Legal Implications of Clinical Investigation

There is an increasing concern among the members of the medical profession with legal rights, obligations and limitations affecting clinical investigation. This is understandable in light of the virtual explosion of clinical investigation within medical science. Clinical investigation is the systematic collection, evaluation and reporting, by or under the supervision of physicians, of data about other human beings for the purpose of advancing scientific medical knowledge. Thus it includes neither investigation relating to animals (even though such investigation may also advance scientific medical knowledge), nor investigation of human beings for purposes unrelated to medical science, nor the trial of unproven procedures in the treatment of patients unless this is also a part of a systematic program of clinical investigation. Nevertheless, clinical investigation need not occur within the physician-patient relationship, which arises when a person seeks and a physician undertakes to furnish medical diagnosis or treatment. For example, a person who volunteers as a subject of clinical investigation does not have a physician-patient relationship with a physician who does not undertake to furnish him any medical benefit

Legal Implications of Clinical Investigation

There is an increasing concern among the members of the medical profession with legal rights, obligations and limitations affecting clinical investigation. This is understandable in light of the virtual explosion of clinical investigation within medical science. Clinical investigation is the systematic collection, evaluation and reporting, by or under the supervision of physicians, of data about other human beings for the purpose of advancing scientific medical knowledge. Thus it includes neither investigation relating to animals (even though such investigation may also advance scientific medical knowledge), nor investigation of human beings for purposes unrelated to medical science, nor the trial of unproven procedures in the treatment of patients unless this is also a part of a systematic program of clinical investigation. Nevertheless, clinical investigation need not occur within the physician-patient relationship, which arises when a person seeks and a physician undertakes to furnish medical diagnosis or treatment. For example, a person who volunteers as a subject of clinical investigation does not have a physician-patient relationship with a physician who does not undertake to furnish him any medical benefit

Identification of candidate genes for alcohol preference by expression profiling of congenic rat strains

BACKGROUND: A highly significant quantitative trait locus (QTL) on chromosome 4 that influenced alcohol preference was identified by analyzing crosses between the iP and iNP rats. Congenic strains in which the iP chromosome 4 QTL interval was transferred to the iNP (NP.P) exhibited the expected increase in alcohol consumption compared with the iNP background strain. This study was undertaken to identify genes in the chromosome 4 QTL interval that might contribute to the differences in alcohol consumption between the alcohol-naïve congenic and background strains. METHODS: RNA from 5 brain regions from each of 6 NP.P and 6 iNP rats was labeled and analyzed separately on an Affymetrix Rat Genome 230 2.0 microarray to look for both cis-regulated and trans-regulated genes. Expression levels were normalized using robust multi-chip average (RMA). Differential gene expression was validated using quantitative real-time polymerase chain reaction. Five individual brain regions (nucleus accumbens, frontal cortex, amygdala, hippocampus, and striatum) were analyzed to detect differential expression of genes within the introgressed QTL interval, as well as genes outside that region. To increase the power to detect differentially expressed genes, combined analyses (averaging data from the 5 discrete brain regions of each animal) were also carried out. RESULTS: Analyses within individual brain regions that focused on genes within the QTL interval detected differential expression in all 5 brain regions; a total of 35 genes were detected in at least 1 region, ranging from 6 genes in the nucleus accumbens to 22 in the frontal cortex. Analysis of the whole genome detected very few differentially expressed genes outside the QTL. Combined analysis across brain regions was more powerful. Analysis focused on the genes within the QTL interval confirmed 19 of the genes detected in individual regions and detected 15 additional genes. Whole genome analysis detected 1 differentially expressed gene outside the interval. CONCLUSIONS: Cis-regulated candidate genes for alcohol consumption were identified using microarray profiling of gene expression differences in congenic animals carrying a QTL for alcohol preference

State-dependent diffusion: thermodynamic consistency and its path integral formulation

The friction coefficient of a particle can depend on its position as it does when the particle is near a wall. We formulate the dynamics of particles with such state-dependent friction coefficients in terms of a general Langevin equation with multiplicative noise, whose evaluation requires the introduction of specific rules. Two common conventions, the Ito and the Stratonovich, provide alternative rules for evaluation of the noise, but other conventions are possible. We show the requirement that a particle's distribution function approach the Boltzmann distribution at long times dictates that a drift term must be added to the Langevin equation. This drift term is proportional to the derivative of the diffusion coefficient times a factor that depends on the convention used to define the multiplicative noise. We explore the consequences of this result in a number examples with spatially varying diffusion coefficients. We also derive path integral representations for arbitrary interpretation of the noise, and use it in a perturbative study of correlations in a simple system.Comment: 18 pages, 8 figures, Accepted to PR

Organism-sediment interactions govern post-hypoxia recovery of ecosystem functioning

Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning.

Mesoscopic conductance and its fluctuations at non-zero Hall angle

We consider the bilocal conductivity tensor, the two-probe conductance and its fluctuations for a disordered phase-coherent two-dimensional system of non-interacting electrons in the presence of a magnetic field, including correctly the edge effects. Analytical results are obtained by perturbation theory in the limit $\sigma_{xx} \gg 1$. For mesoscopic systems the conduction process is dominated by diffusion but we show that, due to the lack of time-reversal symmetry, the boundary condition for diffusion is altered at the reflecting edges. Instead of the usual condition, that the derivative along the direction normal to the wall of the diffusing variable vanishes, the derivative at the Hall angle to the normal vanishes. We demonstrate the origin of this boundary condition from different starting points, using (i) a simplified Chalker-Coddington network model, (ii) the standard diagrammatic perturbation expansion, and (iii) the nonlinear sigma-model with the topological term, thus establishing connections between the different approaches. Further boundary effects are found in quantum interference phenomena. We evaluate the mean bilocal conductivity tensor $\sigma_{\mu\nu}(r,r')$, and the mean and variance of the conductance, to leading order in $1/\sigma_{xx}$ and to order $(\sigma_{xy}/\sigma_{xx})^2$, and find that the variance of the conductance increases with the Hall ratio. Thus the conductance fluctuations are no longer simply described by the unitary universality class of the $\sigma_{xy}=0$ case, but instead there is a one-parameter family of probability distributions. In the quasi-one-dimensional limit, the usual universal result for the conductance fluctuations of the unitary ensemble is recovered, in contrast to results of previous authors. Also, a long discussion of current conservation.Comment: Latex, uses RevTex, 58 pages, 5 figures available on request at [email protected]. Submitted to Phys. Rev.

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy