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Purpose: To evaluate whether anti-drug antibodies (ADAs) are present in the ocular fluid of patients with ranibizumab-recalcitrant neovascular age-related macular degeneration (nAMD). Methods: Two serum ADA-positive ranibizumab-recalcitrant patients and two serum ADA-negative controls were recruited from patients with nAMD treated with ranibizumab monotherapy. Recalcitrance was defined as persistent fluid after ≥6 monthly ranibizumab injections. Serum and aqueous humor ADAs were detected by enzyme-linked immunosorbent assay and immunoprecipitation, respectively. Results: Two of 156 ranibizumab-treated patients were ADA-positive. The patients received six and 14 ranibizumab injections, respectively, up to 4 weeks prior to blood collection. The serum ADA concentration was estimated to be approximately 50,000 ng/mL. Neutralizing ADAs were confirmed in both samples. A specific band was detected by immunoprecipitation only in ADA-positive samples, consistent with the results of enzyme-linked immunosorbent assay. Based on an assessment of the degree of sensitivity of commercially available anti-ranibizumab antibodies, it was estimated that the immunoprecipitation method could detect ADA levels >30 ng. Nevertheless, ADAs were not detected in the aqueous humor of either the experimental or control group. Conclusion: In the aqueous humor, ADAs are either not present or are present at a lower concentration than that which can be detected by immunoprecipitation. This presumably reflects the fact that blood ADA is the product of systemic circulation clearance through anterior elimination of intravitreal ranibizumab. Based on our results, ADAs do not return to the eye in sufficient quantities to interfere with the action of ranibizumab in the vitreous cavity. [ABSTRACT FROM AUTHOR]

The agency of international students has long been neglected and undertheorised, though recent literature indicates that this has started to change. This paper systematically reviews 51 studies that address student agency in international higher education. Focusing on research published in the last two decades (2000–2020), the review draws on studies that foreground student voices, or international students' perspectives, rather than the perspectives of teachers, administrators or policymakers. A detailed discussion of how international student agency is positioned in the literature found that agency appears as either: a research object, as part of a theoretical or conceptual framework, or an emergent finding. Furthermore, our analysis suggests that the term "agency" is often used as a buzzword rather than as a fleshed-out concept. Thus, drawing on this initial analysis, the review synthesises varying but overlapping conceptualisations of international student agency in the literature into an integrative framework. Implications for future research are drawn, based on our findings about the understudied populations and methodological limitations in the literature. [ABSTRACT FROM AUTHOR]

Tripegfilgrastim is a long‐acting granulocyte colony‐stimulating factor (G‐CSF) that has been used to prevent chemotherapy‐induced neutropenia in adults. This study aimed to establish a pharmacokinetic (PK)–pharmacodynamic (PD) model to explore the impact of chemotherapy and tripegfilgrastim on absolute neutrophil counts (ANCs) and to further propose a fixed‐dose regimen in pediatric patients. Because neutrophils affect the clearance of tripegfilgrastim, the semimechanistic PK‐PD model was developed simultaneously by using data from 40 healthy adults and 27 pediatric patients with solid tumors. Tripegfilgrastim PK and ANC dynamics were described with a pharmacodynamics‐mediated drug disposition model assuming quasi‐equilibrium with five transit compartments mimicking neutrophil granulopoiesis. The effect of chemotherapy on neutrophils was included by stimulating the elimination of the G‐CSF receptor at the mitotic cells. Healthy adult and pediatric patients showed significantly different value for dissociation constant of the tripegfilgrastim‐G‐CSF receptor complex (Kd) and apparent volume of distribution (Vd/F). Patients treated with chemotherapy had a higher Vd/F and 62% lower Kd than healthy adults. As the age increased, the absorption rate of tripegfilgrastim was decreased. Body weight affected the G‐CSF receptor‐mediated internalization of tripegfilgrastim, and the baseline ANC value impacted the production rate of G‐CSF receptors. Simulations from the developed model suggested that 1.5, 2.5, 4, and 6 mg single subcutaneous tripegfilgrastim doses for the respective weight groups of 10–20, 21–30, 31–44, and more than 45 kg significantly reduced the duration of Grade 4 neutropenia similar to tripegfilgrastim weight‐based treatment with 100 μg/kg. [ABSTRACT FROM AUTHOR]

A highly sensitive and selective NH3 gas sensor was developed based on single-layer pristine graphene doped with copper(II) oxide (CuO) nanoparticles of a specific size. High-quality single-layer graphene was grown using chemical vapor deposition. Approximately 15 nm-sized CuO colloidal nanoparticles were fabricated by a microwave-assisted thermal method using copper acetate as the precursor, and dimethylformamide as the reducing and stabilizing agent. Pristine graphene was doped with an aqueous suspension of CuO nanoparticles at a coating speed of 1500 rpm using a simple spin coater. CuO nanoparticle doping induces changes in the electronic properties of graphene; in particular, p-type doping significantly altered graphene resistivity in the presence of NH3 gas. Upon exposure of the pristine graphene surface to NH3 gas, NH3 reacted with O2−/ O−/ O2− species on the graphene surface and released electrons into graphene. This caused a change in the concentration of charge carriers in the valence channel of graphene and an increase in graphene resistivity, facilitating real-time NH3 monitoring with quick response and rapid recovery at 25 ℃ and ~ 55% relative humidity. Our results indicated that graphene doped with ~ 15 nm-sized CuO nanoparticles can sense NH3 gas selectively with a resistivity response of ~ 83%. Moreover, the sensor exhibited good reusability, fast response (~ 19 s), and rapid recovery (~ 277 s) with a detection limit of 0.041 ppm and a relative standard deviation of 0.76%. [ABSTRACT FROM AUTHOR]

The rate at which states defend their allies in war has dropped from 81% during 1816–1944 to 7% in 1945–2016. I attribute the decline in honored alliances to a dramatic shift in the military capability of alliances. Contrary to the popular belief that alliances have become stronger after 1945, I find that the post-1945 international system also witnessed a significant increase in the number of weaker alliances. This bimodal distribution of alliances produced a pattern where alliances were either violated upon being attacked or never attacked in the first place, leading to a decline in the rate at which alliances were honored. I support my argument using alliance data over two centuries. This research advances our understanding of military alliances by documenting a polarization of alliances in terms of their military capability post-1945 and by providing an explanation for an empirical puzzle—a sharp decline in the rate of honored alliances after 1945. El porcentaje en que los Estados defienden a sus aliados en una guerra ha descendido del 81% durante el periodo de 1816-1944 al 7% durante el periodo de 1945-2016. Atribuimos el deterioro de las alianzas de honor a un cambio drástico en la capacidad militar de las alianzas. En contra de la creencia popular de que las alianzas se han fortalecido después de 1945, observamos que el sistema internacional posterior a 1945 también ha sido testigo de un aumento significativo del número de alianzas más débiles. Esta distribución bimodal de las alianzas produjo un patrón en el que las alianzas fueron vulneradas al ser atacadas o nunca llegaron a ser atacadas, lo que condujo a un descenso en la tasa de cumplimiento de las alianzas. Apoyamos nuestro argumento en los datos sobre las alianzas a lo largo de dos siglos. Esta investigación profundiza nuestra comprensión de las alianzas militares al documentar una polarización de las alianzas en términos de su capacidad militar después de 1945 y al proporcionar una explicación para un rompecabezas empírico: una fuerte disminución en la tasa de alianzas de honor después de 1945. Le taux auquel les États défendent leurs alliés lors de guerres est passé de 81 % durant la période 1816-1944 à 7 % de 1945 à 2016. J'attribue ce déclin du respect des alliances à un changement radical de leurs capacités militaires. Contrairement à la croyance populaire selon laquelle les alliances se sont renforcées depuis 1945, selon moi, le système international a depuis cette date été le témoin d'une augmentation importante des alliances plus fragiles. Cette distribution bimodale des alliances a généré un schéma dans lequel les alliances étaient soit violées lors d'attaques, soit ne subissaient jamais d'attaques, ce qui a conduit à une diminution du taux de respect des alliances. J'étaye mon propos à l'aide de données sur les alliances collectées durant plus de deux siècles. Cet article de recherche vise à affiner notre compréhension des alliances militaires, en documentant une polarisation des alliances relativement à leurs capacités militaires d'après 1945 et en fournissant une explication au puzzle empirique du fort déclin du taux de respect des alliances après 1945. [ABSTRACT FROM AUTHOR]

In this essay, Soyoung Lee explores the theme of mourning as a way of attending to a fundamental aspect of human experience that is bound to negativity. The essay helps readers to see that experience in a different light by drawing on what is shown to be an internal connection between mourning and having language. The dominant culture of contemporary education is preoccupied with management and control, and this renders hollow the understanding of the negative experience children go through. Such experience, if it is acknowledged at all, is regarded as requiring intervention and perhaps correction. Yet negative experience, as Lee tries to show, is the very source of personal growth. This is to take human experience as wounded, and the wound as the very place for the creation of our own words. A hasty approach toward an individual's suffering, whether in the name of "healing" or "knowledge," becomes a suppression of voice. In its denial of the otherness within the self, it neglects the possibilities of self‐transformation. The essay pursues these ideas through a reading of contrasting works of art: some poetry by Paul Celan (in conjunction with Jacques Derrida's response to it) and Still Walking, a film directed by Hirokazu Kore‐eda. Both artworks deal with their own wounds and words in ways that are instructive. [ABSTRACT FROM AUTHOR]

Social distancing is an effective method for controlling the COVID-19 pandemic by decreasing population mobility, but it has also negatively affected local business sales. This paper explores the spatio-temporal impact of population mobility on local business sales in response to COVID-19 in Seoul, South Korea. First, this study examined the temporal variability by analyzing statistical interaction terms in linear regression models. Second, the spatio-temporal variability was captured using Moran eigenvector spatial filtering (MESF)-based spatially varying coefficients (SVC) models with additional statistical interaction terms. Population mobility and local business sales were estimated from public transportation ridership and restaurant sales, respectively, which were both obtained from spatial big datasets. The analysis results show the existence of various relationships between changes in the population mobility and local business sales according to the corresponding period and region. This study confirms the usability of spatial big datasets and spatio-temporal varying coefficients models for COVID-19 studies and provides support for policy-makers in response to infectious disease. [ABSTRACT FROM AUTHOR]

Eslicarbazepine acetate (ESL) is a prodrug antiseizure medication for the treatment of focal seizures. ESL shows a well‐established pharmacokinetic (PK)‐pharmacodynamic relationship and has similar extrinsic epilepsy‐related factors across ethnicities. This study evaluated and compared ESL safety, tolerability, and PK characteristics between Korean and White subjects. A randomized, double‐blind, placebo‐controlled, single‐ and multiple‐dose escalation study was conducted in healthy Korean and White adults. Participants randomly received a single dose and multiple oral doses of ESL (400–1600 mg) or placebo once daily for 11 days at a ratio of 8:2. Serial blood samples were collected to determine the plasma concentration of ESL and its metabolites (eslicarbazepine, [R‐licarbazepine and oxcarbazepine). Safety and tolerability were assessed throughout the study. A total of 29 Korean and 20 White subjects completed the study. The PK profiles of the metabolites of ESL were similar between Korean and White subjects. The geometric mean ratio (90% confidence interval) of Korean to White subjects for the area under the concentration–time curve within a dosing interval of eslicarbazepine was 1.06 (0.97–1.17) and 0.96 (0.87–1.06) after multiple oral doses of 400 and 1600 mg ESL, respectively. Other PK parameters were also similar between the two ethnic groups. ESL was well‐tolerated in healthy Korean and White subjects, and its PK characteristics were similar between the two ethnic groups. The results of this study support to use the same dosage regimen of ESL in both White and Korean patients with seizures. [ABSTRACT FROM AUTHOR]

Fluorescent or LED nail lamps are used in manicure and pedicure salons to cure nail coatings. These are UV sources, but with significant blue light emissions. Most of the literature emphasizes skin damage and cancer risk from UV exposure rather than blue light-induced damage to visual photoreceptors. Nail technicians using the lamps routinely may have potentially greater exposure than customers. However, there are no data on blue light radiance levels combined with time activity patterns for exposure assessment. This research aimed to determine exposures through simulation experiments, informed by observational studies in seven nail salons. Typical and worst-case time activity patterns were established, and spectral radiance doses determined in the occupational visual field for two LED nail curing lamps. The results showed the effective spectral radiance dose were below the current guideline promulgated by the International Commission on Non-Ionising Radiation Protection. Interestingly, radiances at the corners of one LED nail curing lamp was higher than at the center, which shows the amount of exposure can differ depending on the viewing angle. This research is the first to determine spectral radiance doses. A covered design is highly recommended for blocking the emission of blue light from a nail lamp. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a complex and multifactorial skin disease characterized by skin inflammation and intense pruritus. There are many commercially available treatments such as topical corticosteroids and immunosuppressants to treat of AD, but their effectiveness is limited, and frequent use of these treatments can cause serious side effects. Therefore, the development of new therapeutic agents is necessary for the treatment of AD. Hence, an alternative agent that was derived from natural products that are effective and safe for AD treatment was investigated using experimental models. The biological activity of euscaphic acid has anti-inflammatory, anticoagulant, and antioxidant effects. Despite the various biomedical properties of euscaphic acid, its therapeutic effects on AD have not been well studied. In this study, we investigated the effects of euscaphic acid on skin inflammation and pruritus in AD mouse model. The effects of euscaphic acid were investigated in activated human epidermal keratinocytes and leukemia T lymphoblast cell lines, and Dermatophagoides farina extract and 2,4-dinitrochlorobenzene-induced AD mouse model. Euscaphic acid ameliorated AD properties, such as the expression of inflammatory cytokines and activation of transcription factors. In addition, euscaphic acid reduced critical factors for pruritus such as immunoglobulin E hyperproduction, mast cell invasion, and interleukin-33 expression. Taken together, euscaphic acid could be a potent therapeutic agent for the treatment of AD. [ABSTRACT FROM AUTHOR]

Lymphedema causes inflammation, which provokes fibrosis within the epifascial tissue. Temporal change in fibrosis according to severity of the lymphedema has not been widely investigated. We aimed to study the quantitative changes in epifascial fibrosis during lymphedema treatment using computed tomography (CT). Forty-five patients (mean age: 57.75 ± 11.12 years) who developed lymphedema following gynecologic surgery were included in this retrospective study. Two weeks of complete decongestive therapy and continued self-bandaging or compression garments were prescribed under regular follow-up monitoring. Lower-extremity epifascial fibrosis was quantitatively analyzed on the initial and follow-up CT scans. Circumference, skin fibrosis, subcutaneous tissue, and fibrosis ratio were calculated in the axial scan. Based on the change in lymphedema severity, we divided subjects into 'improved' and 'aggravated' groups. The affected lower extremities showed higher circumference, more skin fibrosis and subcutaneous tissue, and higher fibrosis ratio than the unaffected sides on initial CT scan. At follow-up, compared to the aggravated group, the improved group showed significant decreases in fibrosis of skin and subcutaneous tissue and fibrosis ratio. Subcutaneous fibrosis was reversible with volume resolution of lymphedema. Therapeutic approaches should be established on the basis of the reversible nature of fibrotic changes in patients with lower extremity lymphedema. [ABSTRACT FROM AUTHOR]

Mast cells are primary cells initiating allergic inflammation by the release of various allergic mediators, such as histamine and pro-inflammatory cytokines. Aspalathin (ASP) is the predominant flavonoid found exclusively in rooibos, an herb that has been traditionally used in allergy relief therapy. In the present study, we investigated the beneficial effects of ASP on mast cell-mediated allergic inflammation. For in vivo study, two well-known mast cell-mediated local and systemic allergic inflammation mouse models were used: passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis mouse models (ASA). Oral administration of ASP dose-dependently suppressed immunoglobulin (Ig)E-mediated PCA responses evidenced by Evans blue extravasation, ear thickening, and mast cell degranulation. ASP also significantly mitigated ovalbumin-induced ASA responses, including hypothermia, histamine secretion, and the production of IgE and interleukin-4. Notably, ASP was more effective in suppressing allergic inflammation than nothofagin, another prominent flavonoid known as an anti-allergic component of rooibos. The regulatory mechanism of mast cell activation by ASP was clarified using mast cell line and primary cultured mast cells (RBL-2H3 and mouse bone marrow-derived mast cells). ASP reduced IgE-stimulated mast cells degranulation and intracellular calcium influx by the inhibition of FcεRI signaling pathway (Lyn, Fyn, and Syk). Moreover, ASP reduced pro-inflammatory cytokine expressions by inhibiting two major transcription factors, nuclear factor of activated T cells and nuclear factor-κB. Collectively, we proposed that ASP could be a potential therapeutic candidate for the treatment of mast cell-mediated allergic inflammatory diseases. [ABSTRACT FROM AUTHOR]

