Transformer-Based Spatio-Temporal Analysis for Classification of Aortic Stenosis Severity From Echocardiography Cine Series.

Aortic stenosis (AS) is characterized by restricted motion and calcification of the aortic valve and is the deadliest valvular cardiac disease. Assessment of AS severity is typically done by expert cardiologists using Doppler measurements of valvular flow from echocardiography. However, this limits the assessment of AS to hospitals staffed with experts to provide comprehensive echocardiography service. As accurate Doppler acquisition requires significant clinical training, in this paper, we present a deep learning framework to determine the feasibility of AS detection and severity classification based only on two-dimensional echocardiographic data. We demonstrate that our proposed spatio-temporal architecture effectively and efficiently combines both anatomical features and motion of the aortic valve for AS severity classification. Our model can process cardiac echo cine series of varying length and can identify, without explicit supervision, the frames that are most informative towards the AS diagnosis. We present an empirical study on how the model learns phases of the heart cycle without any supervision and frame-level annotations. Our architecture outperforms state-of-the-art results on a private and a public dataset, achieving 95.2% and 91.5% in AS detection, and 78.1% and 83.8% in AS severity classification on the private and public datasets, respectively. Notably, due to the lack of a large public video dataset for AS, we made slight adjustments to our architecture for the public dataset. Furthermore, our method addresses common problems in training deep networks with clinical ultrasound data, such as a low signal-to-noise ratio and frequently uninformative frames. Our source code is available at: https://github.com/neda77aa/FTC.git.

Strong Evidence for

The boundaries of the chart of nuclides contain exotic isotopes that possess extreme proton-to-neutron asymmetries. Here we report on strong evidence of ^{9}N, one of the most exotic proton-rich isotopes where more than one half of its constitute nucleons are unbound. With seven protons and two neutrons, this extremely proton-rich system would represent the first-known example of a ground-state five-proton emitter. The invariant-mass spectrum of its decay products can be fit with two peaks whose energies are consistent with the theoretical predictions of an open-quantum-system approach; however, we cannot rule out the possibility that only a single resonancelike peak is present in the spectrum.

Beam particle identification and tagging of incompletely stripped heavy beams with HEIST.

A challenge preventing successful inverse kinematics measurements with heavy nuclei that are not fully stripped is identifying and tagging the beam particles. For this purpose, the HEavy ISotope Tagger (HEIST) has been developed. HEIST utilizes two micro-channel plate timing detectors to measure the time-of-flight, a multi-sampling ion chamber to measure energy loss, and a high-purity germanium detector to identify isomer decays and calibrate the isotope identification system. HEIST has successfully identified 198Pb and other nearby nuclei at energies of about 75 MeV/A. In the experiment discussed, a typical cut containing 89% of all 198Pb80+ in the beam had a purity of 86%. We examine the issues of charge state contamination. The observed charge state populations of these ions are presented and, using an adjusted beam energy, are well described by the charge state model GLOBAL.

The SπRIT time projection chamber.

The Superconducting Analyzer for MUlti-particles from RAdioIsotope (SAMURAI) Pion-Reconstruction and Ion-Tracker Time Projection Chamber (SπRIT TPC) was designed to enable measurements of heavy ion collisions with the SAMURAI spectrometer at the RIKEN radioactive isotope beam factory and provides constraints on the equation of state of neutron-rich nuclear matter. The SπRIT TPC has a 50.5 cm drift length and an 86.4 × 134.4 cm2 pad plane with 12 096 pads that are equipped with the generic electronics for TPCs. The SπRIT TPC allows for an excellent reconstruction of particles and provides isotopic resolution for pions and other light charged particles across a wide range of energy losses and momenta. The details of the SπRIT TPC are presented, along with discussion of the TPC performance based on cosmic rays and charged particles emitted in heavy ion collisions.

Probing the Symmetry Energy with the Spectral Pion Ratio.

Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42

Observation of the Exotic Isotope

A ^{13}F resonance was observed following a charge-exchange reaction between a fast ^{13}O beam and a ^{9}Be target. The resonance was found in the invariant-mass distribution of 3p+^{10}C events and probably corresponds to a 5/2^{+} excited state. The ground state was also expected to be populated, but was not resolved from the background. The observed level decays via initial proton emissions to both the ground and first 2^{+} state of ^{12}O, which subsequently undergo 2p decay. In addition, there may also be a significant proton decay branch to the second 2^{+} level in ^{12}O. The wave function associated with the observed level may be collectivized due to coupling to the continuum as is it located just above the threshold for proton decay to the 2_{2}^{+} state of ^{12}O.

