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An analytical investigation on the plastic zone size of a crack near a coated circular inclusion under three different loading conditions of uniaxial tension, uniform tension and pure shear was carried out. Both the crack and coated circular inclusion are embedded in an infinite matrix, with the crack oriented along the radial direction of the inclusion. In the solution procedure, the crack is simulated as a continuous distribution of edge dislocations. With the Dugdale model of small-scale yielding [J. Mech. Phys. Solids 8 (1960) p. 100], two thin strips of yielded plastic zones are introduced at both crack tips. Using the solution for a coated circular inclusion interacting with a single dislocation as the Green's function, the physical problem is formulated into a set of singular integral equations. Using the method of Erdogan and Gupta [Q. J. Appl. Math. 29 (1972) p. 525] and iterative numerical procedures, the singular integral equations are solved numerically for the plastic zone sizes and crack tip opening displacement. [ABSTRACT FROM AUTHOR]

Erbium laser phacoemulsification – a pilot study Introduction From August 1997 to March 1998 a prospective pilot study was performed to examine erbium laser phacoemulsification in cataract surgery under clinical conditions and to determine the side-effects of this method. Patients and method 34 patients (40 eyes) with senile cataract were recruited. Slit lamp findings, keratometry, best corrected visual acuity, refraction, pachymetry, endothelial cell count, and intraocular pressure were determined preoperatively and on postoperative days 1, 4, 14, and 60, according to a standardized protocol (single pulse energy between 10 and 20 mJ, frequency of application 60 Hz, average phacoemulsification time 3 min, and total energy 38.5 J). The operations were done with the erbium laser system MCL 29 (Aesculap-Meditec Co., Jena, Germany). Results A total emulsification of the nucleus was possible in 36 of the 40 eyes (90%) (nucleus hardness 0–3). A partial emulsification of the nucleus (nucleus hardness 3) was possible in 2 eyes (nucleus hardness 4) in 1 eye, and (nucleus hardness 2) in 1 eye. Visual acuity increased from 0.3 preoperatively to 0.8 two months postoperatively (median). Intraocular pressure decreased from 16 mmHg preoperatively to 13 mmHg two months postoperatively (median). The increase of corneal thickness was not statistically significant compared to baseline. The decrease in endothelial cells count was 0.96%. Postoperative complications which are not known in ultrasonic phacoemulsification did not appear in erbium laser phacoemulsification. Conclusion Erbium laser phacoemulsification is a surgical method that makes the emulsification of softer nuclei under clinical conditions possible with a low rate of complications also at the beginning of the learning curve. For harder nuclei technical and surgical parameters have to be optimized. Advantages of erbium laser phacoemulsification compared to ultrasonic phacoemulsification are less energy... [ABSTRACT FROM AUTHOR]

Introduction: Serum carcinoembryonic antigen (CEA) is prognostic for recurrence and survival in treated NSCLC. This prospective observational study evaluated CEA as a prognostic or surveillance biomarker in resectable early NSCLC., Materials and Methods: 18 patients with histologically confirmed early NSCLC (stage I-IIIA) were recruited from October 2019 to January 2021. The serum CEA was measured pre-operatively, and then at 6, 12, 18 and 24 months post-operatively, in conjunction with routine CT and/or CT-PET surveillance scans., Results: All patients had a curative R0 anatomical resection (lobectomy) with concurrent systematic mediastinal nodal dissection via a uniportal minimally invasive approach under single lung ventilation general anaesthesia. There was no operative, in-hospital or 30-day mortality. 7 patients (39%) had an elevated pre-operative baseline CEA level > 5.0ng/ml. The mean number of nodes sampled intraoperatively was 15. At median follow-up of 42 months, 11/18 (61.1%) patients were recurrence-free. There were no deaths and two recurrences (18.2%) amongst patients with a CEA < 5 (n=11). In the CEA > 5 subgroup (n=7), there were two deaths (28.5%) and 5/7 (71.4%) patients had a radiological recurrence. There was no difference in overall survival however disease-free survival (DFS) was significantly inferior in patients with a baseline CEA > 5. Median DFS was not reached in patients with CEA < 5 and 18 months in those with an elevated CEA > 5 (p<0.001) Conclusion: Almost 40% of local NSCLC patients had an elevated baseline CEA suggesting this is a useful prognostic and surveillance biomarker to incorporate in the routine work-up for any newly diagnosed NSCLC. Despite curative R0 resection and extensive intra-operative mediastinal lymph node sampling, an elevated pre-operative CEA was associated with a significantly reduced DFS and may be a surrogate for more aggressive tumour biology. Such patients will benefit from meticulous post resection surveillance and adjuvant therapy beyond conventional TNM criteria.

