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Purpose: Wideband phase‐sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) enables myocardial scar imaging in implantable cardioverter defibrillators (ICD) patients, mitigating hyperintensity artifacts. To address subendocardial scar visibility challenges, a 2D breath‐hold single‐shot electrocardiography‐triggered black‐blood (BB) LGE sequence was integrated with wideband imaging, enhancing scar‐blood contrast. Methods: Wideband BB, with increased bandwidth in the inversion pulse (0.8–3.8 kHz) and T2 preparation refocusing pulses (1.6–5.0 kHz), was compared with conventional and wideband PSIR, and conventional BB, in a phantom and sheep with and without ICD, and in six patients with cardiac devices and known myocardial injury. ICD artifact extent was quantified in the phantom and specific absorption rate (SAR) was reported for each sequence. Image contrast ratios were analyzed in both phantom and animal experiments. Expert radiologists assessed image quality, artifact severity, and scar segments in patients and sheep. Additionally, histology was performed on the sheep's heart. Results: In the phantom, wideband BB reduced ICD artifacts by 62% compared to conventional BB while substantially improving scar‐blood contrast, but with a SAR more than 24 times that of wideband PSIR. Similarly, the animal study demonstrated a considerable increase in scar‐blood contrast with wideband BB, with superior scar detection compared with wideband PSIR, the latter confirmed by histology. In alignment with the animal study, wideband BB successfully eliminated severe ICD hyperintensity artifacts in all patients, surpassing wideband PSIR in image quality and scar detection. Conclusion: Wideband BB may play a crucial role in imaging ICD patients, offering images with reduced ICD artifacts and enhanced scar detection. [ABSTRACT FROM AUTHOR]

Currently, pulmonary vein isolation (PVI) is the gold standard in catheter ablation for atrial fibrillation (AF). However, PVI alone may be insufficient in the management of persistent AF, and complementary methods are being explored. One such method takes an anatomical approach—improving both its success rate and lesion durability may lead to improved treatment outcomes. An additional approach complementary to the anatomical one is also attracting attention, one that focuses on epicardial conduction. This involves ethanol ablation of the vein of Marshall (VOM) and can be very effective in blocking epicardial conduction related to Marshall structure; it is becoming incorporated into standard treatment. However, the pitfall of this "Marshall-PLAN", a method that combines an anatomical approach with ethanol infusion within the VOM (Et-VOM), is that Et-VOM and other line creations are not always successfully completed. This has led to cases of AF and/or atrial tachycardia (AT) recurrence even after completing this lesion set. Investigating effective adjunctive methods will enable us to complete the lesion set with the aim to lower the rates of recurrence of AF and/or AT in the future. [ABSTRACT FROM AUTHOR]

Identification and diagnosis of periprosthetic joint infection (PJI) are challenging, requiring a multi-disciplinary approach involving clinical evaluation, laboratory tests, and imaging studies. MRI is advantageous to alternative imaging techniques due to superior soft tissue contrast and absence of ionizing radiation. However, the presence of metallic implants can cause signal loss and artifacts. Metal artifact suppression (MARS) MRI techniques have been developed that mitigate metal artifacts and improve periprosthetic soft tissue visualization. This paper provides a review of the various MARS MRI techniques, their clinical applicability and accuracy in PJI diagnosis and evaluation, and current challenges and future perspectives. [ABSTRACT FROM AUTHOR]

Significance: Light-sheet fluorescence microscopy is widely used for high-speed, high-contrast, volumetric imaging. Application of this technique to in vivo brain imaging in non-transparent organisms has been limited by the geometric constraints of conventional light-sheet microscopes, which require orthogonal fluorescence excitation and collection objectives. We have recently demonstrated implantable photonic neural probes that emit addressable light sheets at depth in brain tissue, miniaturizing the excitation optics. Here, we propose a microendoscope consisting of a light-sheet neural probe packaged together with miniaturized fluorescence collection optics based on an image fiber bundle for lensless, light-field, computational fluorescence imaging. Aim: Foundry-fabricated, silicon-based, light-sheet neural probes can be packaged together with commercially available image fiber bundles to form microendoscopes for light-sheet light-field fluorescence imaging at depth in brain tissue. Approach: Prototype microendoscopes were developed using light-sheet neural probes with five addressable sheets and image fiber bundles. Fluorescence imaging with the microendoscopes was tested with fluorescent beads suspended in agarose and fixed mouse brain tissue. Results: Volumetric light-sheet light-field fluorescence imaging was demonstrated using the microendoscopes. Increased imaging depth and enhanced reconstruction accuracy were observed relative to epi-illumination light-field imaging using only a fiber bundle. Conclusions: Our work offers a solution toward volumetric fluorescence imaging of brain tissue with a compact size and high contrast. The proof-of-concept demonstrations herein illustrate the operating principles and methods of the imaging approach, providing a foundation for future investigations of photonic neural probe enabled microendoscopes for deep-brain fluorescence imaging in vivo. [ABSTRACT FROM AUTHOR]