First Observation of the Four-Proton Unbound Nucleus

^{18}Mg was observed, for the first time, by the invariant-mass reconstruction of ^{14}O+4p events. The ground-state decay energy and width are E_{T}=4.865(34) MeV and Γ=115(100) keV, respectively. The observed momentum correlations between the five particles are consistent with two sequential steps of prompt 2p decay passing through the ground state of ^{16}Ne. The invariant-mass spectrum also provides evidence for an excited state at an excitation energy of 1.84(14) MeV, which is likely the first excited 2^{+} state. As this energy exceeds that for the 2^{+} state in ^{20}Mg, this observation provides an argument for the demise of the N=8 shell closure in nuclei far from stability. However, in open systems this classical argument for shell strength is compromised by Thomas-Ehrman shifts.

Zebrafish heart regeneration: Factors that stimulate cardiomyocyte proliferation.

Myocardial infarctions (MI) remain a leading cause of global morbidity and mortality, and a reason for this is the inability of adult, mammalian cardiomyocytes to divide post-MI. Recent studies demonstrate a limited population of cardiomyocytes retain their proliferative capacity and understanding how endogenous cardiomyocytes can be stimulated to re-enter the cell cycle is a focus of current research. In this review we discuss the history of zebrafish cardiac regeneration and highlight how different models reveal the molecular pathways important in driving cardiomyocyte proliferation after injury. Understanding the molecules that regulate cell cycle re-entry can provide insights into promoting cardiac repair in humans.

First Observation of Unbound

The structure of the extremely proton-rich nucleus _{8}^{11}O_{3}, the mirror of the two-neutron halo nucleus _{3}^{11}Li_{8}, has been studied experimentally for the first time. Following two-neutron knockout reactions with a ^{13}O beam, the ^{11}O decay products were detected after two-proton emission and used to construct an invariant-mass spectrum. A broad peak of width ∼3.4 MeV was observed. Within the Gamow coupled-channel approach, it was concluded that this peak is a multiplet with contributions from the four lowest ^{11}O resonant states: J^{π}=3/2_{1}^{-}, 3/2_{2}^{-}, 5/2_{1}^{+}, and 5/2_{2}^{+}. The widths and configurations of these states show strong, nonmonotonic dependencies on the depth of the p-^{9}C potential. This unusual behavior is due to the presence of a broad threshold resonant state in ^{10}N, which is an analog of the virtual state in ^{10}Li in the presence of the Coulomb potential. After optimizing the model to the data, only a moderate isospin asymmetry between ground states of ^{11}O and ^{11}Li was found.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Spontaneous loss of B lineage transcription factors leads to pre-B leukemia in Ebf1+/-Bcl-xLTg mice.

Early B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification and commitment. Loss of this critical transcription factor is strongly associated with high-risk, relapsed and therapy-resistant B-cell-acute lymphoblastic leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a normal lifespan. To determine whether prolonged survival of B cells would enable tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1+/-Bcl-xLTg mice, which express the anti-apoptotic factor Bcl-xL in B cells. Approximately half of Ebf1+/-Bcl-xLTg mice develop aggressive oligoclonal leukemia as they age, which engrafts in congenic wild-type recipients without prior conditioning. The neoplastic cells display a pre-B phenotype and express early developmental- and natural killer cell/myeloid-markers inappropriately. In addition, we found tumor cell-specific loss of several transcription factors critical for maintaining differentiation: EBF1, TCF3 and RUNX1. However, in the majority of tumors, loss of Ebf1 expression was not due to loss of heterozygosity. This is the first spontaneous mouse model of pre-B leukemia to demonstrate inappropriate expression of non-B-cell-specific genes associated with loss of Ebf1, Tcf3 and Runx1 expression.

Regional lymph node involvement in patients undergoing liver resection for colorectal cancer metastases.