The properties and functions of chromophores utilized by nature are strongly affected by the environment formed by the protein structure in the cells surrounding them. This concept is transferred here to host-guest complexes with the encapsulated guests acting as an environmental stimulus. A new cyclophane host based on coronene bisimide is presented that can encapsulate a wide variety of planar guest molecules with binding constants up to (4.29 ± 0.32) × 10 10 M -1 in chloroform. Depending on the properties of the chosen guest, the excited state deactivation of the coronene bisimide chromophore can be tuned by the formation of host-guest complexes toward fluorescence, exciplex formation, charge separation, room-temperature phosphorescence (RTP), or thermally activated delayed fluorescence (TADF). The photophysical processes were investigated by UV/vis absorption, emission, and femto- and nanosecond transient absorption spectroscopy. To enhance the TADF, two different strategies were used by employing suitable guests: the reduction of the singlet-triplet gap by exciplex formation and the external heavy atom effect. Altogether, by using supramolecular host-guest complexation, a versatile multimodal chromophore system is achieved with the coronene bisimide cyclophane.

Background & objectives The results of the genetic association studies between the selected candidate genes and hypertension (HT) contradicted across different populations. Majority of the meta-analyses carried out did not consider population genetic ancestry as a confounding factor. Therefore, this meta-analysis attempted to consolidate and re-evaluate the findings of the association between the selected candidate variants (AGT-rs699, CYP11B2-rs1799998, ADRB2-rs1042713 and rs1042714) and HT, by categorizing the genotyping data based on known genetic ancestry, and/or major geographical populations. Methods Publications were retrieved from PubMed, Cochrane and World of Science. The included articles were further divided into different populations based on their known genetic and/or geographical ancestry. Results AGTrs699-G was significantly associated with HT among Indians for (i) allele [P=0.03, Odds ratio (OR): 1.37, 95% Confidence Interval (CI): 1.03-1.82], and (ii) dominant mode of inheritance (P=0.009, OR:1.45, 95% CI: 1.09-1.91). CYP11B2rs1799998-G was significantly associated with HT in Europeans for (i) allele (P=6.9 × 10-5, OR: 0.82, 95% CI: 0.74-0.9), (ii) recessive (P=6.38 × 10-5, OR: 0.7, 95% CI: 0.59-0.83) and (iii) dominant mode of inheritance (P=0.008, OR: 0.81, 95% CI: 0.7-0.94). ADRB2-rs1042713-G was significantly associated with HT in east Asians for (i) allele (P=0.01, OR: 1.26, 95% CI: 1.05-1.51), and (ii) recessive mode of inheritance (P=0.04, OR: 1.36, 95% CI: 1.01-1.83). Interpretation & conclusions Different genotype and allele frequencies in diverse populations result in different genetic associations with HT across populations. This meta-analysis finding provides an update and summary of the genetic association between the selected simple nucleotide polymorphism (SNPs) and HT across different populations and essential insights into selecting appropriate pharmacogenetic marker(s) for effective HT management in populations of different ancestries.

Interleukin-1 receptor-associated kinase 3 (IRAK3) is a pseudokinase mediator in the human inflammatory pathway, and ablation of its function is associated with enhanced antitumor immunity. Traditionally, pseudokinases have eluded "druggability" and have not been considered tractable targets in the pharmaceutical industry. Herein we disclose a CRISPR/Cas9-mediated knockout of IRAK3 in monocyte-derived dendritic cells that results in an increase in IL-12 production upon lipopolysaccharide (LPS) stimulation. Furthermore, we disclose and characterize Degradomer D-1, which displays selective proteasomal degradation of IRAK3 and reproduces the 1L-12p40 increases observed in the CRISPR/Cas9 knockout.

Apologizing is an effective interpersonal conflict resolution strategy, but whether, and if so how, organizations should issue public apologies after crises remains less clear. To assuage the fear of possible crisis reoccurrence, public apologies may be effective when they provide a comprehensive account of what happened and clarify actions taken by the company to address the problems. If this is so, public apologies may be most effective when the crisis source resides within the organization itself, suggesting that the company has control over it. In the current study, we first tested this hypothesis by presenting participants with multiple crisis scenarios (e.g., ignition failures in a new car model) followed by one of two written apologies: one stating that the crisis source was internal to and controllable by the organization, and the other external and uncontrollable. The internal-controllable (IC) public apology proved most effective. We then examined the neural basis of this public apology assessment and found that the frontal polar cortex appears to mediate the assessment of organizational control, and the angular gyrus uses the information for the apology assessment. Examination of complex social interactions, such as the public's reaction to corporate crises, helps to elucidate high-level brain function.

