No time to die: the consensus immunoscore for predicting survival and response to chemotherapy of locally advanced colon cancer patients in a multicenter international study.

The multicenter international Society for Immunotherapy of Cancer (SITC) study of the consensus Immunoscore demonstrated the prediction of survival and response to chemotherapy in 763 Stage III colon cancer (CC) patients. Similar Immunoscore groups were found in elderly patients, and densities of immune cells and intratumoral T-cell repertoire were not decreasing with age in the tumor microenvironment. In two independent cohorts, Immunoscore significantly predicted time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS), including within high-risk (T4 or N2) and low-risk (T1-3, N1) patients. In stratified Cox multivariable analysis for TTR, DFS, and OS, Immunoscore\u27s association to outcomes was independent of the patient\u27s age, sidedness, gender, T-stage, N-stage, and microsatellite instability status. Furthermore, the relative contribution to the risk test showed that Immunoscore had the highest contribution to survival. Importantly Immunoscore predicted the likelihood of response to chemotherapy. Only patients with a high-Immunoscore significantly benefited from chemotherapy. The prognostic value of Immunoscore was confirmed in two independent phase 3 clinical trials (NCCTG-N0147, n = 559; Prodige-IDEA, n = 1062). Moreover, results from IDEA phase 3 randomized trial revealed the predictive value of Immunoscore for response to adjuvant FOLFOX chemotherapy duration. The latest edition of the WHO Digestive System Tumors classification introduced the immune response as measured by Immunoscore as essential and desirable diagnostic criteria for CC, and Immunoscore was introduced into the 2020 ESMO Clinical Practice Guidelines for CC to refine the prognosis and adjust chemotherapy decision-making process in stages II and III patients. These results highlight the clinical utility of Immunoscore

Pion-Kaon Scattering near the Threshold in Chiral SU(2) Perturbation Theory

In the context of chiral SU(2) perturbation theory, pion-kaon scattering is analysed near the threshold to fourth chiral order. The scattering amplitude is calculated both in the relativistic framework and by using an approach similar to heavy baryon chiral perturbation theory. Both methods lead to equivalent results. We obtain relations between threshold parameters, valid to fourth chiral order, where all those combinations of low-energy constants which are not associated with chiral-symmetry breaking terms drop out. The remaining low-energy constants can be estimated using chiral SU(3) symmetry. Unfortunately, the experimental information is not precise enough to test our low-energy theorems.Comment: 38 pages, 5 figures, PhD Thesis, references adde

Fiberoptic Colonoscopic Polypectomies

The development of fiberoptic instruments which permit direct visualization of the entire colonic lumen has made possible the safe removal of polyps from any part of the colon. The avoidance of transabdominal colotomy and polypectomy significantly decreases the mortality and morbidity as well as the duration of hospital stay. We wish to present our experience in performing the endoscopic removal of 128 colonic polyps larger than 0.5 cm in size in 103 patients, located from the cecum to the sigmoid colon and beyond the reach of the rigid sigmoidoscope. The polypectomy procedures via the colonoscope were done without mortality and with only three relatively minor complications, all of which responded to conservative measures. Endoscopic removal of colonic polyps is proposed as a safe, practical alternative to either laparotomy and colotomy or repeated barium enema studies in the management of the patient with a colonic polyp

Functional MRI To Evaluate “Sense of Self” following Perforator Flap Breast Reconstruction

Background: Breast reconstruction is associated with high levels of patient satisfaction. Previous patient satisfaction studies have been subjective. This study utilizes functional magnetic resonance imaging (fMRI) to objectively evaluate “sense of self” following deep inferior epigastric perforator (DIEP) flap breast reconstruction in an attempt to better understand patient perception. Methods: Prospective fMRI analysis was performed on four patients before and after delayed unilateral DIEP flap breast reconstruction, and on four patients after immediate unilateral DIEP flap breast reconstruction. Patients were randomly cued to palpate their natural breast, mastectomy site or breast reconstruction, and external silicone models. Three regions of interest (ROIs) associated with self-recognition were examined using a general linear model, and compared using a fixed effects and random effects ANOVA, respectively. Results: In the delayed reconstruction group, activation of the ROIs was significantly lower at the mastectomy site compared to the natural breast (p<0.01). Ten months following reconstruction, activation of the ROIs in the reconstructed breast was not significantly different from that observed with natural breast palpation. In the immediate reconstruction group, palpation of the reconstructed breast was also similar to the natural breast. This activity was greater than that observed during palpation of external artificial models (p<0.01). Conclusions: Similar activation patterns were observed during palpation of the reconstructed and natural breasts as compared to the non-reconstructed mastectomy site and artificial models. The cognitive process represented by this pattern may be a mechanism by which breast reconstruction improves self-perception, and thus patient satisfaction following mastectomy

