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Nevin Manimala Statistics

Resilience to height loss of articular cartilage of osteoarthritic stifle joints of old pigs, compared with healthy cartilage from young pigs in a tribological pin-on-plate exposure, revealing similar friction forces

PLoS One. 2021 Apr 23;16(4):e0250244. doi: 10.1371/journal.pone.0250244. eCollection 2021.

ABSTRACT

INTRODUCTION: We saw a lack of data on the biomechanical behavior of degenerated articular cartilage (OA) compared with that of healthy cartilage, even though the susceptibility to wear and tear of articular cartilage plays a key role in the progression of osteoarthritis (OA). Therefore, we performed a comparison between naturally occurring OA and healthy cartilage from pigs, before and after tribological stress.

AIM: The aim of the study was to compare OA-cartilage with healthy cartilage and to analyze the resilience to tribological shear stress, which will be measured as height loss (HL), and to friction forces of the cartilage layers. The findings will be substantiated in macro- and microscopical evaluations before and after tribological exposure.

METHODS: We assessed stifle joints of fifteen old and sixteen young pigs from the local abattoir radiologically, macroscopically and histologically to determine possible OA alterations. We put pins from the femoral part of the joints and plates from the corresponding tibial plateaus in a pin-on-plate tribometer under stress for about two hours with about 1108 reciprocating cycles under a pressure of approximately 1 MPa. As a surrogate criterion of wear and tear, the HL was recorded in the tribometer. The heights of the cartilage layers measured before and after the tribological exposure were compared histologically. The condition of the cartilage before and after the tribological exposure was analyzed both macroscopically with an adapted ICRS score and microscopically according to Little et al. (2010). We assessed the friction forces acting between the surfaces of the cartilage pair-specimens.

RESULTS: Articular cartilage taken from old pigs showed significant degenerative changes compared to that taken from the young animals. The macroscopic and microscopic scores showed strong alterations of the cartilage after the tribological exposure. There was a noticeable HL of the cartilage specimens after the first 100 to 300 cycles. The HL after tribological exposure was lower in the group of the old animals with 0.52 mm ± 0.23 mm than in the group of the young animals with 0.86 mm ± 0.26 mm (p < 0.0001). The data for the HL was validated by the histological height measurements with 0.50 mm ± 0.82 mm for the old and 0.79 mm ±0.53 mm for the young animals (p = 0.133). The friction forces measured at the cartilage of the old animals were 2.25 N ± 1.15 N and 1.89 N ± 1.45 N of the young animals (p = 0.3225).

CONCLUSION: Unlike articular cartilage from young pigs, articular cartilage from old pigs showed OA alterations. Tribological shear stress exposure revealed that OA cartilage showed less HL than healthy articular cartilage. Tribological stress exposure in a pin-on-plate tribometer seemed to be an appropriate way to analyze the mechanical stability of articular cartilage, and the applied protocol could reveal weaknesses of the assessed cartilage tissue. Friction and HL seemed to be independent parameters when degenerated and healthy articular cartilage were assessed under tribological exposure in a pin-on- plate tribometer.

PMID:33891624 | DOI:10.1371/journal.pone.0250244

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Nevin Manimala Statistics

The Italian Obstetric Surveillance System: Implementation of a bundle of population-based initiatives to reduce haemorrhagic maternal deaths

PLoS One. 2021 Apr 23;16(4):e0250373. doi: 10.1371/journal.pone.0250373. eCollection 2021.

ABSTRACT

In this before and after cross-sectional analysis, the authors aim to assess the impact of the bundle of research and training initiatives implemented between 2013 and 2018, and coordinated by the Italian Obstetric Surveillance System (ItOSS) to reduce obstetric haemorrhagic emergencies in five selected Italian Regions. To this purpose, the haemorrhagic Maternal Mortality Ratios (MMR) per 100,000 live births were estimated before and after implementing the bundle, through the ItOSS’s vital statistic linkage procedures and incident reporting and Confidential Enquiries. The research and training bundle was offered to all health professionals involved in pregnancy and birth care in the selected regions, representing 40% of national live births, and participating in the ItOSS audit cycle since its institution. The haemorrhagic MMR significantly decreased from 2.49/100,000 live births [95% CI 1.75 to 3.43] in the years 2007-2013 prior to the bundle implementation, to 0.77/100,000 live births [95% CI 0.31 to 1.58] in the years 2014-2018 after its implementation. According to the study results, the bundle of population-based initiatives might have contributed to reducing the haemorrhagic MMR in the participating regions, thus improving the quality of care of the major obstetric haemorrhage.

PMID:33891629 | DOI:10.1371/journal.pone.0250373

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Nevin Manimala Statistics

Intraindividual variation of dose parameters in oncologic CT imaging

PLoS One. 2021 Apr 23;16(4):e0250490. doi: 10.1371/journal.pone.0250490. eCollection 2021.

ABSTRACT

The objective of this study is to identify essential aspects influencing radiation dose in computed tomography [CT] of the chest, abdomen and pelvis by intraindividual comparison of imaging parameters and patient related factors. All patients receiving at least two consecutive CT examinations for tumor staging or follow-up within a period of 22 months were included in this retrospective study. Different CT dose estimates (computed tomography dose index [CTDIvol], dose length product [DLP], size-specific dose estimate [SSDE]) were correlated with patient’s body mass index [BMI], scan length and technical parameters (tube current, tube voltage, pitch, noise level, level of iterative reconstruction). Repeated-measures-analysis was initiated with focus on response variables (CTDIvol, DLP, SSDE) and possible factors (age, BMI, noise, scan length, peak kilovoltage [kVp], tube current, pitch, adaptive statistical iterative reconstruction [ASIR]). A univariate-linear-mixed-model with repeated-measures-analysis followed by Bonferroni adjustments was used to find associations between CT imaging parameters, BMI and dose estimates followed by a subsequent multivariate-mixed-model with repeated-measures-analysis with Bonferroni adjustments for significant parameters. A p-value <0.05 was considered statistically significant. We found all dose estimates in all imaging regions were substantially affected by tube current. The iterative reconstruction significantly influenced all dose estimates in the thoracoabdominopelvic scans as well as DLP and SSDE in chest-CT. Pitch factor affected all dose parameters in the thoracoabdominopelvic CT group. These results provide further evidence that tube current has a pivotal role and potential in radiation dose management. The use of iterative reconstruction algorithms can substantially decrease radiation dose especially in thoracoabdominopelvic and chest-CT-scans. Pitch factor should be kept at a level of ≥1.0 in order to reduce radiation dose.

PMID:33891632 | DOI:10.1371/journal.pone.0250490

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Nevin Manimala Statistics

Clinical Audit of Survival Outcomes and Prognostic Factors in Adolescents and Adults with Medulloblastoma

J Adolesc Young Adult Oncol. 2021 Apr 23. doi: 10.1089/jayao.2021.0034. Online ahead of print.

ABSTRACT

Purpose: Medulloblastomas, comprising 20%-25% of all primary brain tumors in children are much rarer in adulthood. Disease biology varies substantially across different age groups; however, owing to rarity, adults with medulloblastoma are traditionally treated using pediatric protocols. This is a retrospective audit of adolescent and adult medulloblastoma from a comprehensive cancer center. Methods: Data regarding demography, clinical presentation, imaging characteristics, histopathological features, molecular profiling, risk stratification, treatment details, and outcomes were retrieved from medical records. All time-to-event outcomes were analyzed using Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analysis of relevant prognostic factors was done with p value <0.05 being considered statistically significant. Results: A total of 162 patients ≥15 years of age with medulloblastoma were included. The median age was 25 years (range: 15-59 years) with leptomeningeal metastases seen in 31 (19%) patients at initial diagnosis. Following surgery, patients were treated with appropriate risk-stratified adjuvant therapy comprising of craniospinal irradiation plus boost with or without systemic chemotherapy. At a median follow-up of 50 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 53.5% and 59.5%, respectively. The addition of adjuvant systemic chemotherapy did not impact upon survival in standard-risk medulloblastoma. High-risk (HR) disease and anaplastic histology emerged as significant and independent predictors of poor survival on multivariate analysis. Conclusion: Medulloblastoma is a rare tumor in adolescents and adults with key differences in disease biology and resultant outcomes compared with the pediatric population. Contemporary management comprising maximal safe resection followed by appropriate risk-stratified adjuvant therapy provides acceptable survival outcomes.

PMID:33891492 | DOI:10.1089/jayao.2021.0034

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Nevin Manimala Statistics

Comparative Effectiveness of Training with Simulators Versus Traditional Instruction in Veterinary Education: Meta-Analysis and Systematic Review

J Vet Med Educ. 2021 Mar 4:e20200026. doi: 10.3138/jvme-2020-0026. Online ahead of print.

ABSTRACT

One of the greatest challenges in veterinary education is adequately preparing students with the clinical skills they need to be successful healthcare providers. Integration of simulators, devices used to represent real world phenomena under test conditions, into the veterinary curriculum can help address challenges to clinical instruction. The use of simulators in veterinary education is increasing; however, their effectiveness remains unclear. This meta-analysis seeks to synthesize the evidence for simulator training in veterinary education to provide a consensus of effect, guide the integration of simulators into the curriculum, and direct the development of future simulation-based research in veterinary medicine. A systematic search identified 416 potential manuscripts from which 60 articles were included after application of inclusion criteria. Information was extracted from 71 independent experiments. The overall weighted mean effect size for simulator training was g = 0.49 for the random-effects model. The outcome measures of knowledge, time, process, and product all produced statistically significant mean effect sizes favoring simulation (d = 0.41, 0.35, 0.70, 0.53, respectively). A moderator analysis revealed that study characteristics and instructional design features moderated the effectiveness of simulator training. Overall, the results indicate that simulator training in veterinary education can be effective for knowledge and clinical skill outcomes.

PMID:33891532 | DOI:10.3138/jvme-2020-0026

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Nevin Manimala Statistics

Effects of Interfering Cue Separation Distance and Amplitude on the Haptic Detection of Skin Stretch

IEEE Trans Haptics. 2021 Apr 23;PP. doi: 10.1109/TOH.2021.3075387. Online ahead of print.

ABSTRACT

Multi-sensory haptic cues, which contain several types of tactile stimuli that are presented concurrently to the user, have been shown to be useful for conveying information-rich cues. One limitation of multi-sensory cues is that user perception of individual cue components can be hindered by more salient components of the composite cue. In this paper, we investigate how amplitude and distance between cues affect the perception of multi-sensory haptic cues. Specifically, participants’ absolute threshold perception of stretch cues was measured in the presence of interfering squeeze cues using a modular testbed. We evaluated ten conditions of varying interference amplitude and distance between cues. We found that interference cue amplitude and distance between cues both have a statistically significant effect on the absolute perception of stretch cues. As interference cue amplitude increases, and as distance between cues decreases, absolute perception of stretch cues worsens. These results inform design considerations for future wearable multi-sensory haptic devices, so that cue salience can be maximized and interference effects minimized.

PMID:33891556 | DOI:10.1109/TOH.2021.3075387

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Nevin Manimala Statistics

Embedding Quantum Statistical Excitations in a Classical Force Field

J Phys Chem A. 2021 Apr 23. doi: 10.1021/acs.jpca.1c00164. Online ahead of print.

ABSTRACT

Quantum-mechanically driven charge polarization and charge transfer are ubiquitous in biomolecular systems, controlling reaction rates, allosteric interactions, ligand-protein binding, membrane transport, and dynamically driven structural transformations. Molecular dynamics (MD) simulations of these processes require quantum mechanical (QM) information in order to accurately describe their reactive dynamics. However, current techniques-empirical force fields, subsystem approaches, ab initio MD, and machine learning-vary in their ability to achieve a consistent chemical description across multiple atom types, and at scale. Here we present a physics-based, atomistic force field, the ensemble DFT charge-transfer embedded-atom method, in which QM forces are described at a uniform level of theory across all atoms, avoiding the need for explicit solution of the Schrödinger equation or large, precomputed training data sets. Coupling between the electronic and atomistic length scales is effected through an ensemble density functional theory formulation of the embedded-atom method originally developed for elemental materials. Charge transfer is expressed in terms of ensembles of ionic state basis densities of individual atoms, and charge polarization, in terms of atomic excited-state basis densities. This provides a highly compact yet general representation of the force field, encompassing both local and system-wide effects. Charge rearrangement is realized through the evolution of ensemble weights, adjusted at each dynamical time step via chemical potential equalization.

PMID:33891401 | DOI:10.1021/acs.jpca.1c00164

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Ultrahigh-Throughput Experimentation for Information-Rich Chemical Synthesis

Acc Chem Res. 2021 Apr 23. doi: 10.1021/acs.accounts.1c00119. Online ahead of print.

