Better drug therapy for the children of Africa: current impediments to success and potential strategies for improvement

A commentary is presented on the urgent need for a comprehensive effort to improve the practice of pediatric therapeutics in Africa. A call for action is addressed to a variety of practitioners internationally, many of whom possess skills that could be fruitfully applied to the improvement of health outcomes for African children. Successful engagement with the many challenges requires the complementary effort of researchers in basic and clinical pharmacology and toxicology, nurses, pharmacists, physicians, clinical pharmacologists, clinical pharmacists, and political leaders and civil servants. While a comprehensive or systematic review of the relevant literature has not been attempted, the authors have highlighted promising initiatives driven by international agencies and academic networks. Two African perspectives are presented to reinforce the prospect of child health gains that can be achieved through consistent pursuit of optimal therapy for conditions such as respiratory infection, diarrhea, malaria, and HIV/AIDS. There is an imperative for development of north-south and south-south partnerships that will amplify current research efforts and mobilize existing knowledge concerning pediatric drugs. The overall goal is a multidisciplinary commitment to making essential medicines available at the right time, the right place, and in the right formulation for African children from infancy to adolescence

Wider collateral damage to children in the UK because of the social distancing measures designed to reduce the impact of COVID-19 in adults

This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.ML is funded by the National Institute for Health Research (NIHR Doctoral Research Fellowship, DRF-2016-09-021).Published version, Accepted version, Submitted versio

Predicting muscle forces of individuals with hemiparesis following stroke

<p>Abstract</p> <p>Background</p> <p>Functional electrical stimulation (FES) has been used to improve function in individuals with hemiparesis following stroke. An ideal functional electrical stimulation (FES) system needs an accurate mathematical model capable of designing subject and task-specific stimulation patterns. Such a model was previously developed in our laboratory and shown to predict the isometric forces produced by the quadriceps femoris muscles of able-bodied individuals and individuals with spinal cord injury in response to a wide range of clinically relevant stimulation frequencies and patterns. The aim of this study was to test our isometric muscle force model on the quadriceps femoris, ankle dorsiflexor, and ankle plantar-flexor muscles of individuals with post-stroke hemiparesis.</p> <p>Methods</p> <p>Subjects were seated on a force dynamometer and isometric forces were measured in response to a range of stimulation frequencies (10 to 80-Hz) and 3 different patterns. Subject-specific model parameter values were obtained by fitting the measured force responses from 2 stimulation trains. The model parameters thus obtained were then used to obtain predicted forces for a range of frequencies and patterns. Predicted and measured forces were compared using intra-class correlation coefficients, r²values, and model error relative to the physiological error (variability of measured forces).</p> <p>Results</p> <p>Results showed excellent agreement between measured and predicted force-time responses (r²>0.80), peak forces (ICCs>0.84), and force-time integrals (ICCs>0.82) for the quadriceps, dorsiflexor, and plantar-fexor muscles. The <it>model error </it>was within or below the +95% confidence interval of the <it>physiological error </it>for >88% comparisons between measured and predicted forces.</p> <p>Conclusion</p> <p>Our results show that the model has potential to be incorporated as a feed-forward controller for predicting subject-specific stimulation patterns during FES.</p

Changes in the activation and function of the ankle plantar flexor muscles due to gait retraining in chronic stroke survivors

Background A common goal of persons post-stroke is to regain community ambulation. The plantar flexor muscles play an important role in propulsion generation and swing initiation as previous musculoskeletal simulations have shown. The purpose of this study was to demonstrate that simulation results quantifying changes in plantar flexor activation and function in individuals post-stroke were consistent with (1) the purpose of an intervention designed to enhance plantar flexor function and (2) expected muscle function during gait based on previous literature. Methods Three-dimensional, forward dynamic simulations were created to determine the changes in model activation and function of the paretic ankle plantar flexor muscles for eight patients post-stroke after a 12-weeks FastFES gait retraining program. Results An median increase of 0.07 (Range [−0.01,0.22]) was seen in simulated activation averaged across all plantar flexors during the double support phase of gait from pre- to post-intervention. A concurrent increase in walking speed and plantar flexor induced forward center of mass acceleration by the plantar flexors was seen post-intervention for seven of the eight subject simulations. Additionally, post-training, the plantar flexors had an simulated increase in contribution to knee flexion acceleration during double support. Conclusions For the first time, muscle-actuated musculoskeletal models were used to simulate the effect of a gait retraining intervention on post-stroke muscle model predicted activation and function. The simulations showed a new pattern of simulated activation for the plantar flexor muscles after training, suggesting that the subjects activated these muscles with more appropriate timing following the intervention. Functionally, simulations calculated that the plantar flexors provided greater contribution to knee flexion acceleration after training, which is important for increasing swing phase knee flexion and foot clearance

