Generalized Arcsine Law and Stable Law in an Infinite Measure Dynamical System

Limit theorems for the time average of some observation functions in an infinite measure dynamical system are studied. It is known that intermittent phenomena, such as the Rayleigh-Benard convection and Belousov-Zhabotinsky reaction, are described by infinite measure dynamical systems.We show that the time average of the observation function which is not the $L^1(m)$ function, whose average with respect to the invariant measure $m$ is finite, converges to the generalized arcsine distribution. This result leads to the novel view that the correlation function is intrinsically random and does not decay. Moreover, it is also numerically shown that the time average of the observation function converges to the stable distribution when the observation function has the infinite mean.Comment: 8 pages, 8 figure

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Breast cancer risk genes: association analysis in more than 113,000 women

BACKGROUNDGenetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.METHODSWe used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.RESULTSProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.CONCLUSIONSThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)Molecular tumour pathology - and tumour geneticsMTG1 - Moleculaire genetica en pathologie van borstkanke

Retrograde jejunogastric intussusception

Retrograde gastrointestinal intussusception is a rare entity, most commonly reported after gastric resection and gastrojejunostomy. Its occurrence in the absence of previous gastric resection is extremely unusual, with only four cases reported. All cases were associated with previously placed gastrostomy tubes and implicated these as the inciting factor. We present a fifth case and review the literature. The mechanism of this phenomenon is described and recommendations to prevent this potentially fatal complication are made

The role of transanal surgery in the management of T1 rectal cancers

The management of T1 rectal cancers is based on finding the balance between optimal oncologic outcomes and acceptable functional results for the patient. While radical resection involving a proctectomy is considered the most oncologically adequate option, its adverse effects on patient reported outcomes makes this a less than ideal choice in certain circumstances. While local excision can circumvent some of the adverse functional outcomes, its inadequacy in assessing metastatic lymph node disease and the subsequent negative impact of untreated positive lymph nodes on patient prognosis is a cause for concern. As a result, the therapeutic strategy has to be based on patient and disease-related factors in order to identify the best treatment choice that maximizes survival benefit and preserves health-related quality of life. After adequate preoperative staging work up, in selected patients with favorable pathological features, local excision can be considered. These cancers can be removed by transanal local excision or transanal endoscopic microsurgery, depending on the location of the cancer and expertise available. While perioperative morbidity is minimal, close postoperative follow-up is essential

Regional differences in platelet-derived growth factor production by the canine aorta

Platelet-derived growth factor (PDGF) is a potent mitogen and chemotactic agent which may be involved in the formation of proliferative lesions of the arterial system, such as intimal hyperplasia and atherosclerosis. To examine the regional variation in vessel wall production of this mitogen, PDGF production and PDGF A chain mRNA expression by normal arterial wall was studied as a function of vessel location. PDGF production by canine aortic segments was measured after 72 h in organ culture, revealing significantly more PDGF produced by the distal compared to proximal aorta at 77 +/- 10 versus 14 +/- 6 pg/cm(2)/72 h (p < 0.05). Endothelial cells (EC) and smooth muscle cells (SMC), isolated from analogous aortic sites, were grown in tissue culture and the conditioned medium was assayed for PDGF. EC in vitro demonstrated a similar geographic trend in PDGF production (distal = 1,501 +/- 389 pg/mu g DNA/72 h, proximal = 759 +/- 230 pg/mu g DNA/72 h; p = 0.17). PDGF production by SMC in cell culture had a similar pattern with cells from the distal aorta producing 58 +/- 28 pg PDGF/mu g DNA/72 h, compared to cells from the proximal aorta producing 37 +/- 15 pg PDGF/mu g DNA/72 h (p = 0.13). Freshly harvested EC and SMC, isolated from the same aortic sites, were subjected to quantitation of PDGF mRNA levels using a coupled reverse transcriptase and polymerase chain reaction amplification method, with glyceraldehyde-phosphate dehydrogenase (GAPDH) as a control. The ratio of PDGF A chain:GAPDH mRNA was significantly greater in distal aortic SMC, 2.30 +/- 0.99, compared to proximal aortic SMC, 1.27 +/- 0.46 (p = 0.05), but was not significantly different between proximal and distal aortic EC (p = 0.86). These findings demonstrate significant regional differences in PDGF production in the normal canine aorta. Additionally, SMC are implicated as a significant contributor to the regional variation in PDGF production

Perfusion assessment in laparoscopic left-sided/anterior resection (PILLAR II): A multi-institutional study

BACKGROUND: Our primary objective was to demonstrate the utility and feasibility of the intraoperative assessment of colon and rectal perfusion using fluorescence angiography (FA) during left-sided colectomy and anterior resection. Anastomotic leak (AL) after colorectal resection increases morbidity, mortality, and, in cancer cases, recurrence rates. Inadequate perfusion may contribute to AL. The PINPOINT Endoscopic Fluorescence Imaging System allows for intraoperative assessment of anastomotic perfusion

Timing of colonoscopy after resection for colorectal cancer: Are we looking too soon?

BACKGROUND: Based on current National Comprehensive Cancer Network guidelines, colonoscopic surveillance after colorectal cancer resection should begin at 1 year