Test for symmetry in 2×22 \times 2 contingency tables with nonignorable nonresponses

The McNemar test evaluates the hypothesis that two correlated proportion is common in $2 \times 2$ contingency tables with the same categories. This study discusses a test for symmetry in $2 \times 2$ contingency tables with nonignorable nonresponses. The proposed method is based on Takai and Kano (2008), which discusses a test for independence because a dependency assumption between the two observed outcomes is required to obtain an identification. Here, we focus on three models and propose a test for symmetry in $2 \times 2$ contingency tables with nonignorable nonresponses.Comment: 20 page

The use of a selective saturation pulse to suppress t1 noise in two-dimensional 1H fast magic angle spinning solid-state NMR spectroscopy

A selective saturation pulse at fast magic angle spinning (MAS) frequencies (60+ kHz) suppresses t1 noise in the indirect dimension of two-dimensional 1H MAS NMR spectra. The method is applied to a synthetic nucleoside with an intense methyl 1H signal due to triisopropylsilyl (TIPS) protecting groups. Enhanced performance in terms of suppressing the methyl signal while minimising the loss of signal intensity of nearby resonances of interest relies on reducing spin diffusion – this is quantified by comparing two-dimensional 1H NOESY-like spin diffusion spectra recorded at 30 to 70 kHz MAS. For a saturation pulse centred at the methyl resonance, the effect of changing the nutation frequency at different MAS frequencies as well as the effect of changing the pulse duration is investigated. By applying a pulse of duration 30 ms and nutation frequency 725 Hz at 70 kHz MAS, a good compromise of significant suppression of the methyl resonance combined with the signal intensity of resonances greater than 5 ppm away from the methyl resonance being largely unaffected is achieved. The effectiveness of using a selective saturation pulse is demonstrated for both homonuclear 1H – 1H double quantum (DQ)/ single quantum (SQ) MAS and 14N – 1H heteronuclear multiple quantum coherence (HMQC) two-dimensional solid-state NMR experiments

High-resolution NMR-based metabolic detection of microgram biopsies using a 1 mm HRμMAS probe

International audienceA prototype 1 mm High-Resolution micro-Magic Angle Spinning (HRμMAS) probe is described. High quality 1 H NMR spectra were obtained from 490 μg of heterogeneous biospecimens, offering a rich-metabolite profiling. The results demonstrate the potential of HRμMAS as a new NMR analytical tool in metabolomics. Today 1 H HRMAS (High-Resolution Magic-Angle Spinning) NMR (Nuclear Magnetic Resonance) spectroscopy finds great success in laboratory studies of the metabolome in heterogeneous biospecimens such as human and animal biopsies, 1–3 intact cells 4 and whole organisms, 5,6 owing to the nearly non-destructive nature of the technique and the straightforward data acquisition. 7 However, since NMR spectroscopy is an inherently insensitive analytical technique, HRMAS relies on a large sample mass, typically 10–20 mg per NMR data. For this reason, 1 H HRMAS analysis can be a real challenge (or even impossible) when samples – such as cells, organisms and tissue biopsies – are scarce. Moreover, analysis of 10–20 mg of heterogeneous specimens may prevent the investigation of a specific cell. In contrast, the high degree of homogeneity inside a microscopic specimen can offer a more direct NMR spectral analysis and enable a straightforward metabolic evaluation. The immediate advantages of small sample mass (i.e. microgram) analyses are: (1) they simplify the sample preparations such as cultivation and extraction; and (2) offer precise specimen-specific analyses for exploring the invisible phenotypes. The most cost-effective approach to microscopic NMR detection is the use of a miniature detection coil (μcoil). With this technique, the coil is in close proximity to the microscopic sample optimizing the filling-factor (the ratio of the sample volume to the coil detection volume). 8 Fabricating a μcoil for HRMAS analyses is no easy task, especially without sacrificing detection sensitivity and spectral resolution. 9 The commercial μMAS systems currently available (i.e. 0.7 mm Bruker MAS and 0.75 mm JEOL MAS) are designed for solid materials but do not offer adequate spectral resolution (0.002 ppm) for metabolic investigations. Today, the only approach to μMAS for metabolome analyses is the use of an inductively coupled High-Resolution Magic-Angle Coil Spinning (HRMACS) μcoil. 10 The HRMACS technique uses a secondary tuned circuit (i.e. μcoil-resonator), designed to fit inside a standard 4 mm MAS rotor, to convert the standard large volume MAS system into a high-resolution capable μMAS probe. 11,12 The use of HRMACS has show

