Psychiatry takes to the streets: the New York City initiative for the homeless mentally ill

The authors describe New York City's program to remove seriously mentally ill homeless people from the streets to a public hospital. They report on the 298 patients hospitalized during the first year of this program. Most of the patients were male (66%), single (77%), and from outside of New York City (79%) and claimed a history of previous psychiatric hospitalization (92%) and that they had been homeless for more than 1 year (66%). Most of the patients suffered from schizophrenia (80%) and had additional medical diagnoses (73%). Follow-up contact with the patients 2 years after initiation of the program revealed that 55% of the patients either were living in a community setting or were under institutional care.     

Field map estimation with a region growing scheme for iterative 3-point water-fat decomposition.

Robust fat suppression techniques are required for many clinical applications. Multi-echo water-fat separation methods are relatively insensitive to B(0) field inhomogeneity compared to the fat saturation method. Estimation of this field inhomogeneity, or field map, is an essential and important step, which is well known to have ambiguity. For an iterative water-fat decomposition method recently proposed, ambiguities still exist, but are more complex in nature. They were studied by analytical expressions and simulations. To avoid convergence to incorrect field map solutions, an initial guess closer to the true field map is necessary. This can be achieved using a region growing process, which correlates the estimation among neighboring pixels. Further improvement in stability is achieved using a low-resolution reconstruction to guide the selection of the starting pixels for the region growing. The proposed method was implemented and shown to significantly improve the algorithm's immunity to field inhomogeneity.     

The role of internal pilot studies in increasing the efficiency of clinical trials

Investigators often design clinical trials without knowing precisely the values of such necessary parameters as the variances or the event rates in the control group. In order to determine reasonable values for such parameters, they may design a small pilot study external to the main trial. In this paper we propose designs, which we term internal pilot studies, that designate a portion of the main trial as a pilot phase. At the end of the internal pilot study, the investigators recompute preselected parameters and recalculate required sample size. The study then proceeds with the modifications dictated by the internal pilot. Final analyses of the results incorporate all data, disregarding the fact that part of the data came from a pilot phase. As one example of this type of design, we consider a study to compare two normally distributed means. By simulation, we show a numerical example for which the effect of the procedure on the alpha-level is negligible, but the potential gain in power considerable. We urge considering a similar approach for a number of types of endpoints.     

Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels

Serum mast cell tryptase levels are used as a diagnostic criterion and surrogate marker of disease severity in mastocytosis. Approximately 29% of the healthy population lacks alpha tryptase genes; however, it is not known whether lack of alpha tryptase genes leads to variability in tryptase levels or impacts on disease severity in mastocytosis. We have thus analyzed tryptase haplotype in patients with mastocytosis, computing correlations between haplotype and plasma total and mature tryptase levels; and disease category. We found: (1) the distribution of tryptase haplotype in patients with mastocytosis appeared consistent with Hardy-Weinberg equilibrium and the distribution in the general population; (2) the disease severity and plasma tryptase levels were not affected by the number of alpha or beta tryptase alleles in this study; and (3) information about the tryptase haplotype did not provide any prognostic value about the severity of disease. Total and mature tryptase levels positively correlated with disease severity, as well as prothrombin time and partial thromboplastin time, and negatively correlated with the hemoglobin concentration.     

Efficient delivery of RNA interference effectors via in vitro-packaged SV40 pseudovirions

Previously we have shown that in vitro-packaged simian virus 40 (SV40) pseudovirions (IVPs) are an efficient delivery system for supercoiled DNA plasmids of up to 17.7 kb, with or without SV40 sequences. RNA interference (RNAi) is a naturally occurring gene-silencing mechanism mediated by small double-stranded RNA molecules (small interfering RNAs, siRNAs). This study demonstrates the first use of SV40 pseudovirions to deliver into human cells both principal types of RNAi effector molecules: plasmid-expressed short hairpin RNAs (shRNAs) and synthetic siRNAs. We first established the ability of human lymphoblastoid cells to support RNAi, using sequential transduction of .45 cells with packaged plasmid DNA expressing the green fluorescent protein (IVP-GFP), and an shRNA corresponding to the GFP (IVP-shGFP). SV40 mediates DNA transfer of nucleic acid to the cytoplasm, where RNAi-associated cleavage of mRNA principally occurs. Using SV40 pseudovirions, siRNA-mediated RNAi was observed in both .45 cells, after sequential transduction of IVP-GFP and IVP-packaged siRNAs corresponding to GFP (IVP-siGFP), and in HeLa cells stably expressing a GFP transduced with IVP-siGFP. Our findings indicate that SV40 pseudovirions may be a useful addition to the delivery systems currently being used for the transfer of RNAi effector molecules.     

In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone.

The in vitro activity of Ro 23-6240 (AM833), 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7(4-methyl-1-piper azinyl) quinolone-3-carboxylic acid, was compared with those of norfloxacin, enoxacin, ofloxacin, and ciprofloxacin. Ro 23-6240 inhibited the majority of Enterobacteriaceae isolates at a concentration of less than or equal to 0.5 microgram/ml. It was especially active against Shigella sp., Salmonella sp., Escherichia coli, and Yersinia enterocolitica, with an MIC for 90% of the strains of less than or equal to 0.12 microgram/ml. The MIC for 90% of the strains was 1 microgram/ml for Serratia marcescens and 8 micrograms/ml for Pseudomonas aeruginosa. Staphylococcus aureus isolates, including methicillin-resistant strains, were inhibited by less than or equal to 1 microgram/ml. Streptococcal and anaerobic species were inhibited by 8 to 16 micrograms/ml. Ro 23-6240 inhibited beta-lactamase-producing bacteria resistant to broad-spectrum cephalosporins. The overall activity of Ro 23-6240 was similar to those of enoxacin, norfloxacin, and ofloxacin, but less than that of ciprofloxacin. The frequency of spontaneous resistance was low, although resistant bacteria could be isolated by repeated subculture. The activity of Ro 23-6240 was decreased in the presence of magnesium at concentrations similar to those present in urine.     

Water-silicone separated volumetric MR acquisition for rapid assessment of breast implants

Purpose:

To develop a robust T₂‐weighted volumetric imaging technique with uniform water‐silicone separation and simultaneous fat suppression for rapid assessment of breast implants in a single acquisition.

Materials and Methods:

A three‐dimensional (3D) fast spin echo sequence that uses variable refocusing flip angles was combined with a three‐point chemical‐shift technique (IDEAL) and short tau inversion recovery (STIR). Phase shifts of ?π/6, +π/2, and +7π/6 between water and silicone were used for IDEAL processing. For comparison, two‐dimensional images using 2D‐FSE‐IDEAL with STIR were also acquired in axial, coronal, and sagittal orientations.

Results:

Near‐isotropic (true spatial resolution—0.9 × 1.3 × 2.0 mm³) volumetric breast images with uniform water‐silicone separation and simultaneous fat suppression were acquired successfully in clinically feasible scan times (7:00–10:00 min). The 2D images were acquired with the same in‐plane resolution (0.9 × 1.3 mm²), but the slice thickness was increased to 6 mm with a slice gap of 1 mm for complete coverage of the implants in a reasonable scan time, which varied between 18:00 and 22:30 min.

Conclusion:

The single volumetric acquisition with uniform water and silicone separation enables images to be reformatted into any orientation. This allows comprehensive assessment of breast implant integrity in less than 10 min of total examination time. J. Magn. Reson. Imaging 2012;35:1216‐1221. © 2012 Wiley Periodicals, Inc.