BACKGROUND: While the indications for surgery among patients with colorectal cancer liver metastases (CRCLM) are expanding, the role of surgery in patients with hepatic lymph node involvement remains controversial. We report management and outcomes in a population-based cohort of patients undergoing hepatectomy with concomitant hepatic lymphadenectomy for CRCLM. METHODS: All cases of hepatectomy for CRCLM in the Canadian Province of Ontario from 2002 to 2009 were identified using the population-based Ontario Cancer Registry and linked electronic records of treatment. Pathology reports were used to identify concomitant lymphadenectomy with liver resection as well as extent of disease and surgical procedure. RESULTS: Among 1310 patients who underwent resection for CRCLM, 103 (8%) underwent simultaneous regional lymphadenectomy. Seventy-one percent of cases with lymphadenectomy (70/103) had a major liver resection (≥3 segments). Of the 103 lymphadenectomy cases, 80 (78%) were hepatic pedicle, 16 (16%) were celiac and 7 (7%) were para-aortic. The mean number of nodes removed was 2.2 (range 1-15). Ninety-day mortality was 6%. Twenty-nine percent (30/103) of cases had positive nodes. Unadjusted overall survival at 5 years for positive vs negative nodes was 21% vs 42% (p = 0.003); cancer-specific survival was 10% vs 43% (p < 0.001). In adjusted analyses, hepatic node involvement was associated with inferior OS (HR 2.19, p = 0.010) and CSS (HR 3.07, p = 0.002). CONCLUSIONS: Patients with resected CRC liver metastases with regional lymph node involvement have inferior survival compared to patients with negative nodes. Despite this poor prognostic factor, a small proportion of cases with involved nodes will achieve long-term survival.

Clinical outcome of neoadjuvant chemoradiation in locally advanced rectal cancer at a tertiary hospital.

OBJECTIVES: To review the clinical outcome of locally advanced rectal cancer treated with neoadjuvant chemoradiation followed by definitive surgery with or without adjuvant chemotherapy and to elucidate the prognostic factors for treatment outcome. METHODS: This historical cohort study was conducted at a tertiary public hospital in Hong Kong. All patients who had undergone neoadjuvant chemoradiation for locally advanced rectal cancer in our department from November 2005 to October 2014 were recruited. Local recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival of patients were documented. RESULTS: A total of 135 patients who had received neoadjuvant chemoradiation during the study period were reviewed. There were 130 patients who had completed neoadjuvant chemoradiation and surgery. The median follow-up time was 35.1 months. The 3- and 5-year local recurrence-free survival, distant metastasis-free survival, disease-free survival, as well as overall survival rates were 91.8% and 86.7%, 73.9% and 72.1%, 70.1% and 64.6%, as well as 86.5% and 68.4%, respectively. The rate of pathological complete response was 13.8%. The T and N downstaging rate was 49.2% and 63.1%, respectively. The rate of conversion from threatened circumferential resection margin to clearance of margin was 90.6%. Of the 42 cases that were initially deemed to require abdominal perineal resection, 15 (35.7%) were converted to sphincter-sparing surgery. CONCLUSIONS: The treatment outcome of neoadjuvant chemoradiation for locally advanced rectal cancer was comparable with overseas data in terms of local control rate and overall survival. This strategy may increase the chance of achieving a clear surgical margin by downstaging the tumour, especially in patients who presented with threatened circumferential margin.

Pathway to mental health recovery: a qualitative and quantitative study on the needs of Chinese psychiatric inpatients.

BACKGROUND: Exploration of the information and participation needs of psychiatric inpatients is an important step for the implementation of recovery-oriented mental health service. The objective of this study was to explore the information and participation needs of Chinese psychiatric inpatients in the largest psychiatric hospital in Hong Kong. METHODS: The study was divided into two parts. In the first part, eight focus groups with patients, patients' relatives and healthcare professionals were held to identify 22 items of information needs and 16 items of participation needs of Chinese psychiatric inpatients. Basing on the items identified in the first part of the study, a questionnaire was developed to survey on the importance of the different information and participation needs in the second part of the study. Participants were asked to rate in rank order their perceived importance of the items in the questionnaire survey. RESULTS: A hundred and eighty three Chinese psychiatric inpatients completed the questionnaire and the majority of them suffered from schizophrenia (68.3 %). For information needs, the top three needs rated by patients as the most important in descending order were: "Information on the classifications of mental illnesses, signs and symptoms and factors contributing to relapse", "Information on the criteria and arrangements for discharge", and "Information on the importance of psychiatric drug taking and its side effects". For participation needs, the top three needs rated by patients as the most important in descending order were: "Enquiring about personal needs and arrangements", "Keeping in touch with the outside world", and "Learning and practising self-management". CONCLUSIONS: This study reveals that Chinese psychiatric inpatients are concerned about information on their mental illness and its treatments as well as the criteria for discharge. On the other hand, patients are concerned about their personal needs, their self-management, as well as their keeping in touch with the outside world during their hospitalisation. Moreover, patients with different socio-demographic and clinical characteristics have different information and participation needs. The results of the present study serve as a reference for designing guidelines, strategies, and programmes to meet the information needs and participation needs of psychiatric inpatients in Hong Kong.