Glass-phase coordination polymer displaying proton conductivity and guest-accessible porosity

We describe the preparation of the crystalline and glassy state of a coordination polymer displaying proton conduction and guest-accessible porosity. EXAFS and solid-state NMR analyses indicated that pyrophosphate and phosphate ions are the main proton transporters in the glass and that homogeneously distributed 5-chloro-1H-benzimidazole in the glass provide the porosity

Timing of therapeutic interventions against infection-triggered encephalopathy syndrome: a scoping review of the pediatric literature

Our goal was to conduct a scoping review of the literature on the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy in children, focusing on treatment targets and treatment initiation timing. We performed literature searches using PubMed for articles reporting treatments of infection-triggered encephalopathy syndrome/acute encephalopathy. We included articles describing specific treatments for acute encephalopathy with control groups. For the purpose of searching new therapies only experimentally tried in the case series, we also included case series studies without control groups in this review, if the studies contained at least two cases with clear treatment goals. Therapies were classified based on their mechanisms of action into brain protection therapy, immunotherapy, and other therapies. We operationally categorized the timing of treatment initiation as T1 (6–12 h), T2 (12–24 h), T3 (24–48 h), and T4 (>48 h) after the onset of seizures and/or impaired consciousness. Thirty articles were included in this review; no randomized control study was found. Eleven retrospective/historical cohort studies and five case–control studies included control groups with or without specific therapies or outcomes. The targeted conditions and treatment timing varied widely across studies. However, the following three points were suggested to be effective in multiple studies: (1) Careful seizure management and targeted temperature management within 12 h (T1) of onset of febrile seizure/prolonged impaired consciousness without multiple organ failure may reduce the development of acute encephalopathy with biphasic seizures and late reduced diffusion; (2) immunotherapy using corticosteroids, tocilizumab, or plasma exchange within 24 h (T1–T2) of onset of acute necrotizing encephalopathy may reduce sequelae; and (3) anakinra therapy and ketogenic diet demonstrate little evidence of neurologic sequelae reduction, but may reduce seizure frequency and allow for weaning from barbiturates, even when administered weeks (T4) after onset in children with febrile infection-related epilepsy syndrome. Although available studies have no solid evidence in the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy, this scoping review lays the groundwork for future prospective clinical trials

Role of Anomalous Water Constraints in the Efficacy of Pharmaceuticals Probed by 1H Solid‐State NMR

Water plays a complex and central role in determining the structural and reactive properties in numerous chemical systems. In crystalline materials with structural water, the primary focus is often to relate hydrogen bonding motifs to functional properties such as solubility, which is highly relevant in pharmaceutical applications. Nevertheless, understanding the full electrostatic landscape is necessary for a complete structure‐function picture. Herein, a combination of tools including 1H magic angle spinning NMR and X‐ray crystallography are employed to evaluate the local landscape of water in crystalline hydrates. Two hydrates of an anti‐leukemia drug mercaptopurine, which exhibit dramatically different dehydration temperatures (by 90 °C) and a three‐fold difference in the in vivo bioavailability, are compared. The results identify an electrosteric caging mechanism for a kinetically trapped water in the hemihydrate form, which is responsible for the dramatic differences in properties.1H chemical shift tensors are valuable in the structural and dynamical studies of a variety of materials, and are directly measurable with fast MAS spinning experiments. The use of these novel techniques to reveal the structural differences water can adopt in pharmaceutical hydrates is demonstrated.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138433/1/slct201701547_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138433/2/slct201701547-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138433/3/slct201701547.pd

Coordination polymer glass from a protic ionic liquid: proton conductivity and mechanical properties as an electrolyte

