Determinants of Early Recurrence of Cerebral Infarction: The Stroke Data Bank

We Studied 1,273 Patients with Ischemic Cerebral Infarction Who Were Entered into the Stroke Data Bank, a Prospective, Observational Study Involving Four University Hospitals and the Biometry and Field Studies Branch of the National Institute of Neurological Disorders and Stroke. Forty Patients Had Non-Iatrogenic Recurrent Stroke within 30 Days after the Index Cerebral Infarction. using Life Tables, the 30-Day Cumulative± SE Risk of Early Recurrence for All Infarctions Was 3.3±0.4%. the Risk of Early Recurrence Was Greatest for Atherothrombotic Infarction (7.9±2.2%, Eight of 113 Patients) and Least for Lacunar Infarction (2.2±1.2%, Eight of 337 Patients). Both Cardioembolic Infarction (4.3±0.9%, 10 of 246 Patients) and Infarction of Undetermined Cause (3.0±0.5%, 14 of 508 Patients) Had Intermediate Risks. History of Hypertension and Diabetes Mellitus, as Well as Diastolic Hypertension and Elevated Blood Sugar Concentration at Admission, Were Associated with Early Recurrence. Logistic Regression Analysis Estimated the Risk of Early Recurrence to Be 8.56% in Those with Coexisting Hypertension and a Glucose Concentration of 300 Mg/dl Versus 0.77% in the Absence of These Two Abnormalities. Early Recurrence Was Associated with Longer Median Duration of Initial Hospital Stay (27 vs.. 14 Days) and a Higher 30-Day Case—fatality Rate (20% vs.. 7.4%). Increased Weakness Scores Were Associated with Early Recurrent Stroke. Identification of the Determinants of Early Recurrent Stroke May Lead to Better Secondary Prevention and May Help Select High-Risk Patients for Further Study. © 1989 American Heart Association, Inc

Stroke Recurrence within 2 Years after Ischemic Infarction

We Prospectively Studied Stroke Recurrence in 1,273 Patients with Ischemic Stroke Who Were Entered into the Stroke Data Bank. Median Follow-Up Was 13 Months. the 2-Year Cumulative Recurrence Rate among These Patients Was 14.1%. Age, Sex, Race, History of Hypertension, Atrial Fibrillation, or Transient Ischemic Attacks, and Stroke Location Were Not Associated with a Higher Risk of Stroke Recurrence. Patients with an Elevated Blood Pressure, an Abnormal Initial Computed Tomogram, or a History of Diabetes Mellitus Were at a Higher Risk of Stroke Recurrence. in Contrast, Patients with an Infarct of Unknown Cause Were at a Lower Risk of Stroke Recurrence Than Patients with a Denned Stroke Mechanism, Such as Lacune, Embolism, or Atherosclerosis. Amultivaria Te Model Suggests that Patients at the Lowest Risk for Stroke Recurrence Have a Low Diastolic Blood Pressure, No History of Stroke, No History of Diabetes Mellitus, and an Infarct of Unknown Cause. © 1991 American Heart Association, Inc

Early Clinical Differentiation of Cerebral Infarction from Severe Atherosclerotic Stenosis and Cardioembolism

