Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence

The Validity of Peer Review in a General Medicine Journal

All the opinions in this article are those of the authors and should not be construed to reflect, in any way, those of the Department of Veterans Affairs

Capturing flow transformation processes across an uneven seabed in coarse-grained sediment gravity flow deposits

The upper part of the Jurassic stratigraphy of the Los Molles Formation corresponds to deepwater succession deposited with a regional marine transgression during the early postrift stage of the Neuquén Basin. The present study conducted in the location of Chacay Melehue (Argentina) is used to document the interactions between coarse-grained sediment gravity flows and the depositional relief of a seismic-scale mass transport complex (MTC), with metre-scale mounds and decametric protruding clasts, as an analogue for similar configurations in subsurface systems. The 60 m thick succession is exposed along a 6.5 km long oblique downdip longitudinal profile. Exposure quality permits walking out of individual beds. A total of 16 stratigraphic sections (1560 m thick) spaced between 500 m and 100 m, were logged at 1:50 and 1:25 scale. The basal datum of the studied interval is the top of a MTC and the top marker bed is an extensive sandstone bed. Two units studied correspond to very coarse to fine-grained medium-bedded sandstones with abundant pebble-sized clasts (Unit1) and three thick plurimetric distinct beds of poorly-sorted, granular to medium-grained mud-rich sandstone matrix supporting polygenic gravels (Unit2). Distinct thick extensive beds in both units are intercalated with heterolithic successions of thin to medium-bedded very coarse- to coarse-grained or fine-grained sandstones, siltstones and mudstones. The sandstone beds in Unit 1 abruptly pinchout in the proximal part of study area. They are associated with evidence of erosion, sediment bypass and transformation of subaqueous sand-bearing flows. Stratigraphically, sandstone packages in the Unit 2 are increasingly more laterally extensive upwards in the succession. Thickness variations in these beds are related to compensational stacking. The research will inform studies in the architecture of deep-water successions above an uneven seabed inherited from the top of a MTC. The detailed analysis of exhumed examples that record depositional changes in the structure of the flow can lead to the development of predictive stratigraphic models which incorporate details and complexities observed in outcrop and can be applied for the evaluation of the quality of subsurface reservoirs.Fil: Privat, Aurélia. University of Leeds; Reino UnidoFil: Hodgson, David. University of Leeds; Reino UnidoFil: Peakall, Jeffrey. University of Leeds; Reino UnidoFil: Jackson, Christopher A. L.. University of Leeds; Reino UnidoFil: Schwarz, Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; Argentina2016 AAPG/SEG International Convention and ExhibitionBarcelonaEspañaAmerican Association of Petroleum GeologistsSociety of Exploration Geophysicist

The Formation and Coarsening of the Concertina Pattern

The concertina is a magnetization pattern in elongated thin-film elements of a soft material. It is a ubiquitous domain pattern that occurs in the process of magnetization reversal in direction of the long axis of the small element. Van den Berg argued that this pattern grows out of the flux closure domains as the external field is reduced. Based on experimental observations and theory, we argue that in sufficiently elongated thin-film elements, the concertina pattern rather bifurcates from an oscillatory buckling mode. Using a reduced model derived by asymptotic analysis and investigated by numerical simulation, we quantitatively predict the average period of the concertina pattern and qualitatively predict its hysteresis. In particular, we argue that the experimentally observed coarsening of the concertina pattern is due to secondary bifurcations related to an Eckhaus instability. We also link the concertina pattern to the magnetization ripple and discuss the effect of a weak (crystalline or induced) anisotropy

Nitropyrene: DNA binding and adduct formation in respiratory tissues.

Binding of 1-nitro (14C)pyrene (NP) or its metabolites to cellular DNA and protein in cultures of rabbit alveolar macrophages, lung tissue, and tracheal tissue was examined. DNA binding in tracheal tissue (136 +/- 18.3 pmole NP/mg DNA) was four to five times the levels measured in either lung tissue (38 +/- 9.4 pmole NP/mg DNA) or macrophages (26 +/- 7.5 pmole NP/mg DNA). Adduct analysis of DNA isolated from lung tissue incubated with 1-nitro[H3]pyrene in vitro resulted in the identification of 2 to 5% of the NP adducts as C8-deoxyguanosine 1-aminopyrene. NP was also bound to cellular protein in tracheal tissue and lung tissue, and at a lower level in macrophages. Cocultivation of the macrophages with lung and tracheal tissue decreased the DNA binding in tracheal tissue by 45%. Following intratracheal instillation of diesel particles (5 mg) vapor-coated with 14C-NP (380 ppm, 0.085 muCi/mg) particles into rats, 5-8% of the radioactivity remained in the lungs after 20 hr. Most of the diesel particles were also deposited in the lung. Examination of DNA and protein binding in this tissue showed 5 to 12% of the pulmonary 14C bound to protein and no detectable levels of 14C bound to DNA