Variants in membrane trafficking proteins are known to cause rare disorders with severe symptoms. The highly conserved transport protein particle (TRAPP) complexes are key membrane trafficking regulators that are also involved in autophagy. Pathogenic genetic variants in specific TRAPP subunits are linked to neurological disorders, muscular dystrophies, and skeletal dysplasias. Characterizing these variants and their phenotypes is important for understanding the general and specialized roles of TRAPP subunits as well as for patient diagnosis. Patient-derived cells are not always available, which poses a limitation for the study of these diseases. Therefore, other systems, like the yeast Saccharomyces cerevisiae, can be used to dissect the mechanisms at the intracellular level underlying these disorders. The development of CRISPR/Cas9 technology in yeast has enabled a scar-less editing method that creates an efficient humanized yeast model. In this study, core yeast subunits were humanized by replacing them with their human orthologs, and TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC6A, and TRAPPC6B were found to successfully replace their yeast counterparts. This system was used for studying the first reported individual with an autosomal recessive disorder caused by biallelic TRAPPC1 variants, a girl with a severe neurodevelopmental disorder and myopathy. We show that the maternal variant (TRAPPC1 p.(Val121Alafs*3)) is non-functional while the paternal variant (TRAPPC1 p.(His22_Lys24del)) is conditional-lethal and affects secretion and non-selective autophagy in yeast. This parallels defects seen in fibroblasts derived from this individual which also showed membrane trafficking defects and altered Golgi morphology, all of which were rescued in the human system by wild-type TRAPPC1. This study suggests that humanized yeast can be an efficient means to study TRAPP subunit variants in the absence of human cells and can assign significance to variants of unknown significance (VUS). This study lays the foundation for characterizing further TRAPP variants through this system, rapidly contributing to disease diagnosis. [ABSTRACT FROM AUTHOR]

Strawberries in California are grown in specific coastal areas where land is scarce and climate change threatens future production. Strawberry growers are under pressure to adopt sustainable production strategies such as crop rotation, but this practice requires more land than back-to-back planting. The objectives of this research were to quantify the rate of crop rotation across the three main strawberry producing regions in California (Ventura, Santa Maria, and Monterey Bay), and evaluate geographic and edaphic influences on crop rotation. All strawberry fields in the main strawberry producing regions of California were identified by satellite imagery and manual inspection for the years 2017 through 2022. ArcGIS Pro was used to outline each strawberry field and compare among years to determine the period between successive strawberry plantings. Edaphic characteristics and shapefiles for surrounding fields were retrieved from public datasets. The three regions significantly differed in their rates of crop rotation. On average, 95, 52, and 25% of strawberry hectares were rotated each year in the Monterey Bay, Santa Maria, and Ventura regions, respectively. Shorter rotation lengths were associated with reduced distance from the ocean and soil with a higher percentage of sand. Based on 2 years of disease surveys, fields infested with Macrophomina phaseolina tended to be further inland than fields infested with Fusarium oxysporum f. sp. fragariae in the Monterey Bay region. This study determined that distance from the ocean and soil texture are associated with crop rotation lengths in California strawberry production. Enough land may be available in the Santa Maria and Monterey Bay regions for growers to lengthen crop rotations, but water quality, social networks, and financial considerations that were outside the scope of this study are likely to limit the ability for strawberry growers to maximize the duration of crop rotations. [ABSTRACT FROM AUTHOR]

In advanced non-squamous non-small-cell lung cancer (NSCLC), routine testing with next-generation sequencing (NGS) is recommended to identify actionable genomic alterations (AGAs). The therapeutic implications of repeated NGS testing on synchronous and metachronous tumors are unclear. Between February 2017 and October 2020, NSCLC samples from a single institution were reflex-tested using a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina). Thirty-eight patients were identified with multiple NGS results from 82 samples: 11% were from single unifocal, 51% were from synchronous, and 38% were from metachronous tumors. Changes in EGFR, KRAS, PI3KCA, and TP53 variants were found in 22 patients' samples (58%). No changes were seen with longitudinal testing of multiple samples from single unifocal tumors, while changes were observed in 60% of synchronous and 71% of metachronous tumors. Of these, 26% of patients had AGA differences between samples. Acknowledging the limited sample size, a significant difference in overall survival was observed between synchronous separate primaries and metastasis. Repeat NGS testing of synchronous and metachronous NSCLC tumors may identify differing variants in >50% of patients. These changes may reflect separate primary lung carcinomas, tumor heterogeneity among intrapulmonary metastases, and clonal evolution. NGS testing of multiple tumors may enhance the identification of therapeutic targets for treatment decisions. [ABSTRACT FROM AUTHOR]

Objective: While highly prevalent, risk factors for incident polycystic ovary syndrome (PCOS) are poorly delineated. Using a population-based cohort, we sought to identify predictors of incident PCOS diagnosis. Materials and Methods: A matched case–control analysis was completed utilizing patients enrolled in Kaiser Permanente Washington from 2006 to 2019. Inclusion criteria included female sex, age 16–40 years, and ≥3 years of prior enrollment with ≥1 health care encounter. PCOS cases were identified using International Classification of Diseases codes. For each incident case (n = 2,491), 5 patients without PCOS (n = 12,455) were matched based on birth year and enrollment status. Potential risk factors preceding diagnosis included family history of PCOS, premature menarche, parity, race, weight gain, obesity, valproate use, metabolic syndrome, epilepsy, prediabetes, and types 1 and 2 diabetes. Potential risk factors for incident PCOS diagnosis were assessed with univariate and multivariable conditional logistic regressions. Results: Mean age of PCOS cases was 26.9 years (SD 6.8). PCOS cases, compared with non-PCOS, were more frequently nulliparous (70.9% versus 62.4%) and in the 3 years prior to index date were more likely to have obesity (53.8% versus 20.7%), metabolic syndrome (14.5% versus 4.3%), prediabetes (7.4% versus 1.6%), and type 2 diabetes (4.1% versus 1.7%) (p < 0.001 for all comparisons). In multivariable models, factors associated with higher risk for incident PCOS included the following: obesity (compared with nonobese) Class I–II (body–mass index [BMI], 30–40 kg/m2; odds ratio [OR], 3.8; 95% confidence interval [CI], 3.4–4.2), Class III (BMI > 40 kg/m2; OR, 7.5, 95% CI, 6.5–8.7), weight gain (compared with weight loss or maintenance) of 1–10% (OR, 1.7, 95% CI, 1.3–2.1), 10–20% (OR, 1.9; 95% CI, 1.5–2.4), and >20% (OR, 2.6; 95% CI, 1.9–3.6), prediabetes (OR, 2.7; 95% CI, 2.1–3.4), and metabolic syndrome (OR, 1.8: 95% CI, 1.5–2.1). Conclusion: Excess weight gain, obesity, and metabolic dysfunction may play a key role in the ensuing phenotypic expression of PCOS. Treatment and prevention strategies targeted at preventing weight gain in early reproductive years may help reduce the risk of this syndrome. [ABSTRACT FROM AUTHOR]