Bedload‐Bedrock Contrasts Form Enigmatic Low‐Relief Surfaces of the Pyrenees

Low-relief, high-elevation surfaces in mountain belts highlight the dynamic nature of landscapes and have provided evidence for changes in tectonics and/or climate. Yet quantifying when changes occurred from topographic data is challenging and relationships between erosion rate, lithology and precipitation are complex. In the Pyrenees, low-relief, high elevation surfaces are found across both plutonic massifs and the surrounding softer rocks and channel steepness values are relatively uniform between these lithologies. This suggests a weak relationship between erosion rate and lithology despite a clear relationship between the drainage network configuration and the location of the plutonic rocks. We explore this conflicting evidence for strength of the relationship between lithology and erosion rate using a landscape evolution model which accounts for the contrast between bedrock and bedload erodibility. This contrast produces dispersed channel steepness values and predicts the in situ development of low-relief surfaces, under steady forcing conditions

SARS-CoV-2 antibodies detected in human breast milk postvaccination

Importance The SARS-CoV-2 pandemic has infected over a hundred million people worldwide, with almost 2.5 million deaths at the date of this publication. In the United States, Pfizer-BioNTech and Moderna vaccines were first administered to the public starting in December 2020, and no lactating women were included in the initial trials of safety/efficacy. Research on SARS-CoV-2 vaccination in lactating women and the potential transmission of passive immunity to the infant through breast milk is needed to guide patients, clinicians and policy makers during the worldwide effort to curb the spread of this virus. Objective To determine whether SARS-CoV-2 specific immunoglobins are found in breast milk post-vaccination, and to characterize the time course and types of immunoglobulins present. Design Prospective cohort study Setting Providence Portland Medical Center, Oregon, USA Participants Six lactating women who planned to receive both doses of the Pfizer-BioNTech or Moderna vaccine between December 2020 and January 2021. Breast milk samples were collected pre-vaccination and at 11 additional timepoints, with last sample at 14 days post 2nd dose of vaccine. Exposure Two doses of Pfizer-BioNTech or Moderna SARS-CoV-2 vaccine. Main Outcome(s) and Measure(s) Levels of SARS-CoV-2 specific IgA and IgG immunoglobulins in breast milk. Results In this cohort of 6 lactating women who received 2 doses of SARS-CoV-2 vaccine, we observed significantly elevated levels of SARS-CoV-2 specific IgG and IgA antibodies in breast milk beginning at Day 7 after the initial vaccine dose, with an IgG-dominant response. Conclusions and Relevance We are the first to show that maternal vaccination results in SARS-CoV-2 specific immunoglobulins in breast milk that may be protective for infants. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported by generous grants from Nancy Lematta (BAF) and the Chiles Foundation (BAF)

Virus Burden in Lymph Nodes and Blood of Subjects with Primary Human Immunodeficiency Virus Type 1 Infection on Bitherapy

At present, it is not known whether undetectable plasma viremia corresponds to an absence of human immunodeficiency virus type 1 (HIV-1) replication in lymphoid tissues. This issue has been explored in 11 subjects with primary HIV-1 infection treated with zidovudine plus didanosine by evaluating virologic markers in blood and lymphoid tissues 9-18 months after initiation of treatment. These markers include plasma viremia, measured with a sensitive assay with a detection limit of 20 HIV-1 RNA copies/mL, infectious virus titers and proviral DNA in lymph node mononuclear cells, and HIV-1 RNA in lymphoid tissue. Five subjects had plasma viremia < 20 copies/mL and showed no evidence of viral replication in lymphoid tissue. Six subjects had both detectable plasma viremia and evidence of HIV-1 RNA in lymphoid tissue. The results indicate that absence of detectable HIV RNA in lymphoid tissue is associated with viremia levels of HIV-1 RNA < 20 copies/m

Supporting the advancement of science: Open access publishing and the role of mandates

In December 2011 the United States House of Representatives introduced a new bill, the Research Works Act (H.R.3699), which if passed could threaten the public's access to US government funded research. In a digital age when professional and lay parties alike look more and more to the online environment to keep up to date with developments in their fields, does this bill serve the best interests of the community? Those in support of the Research Works Act argue that government open access mandates undermine peer-review and take intellectual property from publishers without compensation, however journals like Journal of Translational Medicine show that this is not the case. Journal of Translational Medicine in affiliation with the Society for Immunotherapy of Cancer demonstrates how private and public organisations can work together for the advancement of science