Meltwater produced by wind–albedo interaction stored in an East Antarctic ice shelf

Surface melt and subsequent firn air depletion can ultimately lead to disintegration of Antarctic ice shelves1,2 causing grounded glaciers to accelerate3 and sea level to rise. In the Antarctic Peninsula, foehn winds enhance melting near the grounding line4, which in the recent past has led to the disintegration of the most northerly ice shelves5,6. Here, we provide observational and model evidence that this process also occurs over an East Antarctic ice shelf, where meltwaterinduced firn air depletion is found in the grounding zone. Unlike the Antarctic Peninsula, where foehn events originate from episodic interaction of the circumpolar westerlies with the topography, in coastal East Antarctica high temperatures are caused by persistent katabatic winds originating from the ice sheet’s interior. Katabatic winds warm and mix the air as it flows downward and cause widespread snow erosion, explaining >3 K higher near-surface temperatures in summer and surface melt doubling in the grounding zone compared with its surroundings. Additionally, these winds expose blue ice and firn with lower surface albedo, further enhancing melt. The in situ observation of supraglacial flow and englacial storage of meltwater suggests that ice-shelf grounding zones in East Antarctica, like their Antarctic Peninsula counterparts, are vulnerable to hydrofracturing7

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

Electronic reminders for pathologists promote recognition of patients at risk for Lynch syndrome: cluster-randomised controlled trial

We investigated success factors for the introduction of a guideline on recognition of Lynch syndrome in patients recently diagnosed with colorectal cancer (CRC) below age 50 or a second CRC below age 70. Pathologists were asked to start microsatellite instability (MSI) testing and report to surgeons with the advice to consider genetic counselling when MSI test or family history was positive. A multicentre cluster-randomised controlled trial (ClinicalTrials.gov, number NCT00141466) was performed in 12 pathology laboratories (clusters), serving 29 community hospitals. All received an introduction to the new guideline. In the intervention group, surgeons received education and tumour test result reminders; pathologists were provided with inclusion criteria cards, an electronic patient inclusion reminder system and feedback on inclusion. Two hundred sixty-six CRC patients were eligible for recognition as at risk for Lynch syndrome. The actual recognition was 18% more successful in the intervention as compared to the control arm (77% (120 of 156) compared to 59% (65 of 110)), with an adjusted odds ratio (OR) = 2.8 (95% confidence interval (CI) 1.1–7.0). The electronic reminder system for pathologists was most strongly associated with recognition of high-risk patients, OR = 4.2 (95% CI 1.7–10.1). An electronic reminder system for pathologists appeared effective for adherence to a new complex guideline and will enhance the recognition of Lynch syndrome

A Minimal Fragment of MUC1 Mediates Growth of Cancer Cells

The MUC1 protein is aberrantly expressed on many solid tumor cancers. In contrast to its apical clustering on healthy epithelial cells, it is uniformly distributed over cancer cells. However, a mechanistic link between aberrant expression and cancer has remained elusive. Herein, we report that a membrane-bound MUC1 cleavage product, that we call MUC1*, is the predominant form of the protein on cultured cancer cells and on cancerous tissues. Further, we demonstrate that transfection of a minimal fragment of MUC1, MUC1*1110, containing a mere forty-five (45) amino acids of the extracellular domain, is sufficient to confer the oncogenic activities that were previously attributed to the full-length protein. By comparison of molecular weight and function, it appears that MUC1* and MUC1*1110 are approximately equivalent. Evidence is presented that strongly supports a mechanism whereby dimerization of the extracellular domain of MUC1* activates the MAP kinase signaling cascade and stimulates cell growth. These findings suggest methods to manipulate this growth mechanism for therapeutic interventions in cancer treatments

Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist’s initiative

According to the Dutch Guideline on Hereditary Colorectal Cancer published in 2008, patients with recently diagnosed colorectal cancer (CRC) should undergo microsatellite instability (MSI) testing by a pathologist immediately after tumour resection if they are younger than 50 years, or if a second CRC has been diagnosed before the age of 70 years, owing to the high risk of Lynch syndrome (MIPA). The aim of the present MIPAPS study was to investigate general distress and cancer-specific distress following MSI testing. From March 2007 to September 2009, 400 patients who had been tested for MSI after newly diagnosed CRC were recruited from 30 Dutch hospitals. Levels of general distress (SCL-90) and cancer-specific distress (IES) were assessed immediately after MSI result disclosure (T1) and 6 months later (T2). Response rates were 23/77 (30%) in the MSI-positive patients and 58/323 (18%) in the MSI-negative patients. Levels of general distress and cancer-specific distress were moderate. In the MSI-positive group, 27% of the patients had high general distress at T1 versus 18% at T2 (p = 0.5), whereas in the MSI-negative group, these percentage were 14 and 18% (p = 0.6), respectively. At T1 and T2, cancer-specific distress rates in the MSI-positive group and MSI-negative group were 39 versus 27% (p = 0.3) and 38 versus 36% (p = 1.0), respectively. High levels of general distress were correlated with female gender, low social support and high perceived cancer risk. Moderate levels of distress were observed after MSI testing, similar to those found in other patients diagnosed with CRC. Immediately after result disclosure, high cancer-specific distress was observed in 40% of the MSI-positive patients

Формування та розвиток загальної теорії стійкості (середина XVIII ст. — 30-і рр. ХХ ст.)

У статті розглянуто історію вивчення стійкості (середина XVIII — початок XX ст., світовий контекст). Досліджено внесок А. Пуанкаре та О.М. Ляпунова в розвиток загальної теорії стійкості. Показано розвиток їх ідей у працях російських та українських учених.В статье рассмотрена история изучения устойчивости (середина XVIII — начало XX в., мировой контекст). Исследован вклад французского ученого А. Пуанкаре и русского ученого А.М. Ляпунова в развитие общей теории устойчивости. Показано дальнейшее развитие их идей в трудах русских и украинских ученых.The history of basic research in stability is given. Contributions from H.Poincaré, a French mathematician, mechanic and physicist, and O. Lapunov, a soviet mathematician and mechanic (working in the Kharkiv university) to development of the general theory of stability are shown. In 1892—1902, O. Lyapunov constructed an original robust mathematical apparatus to study stability of motion. Development of ideas and methods of H.Poincar of H.Poincar³e and O. Lapunov in works of later Ukrainian and Russian scientists is shown

Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer

Cellular mechanisms in basic and clinical gastroenterology and hepatolog