A Comparison of Marginal Likelihood Computation Methods

In a Bayesian analysis, different models can be compared on the basis of theexpected or marginal likelihood they attain. Many methods have been devised to compute themarginal likelihood, but simplicity is not the strongest point of most methods. At the sametime, the precision of methods is often questionable.In this paper several methods are presented in a common framework. The explanation of thedifferences is followed by an application, in which the precision of the methods is testedon a simple regression model where a comparison with analytical results is possible

Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN--DREAMS III): Study design and research methodology

<p>Abstract</p> <p>Background</p> <p>To describe the methodology of the Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study III, an ongoing epidemiological study to estimate the prevalence of Diabetes and Diabetic Retinopathy in rural population of Kanchipuram and Thiravallur districts of Tamil Nadu, India and to elucidate the clinical, anthropometric, biochemical and genetic risk factors associated with diabetic retinopathy in this rural population.</p> <p>Methods</p> <p>Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study III will be a mobile van based epidemiological study; 11,760 participants aged ≥ 40 years will be recruited from the study areas. Eligible subjects will undergo blood sugar estimation to diagnose Diabetes. Oral Glucose Tolerance Test will be done to conform diabetes. All subjects with diabetes will undergo complete information of knowledge, aptitude and practice of diabetes and diabetic retinopathy, Diet questionnaire, demographic data, socioeconomic status, physical activity, anthropometric measurements, and risk of sleep apnoea. A detailed medical and ocular history, a comprehensive eye examination including refraction, slit lamp biomicroscopy examination, indirect ophthalmoscopy, slit lamp biomicroscopy, digital stereo fundus photography and ultrasound of eye will be done in the mobile van. Blood will be collected for biochemical investigations including blood hemoglobin, glycosylated hemoglobin, lipid profile, urea and creatinine, genetic study. Urine will be collected for microalbuminuria. All fundus photographs will be graded at base hospital. Participants who need treatment will be sent to the base hospital. A computerized database is created for the records.</p> <p>Conclusion</p> <p>The study is expected to provide an estimate of the prevalence of Diabetes and Diabetic Retinopathy and also a better understanding of the genetic, anthropometric and socio-economic risk factors associated with Diabetic Retinopathy in a Rural South Indian population.</p

Establishing a Statistical Link between Network Oscillations and Neural Synchrony

Pairs of active neurons frequently fire action potentials or “spikes” nearly synchronously (i.e., within 5 ms of each other). This spike synchrony may occur by chance, based solely on the neurons’ fluctuating firing patterns, or it may occur too frequently to be explicable by chance alone. When spike synchrony above chances levels is present, it may subserve computation for a specific cognitive process, or it could be an irrelevant byproduct of such computation. Either way, spike synchrony is a feature of neural data that should be explained. A point process regression framework has been developed previously for this purpose, using generalized linear models (GLMs). In this framework, the observed number of synchronous spikes is compared to the number predicted by chance under varying assumptions about the factors that affect each of the individual neuron’s firing-rate functions. An important possible source of spike synchrony is network-wide oscillations, which may provide an essential mechanism of network information flow. To establish the statistical link between spike synchrony and network-wide oscillations, we have integrated oscillatory field potentials into our point process regression framework. We first extended a previously-published model of spike-field association and showed that we could recover phase relationships between oscillatory field potentials and firing rates. We then used this new framework to demonstrate the statistical relationship between oscillatory field potentials and spike synchrony in: 1) simulated neurons, 2) in vitro recordings of hippocampal CA1 pyramidal cells, and 3) in vivo recordings of neocortical V4 neurons. Our results provide a rigorous method for establishing a statistical link between network oscillations and neural synchrony

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

The perception of affective touch in Parkinson's disease and its relation to small fibre neuropathy.

Affective touch sensation is conducted by a sub-class of C-fibres in hairy skin known as C-Tactile (CT) afferents. CT afferents respond maximally to gentle skin stroking at velocities between 1-10 cm/sec. Parkinson's disease (PD) is characterised by markedly reduced cutaneous C-fibres. It is not known if affective touch perception is influenced by C fibre density and if affective touch is impaired in PD compared to healthy controls. We predicted that perceived pleasantness to gentle stroking in PD would correlate with C afferent density and that affective touch perception would be impaired in PD compared to healthy controls. Twenty-four PD patients and 27 control subjects rated the pleasantness of brush stroking at an optimum CT stimulation velocity (3cm/sec) and two sub-optimal velocities (0.3cm/sec & 30cm/sec). PD patients underwent quantification of C-fibre density using skin biopsies and corneal confocal microscopy. All participants rated stroking velocity of 3cm/sec as the most pleasant with significantly lower ratings for 0.3cm/sec and 30cm/sec. There was a significant positive correlation between C-fibre density and pleasantness ratings at 3cm/sec and 30cm/sec but not 0.3cm/sec. Mean pleasantness ratings were consistently higher in PD patients compared to control subjects across all three velocities. This study shows that perceived pleasantness to gentle touch correlate significantly with C-fibre density in PD. The higher perceived pleasantness in PD patients compared to controls suggests central sensitisation to peripheral inputs, which may have been enhanced by dopamine therapy. This article is protected by copyright. All rights reserved

