MACHINE LEARNING FOR THING DETECTION, BEHAVIOR ANALYTICS, AND THREAT DETECTION: AN EFFICIENT ELIMINATION METHOD OF REDUNDANT FEATURE-SUBSETS

Techniques are described herein to efficiently detect redundant features in a machine learning process. The techniques are able to compute feature redundancy not only for a single feature at a time, but for any subset of features without the need to naively train and evaluate a classifier for each combination of features

Toll-like receptor signaling in thymic epithelium controls monocyte-derived dendritic cell recruitment and Treg generation

The development of thymic regulatory T cells (Treg) is mediated by Aire-regulated self-antigen presentation on medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), but the cooperation between these cells is still poorly understood. Here we show that signaling through Toll-like receptors (TLR) expressed on mTECs regulates the production of specific chemokines and other genes associated with post-Aire mTEC development. Using single-cell RNA-sequencing, we identify a new thymic CD14(+)Sirp alpha (+) population of monocyte-derived dendritic cells (CD14(+)moDC) that are enriched in the thymic medulla and effectively acquire mTEC-derived antigens in response to the above chemokines. Consistently, the cellularity of CD14(+)moDC is diminished in mice with MyD88-deficient TECs, in which the frequency and functionality of thymic CD25(+)Foxp3(+) Tregs are decreased, leading to aggravated mouse experimental colitis. Thus, our findings describe a TLR-dependent function of mTECs for the recruitment of CD14(+)moDC, the generation of Tregs, and thereby the establishment of central tolerance. Immune tolerance is mediated by the deletion of autoreactive T cells via medullary thymic epithelial cells (mTEC) and dendritic cells (DC), and by the induction of regulatory T cells (Treg). Here the authors show that mTEC receiving toll-like receptor signaling control the recruitment of CD14(+)Sirp alpha (+) DC population that is capable of inducing Treg for establishing tolerance

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Spontaneous spinal epidural haematoma: management and main risk factors in era of anticoagulant / antiplatelet treatment

Aim of the study. Spontaneous spinal epidural haematomas (SSEH) are rare nosological units wherein acute collections of blood develop in the spinal canal. SSEH are usually manifested by sudden severe back pain accompanied by the development of neurological symptoms. In this study, we retrospectively describe management and the main risk factors of SSEH in a series of 14 cases.Material and methods. Between 2010 and 2019, we examined 14 patients (age range 17–89 years, 10 women) diagnosed with SSEH. Eight cases were patients using anticoagulant therapies (six warfarin, one dabigatran, one apixaban) and two others were using ASA of 100 mg/day. The exact localisation and extent of changes was determined from acute magnetic resonance imaging. Three people using warfarin had INR values higher than 3.0 at the time of their diagnosis.Results. Ten patients (71%) were taking oral anticoagulants or antiplatelet agents. In seven patients, SSEH were localised in the lower cervical/thoracic spine. Ten patients (71%) had arterial hypertension. Six patients underwent acute surgery due to rapidly developing spinal cord compression. Eight patients (57%) with slight or mild neurological symptoms were successfully managed without surgery.Conclusions. SSEH should be suspected in any patient receiving anticoagulant/antiplatelet agents who complains of sudden, severe back pain accompanied by neurological symptoms. SSEH is mostly localised in the lower cervical/thoracic spine. Arterial hypertension appears to be a risk factor of SSEH. Early decompression is an important therapeutic approach; in cases with minor neurological deficits, conservative treatment may be chosen

Spontální epidurální krvácení : menagement a hlavní rizikové faktory v době antikoagulační a antiagregační léčby.

