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Understanding how the blood transcriptome of human intracerebral hemorrhage (ICH) differs from ischemic stroke (IS) and matched controls (CTRL) will improve understanding of immune and coagulation pathways in both disorders. This study examined RNA from 99 human whole-blood samples using GeneChip® HTA 2.0 arrays to assess differentially expressed transcripts of alternatively spliced genes between ICH, IS and CTRL. We used a mixed regression model with FDR-corrected p (Dx) < 0.2 and p  < 0.005 and |FC| > 1.2 for individual comparisons. For time-dependent analyses, subjects were divided into four time-points: 0(CTRL), <24 h, 24-48 h, >48 h; 489 transcripts were differentially expressed between ICH and CTRL, and 63 between IS and CTRL. ICH had differentially expressed T-cell receptor and CD36 genes, and iNOS, TLR, macrophage, and T-helper pathways. IS had more non-coding RNA. ICH and IS both had angiogenesis, CTLA4 in T lymphocytes, CD28 in T helper cells, NFAT regulation of immune response, and glucocorticoid receptor signaling pathways. Self-organizing maps revealed 4357 transcripts changing expression over time in ICH, and 1136 in IS. Understanding ICH and IS transcriptomes will be useful for biomarker development, treatment and prevention strategies, and for evaluating how well animal models recapitulate human ICH and IS.

Background: Intracerebral hemorrhage (ICH) has a high morbidity and mortality. The peripheral immune system and cross-talk between peripheral blood and brain have been implicated in the ICH immune response. Thus, we delineated the gene networks associated with human ICH in the peripheral blood transcriptome. We also compared the differentially expressed genes in blood following ICH to a prior human study of perihematomal brain tissue., Methods: We performed peripheral blood whole-transcriptome analysis of ICH and matched vascular risk factor control subjects (n = 66). Gene co-expression network analysis identified groups of co-expressed genes (modules) associated with ICH and their most interconnected genes (hubs). Mixed-effects regression identified differentially expressed genes in ICH compared to controls., Results: Of seven ICH-associated modules, six were enriched with cell-specific genes: one neutrophil module, one neutrophil plus monocyte module, one T cell module, one Natural Killer cell module, and two erythroblast modules. The neutrophil/monocyte modules were enriched in inflammatory/immune pathways; the T cell module in T cell receptor signaling genes; and the Natural Killer cell module in genes regulating alternative splicing, epigenetic, and post-translational modifications. One erythroblast module was enriched in autophagy pathways implicated in experimental ICH, and NRF2 signaling implicated in hematoma clearance. Many hub genes or module members, such as IARS, mTOR, S1PR1, LCK, FYN, SKAP1, ITK, AMBRA1, NLRC4, IL6R, IL17RA, GAB2, MXD1, PIK3CD, NUMB, MAPK14, DDX24, EVL, TDP1, ATG3, WDFY3, GSK3B, STAT3, STX3, CSF3R, PIP4K2A, ANXA3, DGAT2, LRP10, FLOT2, ANK1, CR1, SLC4A1, and DYSF, have been implicated in neuroinflammation, cell death, transcriptional regulation, and some as experimental ICH therapeutic targets. Gene-level analysis revealed 1225 genes (FDR p < 0.05, fold-change > |1.2|) have altered expression in ICH in peripheral blood. There was significant overlap of the 1225 genes with dysregulated genes in human perihematomal brain tissue (p = 7 × 10 -3 ). Overlapping genes were enriched for neutrophil-specific genes (p = 6.4 × 10 -08 ) involved in interleukin, neuroinflammation, apoptosis, and PPAR signaling., Conclusions: This study delineates key processes underlying ICH pathophysiology, complements experimental ICH findings, and the hub genes significantly expand the list of novel ICH therapeutic targets. The overlap between blood and brain gene responses underscores the importance of examining blood-brain interactions in human ICH.

Objectives of the study were to measure recruitment rates in clinical trials and to identify patients, physicians or trials characteristics associated with higher recruitment rates. Among patients who had a clinical trial available for their cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical trial. At least one trial was proposed to 33.1% (113/341) of the eligible patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5% (68/413). In multivariate analyses, trial proposal and enrollment were lower for elderly patients and higher in high cancer stages. Trials from pharmaceutical industry had higher recruitment rates and trials testing hormonal therapy enrolled more patients. Breast cancer patients' accrual to a clinical trial could be improved by trying to systematically identify all eligible patients and propose a trial to those eligible and to whom the treatment is planned to be equivalent to the standard arm of the trial., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Clinical trial recruitment can be impeded by eligibility criteria being too numerous or too restrictive., Purpose: This study's principal objective was to determine whether a specific category of eligibility criteria could be identified as a major barrier to patient enrollment., Methods: Nine phase II or III clinical trials, opened between June 2004 and July 2008, were selected. A retrospective cohort of women diagnosed with invasive, nonmetastatic breast cancer and potentially eligible for these clinical trials was used. All eligibility criteria were sorted into the following categories: definition of disease, precision, safety, ethical and legal, or administrative. A total of 985 patient-trials were evaluated, defined as the experimental unit since one patient could be eligible to more than one trial. Proportions of cases with 'not met' eligibility criteria were assessed for each category in each trial., Results: Two clinical trials had a 'not met' subcategory criterion of over 20%. 'Pathology' and 'consent' subcategory criteria were 'not met' in 24.2% and 92.7% of cases for the NEOCAN and NCIC CTG MA.27 trials, respectively. NCIC CTG MA.27 had the highest proportion of 'not met' subcategory due to an inclusion criterion requiring participation to two companion studies. National Surgical Adjuvant Breast and Bowel Project (NSABP) B-38 had a proportion of 18.8% of cases 'not meeting' the receptor status subcategory criterion. All other subcategories of eligibility criteria assessed were 'not met' by less than 15% of patients. Overall, few subcategories had over 10% of ineligible patients., Limitations: Many eligibility criteria were considered 'nonevaluable' because the information evaluated would have required additional procedures not performed as part of the general practice., Conclusion: The subjects from the study population are not precluded from entry in a trial because of stringent eligibility criteria. Eligibility criteria should reflect as much as possible the whole population to whom the treatment will be offered, with the exception of drugs targeting a specific receptor or pathway where only a subpopulation is hypothesized to benefit from the therapy. In the breast cancer clinical trials evaluated for the present study, no criterion precluding recruitment was shared by many or all trials and no specific eligibility criterion was consistently the reason for patients' ineligibility.

Group homes sometimes face significant neighborhood opposition, and municipalities frequently use maximum occupancy laws to close down these homes. This study examined how the number of residents in Oxford House recovery homes impacted residents' outcomes. Larger homes (i.e., 8 or more residents) may reduce the cost per person and offer more opportunities to exchange positive social support, thus, it was predicted that larger Oxford Houses would exhibit improved outcomes compared to smaller homes. Regression analyses using data from 643 residents from 154 U.S. Oxford Houses indicated that larger House size predicted less criminal and aggressive behavior; additionally, length of abstinence was a partial mediator in these relationships. These findings have been used in court cases to argue against closing down larger Oxford Houses. 125 words.