加湿不要で水素イオンを高速伝導する配位高分子ガラスの合成に成功 --車載用燃料電池の電解質材料として期待--. 京都大学プレスリリース. 2020-05-14.Coordination polymer glass provides solid support for hydrogen fuel cells. 京都大学プレスリリース. 2020-05-14.High proton conducting electrolytes with mechanical moldability are a key material for energy devices. We propose an approach for creating a coordination polymer (CP) glass from a protic ionic liquid for a solid-state anhydrous proton conductor. A protic ionic liquid (dema)(H2PO4), with components which also act as bridging ligands, was applied to construct a CP glass (dema)0.35[Zn(H2PO4)2.35(H3PO4)0.65]. The structural analysis revealed that large Zn–H2PO4−/H3PO4 coordination networks formed in the CP glass. The network formation results in enhancement of the properties of proton conductivity and viscoelasticity. High anhydrous proton conductivity (σ = 13.3 mS cm−1 at 120 °C) and a high transport number of the proton (0.94) were achieved by the coordination networks. A fuel cell with this CP glass membrane exhibits a high open-circuit voltage and power density (0.15 W cm−2) under dry conditions at 120 °C due to the conducting properties and mechanical properties of the CP glass

Engineering Codrug Solid Forms: Mechanochemical Synthesis of an Indomethacin-Caffeine System

This article reports on the preparation and solid-state characterization of an indomethacin 12caffeine drug 12drug cocrystal (or codrug) in a 1:1 stoichiometry. These two active ingredients are frequently coadministered as part of a therapy against strong migraines, in a commercially available fixed dose combination formulation. The X-ray crystal structure of the codrug is characterized by a hydrogen bond interaction between the carboxylic moiety of indomethacin and the purinic nitrogen atom of caffeine. The combination of multinuclear and multidimensional solid-state NMR measurements (1H MAS, 13C and 15N CPMAS, 1H DQ MAS, 13C 121H HETCOR, 14N 121H J- and D-HMQC), as well as IR data, provided spectroscopic evidence about the hydrogen atom position along the hydrogen bond axis, thereby confirming the neutral nature of the cocrystal. Furthermore, dissolution kinetic tests revealed superior bioavailability of indomethacin in the codrug compared to indomethacin alone and to an indomethacin 12caffeine physical mixture. On the other hand, the melting point of indomethacin was slightly lower in the cocrystal rather than in the pure drug

Influence of COVID-19 pandemic on bystander interventions, emergency medical service activities, and patient outcomes in out-of-hospital cardiac arrest in Osaka City, Japan

Background: The coronavirus disease (COVID-19) pandemic may have negatively affected bystander interventions, emergency medical service (EMS) personnel activities, and patient outcomes after out-of-hospital cardiac arrest (OHCA). This study assessed bystander interventions, EMS activities, and patient outcomes during the COVID-19 pandemic era and compared them with those during the non-COVID-19 pandemic era in Osaka City, Japan, where public-access automated external defibrillators (AEDs) are well established. Methods: We conducted this population-based cohort study that included all cases with non-traumatic OHCA treated by EMS personnel and excluded cases with no resuscitation attempt, traumatic cases, cases occurring in healthcare facilities, or cases witnessed by EMS personnel. Data were compared between the COVID-19 pandemic period (February 1, 2020 to July 31, 2020) and the non-COVID-19 pandemic period (February 1, 2019 to July 31, 2019). Results: During the study periods, 1687 patients were eligible for analyses (COVID-19: n = 825; non-COVID-19: n = 862). Patients with OHCA during the COVID-19 pandemic period were significantly less likely to receive bystander cardiopulmonary resuscitation (CPR) (COVID-19: 33.0%; non-COVID-19: 41.3%; p < 0.001) and public-access AED pad application (COVID-19: 2.9%; non-COVID-19: 6.1%; p = 0.002) compared with patients during the non-COVID-19 pandemic period. There were no significant differences in 1-month survival with favorable neurological outcomes between the two periods (COVID-19: 4.6%; non-COVID-19: 6.1%; p = 0.196). Conclusion: The COVID-19 pandemic period did not affect patient outcomes after OHCA but changed bystander behaviors in Osaka City, Japan