Background and Purpose: Hyperacute Cerebral Infarction Trials Require Early Differentiation of Infarction Subtype. Our Aim Was to Determine Clinical Factors Predictive of Infarction Subtype from Data Collected in the Early Hours of Admission. Methods: using the 1,273 Patients Enrolled in the Stroke Data Bank, Stroke Risk Factors and Demographic, Clinical, and Radiological Features Were Compared between the 246 Cardioembolic and 113 Large-Vessel Atherosclerotic Cerebral Infarcts. Results: Stroke Data Bank Definitions Ensured More Transient Ischemic Attacks in Atherosclerotic Infarcts and More Cardiac Disease in Cardioembolic Infarcts, But the Diagnosis Was Distinguished Further using a Logistic Regression Model. Fractional Arm Weakness (Shoulder Different from Hand) (Odds Ratio 3.1, 95% Confidence Interval [CI] 1.6-5.8), Hypertension (Odds Ratio 2.8, CI 1.4-5.3), Diabetes (Odds Ratio 2.5, CI 1.2-5.1) and Male Gender (Odds Ratio=2.2, CI 1.2-4.1) Occurred More Frequently in Patients with Atherosclerotic Than Cardioembolic Infarcts. Reduced Consciousness (Odds Ratio=3.2, CI 1.4-7.3) Was More Frequent in Cardio embolism. for a Male Patient with Hypertension, Diabetes, and Fractional Arm Weakness, the Estimated Odds of an Atherosclerotic Infarction Were 47-Fold that of a Cardioembolic Infarction. Patients with Atherosclerotic Infarcts Were More Likely to Have a Fractional Arm Weakness Regardless of Infarct Size, Whereas, for Those with Cardioembolic Infarctions, Fractional Weakness Was More Frequent in Infarcts Less Than 20 Cc in Volume. Conclusions: Clinical Features that Are Observed at Stroke Onset Can Help Distinguish Cerebral Infarction Subtypes and May Allow for Early Stratification in Therapeutic Trials. © 1992 American Heart Association, Inc

Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging.

Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density imaging (NODDI) is a multi-shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD-related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

SMARCB1 loss induces druggable cyclin D1 deficiency via upregulation of MIR17HG in atypical teratoid rhabdoid tumors

Atypical teratoid rhabdoid tumor (ATRT) is a fatal pediatric malignancy of the central neural system lacking effective treatment options. It belongs to the rhabdoid tumor family and is usually caused by biallelic inactivation of SMARCB1, encoding a key subunit of SWI/SNF chromatin remodeling complexes. Previous studies proposed that SMARCB1 loss drives rhabdoid tumor by promoting cell cycle through activating transcription of cyclin D1 while suppressing p16. However, low cyclin D1 protein expression is observed in most ATRT patient tumors. The underlying mechanism and therapeutic implication of this molecular trait remain unknown. Here, we show that SMARCB1 loss in ATRT leads to the reduction of cyclin D1 expression by upregulating MIR17HG, a microRNA (miRNA) cluster known to generate multiple miRNAs targeting CCND1. Furthermore, we find that this cyclin D1 deficiency in ATRT results in marked in vitro and in vivo sensitivity to the CDK4/6 inhibitor palbociclib as a single agent. Our study identifies a novel genetic interaction between SMARCB1 and MIR17HG in regulating cyclin D1 in ATRT and suggests a rationale to treat ATRT patients with FDA- approved CDK4/6 inhibitors. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156416/2/path5493.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156416/1/path5493_am.pd

Multi-epoch Spectroscopy of IY UMa: Quiescence, Rise, Normal Outburst & Superoutburst

We exploit rare observations covering the time before and during a normal outburst in the deeply-eclipsing SU UMa system IY UMa to study the dramatic changes in the accretion flow and emission at the onset of outburst. Through Doppler tomography we study the emission distribution, revealing classic accretion flow behaviour in quiescence, with the stream-disc impact ionizing the nearby accretion disc. We observe a delay of hours to a couple of days between the rise in continuum and the rise in the emission lines at the onset of the outburst. From line profiles and Doppler maps during normal and superoutburst we conclude that reprocessing of boundary layer radiation is the dominant emission line mechanism in outburst, and that the normal outburst began in the outer disc. The stream-disc impact feature (the `orbital hump') in the H alpha line flux light curve disappears before the onset of the normal outburst, and may be an observable signal heralding an impending outburst.Comment: 14 pages, 12 figures. Accepted for publication in Monthly Notices of the Royal Astronomical Societ

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa.

Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. In 15 patient plasma samples collected at the time of diagnosis as part of the Ghana Breast Health Study and unselected for tumor grade and subtype, ctDNA was detected in a majority of patients based on whole- genome sequencing at high (30×) and low (0.1×) depths. Breast cancer driver copy number alterations were observed in the majority of patients