ABSTRACT

ConspectusThe incorporation of data science is revolutionizing organic chemistry. It is becoming increasingly possible to predict reaction outcomes with accuracy, computationally plan new retrosynthetic routes to complex molecules, and design molecules with sophisticated functions. Critical to these developments has been statistical analysis of reaction data, for instance with machine learning, yet there is very little reaction data available upon which to build models. Reaction data can be mined from the literature, but experimental data tends to be reported in a text format that is difficult for computers to read. Compounding the issue, literature data are heavily biased toward “productive” reactions, and few “negative” reaction data points are reported even though they are critical for training of statistical models. High-throughput experimentation (HTE) has evolved over the past few decades as a tool for experimental reaction development. The beauty of HTE is that reactions are run in a systematic format, so data points are internally consistent, the reaction data are reported whether the desired product is observed or not, and automation may reduce the occurrence of false positive or negative data points. Additionally, experimental workflows for HTE lead to datasets with reaction metadata that are captured in a machine-readable format. We believe that HTE will play an increasingly important role in the data revolution of chemical synthesis. This Account details the miniaturization of synthetic chemistry culminating in ultrahigh-throughput experimentation (ultraHTE), wherein reactions are run in ∼1 μL droplets inside of 1536-well microtiter plates to minimize the use of starting materials while maximizing the output of experimental information. The performance of ultraHTE in 1536-well microtiter plates has led to an explosion of available reaction data, which have been used to identify specific substrate-catalyst pairs for maximal efficiency in novel cross-coupling reactions. The first iteration of ultraHTE focused on the use of dimethyl sulfoxide (DMSO) as a high-boiling solvent that is compatible with the plastics most commonly used in consumable well plates, which generated homogeneous reaction mixtures that are perfect for use with nanoliter-dosing liquid handling robotics. In this way, DMSO enabled diverse reagents to be arrayed in ∼1 μL droplets. Reactions were run at room temperature with no agitation and could be scaled up from the ∼0.05 mg reaction scale to the 1 g scale. Engineering enhancements enabled the use of ultraHTE with diverse and semivolatile solvents, photoredox catalysis, heating, and acoustic agitation. A main driver in the development of ultraHTE was the recognition of the opportunity for a direct merger between miniaturized reactions and biochemical assays. Indeed, a strategy was developed to feed ultraHTE reaction mixtures directly to a mass-spectrometry-based affinity selection bioassay. Thus, micrograms of starting materials could be used in the synthesis and direct biochemical testing of drug-like molecules. Reactions were performed at a reactant concentration of ∼0.1 M in an inert atmosphere, enabling even challenging transition-metal-catalyzed reactions to be used. Software to enable the workflow was developed. We recently initiated the mapping of reaction space, dreaming of a future where transformations, reaction conditions, structure, properties and function are studied in a systems chemistry approach.

PMID:33891404 | DOI:10.1021/acs.accounts.1c00119

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Nevin Manimala Statistics

Artificial Coherent States of Light by Multiphoton Interference in a Single-Photon Stream

Phys Rev Lett. 2021 Apr 9;126(14):143601. doi: 10.1103/PhysRevLett.126.143601.

ABSTRACT

Coherent optical states consist of a quantum superposition of different photon number (Fock) states, but because they do not form an orthogonal basis, no photon number states can be obtained from it by linear optics. Here we demonstrate the reverse, by manipulating a random continuous single-photon stream using quantum interference in an optical Sagnac loop, we create engineered quantum states of light with tunable photon statistics, including approximate weak coherent states. We demonstrate this experimentally using a true single-photon stream produced by a semiconductor quantum dot in an optical microcavity, and show that we can obtain light with g^{(2)}(0)→1 in agreement with our theory, which can only be explained by quantum interference of at least 3 photons. The produced artificial light states are, however, much more complex than coherent states, containing quantum entanglement of photons, making them a resource for multiphoton entanglement.

PMID:33891441 | DOI:10.1103/PhysRevLett.126.143601

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Nevin Manimala Statistics

Higher Suicide Intent in Patients Attempting Suicide With Violent Methods Versus Self-Poisoning

Crisis. 2021 Apr 23:1-8. doi: 10.1027/0227-5910/a000773. Online ahead of print.

ABSTRACT

Background: Suicidal intent for patients attempting suicide using violent methods (VMs) is assumed to be higher than for those using self-poisoning (SP), which may explain the higher mortality observed in follow-up studies. However, this has not been studied prospectively. Aims: We aimed to compare patients attempting suicide using VMs with those using SP regarding suicidal intent, suicidal ideation, depression, and hopelessness during hospital stay and after 1 year. Methods: Patients hospitalized after suicide attempt by VMs (n = 80) or SP (n = 81) completed the Beck scales for Suicide Intent, Suicide Ideation, Depression Inventory, and Hopelessness on admission and at the 12-month follow-up. Results: On admission, those using VMs had higher suicidal intent than those using SP (M = 16.2 vs. 13.3, p < .001), but lower depression scores (M = 22.2 vs. 26.8, p < .05). No significant differences were found in suicidal ideation (M = 20.1 vs. 23.1) or hopelessness (M = 10.1 vs. 11.9). At 12-month follow-up, depression scores decreased significantly for both groups, while hopelessness decreased only for the SP group. Limitations: The statistical power achieved was lower than intended. Conclusion: The higher levels of suicidal intent, but lower levels of depression, may indicate more impulsivity among people attempting suicide using VMs. Suicidal ideation was relatively stable.

PMID:33890826 | DOI:10.1027/0227-5910/a000773