Background and Aims Patients with repaired tetralogy of Fallot remain at risk of life-threatening ventricular tachycardia related to slow-conducting anatomical isthmuses (SCAIs). Preventive ablation of SCAI identified by invasive electroanatomical mapping is increasingly performed. This study aimed to non-invasively identify SCAI using 3D late gadolinium enhancement cardiac magnetic resonance (3D-LGE-CMR). Methods Consecutive tetralogy of Fallot patients who underwent right ventricular electroanatomical mapping (RV-EAM) and 3D-LGE-CMR were included. High signal intensity threshold for abnormal myocardium was determined based on direct comparison of bipolar voltages and signal intensity by co-registration of RV-EAM with 3D-LGE-CMR. The diagnostic performance of 3D-LGE-CMR to non-invasively identify SCAI was determined, validated in a second cohort, and compared with the discriminative ability of proposed risk scores. Results The derivation cohort consisted of 48 (34 ± 16 years) and the validation cohort of 53 patients (36 ± 18 years). In the derivation cohort, 78 of 107 anatomical isthmuses (AIs) identified by EAM were normal-conducting AI, 22 were SCAI, and 7 blocked AI. High signal intensity threshold was 42% of the maximal signal intensity. The sensitivity and specificity of 3D-LGE-CMR for identifying SCAI or blocked AI were 100% and 90%, respectively. In the validation cohort, 85 of 124 AIs were normal-conducting AI, 36 were SCAI, and 3 blocked AI. The sensitivity and specificity of 3D-LGE-CMR were 95% and 91%, respectively. All risk scores showed an at best modest performance to identify SCAI (area under the curve ≤.68). Conclusions 3D late gadolinium enhancement cardiac magnetic resonance can identify SCAI with excellent accuracy and may refine non-invasive risk stratification and patient selection for invasive EAM in tetralogy of Fallot. [ABSTRACT FROM AUTHOR]

Background: A novel method to measure atrial fibrillation cycle length (AF-CL) was recently described, based on the average of 10 consecutive signals (FARS10). FARS10 accurately identified pulmonary vein isolation (PVI)-responders among patients with persistent AF. Whether this method is applicable to patients with paroxysmal AF is unknown. Objective: The aim of this study is to evaluate the prognostic value of FARS10 measurements in patients with paroxysmal AF. Methods and results: We enrolled paroxysmal AF patients undergoing PVI in a prospective multicenter study. After AF induction with a standardized protocol, the AF-CL was measured using FARS-10 method. The primary endpoint was AF/AT-recurrence. One-hundred and four patients were included (61 ± 14 years, 25% females). After a mean follow-up of 12 ± 4 months, AF/AT recurrence rate was 20%. The fastest PV CL (fPV-CL) was independently associated with the primary endpoint at multivariate analysis (HR 1.02, p < 0.001). Every 10 ms increase in fPV-CL, AF recurrences increased by 20%. The value of 160 ms was found to be the optimal cut-off (specificity 81%, sensitivity 76%). Patients with fPV-CL < 160 ms experienced lower AF recurrences as compared to patients with fPV-CL > 160 ms (8% vs. 32% at 1 year; HR = 0.17, p < 0.001). Progression to persistent AF was observed in 13% of patients with fPV-CL > 160 ms. Conclusion: fPV-CL measured with the FARS-10 method accurately predicts PVI success in paroxysmal AF patients undergoing PVI. Patients with slow PV activity (fPV-CL > 160 ms) experience higher AF recurrence rate after PVI and more frequent progression to persistent AF. In 104 patients with paroxysmal atrial fibrillation (AF) undergoing AF ablation, AF was induced at the beginning of the procedure. Pulmonary vein activity was measured using FARS10 measurement (10 consecutive fastest atrial repetitive similar morphology signals). The value of 160 ms was found to be the best cut-off to discriminate outcomes. At 1-year follow-up, patients with fast veins (< 160 ms) experienced significantly fewer AF recurrences as compared to patients with slow veins (> 160 ms). PV activity measured with FARS10 method accurately discriminates pulmonary vein isolation responders, in patients with paroxysmal AF. Abbreviations: AF atrial fibrillation, AT atrial tachycardia, CL cycle length, FARS10: 10 consecutive fastest atrial repetitive similar morphology signal, fPV fastest pulmonary vein, HR hazard ratio, ms milliseconds. [ABSTRACT FROM AUTHOR]

Optical techniques, such as optogenetic stimulation and functional fluorescence imaging, have been revolutionary for neuroscience by enabling neural circuit analysis with cell-type specificity. To probe deep brain regions, implantable light sources are crucial. Silicon photonics, commonly used for data communications, shows great promise in creating implantable devices with complex optical systems in a compact form factor compatible with high volume manufacturing practices. This article reviews recent developments of wafer-scale multifunctional nanophotonic neural probes. The probes can be realized on 200 or 300 mm wafers in commercial foundries and integrate light emitters for photostimulation, microelectrodes for electrophysiological recording, and microfluidic channels for chemical delivery and sampling. By integrating active optical devices to the probes, denser emitter arrays, enhanced on-chip biosensing, and increased ease of use may be realized. Silicon photonics technology makes possible highly versatile implantable neural probes that can transform neuroscience experiments. [ABSTRACT FROM AUTHOR]

A challenge in optical phased arrays (OPAs) is to achieve single-lobe emission using densely spaced emitters without incurring inter-waveguide optical crosstalk. Here, we propose to heuristically optimize the amplitude and phase of each grating antenna in an OPA to correct for optical non-idealities, including fabrication variations and inter-waveguide crosstalk. This method was applied to a silicon photonic integrated circuit with 1 mm-long gratings at 775 nm spacing for operation in a wavelength range of 1450–1650 nm. We achieved a wide two-dimensional beam-steering range of 110° × 28°, evaluated over a 127° × 47° field-of-view (FOV). Within this FOV, we measured an average sidelobe suppression of 8.2 dB and focused on average, 34.5 % of the emitted power into the main lobe. We achieved a peak sidelobe suppression of 14.5 dB and 50 % of the power concentrated in the main lobe. The approach is suitable for applications that require alias-free out-of-plane emission. [ABSTRACT FROM AUTHOR]

Copyright of Manuelle Medizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes. Methods A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years. Results During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients [18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P =.001] and age >50 years (HR 1.7, P =.016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P <.001) was a predictor of VAs. Conclusions ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation. [ABSTRACT FROM AUTHOR]

The infestation of brewing grains with filamentous fungi can have wide-ranging effects, including poor processability during malting and brewing, diminished storage quality, and potential threats to food safety and human health. Darkly pigmented fungi, also known as dematiaceous fungi, that spoil cereal grains during ripening and storage comprise a rich source of extracellular enzymes, including various cellulolytic enzymes and other polysaccharide-degrading enzymes, along with proteolytic enzymes, that can modify the physicochemical properties of cereal grains, contribute to substrate hydrolysis during germination, and may have a negative influence on malting and brewing properties. This review article addresses the potential impact of dark-pigmented fungi on malting and brewing quality beyond food safety. It summarizes the current knowledge on secreted fungal hydrolytic enzymes involved in barley grain degradation and discusses their potential impact in terms of malting and brewing quality, focusing on dematiaceous fungi and those causing black symptomatology on the grain. Overall, this review highlights the necessity for further research into the impact of dark-pigmented fungi on malting and brewing quality. [ABSTRACT FROM AUTHOR]

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC. [ABSTRACT FROM AUTHOR]

Aims The ultra-low-temperature cryoablation (ULTC) ablation system using −196°C N2 cryogen has been reported to create lesions with freeze duration–dependent depth titratable to over 10 mm with minimum attenuation by scar. Cryocure-VT (NCT04893317) was a first-in-human clinical trial evaluating the safety and efficacy of a novel, purpose-built ULTC catheter in endocardial ablation of scar-dependent ventricular tachycardias (VTs). Methods and results This prospective, multi-centre study enrolled patients referred for de novo or second ablations of recurrent monomorphic VT of both ischaemic and non-ischaemic aetiologies. Primary safety and efficacy endpoints of the study were freedom from device- or procedure-related major adverse events (MAEs) up to 30 days post-ablation, acute non-inducibility of clinical VTs at the end of the procedure, and freedom from sustained VT or implantable defibrillator intervention at 6 months. Ultra-low-temperature cryoablation was performed in 64 patients (age 67 ± 11 years, 78% ischaemic, ejection fraction = 35 ± 10%) at 9 centres. The primary acute effectiveness endpoint was achieved in 94% (51/54) of patients in whom post-ablation induction was attempted. There were no protocol-defined MAEs; four procedure-related serious adverse events resolved without clinical sequelae. At 6-month follow-up, 38 patients (60.3%) remained VT-free, and freedom from defibrillator shock was 81.0%, with no significant difference between ischaemic and non-ischaemic cohorts. In 47 patients with defibrillator for at least 6 months prior to the ablation, the VT burden was reduced from median of 4, inter-quartile range (IQR, 1–9) to 0, IQR (0–2). Conclusion In this first-in-human multi-centre experience, endocardial ULTC ablation of monomorphic VT appears safe and effective in patients with both ischaemic-cardiomyopathy and non-ischaemic-cardiomyopathy. Clinical Trial Registration NCT04893317. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Cosmetic Science is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12–1.64, P = 2×10−03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18–1.88, P = 9×10−04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07–4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes. Colitis is one of the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors. Here the authors show that a polygenic risk score for ulcerative colitis can predict immune checkpoint inhibitor-mediated colitis in patients with cancer. [ABSTRACT FROM AUTHOR]

CRK adaptor proteins are important for signal transduction mechanisms driving cell proliferation and positioning during vertebrate central nervous system development. Zebrafish lacking both CRK family members exhibit small, disorganized retinas with 50% penetrance. The goal of this study was to determine whether another adaptor protein might functionally compensate for the loss of CRK adaptors. Expression patterns in developing zebrafish, and bioinformatic analyses of the motifs recognized by their SH2 and SH3 domains, suggest NCK adaptors are well‐positioned to compensate for loss of CRK adaptors. In support of this hypothesis, proteomic analyses found CRK and NCK adaptors share overlapping interacting partners including known regulators of cell adhesion and migration, suggesting their functional intersection in neurodevelopment. [ABSTRACT FROM AUTHOR]

