Estimation of dynamical model parameters taking into account undetectable marker values

Background  

Mathematical models are widely used for studying the dynamic of infectious agents such as hepatitis C virus (HCV). Most often, model parameters are estimated using standard least-square procedures for each individual. Hierarchical models have been proposed in such applications. However, another issue is the left-censoring (undetectable values) of plasma viral load due to the lack of sensitivity of assays used for quantification. A method is proposed to take into account left-censored values for estimating parameters of non linear mixed models and its impact is demonstrated through a simulation study and an actual clinical trial of anti-HCV drugs.     

Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training

Spaced training is generally more effective than massed training for learning and memory, but the molecular mechanisms underlying this trial spacing effect remain poorly characterized. One potential molecular basis for the trial spacing effect is the differential modulation, by distinct temporal patterns of neuronal activity, of protein synthesis-dependent processes that contribute to the expression of specific forms of synaptic plasticity in the mammalian brain. Long-term potentiation (LTP) is a type of synaptic modification that may be important for certain forms of memory storage in the mammalian brain. To explore the role of protein synthesis in the trial spacing effect, we assessed the protein synthesis dependence of hippocampal LTP induced by 100-Hz tetraburst stimulation delivered to mouse hippocampal slices in either a temporally massed (20-s interburst interval) or spaced (5-min interburst interval) fashion. To extend our studies to the behavioral level, we trained mice in fear conditioning using either a massed or spaced training protocol and examined the sensitivity of long-term memory to protein synthesis inhibition. Larger LTP was induced by spaced stimulation in hippocampal slices. This improvement of synaptic potentiation following temporally spaced synaptic stimulation in slices was attenuated by bath application of an inhibitor of protein synthesis. Further, the maintenance of LTP induced by spaced synaptic stimulation was more sensitive to disruption by anisomycin than the maintenance of LTP elicited following massed stimulation. Temporally spaced behavioral training improved long-term memory for contextual but not for cued fear conditioning, and this enhancement of memory for contextual fear was also protein synthesis dependent. Our data reveal that altering the temporal spacing of synaptic stimulation and behavioral training improved hippocampal LTP and enhanced contextual long-term memory. From a broad perspective, these results suggest that the recruitment of protein synthesis-dependent processes important for long-term memory and for long-lasting forms of LTP can be modulated by the temporal profiles of behavioral training and synaptic stimulation.     

Determining an individual's ideal body weight from skeletal measurements: a new method

Determining an individual's "ideal" body weight is fundamental in nutritional therapy. A simulation of the human body to a cylindrical volumetric model permits the calculation of the ideal body weight from the measured height, interacromioclavicular distance, and humeral length. A group of 189 healthy normal volunteers were assessed. The calculated "Pitt" ideal body weight correlated closely (r = 0.88 for males, r = 0.72 for women) with values obtained from the Metropolitan tables. The technique provides an estimate of ideal body weight based upon reproducible, easily obtained measurements of fixed bony landmarks.     

Can the quality and duration of life be integrated? Proposal for a new criterion for decision

Survival is an objective criteria, reliable, easy to measure and easy to analyse. But this criteria, the most important in almost all therapeutic trials, is a very rough one and not all fitted to many questions raised in cancer treatment decision making. We suggest a new criteria, combining quality and quantity of survival, which is equivalent in years of survival at a maximal quality level to the time of survival at a varying level of a cancer patient. This criteria could be usefull in the majority of "palliative" clinical trials (advanced cancers, recurrences, metastatic evolution...).     

Evidence against the involvement of serotonergic neurons in the anti-punishment activity of diazepam in the rat

The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 g in 0.4 l) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 g in 0.5 l) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10^–5–10^–4 M in 0.2 l) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.     

Key Informants’ Perspectives on Childhood Obesity in Vietnam: A Qualitative Study

Maternal and Child Health Journal - Vietnam’s post-war globalization, economic development, and urbanization have contributed to a nutrition transition from traditional diets to...     

Correction to: Factor Structure and Equivalence of Maternal Resources for Care in Bangladesh,Vietnam, and Ethiopia

Maternal and Child Health Journal - The article “Factor Structure and Equivalence of Maternal Resources for Care in Bangladesh, Vietnam, and Ethiopia”, written by Sulochana Basnet,...     

The use of segmented regression for evaluation of an interrupted time series study involving complex intervention: the CaPSAI project experience

Health Services and Outcomes Research Methodology - An interrupted time series with a parallel control group (ITS-CG) design is a powerful quasi-experimental design commonly used to evaluate the...     

Prevalence of Vision Loss and Associations With Age-Related Eye Diseases Among Nursing Home Residents Aged ≥65 Years

ObjectivesTo examine data from Delaware nursing homes to determine prevalence of age-related eye diseases (AREDs), vision impairment, and blindness and to compare the findings with the results of 11 US investigations of vision and eye health in nursing homes.DesignThis is a cross-sectional, retrospective study of nursing home patients.Setting and ParticipantsTwenty nursing homes in Delaware participated in the study, yielding comprehensive eye examination records for 2019 study participants.MethodsSummary statistics and regression analyses.ResultsThe overall prevalence of vision impairment or blindness was 63.8% and was above 60% for each age, sex, and race category. Prevalence of vision impairment or blindness was 68.4% among patients with cataracts, 69.4% among patients with macular degeneration, 70.5% among patients with glaucoma, and 68.4% among patients with diabetic retinopathy. Prevalence of blindness was 14.1%. Among patients with AREDs, prevalence of blindness ranged from 15.0% for patients with cataracts to 22.6% for patients with diabetic retinopathy. When compared with other investigations, we found wide variation in vision and eye factors reported and wide variation in the prevalence of those factors. Only 4 studies diagnosed both AREDs and visual function. Seven studies reported AREDs, and 7 reported vision impairment and/or blindness. Vision impairment or blindness ranged from 29% to 67%; cataract ranged from 32% to 83%; macular degeneration ranged from 4.6% to 70.7%. Glaucoma ranged from 5.3% to 41.4%; diabetic retinopathy ranged from 1.7% to 3.1%.Conclusions and ImplicationsComprehensive eye examinations showed that vision impairment and blindness affected 63.8% of nursing home residents. Compared with other studies, there was a wide range of vision factors reported and wide variation in the prevalence of vision impairment or blindness and AREDs. This investigation suggests the importance of eye care in nursing homes and the importance of reporting standard vision and eye health factors to inform policy and practice.     

Long-pulsed 1064-nm and 755-nm lasers for C1 leg veins on skin type IV patients: a side-by-side comparison

Lasers in Medical Science - Long-pulsed 1064-nm (LP1064) and 755-nm (LP755) lasers have been demonstrated as effective treatments for leg veins. However, few studies of these treatments on Asian...