FABRIC: A National-Scale Programmable Experimental Network Infrastructure

FABRIC is a unique national research infrastructure to enable cutting-edge and exploratory research at-scale in networking, cybersecurity, distributed computing and storage systems, machine learning, and science applications. It is an everywhere-programmable nationwide instrument comprised of novel extensible network elements equipped with large amounts of compute and storage, interconnected by high speed, dedicated optical links. It will connect a number of specialized testbeds for cloud research (NSF Cloud testbeds CloudLab and Chameleon), for research beyond 5G technologies (Platforms for Advanced Wireless Research or PAWR), as well as production high-performance computing facilities and science instruments to create a rich fabric for a wide variety of experimental activities

National BSUG audit of stress urinary incontinence surgery in England

Introduction and hypothesis The aim of the British Society of Urogynaecology (BSUG) 2013 audit for stress urinary incontinence (SUI) surgery was to conduct a national clinical audit looking at the intra- and postoperative complications and provide outcomes for these procedures. This audit was supported by the Healthcare Quality Improvement Partnership (HQIP) and National Health Service (NHS) England. Methods Data were collected for all continence procedures performed in 2013 through the BSUG database. All clinicians in England performing SUI surgery were invited to submit data to a central database. Outcomes data for the different continence procedures were collected and included intraoperative and postoperative complications and the change in continence scores at postoperative follow-up Changing trends in stress incontinence surgery were also assessed. Results We recorded 4993 urinary incontinence procedures from 177 consultants at 110 centres in England: 94.6% were midurethral slings; 86.7% (4331) were submitted by BSUG members with the remaining 13.3% submitted by non-BSUG members. Postoperative follow-up data were available for 3983 (80%) patients: 92.3% (3676) were very much better/much better postoperatively, and 4806 (96.3%) proceeded with no reported complications. There were 187 cases (3.7%) in which a perioperative complication was recorded. Pain persisting >30 days was reported in 1.9% of all patients. Conclusions Surgery for SUI has good outcomes in the short term. Midurethral synthetic slings have been shown to be safe and effective as a treatment option, with >90% being very much/much better at their postoperative follow-up

From voxel to curvature

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Effect of warm intravenous and irrigating fluids on body temperature during transurethral resection of the prostate gland

<p>Abstract</p> <p>Background</p> <p>Transurethral resection of the prostate gland with irrigation fluid at room temperature leads to perioperative hypothermia which could give rise to adverse cardiovascular events in the perioperative period. The use of isothermic irrigation fluid reduces but does not eliminate this risk. Routine use of warm intravenous fluids along with isothermic irrigation had not been documented. This study set out to investigate the effect of the use of warm intravenous fluid together with isothermic irrigation fluid on the body temperature in patients undergoing transurethral resection of the prostate gland.</p> <p>Methods</p> <p>One hundred and twenty consented patients with obstructing benign prostatic hyperplasia were randomly assigned to one of 3 groups. Group 1 received irrigation and intravenous fluids at room temperature, group 2 received warmed irrigation fluid at 38°C along with intravenous fluid at room temperature while group 3 patients received warmed irrigation fluid and warmed intravenous fluids at 38°C. Their perioperative body temperature changes were monitored, analyzed and compared.</p> <p>Results</p> <p>The mean decrease in body temperature at the end of the procedure was significantly greater in group 1 (0.98 ± 0.56°C) than in group 2 (0.42 ± .21°C) (p < 0.001). Significantly more patients in group 1 also experienced shivering. However, in group 3, there was no significant change in the mean body temperature (p > 0.05) and none of them felt cold or shivered.</p> <p>Conclusion</p> <p>It is concluded that the use of isothermic irrigation fluid together with warm intravenous fluids during TURP prevents the occurrence of perioperative hypothermia.</p> <p>Trial registration number</p> <p>CCT-NAPN-15944</p

Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 mu g/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 mu g/l, P = 0.0004; itself higher than the normal level (3.4 mu g/l, range from 0.5 to 17.2 mu g/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level >= 7 mu g/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels >= 7 mu g/l is 46%. Therefore, selection of patients with an AFP level above 7 mu g/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy

Diverse basis of β-catenin activation in human hepatocellular carcinoma: Implications in biology and prognosis

Aim: β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ϵ (CK1ϵ) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC. Methods: Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues. Results: Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001). Conclusion: This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism