Development of a framework to define the functional goals and outcomes of botulinum toxin A spasticity treatment relevant to the child and family living with cerebral palsy using the International Classification of Functioning, Disability and Health for Children and Youth

Objective: To define a sub-set of functional goals and outcomes relevant to children and families living with cerebral palsy following treatment with botulinum toxin type A using the International Classification of Functioning, Disability and Health for Children and Youth. Methods: We identified treatment goals and treatment outcomes from medical case records in 2102 assessments of 239 children with cerebral palsy treated with botulinum toxin between 1994 and 2009. Goals were set through assessment and discussion by experienced clinicians, therapists, parents and children. Results: There were 61 separate goals, mapping to 40 categories, falling mostly within Body Functions: b710 Mobility of joint functions (414 times); b770 Gait pattern functions (374 times); b7351 Tone of muscles of one limb (117 times). A total of 93 separate treatment outcomes were identified, mapping to 51 categories. Two of the 3 most common outcomes correspond to the 2 most common goals (gait pattern and mobility of joint functions). Conclusion: The International Classification of Functioning, Disability and Health for Children and Youth provides a useful framework to categorize the reasons for using botulinum toxin in children and focuses the clinical consultation not only on impairments but also functional outcomes

Transcription activator like effector (TALE)-directed piggyBac transposition in human cells.

Insertional therapies have shown great potential for combating genetic disease and safer methods would undoubtedly broaden the variety of possible illness that can be treated. A major challenge that remains is reducing the risk of insertional mutagenesis due to random insertion by both viral and non-viral vectors. Targetable nucleases are capable of inducing double-stranded breaks to enhance homologous recombination for the introduction of transgenes at specific sequences. However, off-target DNA cleavages at unknown sites can lead to mutations that are difficult to detect. Alternatively, the piggyBac transposase is able perform all of the steps required for integration; therefore, cells confirmed to contain a single copy of a targeted transposon, for which its location is known, are likely to be devoid of aberrant genomic modifications. We aimed to retarget transposon insertions by comparing a series of novel hyperactive piggyBac constructs tethered to a custom transcription activator like effector DNA-binding domain designed to bind the first intron of the human CCR5 gene. Multiple targeting strategies were evaluated using combinations of both plasmid-DNA and transposase-protein relocalization to the target sequence. We demonstrated user-defined directed transposition to the CCR5 genomic safe harbor and isolated single-copy clones harboring targeted integrations

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

Objectives: Lead antituberculosis (anti-TB) molecules with novel mechanisms of action are urgently required to fuel the anti-TB drug discovery pipeline. The aim of this study was to validate the use of the high-throughput spot culture growth inhibition (HT-SPOTi) assay for screening libraries of compounds against Mycobacterium tuberculosis and to study the inhibitory effect of ibuprofen (IBP) and the other 2-arylpropanoic acids on the growth inhibition of M tuberculosis and other mycobacterial species. Methods: The HT-SPOTi method was validated not only with known drugs but also with a library of 47 confirmed anti-TB active compounds published in the ChEMBL database. Three over-the-counter non-steroidal anti-inflammatory drugs were also included in the screening. The 2-arylpropanoic acids, including IBP, were comprehensively evaluated against phenotypically and physiologically different strains of mycobacteria, and their cytotoxicity was determined against murine RAW264.7 macrophages. Furthermore, a comparative bioinformatic analysis was employed to propose a potential mycobacterial target. Results: IBP showed antitubercular properties while carprofen was the most potent among the 2-arylpropanoic class. A 3,5-dinitro-IBP derivative was found to be more potent than IBP but equally selective. Other synthetic derivatives of IBP were less active, and the free carboxylic acid of IBP seems to be essential for its anti-TB activity. IBP, carprofen and the 3,5-dinitro-IBP derivative exhibited activity against multidrug-resistant isolates and stationary phase bacilli. On the basis of the human targets of the 2-arylpropanoic analgesics, the protein initiation factor infB (Rv2839c) of M tuberculosis was proposed as a potential molecular target. Conclusions: The HT-SPOTi method can be employed reliably and reproducibly to screen the antimicrobial potency of different compounds. IBP demonstrated specific antitubercular activity, while carprofen was the most selective agent among the 2-arylpropanoic class. Activity against stationary phase bacilli and multidrug-resistant isolates permits us to speculate a novel mechanism of antimycobacterial action. Further medicinal chemistry and target elucidation studies could potentially lead to new therapies against TB

