronic connectivity. Here, we report a new molecular strategy to boost the electrical performance of transition metal dichalcogenide-based devices via the use of dithiolated conjugated molecules, to simultaneously heal sulfur vacancies in solution-processed transition metal disulfides and covalently bridge adjacent flakes, thereby promoting percolation pathways for the charge transport. We achieve a reproducible increase by one order of magnitude in field-effect mobility (µFE), current ratio (ION/IOFF) and switching time (τS) for liquid-gated transistors, reaching 10-2 cm2 V-1 s-1, 104 and 18 ms, respectively. Our functionalization strategy is a universal route to simultaneously enhance the electronic connectivity in transition metal disulfide networks and tailor on demand their physicochemical properties according to the envisioned applications.European Commission through the Graphene Flagship, the ERC Grants SUPRA2DMAT (GA-833707), FUTURE-PRINT (GA-694101), Hetero2D, GSYNCOR, the EU Grant Neurofibres, the Agence Nationale de la Recherche through the Labex projects CSC (ANR-10-LABX-0026 CSC) and NIE (ANR-11-LABX-0058 NIE) within the Investissement d’Avenir program (ANR-10-120 IDEX-0002-02), the International Center for Frontier Research in Chemistry (icFRC), EPSRC Grants EP/K01711X/1, EP/K017144/1, EP/N010345/1, EP/L016057/1, and the Faraday Institution. The HAADF-STEM characterization was carried out in the Advanced Microscopy Laboratory (Dublin), a Science Foundation Ireland (SFI) supported centre

Nonmarket valuation of water quality in a rural transition economy in Turkey applying an a posteriori bid design

In this paper, we investigate the economic benefits associated with public investments in wastewater treatment in one of the special protected areas along Turkey's touristic Mediterranean coast, the Köyceǧiz-Dalyan watershed. The benefits, measured in terms of boatable, fishable, swimmable and drinkable water quality, are estimated using a public survey format following the contingent valuation (CV) method. The study presented here is the first of its kind in Turkey. The study's main objective is to assess public perception, understanding, and valuation of improved wastewater treatment facilities in the two largest population centers in the watershed, facing the same water pollution problems as a result of lack of appropriate wastewater treatment. We test the validity and reliability of the application of the CV methodology to this specific environmental problem in a rural transition economy and evaluate the transferability of the results within the watershed. In order to facilitate willingness to pay (WTP) value elicitation we apply a novel dichotomous choice procedure where bid design takes place a posteriori instead of a priori. The statistical efficiency of different bid vectors is evaluated in terms of the estimated welfare measures' mean square errors using Monte Carlo simulation. The robustness of bid function specification is analyzed through average WTP and standard deviation estimated using parametric and nonparametric methods. Copyright 2007 by the American Geophysical Union

Localization of Dirac-like excitations in graphene in the presence of smooth inhomogeneous magnetic fields

The present article discusses magnetic confinement of the Dirac excitations in graphene in presence of inhomogeneous magnetic fields. In the first case a magnetic field directed along the z axis whose magnitude is proportional to $1/r$ is chosen. In the next case we choose a more realistic magnetic field which does not blow up at the origin and gradually fades away from the origin. The magnetic fields chosen do not have any finite/infinite discontinuity for finite values of the radial coordinate. The novelty of the two magnetic fields is related to the equations which are used to find the excited spectra of the excitations. It turns out that the bound state solutions of the two-dimensional hydrogen atom problem are related to the spectra of graphene excitations in presence of the $1/r$ (inverse-radial) magnetic field. For the other magnetic field profile one can use the knowledge of the bound state spectrum of a two-dimensional cut-off Coulomb potential to dictate the excitation spectra of the states of graphene. The spectrum of the graphene excitations in presence of the inverse-radial magnetic field can be exactly solved while the other case cannot be. In the later case we give the localized solutions of the zero-energy states in graphene.Comment: 9 pages, 6 figures, to appear in Journal of Physics: Condensed Matte

Embryonic motor activity and implications for regulating motoneuron axonal pathfinding in zebrafish

Zebrafish embryos exhibit spontaneous contractions of the musculature as early as 18–19 h post fertilization (hpf) when removed from their protective chorion. These movements are likely initiated by early embryonic central nervous system activity. We have made the observation that narrowminded mutant embryos (hereafter, nrd−/−) lack normal embryonic motor output upon dechorionation. However, these mutants can swim and respond to tactile stimulation by larval stages of development. nrd−/− embryos exhibit defects in neural crest development, slow muscle development and also lack spinal mechanosensory neurons known as Rohon–Beard (RB) neurons. At early developmental stages (i.e. 21–22 hpf) and while still in their chorions, nrd siblings (nrd+/?) exhibited contractions of the musculature at a rate similar to wild-type embryos. Anatomical analysis indicated that RB neurons were present in the motile embryos, but absent in the non-motile embryos, indicating that the non-motile embryos were nrd−/− embryos. Further anatomical analysis of nrd−/− embryos revealed errors in motoneuron axonal pathfinding that persisted into the larval stage of development. These errors were reversed when nrd−/− embryos were raised in high [K+] beginning at 21 hpf, indicating that the abnormal axonal phenotypes may be related to a lack of depolarizing activity early in development. When activity was blocked with tricaine in wild-type embryos, motoneuron phenotypes were similar to the motoneuron phenotypes in nrd−/− embryos. These results implicate early embryonic activity in conjunction with other factors as necessary for normal motoneuron development

Systematic Analysis of Cell Cycle Effects of Common Drugs Leads to the Discovery of a Suppressive Interaction between Gemfibrozil and Fluoxetine

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia

Filamentous and microtubule-associated septin GTPases guide the reorganization of the microtubule network during epithelial cell polarization