GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved

Common variants at theCHEK2gene locus and risk of epithelial ovarian cancer

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.Other Research Uni

Neurosurgical and Intensive Care Management of Traumatic Brain Injury

Optimal management of patients with traumatic brain injury (TBI) remains a challenge, despite significant improvements in pathophysiologic understanding and treatment strategies in recent decades. Because primary brain injury sustained at the time of trauma is irreversible, the TBI management mainly aims for early detection and treatment of secondary brain injury such as space-occupying intracerebral hematomas and brain edema. Prevention of secondary brain injury requires a high standard of care and understanding of both medical and surgical treatment modalities. This review focuses on practical recommendations for neurosurgical and intensive care management in patients with severe TBI

Slowdown in Global Economic Momentum – Asia and the USA To Remain Growth Drivers of World Economy in 2005

In 2004, despite the sudden jump in oil prices and the ballooning trade deficit, the U.S. economy grew by 4.4%, or more robustly than ever since 1999. In the same year, growth in consumer prices peaked at 3.3% — the highest level in four years. In early February 2005, the U.S. Fed raised its key interest rates by 25 basis points for the sixth time since mid-2004. Whereas Japan slipped back into a period of recession, other Asian economies continued growing apace in 2004. The second half of the year 2004 saw a slowdown in GDP growth momentum in the euro area. Despite positive stimuli from investments, growth rates declined, due to weaker net exports and still very subdued private consumption demand. Consumer restraint can partly be explained by the sluggish growth in real disposable income as a result of higher energy prices, which are also responsible for the rise in inflation. In the first three quarters of 2004, most new Central European EU Member States expanded at a faster pace than in 2003 as a whole. The upward pressure on prices (partly induced by EU accession) was very strong in the new Member States in 2004. In Romania, an EU candidate country, growth rocketed to an outstanding 10.0% in the third quarter. Following weak growth in the fourth quarter of 2004, Austria's economy is regaining steam, but is not immune to the current slowdown in growth in the euro area as a whole. The OeNB's short-term indicator forecasts 0.4% seasonally adjusted growth in Austria's real GDP for the first and 0.5% for the second quarter of 2005 (each compared with the previous quarter).Economic growth

Awake Craniotomy: First year experience and patient perception

- BACKGROUND: Awake craniotomy for brain lesions in or near eloquent brain regions enables neurosurgeons to assess neurologic functions of patients intraoperatively, reducing the risk of permanent neurologic deficits and increasing the extent of resection. - METHODS: A retrospective review was performed of a consecutive series of patients with awake craniotomies in the first year of their introduction to our tertiary noneuniversity-affiliated neurosurgery department. Operation time, complications, and neurologic outcome were assessed, and patient perception of awake craniotomy was surveyed using a mailed questionnaire. - RESULTS: There were 24 awake craniotomies performed in 22 patients for low-grade/high-grade gliomas, cavernomas, and metastases (average 2 cases per month). Mean operation timewas 205 minutes. Failure of awake craniotomy because of intraoperative seizures with subsequent postictal impaired testing or limited cooperation occurred in 2 patients. Transient neurologic deficits occurred in 29% of patients; 1 patient sustained a permanent neurologic deficit. Of the 18 patients (82%) who returned the questionnaire, only 2 patients recalled significant fear during surgery. - CONCLUSIONS: Introducing awake craniotomy to a tertiary noneuniversity-affiliated neurosurgery department is feasible and resulted in reasonable operation times and complication rates and high patient satisfaction

Using the FRDPARRC design methodology to drive innovation in the HETDEX PFIP support adjustable strut assembly

textThis thesis provides background information on the Hobby-Eberly Telescope (HET), HET Dark Energy Experiment (HETDEX), Gough-Stewart platforms (GSP), the Prime Focus Instrument Package (PFIP) support structure, and the design methodology used to design said support structure. Each component is analyzed from the point of view of Professor Alex Slocum’s FRDPARRC design methodology. Each aspect of the design is shown to have been derived by following the steps of Slocum’s design method. Material selection, manufacturing techniques, and integration of off-the-shelf components into the support system are also discussed in reference to FRDPARRC. The assembly procedure for the PFIP structure is outlined. Finally, using specific examples from the detailed design, the FRDPARRC method itself is analyzed and its ability to drive innovation in design is evaluated.Mechanical Engineerin

Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations.

BACKGROUND In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH