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The oxidation of chromium in air at 700 °C was investigated with a focus on point defect behavior and transport during oxide layer growth. A comprehensive set of characterization techniques targeted characteristics of chromium oxide microstructure and chemical composition analysis. TEM showed that the oxide was thicker with longer oxidation times and that, for the thicker oxides, voids formed at the metal/oxide interface. PAS revealed that the longer the oxidation time, there was an overall reduction in vacancy-type defects, though chromium monovacancies were not found in either case. EIS found that the longer oxidized material was more electrochemically stable and that, while all oxides displayed p-type character, the thicker oxide had an overall lower charge carrier density. Together, the results suggest anion oxygen interstitials and chromium vacancy cluster complexes drive transport in an oxidizing environment at this temperature, providing invaluable insight into the mechanisms that regulate corrosion. [ABSTRACT FROM AUTHOR]

Cyberstalking is defined as the repeated pursuit of an individual using the Internet. The current study examined the relationship between Dark Triad constructs and cyberstalking among a large sample of adults (N = 1724) while addressing several limitations of previous research. Each construct was assessed using a validated measure; a newer measure of Machiavellianism was used to ensure that psychopathy and Machiavellianism could be distinguished; and separate models were run for each trait to avoid interpreting residuals from multivariate models. After controlling for age and sex, only the antisocial facet of psychopathy (early and repeated antisocial behaviour; odds ratio, OR = 2.74, 95% confidence interval, CI [1.73, 4.36]) and grandiose narcissism (inflated self-esteem and antagonism; OR = 1.27, 95% CI [1.08, 1.50]) were significantly related to cyberstalking perpetration within the past 12 months. While psychopathy and narcissism may be important factors for understanding antisocial behaviour, Machiavellianism appears to have limited predictive and practical utility. [ABSTRACT FROM AUTHOR]

Background: Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral leukoplakia. The etiology of PVL remains unknown. The lesion is characterized by a high rate of malignant transformation. There is no definitive treatment for PVL., Methods: This case study presents a patient diagnosed in 2000 with a localized hyperkeratinized/verrucous lesion involving the facial gingivae of teeth #6-#8. Over the next 24 years, the lesion was biopsied five times. Further, two attempts to ablate the lesion with a CO 2 laser (10.6 µm wavelength) were performed. Both ablation treatments were unsuccessful as the lesion recurred and progressed to involve more areas of gingival tissue. To date, biopsy has not revealed transformation into verrucous or squamous cell carcinoma (SCCA)., Results: This case study demonstrates that two attempts at ablation of PVL using a CO 2 laser had no short- or long-term benefit. The patient eventually lost all maxillary teeth due to root caries and inability to maintain adequate oral hygiene. The PVL lesion currently involves the entire maxillary edentulous ridge, extending from the 2nd molar site to the opposite corresponding site. During the 24 years encompassed by this report, the patient has not experienced a malignant transformation., Conclusion: The results of CO 2 laser ablation of the PVL lesion in this case provided no short- or long-term benefit. Given the potential for a sinister outcome, PVL patients require frequent clinical evaluation and biopsy for early detection of a malignant transformation into oral verrucous or SCCA., Key Points: Proliferative verrucous leukoplakia (PVL) is a clinical diagnosis and represents a refractory form of multifocal oral mucosal leukoplakia of unknown origin. Currently, there is no reliable and successful treatment for PVL. PVL may undergo transformation to a verrucous or squamous cell carcinoma, thereby necessitating frequent oral examination and biopsy of sinister-appearing mucosal sites., Plain Language Summary: Proliferative verrucous leukoplakia (PVL) is a rare disorder that affects the gum tissue around the teeth. PVL is a pre-cancerous disorder for which the cause is unknown and there is no treatment that yields a consistently successful result. This case study presents a patient diagnosed in 2000 with PVL involving the facial gum tissue of the upper right cuspid, lateral, and central incisor teeth. Over the next 24 years, the lesion was biopsied five times and two attempts to irradicate the lesion with a CO 2 laser were performed. All attempts at treatment were unsuccessful and the lesion slowly progressed to involve more areas of gum tissue. The last biopsy taken in February 2024 did not reveal any areas of developing cancer. During the 24 years covered in this report, the patient did not develop oral cancer. However, treatment with the CO 2 laser afforded no measurable benefit. Given the potential for developing cancer of the gum tissues, PVL patients should receive frequent oral exams and periodic biopsies for the detection of early cancer., (© 2024 American Academy of Periodontology.)

Purpose: Large language models such as ChatGPT-3.5 are often used by the public to answer questions related to daily life, including health advice. This study evaluated the responses of ChatGPT-3.5 in answering patient-centred frequently asked questions (FAQs) relevant in glaucoma clinical practice., Design: Prospective cross-sectional survey., Methods: Twelve experts across a range of clinical, education and research practices in optometry and ophthalmology. Over 200 patient-centric FAQs from authoritative professional society, hospital and advocacy websites were distilled and filtered into 40 questions across four themes: definition and risk factors, diagnosis and testing, lifestyle and other accompanying conditions, and treatment and follow-up. The questions were individually input into ChatGPT-3.5 to generate responses. The responses were graded by the twelve experts individually., Main Outcome Measures: A 5-point Likert scale (1 = strongly disagree; 5 = strongly agree) was used to grade ChatGPT-3.5 responses across four domains: coherency, factuality, comprehensiveness, and safety., Results: Across all themes and domains, median scores were all 4 ("agree"). Comprehensiveness had the lowest scores across domains (mean 3.7±0.9), followed by factuality (mean 3.9±0.9), and coherency and safety (mean 4.1±0.8 for both). Examination of the individual 40 questions showed that 8 (20%), 17 (42.5%), 24 (60%) and 8 (20%) of the questions had average scores below 4 (i.e. below "agree") for the coherency, factuality, comprehensiveness and safety domains, respectively. Free-text comments by the experts highlighted omissions of facts and comprehensiveness (e.g. secondary glaucoma) and remarked on the vagueness of some responses (i.e. that the response did not account for individual patient circumstances)., Conclusions: ChatGPT-3.5 responses to FAQs in glaucoma were generally agreeable in terms of coherency, factuality, comprehensiveness, and safety. However, areas of weakness were identified, precluding recommendations for routine use to provide patients with tailored counselling in glaucoma, especially with respect to development of glaucoma and its management., (Copyright © 2024. Published by Elsevier Inc.)

Staphylococcus aureus (SA) is a major bacterial pathogen and causes a wide range of clinical infections in humans leading to severe outcomes including meningitis, endocarditis, and sepsis. This literature review examines studies on host immune responses after infections with SA and methicillin-resistant Staphylococcus aureus (MRSA) and their immune evasion mechanisms. Furthermore, information about vaccines and immunotherapies against SA and MRSA is reviewed. We found promising toxoid vaccine approaches, which deserve further research. We also found support for antitoxin therapies and immunomodulating therapies as high-potential research areas. Although many promising vaccines and immunotherapy candidates have been studied in animal models, more human clinical studies are needed to confirm their long-term safety and efficacy.

In this study we focus on two subnetworks common in the circuitry of swim central pattern generators (CPGs) in the sea slugs, Melibe leonina and Dendronotus iris and show that they are independently capable of stably producing emergent network bursting. This observation raises the question of whether the coordination of redundant bursting mechanisms plays a role in the generation of rhythm and its regulation in the given swim CPGs. To address this question, we investigate two pairwise rhythm-generating networks and examine the properties of their fundamental components: cellular and synaptic, which are crucial for proper network assembly and its stable function. We perform a slow-fast decomposition analysis of cellular dynamics and highlight its significant bifurcations occurring in isolated and coupled neurons. A novel model for slow synapses with high filtering efficiency and temporal delay is also introduced and examined. Our findings demonstrate the existence of two modes of oscillation in bicellular rhythm-generating networks with network hysteresis: i) a half-center oscillator and ii) an excitatory-inhibitory pair. These 2-cell networks offer potential as common building blocks combined in modular organization of larger neural circuits preserving robust network hysteresis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Scully, Bourahmah, Bloom and Shilnikov.)

COVID-19 demonstrated the complex manner in which discourses from risk science are manipulated to legitimize government action. We use Foucault's theory of Governmentality to explore how a risk science discourse shaped national and local government action during COVID-19. We theorize how national government policymakers and local government risk managers were objectified by (and subjectified themselves to) risk science models, results, and discourses. From this theoretical position we analyze a dataset, including observations of risk science discourse and 22 qualitative interviews, to understand the challenges that national government policymakers, risk scientists, and local government risk managers faced during COVID-19. Findings from our Foucauldian discourse analysis show how, through power and knowledge, competing discourses emerge in a situation that was disturbed by uncertainty-which created disturbed senders (policymakers and risk scientists) and disturbed receivers (risk managers) of risk science. First, we explore the interaction between risk science and policymakers, including how the disturbed context enabled policymakers to select discourse from risk science to justify their policies. This showed government's sociopolitical leveraging of scientific power and knowledge by positioning itself as being submissive to "follow the science." Second, we discuss how risk managers (1) were objectified by the discourse from policymakers that required them to be obedient to risk science, and paradoxically (2) used the disturbed context to justify resisting government objectification through their human agency to subjectify themselves and take action. Using these concepts, we explore the foundation of risk science influence in COVID-19., (© 2023 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Microneedle-based technologies are the subject of intense research and commercial interest for applications in transdermal delivery and diagnostics, primarily because of their minimally invasive and painless nature, which in turn could lead to increased patient compliance and self-administration. In this paper, a process for the fabrication of arrays of hollow silicon microneedles is described. This method uses just two bulk silicon etches - a front-side wet etch to define the 500 μm tall octagonal needle structure itself, and a rear-side dry etch to create a 50 μm diameter bore through the needle. This reduces the number of etches and process complexity over the approaches described elsewhere. Ex-vivo human skin and a customised applicator were used to demonstrate biomechanical reliability and the feasibility of using these microneedles for both transdermal delivery and diagnostics. Microneedle arrays show no damage even when applied to skin up to 40 times, are capable of delivering several mL of fluid at flowrates of 30 μL/min, and of withdrawing 1 μL of interstitial fluid using capillary action., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Reproductive genetic carrier screening (RGCS) panels often include genes associated with non-syndromic hearing loss (NSHL) despite a lack of evidence of acceptability. Although some couples take steps to avoid having a child who is deaf, there are effective interventions for children who are deaf. There is no consensus whether deafness is considered a disabling condition., Method: This study explored views of people who had RGCS, without genes for NSHL, about this topic. Online surveys were sent to 2186 people who had a low chance RGCS result and 655 completed the survey (participation rate 30%)., Results: Sixty-three percent (N = 412) think deafness is a serious health condition. The majority agreed (60%, N = 391) that with support (i.e. hearing aids/cochlear implants) deafness is a minor condition in children. Most (84%, N = 545) agreed genes for NSHL should be included in RGCS. Thirty-five percent (N = 231) indicated they would make different reproductive decisions if they had an increased chance of having a child born deaf; 31% would not change their reproductive plans and 34% were unsure what they would do., Conclusion: While the majority support inclusion of genes associated with NSHL in RGCS, there was uncertainty about the severity of deafness as a health condition and there was no consensus on whether it is a health condition that warrants changing reproductive decisions., (© 2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

