Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Detecting hierarchical organization of pervasive communities by modular decomposition of Markov chain.

Connecting nodes that contingently co-appear, which is a common process of networking in social and biological systems, normally leads to modular structure characterized by the absence of definite boundaries. This study seeks to find and evaluate methods to detect such modules, which will be called 'pervasive' communities. We propose a mathematical formulation to decompose a random walk spreading over the entire network into localized random walks as a proxy for pervasive communities. We applied this formulation to biological and social as well as synthetic networks to demonstrate that it can properly detect communities as pervasively structured objects. We further addressed a question that is fundamental but has been little discussed so far: What is the hierarchical organization of pervasive communities and how can it be extracted? Here we show that hierarchical organization of pervasive communities is unveiled from finer to coarser layers through discrete phase transitions that intermittently occur as the value for a resolution-controlling parameter is quasi-statically increased. To our knowledge, this is the first elucidation of how the pervasiveness and hierarchy, both hallmarks of community structure of real-world networks, are unified.

Hydrogen Bonding Propagated Phase Separation in Quasi-Epitaxial Single Crystals: A Pd-Br Molecular Insulator.

In condensed matter, phase separation is strongly related to ferroelasticity, ferroelectricity, ferromagnetism, electron correlation, and crystallography. These ferroics are important for nano-electronic devices such as non-volatile memory. However, the quantitative information regarding the lattice (atomic) structure at the border of phase separation is unclear in many cases. Thus, to design electronic devices at the molecular level, a quantitative electron-lattice relationship must be established. Herein, we elucidated a PdII-PdIV/PdIII-PdIII phase transition and phase separation mechanism for [Pd(cptn)2Br]Br2 (cptn = 1R,2R-diaminocyclopentane), propagated through a hydrogen-bonding network. Although the Pd···Pd distance was used to determine the electronic state, the differences in the Pd···Pd distance and the optical gap between Mott-Hubbard (MH) and charge-density-wave (CDW) states were only 0.012 Å and 0.17 eV, respectively. The N-H···Br···H-N hydrogen-bonding network functioned as a jack, adjusting the structural difference dynamically, and allowing visible ferroelastic phase transition/separation in a fluctuating N2 gas flow. Additionally, the effect of the phase separation on the spin susceptibility and electrical conductivity were clarified to represent the quasi-epitaxial crystals among CDW-MH states. These results indicate that the phase transitions and separations could be controlled via atomic and molecular level modifications, such as the addition of hydrogen bonding.

Ni(III) Mott-Hubbard-like State Containing High-Spin Ni(II) in a Semiconductive Bromide-Bridged Ni-Chain Compound.

Halogen-bridged linear chain metal complexes (MX-Chains) are fascinating compounds that have a quasi-one-dimensional (1D) electronic system. In this study, we synthesized the first Ni-based MX-Chain compound having hydroxy groups, i.e., [Ni(dabdOH)2Br]Br2·[Ni(dabdOHx)2Br]0.5·(2-PrOH)0.25·(MeOH)0.25 (1·solvent, x = ∼0.6, dabdOH = (2S,3S)-2,3-diaminobutane-1,4-diol). Single-crystal X-ray diffraction revealed that the MX-Chains in 1·solvent formed sheets and single-chain structures in the superlattice. It suggested an MH-like state, whereas the polarized reflection and Raman spectra suggested a CDW-like state. Magnetic and electron spin resonance measurements revealed that both high-spin Ni(II) (∼15%) and low-spin Ni(III) (∼85%) sites are present in the chain structures, i.e., the metal sites show mixed valency. Therefore, we concluded that 1·solvent adopts an intermediate state between the MH and CDW states. Moreover, a single crystal of 1·solvent exhibited semiconductive characteristics along the chain direction. This finding represents a new structural and electronic state of 1D electronic systems as well as MX-Chains.

Primary Percutaneous Coronary Intervention in Elderly Patients With Acute Myocardial Infarction　- An Analysis From a Japanese Nationwide Claim-Based Database.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) is strongly recommended by guidelines for patients presenting with acute myocardial infarction (AMI), but its applications in elderly patients are less clear.Methods and Results:The JROAD-DPC is a Japanese nationwide registry for patients with cardiovascular diseases combined with an administrative claim-based database. Among 2,369,165 records from 2012 to 2015, data for 115,407 AMI patients were extracted for this study. Elderly patients (≥75 years) comprised 45,645 subjects (39.6%), and received pPCI less frequently (62.2%) than younger patients (79.2%, P<0.001). Clinical variables such as higher age, female sex, higher Killip class, and renal dysfunction, but not functional status on admission, were predictors of non-application of pPCI. Endpoint 30-day mortality increased with aging, and was significantly higher in elderly patients (10.7%) than in younger patients (3.8%, P<0.001). Indeed, pPCI was independently associated with lower 30-day mortality only in subgroups of patients aged ≥60 years. Propensity score-matching analysis confirmed a similar reduction in endpoint 30-day mortality with pPCI in elderly patients. Duration of hospitalization was significantly shorter and functional ability on discharge was significantly better in elderly patients who underwent pPCI. CONCLUSIONS: Elderly patients with AMI underwent pPCI less frequently, but it was consistently associated with better clinical outcome in these patients. Our findings support the proactive application of pPCI for elderly AMI patients when they are eligible for an invasive strategy.

In vivo assessment of vasa vasorum neovascularization using intravascular ultrasound: A comparison between acute coronary syndrome and stable angina pectoris.