Aim of the study. Spontaneous spinal epidural haematomas (SSEH) are rare nosological units wherein acute collections of blood develop in the spinal canal. SSEH are usually manifested by sudden severe back pain accompanied by the development of neurological symptoms. In this study, we retrospectively describe management and the main risk factors of SSEH in a series of 14 cases. Material and methods. Between 2010 and 2019, we examined 14 patients (age range 17-89 years, 10 women) diagnosed with SSEH. Eight cases were patients using anticoagulant therapies (six warfarin, one dabigatran, one apixaban) and two others were using ASA of 100 mg/day. The exact localisation and extent of changes was determined from acute magnetic resonance imaging. Three people using warfarin had INR values higher than 3.0 at the time of their diagnosis. Results. Ten patients (71%) were taking oral anticoagulants or a ntiplatelet agents. In seven patients, SSEH were localised in the lower cervical/thoracic spine. Ten patients (71%) had arterial hypertension. Six patients underwent acute surgery due to rapidly developing spinal cord compression. Eight patients (57%) with slight or mild neurological symptoms were successfully managed without surgery. Conclusions. SSEH should be suspected in any patient receiving anticoagulant/anti platelet agents who complains of sudden, severe back pain accompanied by neurological symptoms. SSEH is mostly localised in the lower cervical/thoracic spine. Arterial hypertension appears to be a risk factor of SSEH. Early decompression is an important therapeutic approach; in cases with minor neurological deficits, conservative treatment may be chosen.Cíl studie. Spontánní spinální epidurální hematomy (SSEH) jsou vzácné nozologické jednotky, u kterých dochází k akutnímu hromadění krve v míšním kanálu. SSEH se obvykle projevují náhlou silnou bolestí zad doprovázenou rozvojem neurologických příznaků. V této studii retrospektivně popisujeme léčbu a hlavní rizikové faktory SSEH na sérii 14 případů. Materiály a metody. V letech 2010–2019 jsme vyšetřili 14 pacientů (věkové rozmezí 17–89 let, 10 žen) s diagnózou SSEH. Osm případů byli pacienti užívající antikoagulační léčbu (šest warfarin, jeden dabigatran, jeden apixaban) a dva další užívali ASA v dávce 100 mg/den. Přesná lokalizace a rozsah změn byl stanoven z akutní magnetické rezonance. Tři lidé užívající warfarin měli v době diagnózy hodnoty INR vyšší než 3,0. Výsledek. Deset pacientů (71 %) užívalo perorální antikoagulancia nebo antiagregancia. U sedmi pacientů byly SSEH lokalizovány v dolní krční/hrudní páteři. Deset pacientů (71 %) mělo arteriální hypertenzi. Šest pacientů podstoupilo akutní operaci kvůli rychle se rozvíjející kompresi míchy. Osm pacientů (57 %) s mírnými nebo mírnými neurologickými příznaky bylo úspěšně zvládnuto bez operace. Závěry. SSEH by měl být podezřelý u každého pacienta užívajícího antikoagulancia/antiagregancia, který si stěžuje na náhlou silnou bolest zad doprovázenou neurologickými příznaky. SSEH je většinou lokalizován v dolní části krční/hrudní páteře. Arteriální hypertenze se zdá být rizikovým faktorem SSEH. Časná dekomprese je důležitým terapeutickým přístupem; v případech s menším neurologickým deficitem lze zvolit konzervativní léčbu

Impact of Delaying the Addition of Anti-EGFR in First Line of RAS Wild-Type Metastatic Colorectal Cancer: A Propensity-Weighted Pooled Data Analysis

The first-line therapy of patients with RAS wild-type (WT) non-resectable metastatic colorectal cancer (mCRC) is usually 5-fluorouracil-based chemotherapy with either bevacizumab or an anti-epidermal growth factor receptor (EGFR). The addition of anti-EGFR antibodies is commonly delayed in clinical practice because of late RAS testing results. Our objective was to evaluate the impact on overall survival (OS) of a delayed anti-EGFR introduction strategy. This study pooled the data of two large retrospective studies. Patients with RAS WT non-resectable mCRC, treated in first line by a doublet chemotherapy with an anti-EGFR introduced with a delay of 2 to 4 cycles, were compared to an anti-EGFR and to an anti-VEGF that was introduced immediately. Patients numbering 305 in the delayed anti-EGFR group, 401 in the immediate anti-EGFR group, and 129 in the immediate anti-VEGF group were analyzed. After propensity scoring, there was no difference between the characteristics of the three groups. Median OS was 28.6 months (95% CI: 23.5–34.1) in the immediate anti-EGFR group, 35.1 (95% CI: 29.9–43.5) in the delayed anti-EGFR group, and 32.4 (95% CI: 25.4–44.8) in the immediate anti-VEGF group. There was no significant difference concerning median OS (p = 0.24) or progression-free survival (p = 0.56). This study suggests that delaying the introduction of an anti-EGFR has no deleterious impact on survival compared to the immediate introduction of an anti-VEGF or of an anti-EGFR