Preventing Fetal Alcohol Spectrum Disorder in Aboriginal Communities: A Methods Development Project

The authors describe their three-year project working collaboratively with Aboriginal communities to prevent fetal alcohol spectrum disorder

Characterizing the Optical Variability of Bright Blazars: Variability-based Selection of Fermi Active Galactic Nuclei

We investigate the use of optical photometric variability to select and identify blazars in large-scale time-domain surveys, in part to aid in the identification of blazar counterparts to the ∼30% of γ -ray sources in the Fermi 2FGL catalog still lacking reliable associations. Using data from the optical LINEAR asteroid survey, we characterize the optical variability of blazars by fitting a damped random walk model to individual light curves with two main model parameters, the characteristic timescales of variability τ , and driving amplitudes on short timescales σ . Imposing cuts on minimum τ and σ allows for blazar selection with high efficiency E and completeness C. To test the efficacy of this approach, we apply this method to optically variable LINEAR objects that fall within the several arcminute error ellipses of γ -ray sources in the Fermi 2FGL catalog. Despite the extreme stellar contamination at the shallow depth of the LINEAR survey, we are able to recover previously associated optical counterparts to Fermi active galactic nuclei with E ≥ 88% and C = 88% in Fermi 95% confidence error ellipses having semimajor axis r < 8'. We find that the suggested radio counterpart to Fermi source 2FGL J1649.6+5238 has optical variability consistent with other γ -ray blazars and is likely to be the γ -ray source. Our results suggest that the variability of the non-thermal jet emission in blazars is stochastic in nature, with unique variability properties due to the effects of relativistic beaming. After correcting for beaming, we estimate that the characteristic timescale of blazar variability is ∼3 years in the rest frame of the jet, in contrast with the ∼320 day disk flux timescale observed in quasars. The variability-based selection method presented will be useful for blazar identification in time-domain optical surveys and is also a probe of jet physics

Chromatic Illumination Discrimination Ability Reveals that Human Colour Constancy Is Optimised for Blue Daylight Illuminations

The phenomenon of colour constancy in human visual perception keeps surface colours constant, despite changes in their reflected light due to changing illumination. Although colour constancy has evolved under a constrained subset of illuminations, it is unknown whether its underlying mechanisms, thought to involve multiple components from retina to cortex, are optimised for particular environmental variations. Here we demonstrate a new method for investigating colour constancy using illumination matching in real scenes which, unlike previous methods using surface matching and simulated scenes, allows testing of multiple, real illuminations. We use real scenes consisting of solid familiar or unfamiliar objects against uniform or variegated backgrounds and compare discrimination performance for typical illuminations from the daylight chromaticity locus (approximately blue-yellow) and atypical spectra from an orthogonal locus (approximately red-green, at correlated colour temperature 6700 K), all produced in real time by a 10-channel LED illuminator. We find that discrimination of illumination changes is poorer along the daylight locus than the atypical locus, and is poorest particularly for bluer illumination changes, demonstrating conversely that surface colour constancy is best for blue daylight illuminations. Illumination discrimination is also enhanced, and therefore colour constancy diminished, for uniform backgrounds, irrespective of the object type. These results are not explained by statistical properties of the scene signal changes at the retinal level. We conclude that high-level mechanisms of colour constancy are biased for the blue daylight illuminations and variegated backgrounds to which the human visual system has typically been exposed

Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015