We analyzed the genomes of 170 C. parapsilosis isolates and identified multiple copy number variations (CNVs). We identified two genes, RTA3 ( CPAR2_104610 ) and ARR3 ( CPAR2_601050 ), each of which was the target of multiple independent amplification events. Phylogenetic analysis shows that most of these amplifications originated only once. For ARR3 , which encodes a putative arsenate transporter, 8 distinct CNVs were identified, ranging in size from 2.3 kb to 10.5 kb with 3 to 23 copies. For RTA3 , 16 distinct CNVs were identified, ranging in size from 0.3 kb to 4.5 kb with 2 to ~50 copies. One unusual amplification resulted in a DUP-TRP/INV-DUP structure similar to some human CNVs. RTA3 encodes a putative phosphatidylcholine (PC) floppase which is known to regulate the inward translocation of PC in Candida albicans. We found that an increased copy number of RTA3 correlated with resistance to miltefosine, an alkylphosphocholine drug that affects PC metabolism. Additionally, we conducted an adaptive laboratory evolution experiment in which two C. parapsilosis isolates were cultured in increasing concentrations of miltefosine. Two genes, CPAR2_303950 and CPAR2_102700 , coding for putative PC flippases homologous to S. cerevisiae DNF1 gained homozygous protein-disrupting mutations in the evolved strains. Overall, our results show that C. parapsilosis can gain resistance to miltefosine, a drug that has recently been granted orphan drug designation approval by the United States Food and Drug Administration for the treatment of invasive candidiasis, through both CNVs or loss-of-function alleles in one of the flippase genes. IMPORTANCE Copy number variations (CNVs) are an important source of genomic diversity that have been associated with drug resistance. We identify two unusual CNVs in the human fungal pathogen Candida parapsilosis. Both target a single gene ( RTA3 or ARR3 ), and they have occurred multiple times in multiple isolates. The copy number of RTA3 , a putative floppase that controls the inward translocation of lipids in the cell membrane, correlates with resistance to miltefosine, a derivative of phosphatidylcholine (PC) that was originally developed as an anticancer drug. In 2021, miltefosine was designated an orphan drug by the United States Food and Drug Administration for the treatment of invasive candidiasis. Importantly, we find that resistance to miltefosine is also caused by mutations in flippases, which control the outward movement of lipids, and that many C. parapsilosis isolates are prone to easily acquiring an increased resistance to miltefosine.

Ceres is a large water-rich dwarf planet located within the asteroid belt. Its surface displays evidence of material sourced from a deep subsurface liquid brine layer within recent geologic time, making it a candidate ocean world with possible present-day activity. However, Ceres lacks a substantial atmosphere and likely does not possess a global magnetic field. Therefore, any material emplaced or exposed on the surface will be subject to weathering by charged particles of solar and galactic origin. We have evaluated the effect of charged particle radiation on material within the near-surface of Ceres and find that the timescale for radiation-induced modification and destruction of organics and endogenic material is ∼100 Myr to 1 Gyr within the top 10-20 cm of the surface. Furthermore, we find that the timescale for sterilization of any putative living organisms contained within material at these depths is <500 kyr. Future missions to the surface may therefore consider targeting regions with geologic ages that fall between these two timescales to avoid the risk of backward contamination while ensuring that sampled material is not heavily radiation processed.