McGill University

About: McGill University is a education organization based out in Montreal, Quebec, Canada. It is known for research contribution in the topics: Population & Poison control. The organization has 72688 authors who have published 162565 publications receiving 6966523 citations. The organization is also known as: Royal institution of advanced learning & University of McGill College.

Planck 2013 results. VII. HFI time response and beams

Abstract: This paper characterizes the effective beams, the effective beam window functions and the associated errors for the Planck High Frequency Instrument (HFI) detectors. The effective beam is the angular response including the effect of the optics, detectors, data processing and the scan strategy. The window function is the representation of this beam in the harmonic domain which is required to recover an unbiased measurement of the cosmic microwave background angular power spectrum. The HFI is a scanning instrument and its effective beams are the convolution of: a) the optical response of the telescope and feeds; b) the processing of the time-ordered data and deconvolution of the bolometric and electronic transfer function; and c) the merging of several surveys to produce maps. The time response transfer functions are measured using observations of Jupiter and Saturn and by minimizing survey difference residuals. The scanning beam is the post-deconvolution angular response of the instrument, and is characterized with observations of Mars. The main beam solid angles are determined to better than 0.5% at each HFI frequency band. Observations of Jupiter and Saturn limit near sidelobes (within 5 degrees) to about 0.1% of the total solid angle. Time response residuals remain as long tails in the scanning beams, but contribute less than 0.1% of the total solid angle. The bias and uncertainty in the beam products are estimated using ensembles of simulated planet observations that include the impact of instrumental noise and known systematic effects. The correlation structure of these ensembles is well-described by five errors eigenmodes that are sub-dominant to sample variance and instrumental noise in the harmonic domain. A suite of consistency tests provide confidence that the error model represents a sufficient description of the data. The total error in the effective beam window functions is below 1% at 100 GHz up to multiple l similar to 1500, below 0.5% at 143 and 217 GHz up to l similar to 2000.

Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study.

Abstract: Summary Background Tumour mutational burden (TMB) has been retrospectively correlated with response to immune checkpoint blockade. We prospectively explored the association of high tissue TMB (tTMB-high) with outcomes in ten tumour-type-specific cohorts from the phase 2 KEYNOTE-158 study, which assessed the anti-PD-1 monoclonal antibody pembrolizumab in patients with selected, previously treated, advanced solid tumours. Methods In the multi-cohort, open-label, non-randomised, phase 2 KEYNOTE-158 study, patients were enrolled from 81 academic facilities and community-based institutions across 21 countries in Africa, the Americas, Asia, and Europe. Eligible patients were aged 18 years or older, had a histologically or cytologically confirmed advanced (ie, unresectable or metastatic, or both) incurable solid tumour (eligible tumour types were anal, biliary, cervical, endometrial, mesothelioma, neuroendocrine, salivary, small-cell lung, thyroid, and vulvar), progression on or intolerance to one or more lines of standard therapy, had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) assessed by independent central radiological review, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, adequate organ function, and a tumour sample for biomarker analysis. Participants were given pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles. Tissue TMB (tTMB) was assessed in formalin-fixed paraffin-embedded tumour samples using the FoundationOne CDx assay (Foundation Medicine, Cambridge, MA, USA). The prespecified definition of tTMB-high status was at least 10 mutations per megabase. The primary endpoint was the proportion of patients with an objective response (complete or partial response) as per Response Evaluation Criteria in Solid Tumours (version 1.1) by independent central review. This prespecified analysis assessed the association between antitumour activity and tTMB in treated patients with evaluable tTMB data. Efficacy was assessed in all participants who received at least one dose of pembrolizumab, had evaluable tTMB data, and were enrolled at least 26 weeks before data cutoff (June 27, 2019), and safety was assessed in all participants who received at least one dose of pembrolizumab and had tTMB-high status. KEYNOTE-158 is registered at ClinicalTrials.gov, NCT02628067, and is ongoing. Findings Between Jan 15, 2016, and June 25, 2019, 1073 patients were enrolled. 1066 participants were treated as of data cutoff (June 27, 2019), of whom 805 (76%) were evaluable for TMB, and 105 (13%) of 805 had tTMB-high status and were assessed for safety. 1050 (98%) of 1066 patients enrolled by at least 26 weeks before data cutoff, of whom 790 (75%) were evaluable for TMB and included in efficacy analyses. 102 (13%) of these 790 patients had tTMB-high status (≥10 mutations per megabase), and 688 (87%) patients had non-tTMB-high status ( Interpretation tTMB-high status identifies a subgroup of patients who could have a robust tumour response to pembrolizumab monotherapy. tTMB could be a novel and useful predictive biomarker for response to pembrolizumab monotherapy in patients with previously treated recurrent or metastatic advanced solid tumours. Funding Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.