Observation of long-range three-body coulomb effects in the decay of (16)Ne.

The interaction of an E/A=57.6-MeV ^{17}Ne beam with a Be target is used to populate levels in ^{16}Ne following neutron knockout reactions. The decay of ^{16}Ne states into the three-body ^{14}O+p+p continuum is observed in the High Resolution Array (HiRA). For the first time for a 2p emitter, correlations between the momenta of the three decay products are measured with sufficient resolution and statistics to allow for an unambiguous demonstration of their dependence on the long-range nature of the Coulomb interaction. Contrary to previous measurements, our measured limit Γ<80 keV for the intrinsic decay width of the ground state is not in contradiction to the small values (of the order of keV) predicted theoretically.

Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants.

BACKGROUND: In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. OBJECTIVE: The objective of this study is to compare BDNF concentrations of subjects with loss-of-function (LOF) and gain-of-function (GOF) MC4R variants with those of controls with common sequence MC4R. METHODS: Circulating BDNF was measured in two cohorts with known MC4R sequence: 148 subjects of Pima Indian heritage ((mean±s.d.): age, 15.7±6.5 years; body mass index z-scores (BMI-Z), 1.63±1.03) and 69 subjects of Hispanic heritage (10.8±3.6 years; BMI-Z, 1.57±1.07). MC4R variants were characterized in vitro by cell surface expression, receptor binding and cyclic AMP response after agonist administration. BDNF single-nucleotide polymorphisms (SNPs) rs12291186, rs6265 and rs7124442 were also genotyped. RESULTS: In the Pima cohort, no significant differences in serum BDNF was observed for 43 LOF subjects versus 65 LOF-matched controls (age, sex and BMI matched; P=0.29) or 20 GOF subjects versus 20 GOF-matched controls (P=0.40). Serum BDNF was significantly associated with genotype for BDNF rs12291186 (P=0.006) and rs6265 (P=0.009), but not rs7124442 (P=0.99); BDNF SNPs did not interact with MC4R status to predict serum BDNF. In the Hispanic cohort, plasma BDNF was not significantly different among 21 LOF subjects, 20 GOF subjects and 28 controls (P=0.79); plasma BDNF was not predicted by BDNF genotype or BDNF-x-MC4R genotype interaction. CONCLUSIONS: Circulating BDNF concentrations were not significantly associated with MC4R functional status, suggesting that peripheral BDNF does not directly reflect hypothalamic BDNF secretion and/or that MC4R signaling is not a significant regulator of the bulk of BDNF expression in humans.

Democratic decay of 6Be exposed by correlations.

The interaction of an E/A=70-MeV (7)Be beam with a Be target was used to populate levels in (6)Be following neutron knockout reactions. The three-body decay of the ground and first excited states into the α+p+p exit channel were detected in the High Resolution Array. Precise three-body correlations extracted from the experimental data allowed us to obtain insight into the mechanism of the three-body democratic decay. The correlation data are in good agreement with a three-cluster-model calculation and thus validate this theoretical approach over a broad energy range.

Correlations in intermediate energy two-proton removal reactions.

We report final-state-exclusive measurements of the light charged fragments in coincidence with (26)Ne residual nuclei following the direct two-proton removal from a neutron-rich (28)Mg secondary beam. A Dalitz-plot analysis and comparisons with simulations show that a majority of the triple-coincidence events with two protons display phase-space correlations consistent with the (two-body) kinematics of a spatially correlated pair-removal mechanism. The fraction of such correlated events, 56(12)%, is consistent with the fraction of the calculated cross section, 64%, arising from spin S=0 two-proton configurations in the entrance-channel (shell-model) (28)Mg ground state wave function. This result promises access to an additional and more specific probe of the spin and spatial correlations of valence nucleon pairs in exotic nuclei produced as fast secondary beams.