UCL University College London Eprints
UCL Eprints collects the work of UCL researchers and makes it freely available over the web, helping the worldwide scholarly community to discover UCL research. Institutional repositories like UCL Eprints complement the traditional academic publishing and scholarly communications processes. They raise the visibility of research and help to maximise its impact. UCL researchers are encouraged to deposit a copy of each journal article, conference paper, working paper, and any other research output, in the UCL Eprints at the earliest opportunity, ensuring that their research reaches as wide an audience as possible.
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Assessing the impact of mHealth interventions in low- and middle-income countries - what has been shown to work? - Hall, CS; Fottrell, E; Wilkinson, S; Byass, P
Low-cost mobile devices, such as mobile phones, tablets, and personal digital assistants, which can access voice and data services, have revolutionised access to information and communication technology worldwide. These devices have a major impact on many aspects of people's lives, from business and education to health. This paper reviews the current evidence on the specific impacts of mobile technologies on tangible health outcomes (mHealth) in low- and middle-income countries (LMICs), from the perspectives of various stakeholders.
The value of the pragmatic-explanatory continuum indicator summary wheel in an ongoing study: The bullous pemphigoid steroids and tetracyclines study - Bratton, DJ; Nunn, AJ; Wojnarowska, F; Kirtschig, G; Sandell, A; Williams, HC
Background: The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool is intended to be used in the design phase of trials to help investigative teams design trials in-line with their purpose. Our team applied this tool to an ongoing trial (BLISTER) to determine whether the initial suggestion among some team members that the trial could be described as largely pragmatic was the consensus.Methods: Each of the six members of the BLISTER trial team was sent a blank PRECIS wheel to independently complete. The results obtained were averaged and plotted on a single PRECIS wheel to illustrate the degree of pragmatism of the...
Tuberculosis Treatment trials past and present: Old and new challenges - Nunn, A
The principles determining the conduct of clinical trials in tuberculosis (TB) have changed very little since the 1940s when the British Medical Research Council's streptomycin trial was conducted. Many of the challenges facing researchers remain the same, but the advent of highly effective treatments, under controlled conditions, has resulted in the need for much larger studies with non-inferiority designs. The intention-to-treat population is the right choice for superiority trials because it is conservative with respect to any differences that might exist between study arms; this is not however appropriate when the aim is to demonstrate that no difference exists as...
Cognitive dynamics: From attractors to active inference - Friston, K; Auletta, G; Sengupta, B
This paper combines recent formulations of self-organization and neuronal processing to provide an account of cognitive dynamics from basic principles. We start by showing that inference (and autopoiesis) are emergent features of any (weakly mixing) ergodic random dynamical system. We then apply the emergent dynamics to action and perception in a way that casts action as the fulfillment of (Bayesian) beliefs about the causes of sensations. More formally, we formulate ergodic flows on global random attractors as a generalized descent on a free energy functional of the internal states of a system. This formulation rests on a partition of states...
Consequences of converting graded to action potentials upon neural information coding and energy efficiency. - Sengupta, B; Laughlin, SB; Niven, JE
Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+) and K(+) channels, with generator potential and graded potential models lacking voltage-gated Na(+) channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na(+) channels necessary for action potential generation increase...
Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents. - Chagas, AM; Theis, L; Sengupta, B; Stüttgen, MC; Bethge, M; Schwarz, C
Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of "how much" information is conveyed by primary afferents, using the direct method (DM), a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s). Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on "what" is coded by primary afferents. Amongst the kinematic variables tested--position, velocity, and acceleration--primary afferent spikes encoded velocity...
A naturally occurring amino acid substitution in the voltage-dependent sodium channel selectivity filter affects channel gating - Wu, M; Ye, N; Zakon, HH; Sengupta, B
The pore of sodium channels contains a selectivity filter made of 4 amino acids, D/E/K/A. In voltage sensitive sodium channel (Nav) channels from jellyfish to human the fourth amino acid is Ala. This Ala, when mutated to Asp, promotes slow inactivation. In some Nav channels of pufferfishes, the Ala is replaced with Gly. We studied the biophysical properties of an Ala-to-Gly substitution (A1529G) in rat Nav1.4 channel expressed in Xenopus oocytes alone or with a β1 subunit. The Ala-to-Gly substitution does not affect monovalent cation selectivity and positively shifts the voltage-dependent inactivation curve, although co-expression with a β1 subunit eliminates...
Balanced excitatory and inhibitory synaptic currents promote efficient coding and metabolic efficiency. - Sengupta, B; Laughlin, SB; Niven, JE
A balance between excitatory and inhibitory synaptic currents is thought to be important for several aspects of information processing in cortical neurons in vivo, including gain control, bandwidth and receptive field structure. These factors will affect the firing rate of cortical neurons and their reliability, with consequences for their information coding and energy consumption. Yet how balanced synaptic currents contribute to the coding efficiency and energy efficiency of cortical neurons remains unclear. We used single compartment computational models with stochastic voltage-gated ion channels to determine whether synaptic regimes that produce balanced excitatory and inhibitory currents have specific advantages over other...
The effect of cell size and channel density on neuronal information encoding and energy efficiency. - Sengupta, B; Faisal, AA; Laughlin, SB; Niven, JE
Identifying the determinants of neuronal energy consumption and their relationship to information coding is critical to understanding neuronal function and evolution. Three of the main determinants are cell size, ion channel density, and stimulus statistics. Here we investigate their impact on neuronal energy consumption and information coding by comparing single-compartment spiking neuron models of different sizes with different densities of stochastic voltage-gated Na(+) and K(+) channels and different statistics of synaptic inputs. The largest compartments have the highest information rates but the lowest energy efficiency for a given voltage-gated ion channel density, and the highest signaling efficiency (bits spike(-1)) for...
Management of tuberculous constrictive pericarditis and tuberculous pericardial effusion in Transkei: Results at 10 years follow-up - Strang, JIG; Nunn, AJ; Johnson, DA; Casbard, A; Girling, DJ; Gibson, DG
Background: Tuberculous pericarditis is common in Transkei (Eastern Cape). Two randomized trials showed benefits at two years for prednisolone in patients with constrictive pericarditis, and open drainage plus prednisolone in patients with pericardial effusion. Aim: To see whether the advantages of prednisolone and open drainage were maintained up to 10 years. Design: Follow-up of randomized, double-blind, placebo-controlled trials. Methods: All 383 patients (143 constriction, 240 effusion) received the same anti-tuberculosis chemotherapy. They were randomized to prednisolone or placebo for the first 11 weeks, and were followed-up over 10 years. Among the 240 with effusion, 122 were also randomized to immediate...
'Chemical condoms' for the prevention of HIV infection: Evaluation of novel agents against SHIV in vitro and in vivo - Weber, J; Kitchen, V; Nunn, A; McCormack, S; Stone, A; Darbyshire, J; O'Connor, T; Jeffries, D; Stott, J; Almond, N
Background: Vaginal agents which are antiviral and/or inhibit the entry of HIV into the cell could prevent heterosexual transmission of HIV, and protect women who cannot negotiate condom use. Methods: Four agents have been investigated for activity in vitro and in vivo against SHIV: two anionic polymers, dextrin-2-sulphate (D2S) and PRO 2000 (P2K), and two virucidal agents; a non-ionic detergent, nonoxynol-9 (N9) and a cyclic peptide ionophore, gramicidin-D (GD). All four agents were investigated in rhesus macaques, using an intra-vaginal challenge of two inoculations of 1 × 10 50% tissue culture infectious doses (TCID)of SHIV. Results: D2S, P2K, GD and...