BACKGROUND: Previous studies have suggested that vasa vasorum (VV) neovascularization plays an important role in the progression and vulnerability of coronary atherosclerotic plaque. METHODS: A total of 130 patients with coronary artery disease including 75 acute coronary syndrome (ACS) cases and 55 stable angina pectoris (SAP) cases were studied. By using intravascular ultrasound (IVUS), VV was defined as a small (<1mm) tubular or vesicular, low-echoic structure observed exterior to the media. Prevalence and maximal number of VV were compared between patients with ACS versus SAP. RESULTS: The prevalence of VV at the culprit lesion was similar between the 2 groups (97% vs. 93%, p=0.216). On the other hand, it was significantly higher in ACS than SAP at both reference sites (proximal: 93% vs. 81%, p=0.047 and distal: 88% vs. 60%, p<0.001, respectively). The maximum number of VV was significantly higher in ACS than in SAP (at the culprit lesion: 2.8±1.3 vs. 1.8±1.0, p<0.001, at the proximal reference: 1.9±1.1 vs. 1.3±0.9, p=0.003 and distal reference: 1.7±1.1 vs. 1.1±1.1, p=0.003, respectively). CONCLUSIONS: VV neovascularization of coronary arteries was more enhanced in patients with ACS than in those with SAP, supporting its relation to plaque vulnerability. VV detected by widely used IVUS could be an adequate surrogate marker for plaque vulnerability in vivo.

Application of a quality by design approach to the cell culture process of monoclonal antibody production, resulting in the establishment of a design space.

This case study describes the application of Quality by Design elements to the process of culturing Chinese hamster ovary cells in the production of a monoclonal antibody. All steps in the cell culture process and all process parameters in each step were identified by using a cause-and-effect diagram. Prospective risk assessment using failure mode and effects analysis identified the following four potential critical process parameters in the production culture step: initial viable cell density, culture duration, pH, and temperature. These parameters and lot-to-lot variability in raw material were then evaluated by process characterization utilizing a design of experiments approach consisting of a face-centered central composite design integrated with a full factorial design. Process characterization was conducted using a scaled down model that had been qualified by comparison with large-scale production data. Multivariate regression analysis was used to establish statistical prediction models for performance indicators and quality attributes; with these, we constructed contour plots and conducted Monte Carlo simulation to clarify the design space. The statistical analyses, especially for raw materials, identified set point values, which were most robust with respect to the lot-to-lot variability of raw materials while keeping the product quality within the acceptance criteria.

Effect of an in-plane ligand on the electronic structures of bromo-bridged nano-wire Ni-Pd mixed-metal complexes, [Ni(1-x)Pd(x)(bn)2Br]Br2 (bn = 2S,3S-diaminobutane).

Single crystals of quasi-one-dimensional bromo-bridged Ni-Pd mixed-metal complexes with 2S,3S-diaminobutane (bn) as an in-plane ligand, [Ni(1-x)Pd(x)(bn)(2)Br]Br(2), were obtained by using an electrochemical oxidation method involving mixed methanol/2-propanol (1:1) solutions containing different ratios of [Ni(II)(bn)(2)]Br(2) and [Pd(II)(bn)(2)]Br(2). To investigate the competition between the electron-correlation of the Ni(III) states, or Mott-Hubbard states (MH), and the electron-phonon interaction of the Pd(II)-Pd(IV) mixed valence states, or charge-density-wave states (CDW), in the Ni-Pd mixed-metal compounds, X-ray structure analyses, X-ray oscillation photograph, and Raman, IR, ESR, and single-crystal reflectance spectra were analyzed. In addition, the local electronic structures of Ni-Pd mixed-metal single crystals were directly investigated by using scanning tunneling microscopy (STM) at room temperature and ambient pressure. The oxidation states of [Ni(1-x)Pd(x)(bn)(2)Br]Br(2) changed from a M(II)-M(IV) mixed valence state to a M(III) MH state at a critical mixing ratio (x(c)) of approximately 0.8, which is lower than that of [Ni(1-x)Pd(x)(chxn)(2)Br]Br(2) (chxn = 1R,2R-diaminocyclohexane) (x(c) approximately 0.9) reported previously. The lower value of x(c) for [Ni(1-x)Pd(x)(bn)(2)Br]Br(2) can be explained by the difference in their CDW dimensionalities because the three-dimensional CDW ordering in [Pd(bn)(2)Br]Br(2) observed by using X-ray diffuse scattering stabilizes the Pd(II)-Pd(IV) mixed valence state more than two-dimensional CDW ordering in [Pd(chxn)(2)Br]Br(2) does, which has been reported previously.

Quantitative assessment of regional myocardial flow reserve using tc-99m-sestamibi imaging.

BACKGROUND: The aims of this study were to develop a method for quantitative estimation of the myocardial blood flow index (MBFI) and myocardial flow reserve (MFR) of the whole left ventricle using (99m)technetium (Tc-99m)-sestamibi imaging. METHODS AND RESULTS: Twenty-two patients with suspected coronary artery disease and 7 controls underwent both Tc-99m-sestamibi imaging and O-15 water positron emission tomography (PET). The global MBFI was calculated on the basis of the microsphere model from the ratio of the myocardial count to the area under the time - activity curve on the aortic arch. The regional MBFI was calculated from the relative distributions of Tc-99m-sestamibi uptake values. The regional MBFI and MFR (Tc-MFR) obtained using single-photon emission computed tomography were compared with the myocardial blood flow (MBF) and MFR (PET-MFR) obtained using PET as the gold standard. Regional MBFI significantly correlated with the MBF obtained using PET. Regional Tc-MFR also correlated with the regional PET-MFR, with some underestimation. CONCLUSION: These results indicate that regional MBF and MFR may be estimated by dynamic Tc-99m-sestamibi imaging and can be used for the early detection and estimation of the functional severity of coronary lesions without the need for a PET camera.