Intensive Care Delirium Screening Checklist: evaluation of a new screening tool

Abstract: Objective: Delirium in the intensive care unit is poorly defined. Clinical evaluation is difficult in the setting of unstable, often intubated patients. A screening tool may improve the detection of delirium. Method: We created a screening checklist of eight items based on DSM criteria and features of delirium: altered level of consciousness, inattention, disorientation, hallucination or delusion, psychomotor agitation or retardation, inappropriate mood or speech, sleep/wake cycle disturbance, and symptom fluctuation. During 3 months, all patients admitted to a busy medical/surgical intensive care unit were evaluated, and the scale score was compared to a psychiatric evaluation. Results: In 93 patients studied, 15 developed delirium. Fourteen (93%) of them had a score of 4 points or more. This score was also present in 15 (19%) of patients without delirium, 14 of whom had a known psychiatric illness, dementia, a structural neurological abnormality or encephalopathy. A ROC analysis was used to determine the sensitivity and specificity of the screening tool. The area under the ROC curve is 0.9017. Predicted sensitivity is 99% and specificity is 64%. Conclusion: This study suggests that the Intensive Care Delirium Screening Checklist can easily be applied by a clinician or a nurse in a busy critical care setting to screen all patients even when communication is compromised. The tool can be utilized quickly and helps to identify delirious patients. Earlier diagnosis may lead to earlier intervention and better patient care.

Role of the histone deacetylase complex in acute promyelocytic leukaemia

Abstract: Non-liganded retinoic acid receptors (RARs) repress transcription of target genes by recruiting the histone deacetylase complex1,2,3 through a class of silencing mediators termed SMRT or N-CoR4,5. Mutant forms of RARα, created by chromosomal translocations with either the PML (for promyelocytic leukaemia)6,7,8 or the PLZF (for promyelocytic leukaemia zinc finger)9,10 locus, are oncogenic and result in human acute promyelocytic leukaemia (APL). PML–RARα APL patients achieve complete remission following treatments with pharmacological doses of retinoic acids (RA); in contrast, PLZF–RARα patients respond very poorly, if at all11. Here we report that the association of these two chimaeric receptors with the histone deacetylase (HDAC) complex helps to determine both the development of APL and the ability of patients to respond to retinoids. Consistent with these observations, inhibitors of histone deacetylase dramatically potentiate retinoid-induced differentiation of RA-sensitive, and restore retinoid responses of RA-resistant, APL cell lines. Our findings suggest that oncogenic RARs mediate leukaemogenesis through aberrant chromatin acetylation, and that pharmacological manipulation of nuclear receptor co-factors may be a useful approach in the treatment of human disease.

Applied Functional Data Analysis: Methods and Case Studies

Abstract: Introduction- Life Course Data in Criminology- The Nondurable Goods Index- Bone Shapes from a Paleopathology Study- Modeling Reaction Time Distributions- Zooming in on Human Growth- Time Warping Handwriting and Weather Records- How do Bone Shapes Indicate Arthritis?- Functional Models for Test Items- Predicting Lip Acceleration from Electromyography- Variable Seasonal Trend in the Goods Index- The Dynamics of Handwriting Printed Characters- A Differential Equation for Juggling