School Personnel Lived Experiences Related to High School Engineering Education and the Covid-19 Pandemic

This study investigated the teaching experiences of three school personnel at a public high school during the 2020–2021 school year as they implemented a unique science, technology, engineering, arts, and math (STEAM) unit with in-person and virtual students in their engineering classes during the Covid-19 pandemic. A research team interviewed two teachers and one administrator at the school to better understand the nuances of pre-college engineering during a pandemic year and how changes in school and district policy affected the instructional delivery of STEAM projects. Narrative analytic methods were utilized to understand each participant’s experience and an inductive content thematic approach was used to develop the findings. The participants described varied experiences navigating instruction during the pandemic, particularly when adapting hands-on STEAM projects for virtual or hybrid teaching. All three participants thought deeply about how to best meet the needs of students while attempting to support equitable instruction. The findings of this study indicate that pre-college engineering in the pandemic was challenging for the participants, but not impossible, and that this setting was an appropriate context for STEAM projects that provided students with a mechanism for collaboration and engagement

The accuracy and completeness for receipt of colorectal cancer care using Veterans Health Administration administrative data.

The National Comprehensive Cancer Network and the American Society of Clinical Oncology have established guidelines for the treatment and surveillance of colorectal cancer (CRC), respectively. Considering these guidelines, an accurate and efficient method is needed to measure receipt of care

The roles of motivation and ability in controlling the consequences of stereotype suppression

Two experiments investigated the conditions under which previously suppressed stereotypes are applied in impression formation. In Experiment 1, the extent to which a previously suppressed racial stereotype influenced subsequent impressions depended on the race of the target who was subsequently encountered. Whereas impressions of race-unspecified targets were assimilated to the stereotype following its suppression, no such effects were observed when the target belonged to the racial group whose stereotype had been initially suppressed. These results demonstrate that when perceivers are motivated to avoid stereo-typing individuals, the influence of a stereotype that has been previously activated through suppression is minimized. Experiment 2 demonstrated that these processing goals effectively reduce the impact of suppression-activated stereotypes only when perceivers have sufficient capacity to enact the goals. These results suggest that both sufficient motivation and capacity are necessary to prevent heightened stereotyping following stereotype suppression

Therapeutic Intervention for Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS): A Systematic Review and Meta-Analysis

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has been treated with several different interventions with limited success. This meta-analysis aims to review all trials reporting on therapeutic intervention for CP/CPPS using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). Methods We searched Medline, PubMed, the Cochrane Pain, Palliative & Supportive Care Trials, the Cochrane Register of Controlled Trials, CINAHL, ClinicalTrials.gov, and the NIDDK website between 1947 and December 31, 2011 without language or study type restrictions. All RCTs for CP/CPPS lasting at least 6 weeks, with a minimum of 10 participants per arm, and using the NIH-CPSI score, the criterion standard for CP/CPPS, as an outcome measure were included. Data was extracted from each study by two independent reviewers. Gillbraith and I-squared plots were used for heterogeneity testing and Eggers and Peters methods for publication bias. Quality was assessed using a component approach and meta-regression was used to analyze sources of heterogeneity. Results: Mepartricin, percutaneous tibial nerve stimulation (PTNS), and triple therapy comprised of doxazosin + ibuprofen + thiocolchicoside (DIT) resulted in clinically and statistically significant reduction in NIH-CPSI total score. The same agents and aerobic exercise resulted in clinically and statistically significant NIH-CPSI pain domain score reduction. Acupuncture, DIT, and PTNS were found to produce statistically and clinically significant reductions in the NIH-CPSI voiding domain. A statistically significant placebo effect was found for all outcomes and time analysis showed that efficacy of all treatments increased over time. Alpha-blockers, antibiotics, and combinations of the two failed to show statistically or clinically significant NIH-CPSI reductions. Conclusion: Results from this meta-analysis reflect our current inability to effectively manage CP/CPPS. Clinicians and researchers must consider placebo effect and treatment efficacy over time and design studies creatively so we can more fully elucidate the etiology and role of therapeutic intervention in CP/CPPS.