Repeating patterns of synovial joints are a highly conserved feature of articulated digits, with variations in joint number and location resulting in diverse digit morphologies and limb functions across the tetrapod clade. During the development of the amniote limb, joints form iteratively within the growing digit ray, as a population of distal progenitors alternately specifies joint and phalanx cell fates to segment the digit into distinct elements. While numerous molecular pathways have been implicated in this fate choice, it remains unclear how they give rise to a repeating pattern. Here, using single-cell RNA sequencing and spatial gene expression profiling, we investigate the transcriptional dynamics of interphalangeal joint specification in vivo. Combined with mathematical modeling, we predict that interactions within the BMP signaling pathway—between the ligand GDF5, the inhibitor NOGGIN, and the intracellular effector pSMAD—result in a self-organizing Turing system that forms periodic joint patterns. Our model is able to recapitulate the spatiotemporal gene expression dynamics observed in vivo, as well as phenocopy digit malformations caused by BMP pathway perturbations. By contrasting in silico simulations with in vivo morphometrics of two morphologically distinct digits, we show how changes in signaling parameters and growth dynamics can result in variations in the size and number of phalanges. Together, our results reveal a self-organizing mechanism that underpins amniote digit segmentation and its evolvability and, more broadly, illustrate how Turing systems based on a single molecular pathway may generate complex repetitive patterns in a wide variety of organisms. [ABSTRACT FROM AUTHOR]

Copyright of TW: Zeitschrift fuer Tourismuswissenschaft is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The thickness and other quality aspects of pharmaceutical coatings can be significantly impacted by coating process conditions. Under certain circumstances, they can notably influence the drug product performance such as dissolution profiles. Typically, a target coating thickness range is defined in the coating process. The coating thickness is conventionally measured off-line via weight or diameter gain. However, these established methods do not allow real-time monitoring of the product quality during the coating process. Further, options to react to any deviations are limited due to the lack of real-time information on the actual process and product state. The focus of this study was the development of a data-driven approach for real-time process control. Methods: Optical coherence tomography (OCT) is a novel technique for in-line monitoring of pharmaceutical coating processes, which acquires coherent and accurate data on coating thickness and other quality attributes in real-time. Using the quality by design (QbD) principles, this study developed and implemented an integrated approach for tracking the process and the coating layer quality in real-time. Data on coating thickness and roughness were compared with data obtained from optimal process conditions. Results: The integrated real-time process monitoring and control approach was executed and tested in a laboratory scale pan coating process. Coating runs with standard conditions and with intentional process upsets were performed. Using the real-time process trajectory to actively control the coating process, the dissolution profiles of the coated tablets produced in the event runs matched the optimal profiles well. Conclusion: Tracking the coating process trajectory via OCT is a novel method for controlling the coating process and the related product quality attributes in real-time. It can help to realise full benefits of real-time control in addition to end-point determination and can support product development activities as well as the operation during commercial manufacturing. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is a useful tool for polymorphic form-monitoring during the crystallization process. However, its application to solute concentration estimation in two-phase systems like crystallization is rare, as the Raman signal is influenced by various changing factors in the crystallization process. The development of a robust calibration model that covers all variations is complex and represents a major challenge for the implementation of Raman spectroscopy for in-line monitoring and control of the solution crystallization process. This paper describes the development of a Raman-based calibration model for estimating the solute concentration of the active pharmaceutical ingredient ceritinib. Several different calibration approaches were tested, which included both temperature and spectra of clear solutions and slurries/suspensions. It was found that the concentration of the ceritinib solution could not be accurately predicted when suspended crystals were present. To overcome this challenge, the approach was enhanced by including additional variables related to crystal size and solid concentration obtained via in-line process microscopy (chord-length distribution percentiles D10, D50 and D90) and turbidity. Partial least squares regression (PLSR) and artificial neural network (ANN) models were developed and compared based on root mean square error (RMSE). ANN models estimated the solute concentration with high accuracy, with the prediction error not exceeding 1% of the nominal solute concentration. [ABSTRACT FROM AUTHOR]

All realizations of the European Vertical Reference System (EVRS) computed so far are solely based on geopotential differences obtained by spirit leveling/gravimetry. As such, there are no direct connections between height benchmarks separated by large water bodies. In this study, such connections are added by means of model-based hydrodynamic leveling resulting in a new, yet unofficial realization of the EVRS. The model-derived mean water levels used in computing the hydrodynamic leveling connections were obtained from the Nemo-Nordic (Baltic Sea) and 3D DCSM-FM (northwest European continental shelf) hydrodynamic models. The impact of model-based hydrodynamic leveling on the European Vertical Reference Frame is significant, especially for France and Great Britain. Compared to a solution which only uses spirit leveling/gravimetry, the differences in these countries reach tens to hundreds of kgal mm . We also observed an improved agreement with normal heights obtained by differencing GNSS and the European gravimetric quasi-geoid 2015 (EGG2015) heights. In Great Britain, the south-north slope of 48 mm deg - 1 present in the solution which uses only spirit leveling/gravimetry data reduced to 2.2 mm deg - 1 . In France, the improvement is confined to the southwest. The choice of the period over which water levels are averaged has an impact on the results as it determines, among others, the set of tide gauges available to establish the hydrodynamic leveling connections. When using an averaging period that can be considered as the least preferred choice based on three established criteria, the positive impact for France has gone. For Great Britain, the estimated south-north slope became 12.6 mm deg - 1 . This is larger than the slope obtained using the most preferred averaging period but still substantially lower compared to the slope associated with a solution that uses only spirit leveling/gravimetry. [ABSTRACT FROM AUTHOR]

Aims Although the mechanism of an atrial tachycardia (AT) can usually be elucidated using modern high-resolution mapping systems, it would be helpful if the AT mechanism and circuit could be predicted before initiating mapping. Objective We examined if the information gathered from the cycle length (CL) of the tachycardia can help predict the AT-mechanism and its localization. Methods One hundred and thirty-eight activation maps of ATs including eight focal-ATs, 94 macroreentrant-ATs, and 36 localized-ATs in 95 patients were retrospectively reviewed. Maximal CL (MCL) and minimal CL (mCL) over a minute period were measured via a decapolar catheter in the coronary sinus. CL-variation and beat-by-beat CL-alternation were examined. Additionally, the CL-respiration correlation was analysed by the RhythmiaTM system. : Both MCL and mCL were significantly shorter in macroreentrant-ATs [MCL = 288 (253–348) ms, P = 0.0001; mCL = 283 (243–341) ms, P = 0.0012], and also shorter in localized-ATs [MCL = 314 (261–349) ms, P = 0.0016; mCL = 295 (248–340) ms, P = 0.0047] compared to focal-ATs [MCL = 506 (421–555) ms, mCL = 427 (347–508) ms]. An absolute CL-variation (MCL-mCL) < 24 ms significantly differentiated re-entrant ATs from focal-ATs with a sensitivity = 96.9%, specificity = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 66.7%. The beat-by-beat CL-alternation was observed in 10/138 (7.2%), all of which showed the re-entrant mechanism, meaning that beat-by-beat CL-alternation was the strong sign of re-entrant mechanism (PPV = 100%). Although the CL-respiration correlation was observed in 28/138 (20.3%) of ATs, this was predominantly in right-atrium (RA)-ATs (24/41, 85.7%), rather than left atrium (LA)-ATs (4/97, 4.1%). A positive CL-respiration correlation highly predicted RA-ATs (PPV = 85.7%), and negative CL-respiration correlation probably suggested LA-ATs (NPV = 84.5%). Conclusion Detailed analysis of the tachycardia CL helps predict the AT-mechanism and the active AT chamber before an initial mapping. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a major contributor to the onset and progression of cardiovascular disease (CVD). Cholesterol‐loaded foam cells play a pivotal role in forming atherosclerotic plaques. Induction of cholesterol efflux from these cells may be a promising approach in treating CVD. The reverse cholesterol transport (RCT) pathway delivers cholesteryl ester (CE) packaged in high‐density lipoproteins (HDL) from non‐hepatic cells to the liver, thereby minimising cholesterol load of peripheral cells. RCT takes place via a well‐organised interplay amongst apolipoprotein A1 (ApoA1), lecithin cholesterol acyltransferase (LCAT), ATP binding cassette transporter A1 (ABCA1), scavenger receptor‐B1 (SR‐B1), and the amount of free cholesterol. Unfortunately, modulation of RCT for treating atherosclerosis has failed in clinical trials owing to our lack of understanding of the relationship between HDL function and RCT. The fate of non‐hepatic CEs in HDL is dependent on their access to proteins involved in remodelling and can be regulated at the structural level. An inadequate understanding of this inhibits the design of rational strategies for therapeutic interventions. Herein we extensively review the structure–function relationships that are essential for RCT. We also focus on genetic mutations that disturb the structural stability of proteins involved in RCT, rendering them partially or completely non‐functional. Further studies are necessary for understanding the structural aspects of RCT pathway completely, and this review highlights alternative theories and unanswered questions. [ABSTRACT FROM AUTHOR]

