Повторный гидравлический разрыв пласта в горизонтальных скважинах с нецементируемым хвостовиком

Myocardial perfusion imaging with 99mTc-tetrofosmin is based on the assumption of a linear correlation between myocardial blood flow (MBF) and tracer uptake. However, it is known that 99mTc-tetrofosmin uptake is directly related to energy-depen-dent transport processes, such as Na/H ion channel activity, as well as cellular and mitochondrial membrane potentials. Therefore, cellular alterations that affect these energy-depen-dent transport processes ought to influence 99mTc-tetrofosmin uptake independently of blood flow. Because metabolism (18F-FDG)–perfusion (99mTc-tetrofosmin) mismatch myocardium (MPMM) reflects impaired but viable myocardium showing cel-lular alterations, MPMM was chosen to quantify the blood flow– independent effect of cellular alterations on 99mTc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF (MBF_micr; 15O-water PET) and 99mTc-tetrofosmin uptake i

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Dual addressing of thymidine synthesis pathways for effective targeting of proliferating melanoma

Here, we examined the potential of blocking the thymidine de novo synthesis pathways for sensitizing melanoma cells to the nucleoside salvage pathway targeting endogenous DNA irradiation. Expression of key nucleotide synthesis and proliferation enzymes thymidylate synthase (TS) and thymidine kinase 1 (TK1) was evaluated in differentiated (MITFhigh [microphthalmia-associated transcription factor] IGR1) and invasive (MITFmedium IGR37) melanoma cells. For inhibition of de novo pathways cells were incubated either with an irreversible TS inhibitor 5-fluoro-2-deoxyuridine (FdUrd) or with a competitive dihydrofolate-reductase (DHFR) inhibitor methotrexate (MTX). Salvage pathway was addressed by irradiation-emitting thymidine analog [I-123/125]-5-iodo-4-thio-2-deoxyuridine (I-123/125-ITdU). The in vivo targeting efficiency was visualized by single-photon emission computed tomography. Pretreatment with FdUrd strongly increased the cellular uptake and the DNA incorporation of I-125-ITdU into the mitotically active IGR37 cells. This effect was less pronounced in the differentiated IGR1 cells. In vivo, inhibition of TS led to a high and preferential accumulation of I-123-ITdU in tumor tissue. This preclinical study presents profound rationale for development of therapeutic approach by highly efficient and selective radioactive targeting one of the crucial salvage pathways in melanomas

Radiology Case Reports

Detection of multiple intracranial hemorrhages in a child with acute lymphocytic leukemia (ALL) by susceptibility weighted imaging (SWI