How to Resolve an Ethical Dilemma Concerning Randomized Clinical Trials

An apparent ethical dilemma arises when physicians consider enrolling their patients in randomized clinical trials. Suppose that a randomized clinical trial comparing two treatments is in progress, and a physician has an opinion about which treatment is better. The physician has a duty to promote the patient's best medical interests and therefore seems to be obliged to advise the patient to receive the treatment that the physician prefers. This duty creates a barrier to the enrollment of patients in randomized clinical trials.1-10 Two strategies are often used to resolve the dilemma in favor of enrolling patients in clinical trials

Probing theories of gravity with phase space-inferred potentials of galaxy clusters

Modified theories of gravity provide us with a unique opportunity to generate innovative tests of gravity. In Chameleon f(R) gravity, the gravitational potential differs from the weak-field limit of general relativity (GR) in a mass dependent way. We develop a probe of gravity which compares high mass clusters, where Chameleon effects are weak, to low mass clusters, where the effects can be strong. We utilize the escape velocity edges in the radius/velocity phase space to infer the gravitational potential profiles on scales of 0.3–1 virial radii. We show that the escape edges of low mass clusters are enhanced compared to GR, where the magnitude of the difference depends on the background field value |fR0¯¯¯¯¯|. We validate our probe using N-body simulations and simulated light cone galaxy data. For a Dark Energy Spectroscopic Instrument Bright Galaxy Sample, including observational systematics, projection effects, and cosmic variance, our test can differentiate between GR and Chameleon f(R) gravity models, |fR0¯¯¯¯¯|=4×10−6 (2×10−6) at >5σ (>2σ), more than an order of magnitude better than current cluster-scale constraints

Deterministic Partial Differential Equation Model for Dose Calculation in Electron Radiotherapy

Treatment with high energy ionizing radiation is one of the main methods in modern cancer therapy that is in clinical use. During the last decades, two main approaches to dose calculation were used, Monte Carlo simulations and semi-empirical models based on Fermi-Eyges theory. A third way to dose calculation has only recently attracted attention in the medical physics community. This approach is based on the deterministic kinetic equations of radiative transfer. Starting from these, we derive a macroscopic partial differential equation model for electron transport in tissue. This model involves an angular closure in the phase space. It is exact for the free-streaming and the isotropic regime. We solve it numerically by a newly developed HLLC scheme based on [BerCharDub], that exactly preserves key properties of the analytical solution on the discrete level. Several numerical results for test cases from the medical physics literature are presented.Comment: 20 pages, 7 figure

Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis

Estimation of the rigid-body motion from three-dimensional images using a generalized center-of-mass points approach

We present an analytical method for the estimation of rigid-body motion in sets of three-dimensional (3-D) SPECT and PET slices. This method utilizes mathematically defined generalized center-of-mass points in images, requiring no segmentation. It can be applied to compensation of the rigid-body motion in both SPECT and PET, once a series of 3-D tomographic images are available. We generalized the formula for the center-of-mass to obtain a family of points comoving with the object\u27s rigid-body motion. From the family of possible points we chose the best three points which resulted in the minimum root-mean-square difference between images as the generalized center-of-mass points for use in estimating motion. The estimated motion was used to sum the sets of tomographic images, or incorporated in the iterative reconstruction to correct for motion during reconstruction of the combined projection data. For comparison, the principle-axes method was also applied to estimate the rigid-body motion from the same tomographic images. To evaluate our method for different noise levels, we performed simulations with the MCAT phantom. We observed that though noise degraded the motion-detection accuracy, our method helped in reducing the motion artifact both visually and quantitatively. We also acquired four sets of the emission and transmission data of the Data Spectrum Anthropomorphic Phantom positioned at four different locations and/or orientations. From these we generated a composite acquisition simulating periodic phantom movements during acquisition. The simulated motion was calculated from the generalized center-of-mass points calculated from the tomographic images reconstructed from individual acquisitions. We determined that motion-compensation greatly reduced the motion artifact. Finally, in a simulation with the gated MCAT phantom, an exaggerated rigid-body motion was applied to the end-systolic frame. The motion was estimated from the end-diastolic and end-systolic images, and used to sum them into a summed image without obvious artifact. Compared to the principle-axes method, in two of the three comparisons with anthropomorphic phantom data our method estimated the motion in closer agreement to the Polaris system than the principal-axes method, while the principle-axes method gave a more accurate estimation of motion in most cases for the MCAT simulations. As an image-driven approach, our method assumes angularly com plete data sets for each state of motion. We expert this method to be applied in correction of respiratory motion in respiratory gated SPECT, and respiratory or other rigid-body motion in PET. © 2006 IEEE

Prevalence of Streptococci and Increased Polymicrobial Diversity Associated with Cystic Fibrosis Patient Stability

Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing. We show that outpatient sputum samples have significantly higher bacterial diversity than inpatients, but maintenance treatment with tobramycin did not impact overall diversity. Contrary to the current dogma in the field that Pseudomonas aeruginosa is the dominant organism in the majority of cystic fibrosis patients, Pseudomonas constituted the predominant genera in only half the patient samples analyzed and reported here. The increased fractional representation of Streptococcus in the outpatient cohort relative to the inpatient cohort was the strongest predictor of clinically stable lung disease. The most prevalent streptococci included species typically associated with the oral cavity (Streptococcus salivarius and Streptococcus parasanguis) and the Streptococcus milleri group species. These species of Streptococcus may play an important role in increasing the diversity of the cystic fibrosis lung environment and promoting patient stability

Racism, anti-racist practice and social work: articulating the teaching and learning experiences of Black social workers

In the mid 1990s a Black practice teacher programme was established in Manchester and Merseyside with the primary aim to increase the number of Black practice teachers in social work organisations, and in turn provide a supportive and encouraging learning environment for Black student social workers whilst on placement. In the north‐west of England research has been undertaken, to establish the quality of the practice teaching and student learning taking place with Black practice teachers and students. This paper is an exploration of the ideas generated within the placement process that particularly focused on the discourse of racism and ant‐racist practice. Black students and practice teachers explain their understanding of racism and anti‐racist practice within social work. From the research, the paper will critique some of the ideas concerning anti‐racism. In particular, it will question whether anti‐racist social work practice needs to be re‐evaluated in the light of a context with new migrants, asylum seekers and refugees. It will concluded, by arguing that whilst the terms anti‐racism, Black and Minority Ethnic have resonance as a form of political strategic essentialism, it is important to develop more positive representations in the future

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Hard-boiled Ecologies: Ross Macdonald’s Environmental Crime Fiction

Although Ross Macdonald’s position in the annals of great American hardboiled crime writers is unquestioned, what often been overlooked in the study of his works are the underlying environmental preoccupations that frequently serve as the background to, or context for, crime. This context of ecological violence is forcefully manifested in two of Macdonald’s later Archer novels The Underground Man (1971) and Sleeping Beauty (1973). This essay scrutinizes the environmental imperatives of Macdonald’s work, arguing that the damage and destruction inflicted upon the environment in these two texts becomes symbiotically connected to the broader, morally fraught social milieu of the city