Background: The impact of filtering on bipolar electrograms (EGMs) has not been systematically examined. We tried to clarify the optimal filter configuration for ventricular tachycardia (VT) ablation. Methods: Fifteen patients with VT were included. Eight different filter configurations were prospectively created for the distal bipoles of the ablation catheter: 1.0–250, 10–250, 100–250, 30–50, 30–100, 30–250, 30–500, and 30–1000 Hz. Pre‐ablation stable EGMs with good contact (contact force > 10 g) were analyzed. Baseline fluctuation, baseline noise, bipolar peak‐to‐peak voltage, and presence of local abnormal ventricular activity (LAVA) were compared between different filter configurations. Results: In total, 2276 EGMs with multiple bipolar configurations in 246 sites in scar and border areas were analyzed. Baseline fluctuation was only observed in the high‐pass filter of (HPF) ≤ 10 Hz (p <.001). Noise level was lowest at 30–50 Hz (0.018 [0.012–0.029] mV), increased as the low‐pass filter (LPF) extended, and was highest at 30–1000 Hz (0.047 [0.041–0.061] mV) (p <.001). Conversely, the HPF did not affect the noise level at ≤30 Hz. As the HPF extended to 100 Hz, bipolar voltages significantly decreased (p <.001), but were not affected when the LPF was extended to ≥100 Hz. LAVAs were most frequently detected at 30–250 Hz (207/246; 84.2%) and 30–500 Hz (208/246; 84.6%), followed by 30–1000 Hz (205/246; 83.3%), but frequently missed at LPF ≤ 100 Hz or HPF ≤ 10 Hz (p <.001). A 50‐Hz notch‐filter reduced the bipolar voltage by 43.9% and LAVA‐detection by 34.5% (p <.0001). Conclusion: Bipolar EGMs are strongly affected by filter settings in scar/border areas. In all, 30–250 or 30–500 Hz may be the best configuration, minimizing the baseline fluctuation, baseline noise, and detecting LAVAs. Not applying the 50‐Hz notch filter may be beneficial to avoid missing VT substrate. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the current resistance situation concerning routinely used antibiotics for treatment in odontogenic abscesses. Materials and methods: This retrospective study assessed patients with deep space head and neck infections who were treated by surgical intervention under general anesthesia at our department. The target parameter was the ascertainment of the resistance rates in order to identify the bacterial spectrum, sites in the body, length of inpatient stay, and the age and sex of the patients. Results: A total of 539 patients, 268 (49.7%) males and 271 (50.3%) females were included in the study. The mean age was 36.5 ± 22.1 years. There was no significant difference between the two sexes with regard to the mean duration of hospitalization (p = 0.574). The predominant bacteria in the aerobic spectrum were streptococci of the viridans group and staphylococci, in the anaerobic spectrum Prevotella and Propionibacteria spp. Rates of resistance to clindamycin were between 34 and 47% in both the facultative and obligate anaerobic spectrum. Increased resistance was likewise found in the facultative anaerobic spectrum, with 94% resistance to ampicillin and 45% to erythromycin. Conclusion: Due to the increasing levels of resistance to clindamycin, their use in empiric antibiotic treatment for deep space head and neck infections should be viewed critically. Clinical relevance: Resistance rates continue to increase compared to previous studies. The use of these antibiotic groups in patients with a penicillin allergy needs to be called into question and alternative medications sought. [ABSTRACT FROM AUTHOR]

Advances in chip-scale photonic-electronic integration are enabling a new generation of foundry-manufacturable implantable silicon neural probes incorporating nanophotonic waveguides and microelectrodes for optogenetic stimulation and electrophysiological recording in neuroscience research. Further extending neural probe functionalities with integrated microfluidics is a direct approach to achieve neurochemical injection and sampling capabilities. In this work, we use two-photon polymerization 3D printing to integrate microfluidic channels onto photonic neural probes, which include silicon nitride nanophotonic waveguides and grating emitters. The customizability of 3D printing enables a unique geometry of microfluidics that conforms to the shape of each neural probe, enabling integration of microfluidics with a variety of existing neural probes while avoiding the complexities of monolithic microfluidics integration. We demonstrate the photonic and fluidic functionalities of the neural probes via fluorescein injection in agarose gel and photoloysis of caged fluorescein in solution and in fixed brain tissue. [ABSTRACT FROM AUTHOR]

Antibacterial nonwoven fabrics, incorporated with Ag, have been applied as masks and air conditioner filters to prevent the spread of disease from airborne respiratory pathogens. In this work, we present a comparison study of Ag ions: Ag and AgCu nanoparticles (NPs) coated onto nonwoven fabrics intended for use as air conditioner antibacterial filters. We illustrate their color changes and durability running in air conditioners using antibacterial activity testing and X-ray Photoelectron Spectroscopic (XPS) analysis. We found that AgCu NPs showed the best antibacterial efficacy and durability. XPS analysis indicated that the Ag concentration, on both the AgCu and Ag- NP-coated fibers, changed little. On the contrary, the Ag concentration on Ag ion-coated fibers decreased by ~30%, and the coated NPs aggregated over time. The color change in AgCu NP-coated fabric, from yellow to white, is caused by oxide shell formation over the NPs, with nearly 46% oxidized silver. Our results, both from antibacterial evaluation and wind blowing tests, indicate that AgCu NP-coated fibers have higher durability, while Ag ion-coated fibers have little durability in such applications. The enhanced durability of the AgCu NP-coated antibacterial fabrics can be attributed to stronger NP–fiber interactions and greater ion release. [ABSTRACT FROM AUTHOR]

Copyright of Ius Humani is the property of Ius Humani and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS), in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval. The emergence of novel KRAS-targeted therapies warrants the development of evidence-based consensus recommendations to help clinicians better understand and contextualize the available data. A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on recommendations for the treatment of advanced KRAS G12C-mutated NSCLC. The panel agreed that testing for KRAS G12C should be performed as part of a comprehensive panel that includes current standard-of-care biomarkers. Sotorasib, the only approved KRAS G12C inhibitor in Canada, is recommended for patients with advanced KRAS G12C-mutated NSCLC who progressed on guideline-recommended first-line standard of care for advanced NSCLC without driver alterations (immune-checkpoint inhibitor(s) [ICIs] +/− chemotherapy). Sotorasib could also be offered as second-line therapy to patients who progressed on ICI monotherapy that are not candidates for a platinum doublet and those that received first-line chemotherapy with a contraindication to ICIs. Preliminary data indicate the activity of KRAS G12C inhibitors in brain metastases; however, the evidence is insufficient to make specific recommendations. Regular liver function monitoring is recommended when patients are prescribed KRAS G12C inhibitors due to risk of hepatotoxicity. [ABSTRACT FROM AUTHOR]