Socio-economic status of fisherwomen community in coastal Vizianagaram district of Andhra Pradesh, India

The socio-economics of six fisherwomen co-operative societies in coastal Vizianagaram district of Andhra Pradesh were studied through field surveys by interviewing a total of 185 respondents. Respondents were mostly middle aged (31 – 56 years; 61.6%) living in nuclear families (64.9%). Majority of the fisherwomen were found illiterate (88.1%). A greater proportion (84.9%) of fisherwomen involved in fish marketing as a primary occupation followed by salting and curing (9.73%) and pickling of fishes (5.4%). More than half (56.2%) of the respondents earned > Rs. 25,000 (USD$ 1 = Rs. 75) every month. The study revealed that the socio-economic condition of the fisherwomen in the study area is poor, with a high percentage of the illiteracy. Necessary steps should be taken by the Governments organizations, NGOs and respective stakeholders to improve the literacy level as well as livelihood status

An Instrumented Walking-Aid to Assess and Retrain Gait

An instrumented walking-aid, the iWA system, has been developed to measure kinematic and kinetic properties of walking aid (WA) use and deliver feedback to improve gait. The clinical requirements, technical specification and design of the system are developed through clinical collaboration. The development of the system is described, including hardware components and data analysis used to process the measured data for assessment. The system measurements are validated under controlled laboratory conditions. The iWA system is evaluated in a typical UK clinical environment by a participant in a rehabilitation session. The resultant data successfully capture the quality of the participant’s walking aid use and agree with clinical opinion, supporting the efficacy of this approach

Nano-formulation of Ethambutol with multifunctional Graphene Oxide and magnetic nanoparticles retains Its anti-tubercular activity with prospects of improving chemotherapeutic efficacy

Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human and cattle every year worldwide. More than 50 years after its discovery, ethambutol continues to be an effective part of the World Health Organization’s recommended frontline chemotherapy against TB. However, the lengthy treatment regimens consisting of a cocktail of antibiotics affect patient compliance. There is an urgent need to improve the current therapy so as to reduce treatment duration and dosing frequency. In this study, we have designed a novel anti-TB multifunctional formulation by fabricating graphene oxide with iron oxide magnetite nanoparticles serving as a nano-carrier on to which ethambutol was successfully loaded. The designed nanoformulation was characterised using various analytical techniques. The release of ethambutol from anti-TB multifunctional nanoparticles formulation was found to be sustained over a significantly longer period of time in phosphate buffer saline solution at two physiological pH (7.4 and 4.8). Furthermore, the nano-formulation showed potent anti-tubercular activity while remaining non-toxic to the eukaryotic cells tested. The results of this in vitro evaluation of the newly designed nano-formulation endorse its further development in vivo

Transit reliant neighborhoods

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Architecture, 2000.Includes bibliographical references (leaves 53-54).Cities are all about people and places. Travel occurs because people want to get to places - places of work, places of residence, places of shopping and so on. Hence, it is people and places that are more important, not transportation. Ideally, we want to minimize travel so we can spend more time socializing , at desired destinations, rather than on transit. However, the paradigm of city design seems to have shifted over the years - from people and places to automobiles. The cumulative effects of planning for efficient movement of the car and enhanced automobility have revealed themselves in the form of urban sprawl, energy depletion, air and noise pollution, climate change, road fatalities, and segregation of people by class and race. For the sake of social equity and sustainability, it is thus important to increase reliance on transit services. However, merely infusing transit services into an auto-based environment is not likely to reap many rewards or radically change behavior. The fact that availability of subsidized transit services (in almost all regions of the US) has not lured the middle class out of their cars indicates a loophole in the present understanding of its usability. Many argue that one can only lessen the use of car by demand-management strategies, such as constraints on parking, increase in automobile and gasoline prices, and guaranteed rides home for car-poolers. Does this imply that in the absence of punitive pricing on automobile usage, the transit services are doomed to fail? This Thesis argues that transit ridership depends more on the way transit service relates to its location - and if we want to enhance transit usage, the 'transit service'-'urban form ' nexus matters. Based on this premise, the thesis explores how urban form influences transit usage and how development should be directed in order to increase reliance on mass transit.by by Kiran B. Mathema.S.M

A System in the Wild: Deploying a Two Player Arm Rehabilitation System for Children With Cerebral Palsy in a School Environment

This paper outlines a system for arm rehabilitation for children with upper-limb hemiplegia resulting from cerebral palsy. Our research team designed a two-player, interactive (competitive or collaborative) computer play therapy system that provided powered assistance to children while they played specially designed games that promoted arm exercises. We designed the system for a school environment. To assess the feasibility of deploying the system in a school environment, the research team enlisted the help of teachers and staff in nine schools. Once the system was set up, it was used to deliver therapy without supervision from the research team. Ultimately, the system was found to be suitable for use in schools. However, the overriding need for schools to focus on academic activities meant that children could not use the system enough to achieve the amount of use desired for therapeutic benefit. In this paper, we identify the key challenges encountered during this study. For example, there was a marked reluctance to report system issues (which could have been fixed) that prevented children from using the system. We also discuss future implications of deploying similar studies with this type of system

Density Based Traffic Control

The project is aimed at designing a density based dynamic traffic signal system where the timing of signal will change automatically on sensing the traffic density at any junction. Traffic congestion is a severe problem in most cities across the world and therefore it is time to shift more manual mode or fixed timer mode to an automated system with decision making capabilities. Present day traffic signaling system is fixed time based which may render inefficient if one lane is operational than the others. To optimize this problem we have made a framework for an intelligent traffic control system. Sometimes higher traffic density at one side of the junction demands longer green time as compared to standard allotted time We, therefore propose here a mechanism in which the time period of green light and red light is assigned on the basis of the density of the traffic present at that time. This is achieved by using PIR(proximity Infrared sensors). Once the density is calculated, the glowing time of green light is assigned by the help of the microcontroller (Arduino). The sensors which are present on sides of the road will detect the presence of the vehicles and sends the information to the microcontroller where it will decide how long a flank will be open or when to change over the signal lights. In subsequent sections, we have elaborated the procedure of this framework

Sanitation work: Realizing equity and inclusion in WASH

Recognition of the human right to water, sanitation and hygiene (WASH), and equity and inclusion concerns around gender, disability and age have led to crucial change in WASH programmes and policy, responding to commonly hidden issues such as menstrual hygiene, inclusive facilities for people with disabilities, and affordable services for residents of informal settlements. Despite progress toward realizing the rights of end users “to” sanitation, this crucial body of work has overlooked the rights of an unseen, diverse population working “in” these services, including those who handle human waste. There are increasing calls within and beyond WASH for sanitation workers - marginalized by their informal and hazardous roles, and intersections of caste, religion and gender - to realize their rights to safe working conditions and social security. Yet, sanitation work has received little attention from equity and inclusion WASH scholars, despite the pressing need to challenge dominant technical, health-centric framings of sanitation that can overlook workers' lived realities. We argue for an intersectional, interdisciplinary approach to support sanitation workers to realize rights to fair living and working conditions, including inclusive WASH infrastructure at work. We draw on the limited literature available to highlight gaps in, and show the importance of the sub-sector of equity and inclusion to engage further with the lived realities of sanitation workers. Increased collaboration between sanitation workers, activists, and allies working on inclusion, labor rights, fecal sludge and solid waste management is paramount to realize sanitation workers' rights and to truly provide “inclusive” sanitation for all by 2030