Objective: The purpose of this study was to evaluate the applicability of data obtained from a wearable activity tracker (Fitbit Charge HR) to medical research. This was performed by comparing the wearable activity tracker (Fitbit Charge HR) with actigraphy (Actiwatch 2) for sleep evaluation and circadian rest-activity rhythm measurement., Methods: Sixteen healthy young adults (female participants, 62.5%; mean age, 22.8 years) wore the Fitbit Charge HR and the Actiwatch 2 on the same wrist; a sleep log was recorded over a 14-day period. We compared the sleep variables and circadian rest-activity rhythm measures with Wilcoxon signed-rank tests and Spearman's correlations., Results: The periods and acrophases of the circadian rest-activity rhythms and the sleep start times did not differ and correlated significantly between the Fitbit Charge HR and the Actiwatch 2. The Fitbit Charge HR tended to overestimate the sleep durations compared with the Actiwatch 2. However, the sleep durations showed high correlation between the two devices for all days., Conclusion: We found that the Fitbit Charge HR showed high accuracy in sleep evaluation and circadian rest-activity rhythm measurement when compared with actigraphy for healthy young adults. The results suggest that the Fitbit Charge HR could be applicable on medical research as an alternative tool to actigraphy for sleep evaluation and measurement of the circadian rest-activity rhythm.

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs) contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV) were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the "foetal cardiac gene programme" which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability.

While social media has become an important platform for social reputation, the emotional responses of users toward bad news have not been investigated thoroughly. We analyzed a total of 20,773 Twitter messages by 15,513 users to assess the influence of bad news and public apology in social media. Based on both computerized, quantitative sentiment analysis and in-depth qualitative analysis, we found that rapid public apology effectively and immediately reduced the level of negative sentiment, where the degree of change in sentiments differed by the type of interactions users engaged in. The majority of users who directly conversed with corporate representatives on the new media were not typical consumers, but experts and practitioners. We extend the existing cognitive model and suggest the audiences' psychological reaction model to describe the information processing process during and after an organizational crisis and response. We also discuss various measures through which companies can respond to a crisis properly in social media in a fashion that is different from conventional mass media.

The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method's performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs.

Background: Dengue is a major public health problem in many tropical and sub-tropical countries. Vascular leakage and shock are identified as the major causes of deaths in patients with severe dengue. Studies have suggested the potential role of Fc gamma receptors I (FcγRI) in the pathogenesis of dengue. We hypothesized that the circulating level of Fcγ receptor I could potentially be used as an indicator in assisting early diagnosis of severe dengue., Results: A selected cohort of 66 dengue patients including 42 dengue with signs of vascular leakage, and 24 dengue without signs of vascular leakage were identified and were afterwards referred to as 'cases' and 'controls' respectively. Thirty seven normal healthy controls were also recruited in this study. The circulating level of FcγRI was quantified from the serum using enzyme-link immunosorbent assay (ELISA). The levels of FcγRI in both groups of patients with and without vascular leakage were found to be significantly higher than the normal healthy controls (P < 0.001). However, there was no significant difference found between patients with vascular leakage and those without vascular leakage (p = 0.777)., Conclusion: We suggest that FcγRI is not associated with the vascular leakage in dengue. However, further studies are necessary to delineate the role of FcγRI in antibody-dependent enhancement (ADE) mechanism.

The ultimate goal of human genetics is to understand the role of genome variation in elucidating human traits and diseases. Besides single nucleotide polymorphism (SNP), copy number variation (CNV), defined as gains or losses of a DNA segment larger than 1 kb, has recently emerged as an important tool in understanding heritable source of human genomic differences. It has been shown to contribute to genetic susceptibility of various common and complex diseases. Despite a handful of publications, its role in cardiovascular diseases remains largely unknown. Here, we deliberate on the currently available technologies for CNV detection. The possible utility and the potential roles of CNV in exploring the mechanisms of cardiac remodeling in hypertension will also be addressed. Finally, we discuss the challenges for investigations of CNV in cardiovascular diseases and its possible implications in diagnosis of hypertension-related left ventricular hypertrophy (LVH).

Type IV collagen, the major component of basement membrane (BM), demonstrates a stage- and position-specific distribution of its isoforms during tooth development. To determine its localization in BM of odontogenic neoplasms, immunohistochemistry using six anti-alpha(IV) chain-specific monoclonal antibodies was performed. Results disclosed that BM demonstrated an irregular alpha(IV) chain profile in malignant odontogenic tumors as compared to benign odontogenic neoplasms. No alpha3(IV) chains were detected. Expression of alpha1(IV)/alpha2(IV) and alpha5(IV)/alpha6(IV) chains was stronger in desmoplastic ( n=3) than in ordinary (n=5) ameloblastomas. The adenomatoid odontogenic tumor ( n=2) distinctly expressed these chains in BM of cribriform areas and hyaline materials (which was also alpha4(IV)-positive), but weakly around epithelial whorls/rosettes/nests and mineralized foci. These five chains also stained BM and tumor cells of ameloblastic fibroma ( n=3) and ameloblastic fibro-odontosarcoma (n=1), but not the inductive hard tissues. Ameloblastic carcinoma ( n=2) showed specific alpha1(IV)/alpha2(IV) chain loss, while primary intraosseous carcinoma ( n=1) demonstrated a discontinuous alpha1(IV)/alpha2(IV) and alpha5(IV)/alpha6(IV) staining pattern. The present results suggest that modification and remodeling of BM collagen IValpha chains occur during odontogenic neoplasms' progression.