Feature Re-calibration based Multiple Instance Learning for Whole Slide Image Classification

Whole slide image (WSI) classification is a fundamental task for the diagnosis and treatment of diseases; but, curation of accurate labels is time-consuming and limits the application of fully-supervised methods. To address this, multiple instance learning (MIL) is a popular method that poses classification as a weakly supervised learning task with slide-level labels only. While current MIL methods apply variants of the attention mechanism to re-weight instance features with stronger models, scant attention is paid to the properties of the data distribution. In this work, we propose to re-calibrate the distribution of a WSI bag (instances) by using the statistics of the max-instance (critical) feature. We assume that in binary MIL, positive bags have larger feature magnitudes than negatives, thus we can enforce the model to maximize the discrepancy between bags with a metric feature loss that models positive bags as out-of-distribution. To achieve this, unlike existing MIL methods that use single-batch training modes, we propose balanced-batch sampling to effectively use the feature loss i.e., (+/-) bags simultaneously. Further, we employ a position encoding module (PEM) to model spatial/morphological information, and perform pooling by multi-head self-attention (PSMA) with a Transformer encoder. Experimental results on existing benchmark datasets show our approach is effective and improves over state-of-the-art MIL methods.Comment: MICCAI 202

看護系大学生における外国人保健医療サービス提供に関する認識: 日本と韓国の大学における調査から

Aim: This study was performed to examine associations between nursing students’ knowledge and interest regarding foreign nationals’ medical health challenges and international exchange experience among Korean and Japanese undergraduate nursing students. Methods: An anonymous self-administered structured questionnaire survey was conducted among 200 Korean nursing students in April 2016, and 78 Japanese nursing students in August 2015; both groups were in their 4th year of study at a university. The questionnaire elicited responses related to knowledge and interest regarding foreign nationals’ medical health challenges in Korea or Japan, likelihood of caring for foreign nationals as nurses, and experience related to international exchange. Results: A total of 183（ 91.5%） Korean students and 68（ 91.9%） Japanese students participated in this study. Among Korean students, 120（ 65.6%） reported being aware of foreign nationals’ medical health challenges, while only 23 （33.8%） Japanese participants gave this response. There were significant differences in knowledge and interest scores regarding foreign nationals’ medical health challengesaccording to experience of international exchange in both Korean and Japanese study participants （Mann?Whitney U test, P = 0.001, P = 0.003, respectively）. Korean study participants demonstrated recognition of medical health care provision for foreign nationals as nurses regardless of international exchange experience leve（l Mann?Whitney U test, P = 0.841）, although international exchange experience level was significantly related to recognition of medical health care provision for foreign nationals as nurses among Japanese nursing students（ Mann?Whitney U test, P = 0.030）. Conclusions: Korea and Japan have similar characteristics, such as homogenous and monoculture countries until recently. However, this study demonstrated differences in sensitivity and recognition regarding medical healthcare provision for foreign nationals among Korean and Japanese nursing students. It is necessary to assess the factors responsible for this difference, to prepare nursing students for medical healthcare provision in the global society.目的?本研究は，韓国と日本の看護系大学生における外国人保健医療の知識・関心と国際交流経験の関連を検討することを目的としている．方法?韓国から2016年4月に200人，日本から2015年8月に78人の日本人看護系大学生，いずれも4年生を対象に無記名自記式質問紙による調査が実施された．質問紙内容は，外国人保健医療の知識・関心，将来的な看護職としての外国人保健医療提供可能性の自覚，国際交流経験について構成された．結果?韓国人学生183人（91.5％），日本人学生68人（91.9％）から有効回答を得た．韓国人学生中120人（65.6％）が外国人保健医療ニーズについて認識していたが，日本人学生では23人（33.8％）のみであった．両国の看護学生において，外国人保健医療の知識・関心は，国際交流経験の豊富さと関連していた（マンホイットニーU test， P＝0.001，P＝0.003）．韓国人学生は，国際交流経験の豊富さに関係なく，将来的な看護職としての外国人保健医療提供可能性の自覚をもっていたが（Mann－Whitney U test， P＝0.841），日本人学生では，国際交流経験の豊富さが将来的な看護職としての外国人保健医療提供可能性の自覚に統計的有意に関連していた（Mann－Whitney U test， P＝0.030）．結論?韓国も日本も最近まで単一民族・文化の国であったという類似の特徴を持つが，本調査では両国の看護学生において，外国人保健医療への感度や将来的な看護職としての外国人保健医療提供可能性の自覚に違いが認められた．今後，グローバル社会における外国人保健医療に対応していくために，両国のこういった違いに影響する関連要因について詳細に検証する必要がある

Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy

The dorsal root ganglion (DRG) is a highly vulnerable site in diabetic neuropathy. Under diabetic conditions, the DRG is subjected to tissue ischemia or lower ambient oxygen tension that leads to aberrant metabolic functions. Metabolic dysfunctions have been documented to play a crucial role in the pathogenesis of diverse pain hypersensitivities. However, the contribution of diabetes-induced metabolic dysfunctions in the DRG to the pathogenesis of painful diabetic neuropathy remains ill-explored. In this study, we report that pyruvate dehydrogenase kinases (PDK2 and PDK4), key regulatory enzymes in glucose metabolism, mediate glycolytic metabolic shift in the DRG leading to painful diabetic neuropathy. Streptozotocin-induced diabetes substantially enhanced the expression and activity of the PDKs in the DRG, and the genetic ablation of Pdk2 and Pdk4 attenuated the hyperglycemia-induced pain hypersensitivity. Mechanistically, Pdk2/4 deficiency inhibited the diabetes-induced lactate surge, expression of pain-related ion channels, activation of satellite glial cells, and infiltration of macrophages in the DRG, in addition to reducing central sensitization and neuroinflammation hallmarks in the spinal cord, which probably accounts for the attenuated pain hypersensitivity. Pdk2/4-deficient mice were partly resistant to the diabetes-induced loss of peripheral nerve structure and function. Furthermore, in the experiments using DRG neuron cultures, lactic acid treatment enhanced the expression of the ion channels and compromised cell viability. Finally, the pharmacological inhibition of DRG PDKs or lactic acid production substantially attenuated diabetes-induced pain hypersensitivity. Taken together, PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic DRG, thereby contributing to the pathogenesis of painful diabetic neuropathy

Low-temperature formation of epitaxial graphene on 6H-SiC induced by continuous electron beam irradiation

It is observed that epitaxial graphene forms on the surface of a 6H-SiC substrate by irradiating electron beam directly on the sample surface in high vacuum at relatively low temperature (similar to 670 degrees C). The symmetric shape and full width at half maximum of 2D peak in the Raman spectra indicate that the formed epitaxial graphene is turbostratic. The gradual change of the Raman spectra with electron beam irradiation time increasing suggests that randomly distributed small grains of epitaxial graphene form first and grow laterally to cover the entire irradiated area. The sheet resistance of epitaxial graphene film is measured to be similar to 6.7 k Omega/sq.open4

Relation between Anemia and Vulnerable Coronary Plaque Components in Patients with Acute Coronary Syndrome: Virtual Histology-Intravascular Ultrasound Analysis

The aim of the present study was to evaluate the plaque components and the predictors of thin-cap fibroatheroma (TCFA) in anemic patients with acute coronary syndrome using virtual histology-intravascular ultrasound (VH-IVUS). Anemia was defined according to criteria of the World Health Organization, (i.e. , hemoglobin levels < 13 g/dL in men and < 12 g/dL in women) and we compared VH-IVUS findings between anemia group (171 patients, 260 lesions) and non-anemia group (569 patients, 881 lesions). Anemia group had greater % necrotic core (NC) volume (21% ± 9% vs 19% ± 9%, P = 0.001) compared with non-anemia group. Hemoglobin level correlated negatively with absolute NC volume (r = -0.235, P < 0.001) and %NC volume (r = -0.209, P < 0.001). Independent predictors of TCFA by multivariate analysis were diabetes mellitus (odds ratio [OR], 2.213; 95% confidence interval [CI], 1.403-3.612, P = 0.006), high-sensitivity C-reactive protein (OR, 1.143; 95% CI, 1.058-1.304, P = 0.012), microalbuminuria (albumin levels of 30 to 300 mg/g of creatinine) (OR, 2.124; 95% CI, 1.041-3.214, P = 0.018), and anemia (OR: 2.112; 95% CI 1.022-3.208, P = 0.028). VH-IVUS analysis demonstrates that anemia at the time of clinical presentation is associated with vulnerable plaque component in patients with acute coronary syndrome

IS6110-Restriction Fragment Length Polymorphism and Spoligotyping Analysis of Mycobacterium tuberculosis Clinical Isolates for Investigating Epidemiologic Distribution in Korea

The Beijing family of Mycobacterium tuberculosis has been emerging in the world. However, there are few nationwide data of genotypic distribution in Korea. This study aimed to identify the genotypic diversity of clinical isolates of M. tuberculosis and to demonstrate the population of Beijing family in Korea. We collected 96 clinical M. tuberculosis isolates from 11 university hospitals nationwide in Korea from 2008 to 2009. We observed 24 clusters in IS6110-RFLP analysis and 19 patterns in spoligotyping. Seventy-five isolates were confirmed to be Beijing family. Two isolates of the K strain and 12 isolates of the K family strain were also found. We found that drug resistance phenotypes were more strongly associated with Beijing family than non-Beijing family (P=0.003). This study gives an overview of the distribution of genotypes of M. tuberculosis in Korea. These findings indicate that we have to pay more attention to control of M. tuberculosis strains associated with the Beijing family

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.