This work concerns two stages of research into plasma nitriding (change of nitriding steel and modification of nitriding parameters). In the first stage, pins obtained from currently used steel were compared with pins made of an alternative material available on the market, using the same nitriding process parameters. As a result of the metallographic tests carried out, in the first case, the presence of a thin, porous, and heterogeneous nitrided layer or its absence was found, with the core in its raw state and not thermally improved. In the second case, the presence of a nitrided layer of small thickness with noticeable porosity on the surface of the sample was found, but with a core after heat treatment (incorrect process parameters). Therefore, modification of the parameters of the nitriding process was proposed, in terms of a mixture of gases, currents, time, and temperature of the nitriding process. As a result, a satisfactory effective thickness of the nitrided layer was obtained, consisting of a white near-surface zone with ε and ε + γ′-type nitrides with a thickness of 8.7 to 10.2 µm, and a dark zone of internal nitriding with γ′ nitrides. The nitrides layer was continuous, compact, and well adhered to the steel surface. In the core of the samples, the presence of a fine-needle tempering sorbite structure with a small amount of fine bainite, which is correct for the steel after heat treatment and nitriding, was found. The most favorable parameters of the ion nitriding process were gas flow rate (1.5 L/min N; 0.4 L/min H; 0.3 L/min Ar); currents (BIAS—410 V 4.0 A, SCREEN—320 V 4.0 A); time (26 h and 35 min); and temperature (550 °C). [ABSTRACT FROM AUTHOR]

Copyright of Kemija u Industriji is the property of Croatian Society of Chemical Engineers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Glacier tourism is an important form of travel in the Alps that is currently threatened by climate change. Previous studies have shown that glaciers are retreating worldwide, and media coverage has led to the development of last-chance tourism. However, few studies have focused on the European Alps, and glacier site visitors have not been segmented based on their motivations yet, hindering the understanding of different profiles. Therefore, using a latent class analysis, this study reveals that the 1330 survey respondents from six glacier tourism sites (Montenvers, Nid d'Aigle, Glacier Blanc, Rhône Glacier, Aletsch Glacier, and Franz–Josefs–Höhe/Pasterze) in three alpine countries (France, Switzerland, and Austria) can be segmented into four classes based on their motivations and other factors. Among them, the "last chance" and "climate visitor" classes were identified, representing between 50% and 57% of the respondents from the investigated sites. The results also indicate that visitors' motivations are stable across sites and that glaciers are the object of last-chance tourism. This research contributes to the fields of glacier tourism and last-chance tourism by proposing a segmentation of visitors and allowing the generalisation of the presence of last-chance tourism for glacier tourism sites in the Alps. [ABSTRACT FROM AUTHOR]

The 12‐lead electrocardiogram (ECG) is a fundamental modality to help determine the mechanism and the localization of atrial tachycardias (ATs). Although macroreentrant ATs and focal ATs typically show F‐waves and discrete P‐waves respectively on the 12‐lead ECG, this is not universally the case in scar‐related ATs.1, We present three cases clearly showing the discrepancy between the AT morphology on the 12‐lead ECG and the AT‐mechanism. [ABSTRACT FROM AUTHOR]

The infrapatellar fat pad (IPFP) has been implicated as a source of postoperative knee pain. Imaging the IPFP is challenging in patients with total knee arthroplasty (TKA) due to metallic susceptibility artifact. Multi‐Acquisition Variable‐Resonance Image Combination (MAVRIC)‐based T2 Mapping has been developed to mitigate this artifact and can generate quantitative T2 data. Objectives of this study were to (1) measure T2 values of the IPFP in patients with TKAs using a MAVRIC based T2 mapping technique and (2) determine if IPFP T2 values are related to the degree of fat pad scarring or clinical magnetic resonance imaging (MRI) findings. Twenty‐eight subjects (10 males, 18 females, Age: 66 + 7.2 years [Mean ± standard deviations]) undergoing clinical MRIs were sequentially recruited. Morphological imaging and quantitative T2 mapping sequences were performed on a clinical 1.5 T scanner. The morphologic images were graded for the presence and severity of fat pad scarring and clinical outcomes. T2 values were calculated in the total fat pad volume, a normal regions of interest (ROI), and an abnormal ROI. T2 values were shortened in the total IPFP volume (p = 0.001) and within abnormal regions (p = 0.003) in subjects with more severe IPFP scarring. The difference between T2 values in normal−abnormal regions was greater in subjects with severe versus no scarring (+1426.1%, p = 0.008). T2 values were elevated in patients with MRI findings of osteolysis (+32.3%, p = 0.02). These findings indicate that MAVRIC‐based T2 Mapping may be used as a quantitative biomarker of postoperative IPFP scarring in individuals following TKA. [ABSTRACT FROM AUTHOR]

Laser beam scanning is central to many applications, including displays, microscopy, three-dimensional mapping, and quantum information. Reducing the scanners to microchip form factors has spurred the development of very-large-scale photonic integrated circuits of optical phased arrays and focal plane switched arrays. An outstanding challenge remains to simultaneously achieve a compact footprint, broad wavelength operation, and low power consumption. Here, we introduce a laser beam scanner that meets these requirements. Using microcantilevers embedded with silicon nitride nanophotonic circuitry, we demonstrate broadband, one- and two-dimensional steering of light with wavelengths from 410 nm to 700 nm. The microcantilevers have ultracompact ~0.1 mm2 areas, consume ~31 to 46 mW of power, are simple to control, and emit a single light beam. The microcantilevers are monolithically integrated in an active photonic platform on 200-mm silicon wafers. The microcantilever-integrated photonic circuits miniaturize and simplify light projectors to enable versatile, power-efficient, and broadband laser scanner microchips. This work presents ultracompact and low-power laser beam scanners using microcantilevers embedded with nanophotonic circuits. These chip-scale devices are made in a semiconductor foundry and project visible light patterns in one or two dimensions. [ABSTRACT FROM AUTHOR]

Copyright of Manuelle Medizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)