Democracy: the forgotten challenge for bioethics in the developing countries

<p>Abstract</p> <p>Background</p> <p>Bioethics as a field related to the health system and health service delivery has grown in the second half of the 20^thcentury, mainly in North America. This is attributed, the author argues, to mainly three kinds of development that took place in the developed countries at a pace different than the developing countries. They are namely: development of the health system; moral development; and political development.</p> <p>Discussion</p> <p>This article discusses the factors that impede the development of the field of bioethics from an academic activity to a living field that is known and practiced by the people in the developing countries. They are quite many; however, the emphasis here is on role of the political structure in the developing countries and how it negatively affects the development of bioethics. It presents an argument that if bioethics is to grow within the system of health service, it should be accompanied by a parallel changes in the political mindsets in these countries.</p> <p>Summary</p> <p>For bioethics to flourish in developing countries, it needs an atmosphere of freedom where people can practice free moral reasoning and have full potential to take their life decisions by themselves. Moreover, bioethics could be a tool for political change through the empowerment of people, especially the vulnerable.</p> <p>To achieve that, the article is proposing a practical framework for facilitating the development of the field of bioethics in the developing countries.</p

Prognostic importance of plasma total magnesium in a cohort of cats with azotemic chronic kidney disease

BACKGROUND: Hypomagnesemia is associated with increased mortality and renal function decline in humans with chronic kidney disease (CKD). Magnesium is furthermore inversely associated with fibroblast growth factor 23 (FGF23), an important prognostic factor in CKD in cats. However, the prognostic significance of plasma magnesium in cats with CKD is unknown. OBJECTIVES: To explore associations of plasma total magnesium concentration (tMg) with plasma FGF23 concentration, all-cause mortality, and disease progression in cats with azotemic CKD. ANIMALS: Records of 174 client-owned cats with IRIS stage 2-4 CKD. METHODS: Cohort study. Cats with azotemic CKD were identified from the records of two London-based first opinion practices (1999-2013). Possible associations of baseline plasma tMg with FGF23 concentration and risks of death and progression were explored using, respectively, linear, Cox, and logistic regression. RESULTS: Plasma tMg (reference interval, 1.73-2.57 mg/dL) was inversely associated with plasma FGF23 when controlling for plasma creatinine and phosphate concentrations (partial correlation coefficient, -0.50; P < .001). Hypomagnesemia was observed in 12% (20/174) of cats, and independently associated with increased risk of death (adjusted hazard ratio, 2.74; 95% confidence interval [CI], 1.35-5.55; P = .005). The unadjusted associations of hypermagnesemia (prevalence, 6%; 11/174 cats) with survival (hazard ratio, 2.88; 95% CI, 1.54-5.38; P = .001), and hypomagnesemia with progressive CKD (odds ratio, 17.7; 95% CI, 2.04-154; P = .009) lost significance in multivariable analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypomagnesemia was associated with higher plasma FGF23 concentrations and increased risk of death. Measurement of plasma tMg augments prognostic information in cats with CKD, but whether these observations are associations or causations warrants further investigation

Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study)

Background Improving adherence to ocular hypertension (OH)/glaucoma therapy is highly likely to prevent or reduce progression of optic nerve damage. The present study used a behaviour change counselling intervention to determine whether education and support was beneficial and cost-effective in improving adherence with glaucoma therapy. Methods A randomised controlled trial with a 13-month recruitment and 8-month follow-up period was conducted. Patients with OH/glaucoma attending a glaucoma clinic and starting treatment with travoprost were approached. Participants were randomised into two groups and adherence was measured over 8 months, using an electronic monitoring device (Travalert® dosing aid, TDA). The control group received standard clinical care, and the intervention group received a novel glaucoma education and motivational support package using behaviour change counselling. Cost-effectiveness framework analysis was used to estimate any potential cost benefit of improving adherence. Results Two hundred and eight patients were recruited (102 intervention, 106 control). No significant difference in mean adherence over the monitoring period was identified with 77.2% (CI, 73.0, 81.4) for the control group and 74.8% (CI, 69.7, 79.9) for the intervention group (p = 0.47). Similarly, there was no significant difference in percentage intraocular pressure reduction; 27.6% (CI, 23.5, 31.7) for the control group and 25.3% (CI, 21.06, 29.54) for the intervention group (p = 0.45). Participants in the intervention group were more satisfied with information about glaucoma medication with a mean score of 14.47/17 (CI, 13.85, 15.0) compared with control group which was 8.51 (CI, 7.72, 9.30). The mean intervention cost per patient was GB£10.35 (<US$16) and not cost-effective. Conclusions Adherence with travoprost was high and not further increased by the intervention. Nevertheless, the study demonstrated that provision of information, tailored to the individual, was inexpensive and able to achieve high patient satisfaction with respect to information about glaucoma medication. Measurement of adherence remains problematic since awareness of study participation may cause a change in participant behaviour