A Generalized Estimator of the Attributable Benefit of an Optimal Treatment Regime

Summary For many diseases where there are several treatment options often there is no consensus on the best treatment to give individual patients. In such cases, it may be necessary to define a strategy for treatment assignment; that is, an algorithm that dictates the treatment an individual should receive based on their measured characteristics. Such a strategy or algorithm is also referred to as a treatment regime. The optimal treatment regime is the strategy that would provide the most public health benefit by minimizing as many poor outcomes as possible. Using a measure that is a generalization of attributable risk (AR) and notions of potential outcomes, we derive an estimator for the proportion of events that could have been prevented had the optimal treatment regime been implemented. Traditional AR studies look at the added risk that can be attributed to exposure of some contaminant; here we will instead study the benefit that can be attributed to using the optimal treatment strategy. We will show how regression models can be used to estimate the optimal treatment strategy and the attributable benefit of that strategy. We also derive the large sample properties of this estimator. As a motivating example, we will apply our methods to an observational study of 3856 patients treated at the Duke University Medical Center with prior coronary artery bypass graft surgery and further heart‐related problems requiring a catheterization. The patients may be treated with either medical therapy alone or a combination of medical therapy and percutaneous coronary intervention without a general consensus on which is the best treatment for individual patients.     

A Triple-Arginine Motif in the Amino-Terminal Domain and Oligomerization Are Required for HIV-1 Inhibition by Human MX2

We have employed molecular genetic approaches to understand the domain organization of the HIV-1 resistance factor myxovirus resistance 2 (MX2). First, we describe an essential triple-arginine motif in the amino-terminal domain. Second, we demonstrate that this 91-residue domain mediates antiviral activity when appended to heterologous proteins, and we provide genetic evidence that protein oligomerization is required for MX2 function. These insights will facilitate future work aiming to elucidate MX2''s mechanism of action.     

Study of multiparameter respiratory pattern complexity in surgical critically ill patients during weaning trials

Background  

Separation from mechanical ventilation is a difficult task, whereas conventional predictive indices have not been proven accurate enough, so far. A few studies have explored changes of breathing pattern variability for weaning outcome prediction, with conflicting results. In this study, we tried to assess respiratory complexity during weaning trials, using different non-linear methods derived from theory of complex systems, in a cohort of surgical critically ill patients.     

Hotspots of endemic terrestrial invertebrates in southern Greece

In the present paper we identify biodiversity hotspots of endemic terrestrial invertebrates in southern Greece, using four different criteria and five taxonomic groups. The hotspots identification procedure was facilitated by the use of the MapInfoPro G.I.S. software. We mapped the known distribution of 424 endemic species on a digital map of southern Greece in 548 10 × 10 km² grids. The total number of registrations (records per grid) is 3826 in 465 grids. Registrations are unevenly distributed in the five sub-regions of the study area, a fact that results from both the unequal collecting effort applied in each sub-region and their different levels of endemism. We first identified the hotspots for each individual taxonomic group, and then for the total species pool. Finally, we analyzed the species saturation pattern in order to find the minimum number of grids needed for the inclusion of 85% of the total number of species. The most important hotspots are mostly at the higher mountains of the study area, especially on Taygetos and Idi Mts. We also give a brief evaluation of the performance of the four criteria used in the case of endemic species analyses.     

Lethal nonagouti (ax): Description of a second embryonic lethal at the agouti locus

The time and mode of action of the homozygous a^x gene, lethal nonagouti, has been investigated on the inbred AX/Pa background. Heterozygotes were mated inter se to produce 25% homozygous embryos and heterozygotes were mated with homozygous, nonagouti mice to provide control litters. Comparisons of the frequency of mating success, the ratio of implantation sites to ovarian ovulation sites, and the average litter sizes between experimental and control matings all indicated that a^x/a^x embryos are not lost prior to implantation. Histological examination of pregnant uteri indicated that a^x/a^x embryos are first evident as abnormal blastocysts at 4.5 days post coitum (pc). These implant and develop to varying degrees, some differentiating trophoblast giant cells and a primitive endoderm layer. Growth is retarded and only small, disorganized clumps of tissue remain by 7.5 and 8.5 days pc. The time and mode of gene action of lethal nonagouti is thus different from its allele, lethal Yellow.