Sociopolitical Control in Urban Kenya: The Sociopolitical Control Scale in Nairobi, Mombasa, and Kisumu

There is popular belief among Kenyans that their government inappropriately distributes resources unequally between different regions in Kenya. A modified version of Zimmerman and Zahniser\u27s (1991) Sociopolitical Control Scale (SPCS) tested for differences in perceived sociopolitical control (SPC) between residents of Kenya\u27s three biggest cities, Nairobi (n = 49), Mombasa (n = 50), and Kisumu (n = 51). Hypotheses were based on expected levels of leadership competence (LC) and policy control (PC), two sub-scales that combine to create SPC. Contrary to the hypothesis, results indicated no significant differences in levels of SPC among the cities. Results could indicate a shared urban culture throughout these cities, or could be due to methodological issues. Suggestions for creating a Kenya-specific SPCS are outlined

Practice Parameter: Diagnostic assessment of the child with cerebral palsy: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter the authors reviewed available evidence on the assessment of a child suspected of having cerebral palsy (CP), a nonprogressive disorder of posture or movement due to a lesion of the developing brain. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: CP is a common problem, occurring in about 2 to 2.5 per 1,000 live births. In order to establish that a brain abnormality exists in children with CP that may, in turn, suggest an etiology and prognosis, neuroimaging is recommended with MRI preferred to CT (Level A). Metabolic and genetic studies should not be routinely obtained in the evaluation of the child with CP (Level B). If the clinical history or findings on neuroimaging do not determine a specific structural abnormality or if there are additional and atypical features in the history or clinical examination, metabolic and genetic testing should be considered (Level C). Detection of a brain malformation in a child with CP warrants consideration of an underlying genetic or metabolic etiology. Because the incidence of cerebral infarction is high in children with hemiplegic CP, diagnostic testing for coagulation disorders should be considered (Level B). However, there is insufficient evidence at present to be precise as to what studies should be ordered. An EEG is not recommended unless there are features suggestive of epilepsy or a specific epileptic syndrome (Level A). Because children with CP may have associated deficits of mental retardation, ophthalmologic and hearing impairments, speech and language disorders, and oral-motor dysfunction, screening for these conditions should be part of the initial assessment (Level A). CONCLUSIONS: Neuroimaging results in children with CP are commonly abnormal and may help determine the etiology. Screening for associated conditions is warranted as part of the initial evaluation

Uphill acceleration in a spatially modulated electrostatic field particle accelerator

Spatially modulated electrostatic fields can be designed to efficiently accelerate particles by exploring the relations between the amplitude, the phase velocity, the shape of the potential and the initial velocity of the particle. The acceleration process occurs when the value of the velocity excursions of the particle surpass the phase velocity of the carrier, as a resonant mechanism. The ponderomotive approximation based on the Lagrangian average is usually applied in this kind of system in non-accelerating regimes. The mean dynamics of the particle is well described by this approximation far from resonance. However, the approximation fails to predict some interesting features of the model near resonance, such as the uphill acceleration phenomenon. A canonical perturbation theory is more accurate in these conditions. In this work we compare the results from the Lagrangian average and from a canonical perturbation theory, focusing in regions where the results of these two approaches differ from each other

Dysfunction of axonal membrane conductances in adolescents and young adults with spinal muscular atrophy

Spinal muscular atrophy is distinct among neurodegenerative conditions of the motor neuron, with onset in developing and maturing patients. Furthermore, the rate of degeneration appears to slow over time, at least in the milder forms. To investigate disease pathophysiology and potential adaptations, the present study utilized axonal excitability studies to provide insights into axonal biophysical properties and explored correlation with clinical severity. Multiple excitability indices (stimulus–response curve, strength–duration time constant, threshold electrotonus, current–threshold relationship and recovery cycle) were investigated in 25 genetically characterized adolescent and adult patients with spinal muscular atrophy, stimulating the median motor nerve at the wrist. Results were compared with 50 age-matched controls. The Medical Research Council sum score and Spinal Muscular Atrophy Functional Rating Scale were used to define the strength and motor functional status of patients with spinal muscular atrophy. In patients with spinal muscular atrophy, there were reductions in compound muscle action potential amplitude (P < 0.0005) associated with reduction in stimulus response slope (P < 0.0005), confirming significant axonal loss. In the patients with mild or ambulatory spinal muscular atrophy, there was reduction of peak amplitude without alteration in axonal excitability; in contrast, in the non-ambulatory or severe spinal muscular atrophy cohort prominent changes in axonal function were apparent. Specifically, there were steep changes in the early phase of hyperpolarization in threshold electrotonus (P < 0.0005) that correlated with clinical severity. Additionally, there were greater changes in depolarizing threshold electrotonus (P < 0.0005) and prolongation of the strength-duration time constant (P = 0.001). Mathematical modelling of the excitability changes obtained in patients with severe spinal muscular atrophy supported a mixed pathology comprising features of axonal degeneration and regeneration. The present study has provided novel insight into the pathophysiology of spinal muscular atrophy, with identification of functional abnormalities involving axonal K+ and Na+ conductances and alterations in passive membrane properties, the latter linked to the process of neurodegeneration

Технологические решения для строительства разведочной вертикальной скважины глубиной 2680 метров на газовом месторождении (ХМАО)

Технологические решения для строительства разведочной вертикальной скважины глубиной 2680 метров на газовом месторождении (ХМАО).Technological solutions for the construction of an exploration vertical well with a depth of 2680 meters at the gas field (KHMAO)

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

Ataluren treatment of patients with nonsense mutation dystrophinopathy

Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. Methods: Randomized, double‐blind, placebo‐controlled study; males ≥5 years with nm‐dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N = 57); ataluren 20, 20, 40 mg/kg (N = 60); or placebo (N = 57) for 48 weeks. The primary endpoint was change in 6‐Minute Walk Distance (6MWD) at Week 48. Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ = 31.3 meters, post hoc P = 0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. Conclusions: As the first investigational new drug targeting the underlying cause of nm‐dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need