Diverse environmental cues drive the size of reproductive aggregation in a rheophilic fish

BackgroundAnimal migrations are periodic and relatively predictable events, and their precise timing is essential to the reproductive success. Despite large scientific effort in monitoring animal reproductive phenology, identification of complex environmental cues that determine the timing of reproductive migrations and temporal changes in the size of reproductive aggregations in relation to environmental variables is relatively rare in the current scientific literature.MethodsWe tagged and tracked 1702 individuals of asp (Leuciscus aspius), a large minnow species, and monitored with a resolution of one hour the size of their reproductive aggregations (counts of sexes present at the breeding grounds standardized by the sum of individuals in the season) over seven breeding seasons using passive integrated transponder tag systems. We examined the size of reproductive aggregations in relation to environmental cues of day number within a reproductive season (intra-year seasonality), water temperature, discharge, hour in a day (intra-day pattern), temperature difference between water and air, precipitation, atmospheric pressure, wind speed and lunar phase. A generalized additive model integrating evidence from seven breeding seasons and providing typical dynamics of reproductive aggregations was constructed.Results We demonstrated that all environmental cues considered contributed to the changes in the size of reproductive aggregations during breeding season, and that some effects varied during breeding season. Our model explained approximately 50% of the variability in the data and the effects were sex-dependent (models of the same structure were fitted to each sex separately, so that we effectively stratified on sex). The size of reproductive aggregations increased unimodally in response to day in season, correlated positively with water temperature and wind speed, was highest before and after the full moon, and highest at night (interacting with day in a season). Males responded negatively and females positively to increase in atmospheric pressure.Conclusion The data demonstrate complex utilization of available environmental cues to time reproductive aggregations in freshwater fish and their interactions during the reproductive season. The study highlights the need to acquire diverse data sets consisting of many environmental cues to achieve high accuracy of interpretation of reproductive timing.Peer reviewe

A novel conditional Aire allele enables cell-specific ablation of the immune tolerance regulator Aire

Medullary thymic epithelial cell (mTEC)-restricted expression of autoimmune regulator (Aire) is essential for establishment of immune tolerance. Recently, Aire was also shown to be expressed in cells of hematopietic and reproductive lineages. Thus, the generation of Aire(fl/fl) mouse strain enables the investigation of the cell-specific function of Aire

Fibroblast Activation Protein Expressing Mesenchymal Cells Promote Glioblastoma Angiogenesis

Fibroblast activation protein (FAP) is a membrane-bound protease that is upregulated in a wide range of tumours and viewed as a marker of tumour-promoting stroma. Previously, we demonstrated increased FAP expression in glioblastomas and described its localisation in cancer and stromal cells. In this study, we show that FAP+ stromal cells are mostly localised in the vicinity of activated CD105+ endothelial cells and their quantity positively correlates with glioblastoma vascularisation. FAP+ mesenchymal cells derived from human glioblastomas are non-tumorigenic and mostly lack the cytogenetic aberrations characteristic of glioblastomas. Conditioned media from these cells induce angiogenic sprouting and chemotaxis of endothelial cells and promote migration and growth of glioma cells. In a chorioallantoic membrane assay, co-application of FAP+ mesenchymal cells with glioma cells was associated with enhanced abnormal angiogenesis, as evidenced by an increased number of erythrocytes in vessel-like structures and higher occurrence of haemorrhages. FAP+ mesenchymal cells express proangiogenic factors, but in comparison to normal pericytes exhibit decreased levels of antiangiogenic molecules and an increased Angiopoietin 2/1 ratio. Our results show that FAP+ mesenchymal cells promote angiogenesis and glioma cell migration and growth by paracrine communication and in this manner, they may thus contribute to glioblastoma progression