To test the hypothesis that dynamic conformal arc therapy (DCAT) in Monaco, compared with volumetric modulated arc therapy (VMAT), maintains plan quality with higher delivery efficiency for lung stereotactic body radiotherapy (SBRT) and to investigate dosimetric benefits of DCAT with active breath-hold (DCAT+ABH), compared with free-breathing (DCAT+FB) for varying tumor sizes and motions. Fifty DCAT plans were used for lung SBRT. Randomly selected 17 DCAT plans were evaluated with respect to the retrospectively generated volumetric modulated arc therapy (VMAT) plans. The maximum dose at 2 cm from planning target volume (PTV) in any direction (D2cm/Rx), the ratio of 50% prescription isodose volume to the PTV (R50%), conformity index (CI), the lung volume receiving ≥20 Gy (V20), and monitor unit (MU) were evaluated. A t -test was used to evaluate the difference of plan quality between DCAT and VMAT. Internal target volume (ITV)/integrated-gross target volume (GTV) attributed by intra-fraction motion and lung V20 were stratified for DCAT+ABH and DCAT+FB across varying GTVs. DCAT maintained plan quality (p = 0.154 for D2cm/Rx, p = 0.089 for R50%, p = 0.064 for CI, and p = 0.780 for lung V20) while reducing MUs up to 30% (p <0.001) from 2748 MU (VMAT) to 1868 MU (DCAT). DCAT+ABH, compared to DCAT+FB, reduced tumor motion, resulting in 19% volume reduction of PTV and 60% reduction in lung V20, on average. The difference in lung V20 between DCAT+ABH and DCAT+FB increased as the target size increased. The DCAT is a favorable approach compared with VMAT. These results support the utility of DCAT as a routine planning platform for lung SBRT, especially when utilized with respiratory motion management using the ABH. [ABSTRACT FROM AUTHOR]

The contemporary neighborhood literature discusses the complex relationships among neighborhood environments, social support, and parenting. Grounded in the Person-Process-Context-Time (PPCT) model, we examined how different sources of social support interact with Korean mothers' perception of disorder in their neighborhoods, and if social support increases or decreases their parenting stress in rural and metropolitan areas. Using STATA 14.0, we conducted multiple regression modeling including tests for interaction effects. Our sample (from the 8th Wave PSKC) included 1,300 mothers of seven-year-old children who were transitioning to first grade. The results showed that for metropolitan mothers, support from neighbors was important. Interestingly, receiving social support from friends/colleagues could increase or reduce their parenting stress depending on the type of residential neighborhood. Both rural and metropolitan mothers who reported negative impressions of their neighborhood environment experienced more parenting stress. However, these relationships disappeared when controlling for the interactions between mothers' perception of disorder in their neighborhood and social support. These findings suggest that the social support that mothers receive from neighbors, and friends/colleagues, in general, play an important role in relieving parenting stress when raising first graders. However, living in disorganized, unsafe, or stressful neighborhood environments may restrict mothers' parenting choices due to anxiety and limited outdoor space, resulting in increased parenting stress. Therefore, careful consideration of neighborhood characteristics is required to develop community-based parenting support services as part of family-friendly policies to effectively reduce the burden of parenting school-aged children in Korea. [ABSTRACT FROM AUTHOR]

This special issue explores contemporary family issues in South Korea using two major national datasets, the Korean Longitudinal Study of Aging (KloSA) and the Panel Study on Korean Children (PSKC) to commemorate the first special session offered by the Korean Families Focus Group at the annual conference of National Council on Family Relations (NCFR) in 2019.

People with knee osteoarthritis walk with excessive muscle co-contraction that can accelerate disease progression. Central pain sensitization is common in people with knee osteoarthritis and may be related to walking patterns. The objective of this study was to examine the relation of central pain sensitization with muscle co-contraction during walking in people with knee osteoarthritis. This study reports secondary analysis from baseline data of two clinical trials (n = 90 participants with knee osteoarthritis). The presence of central pain sensitization was measured by mechanical temporal summation at the patella and the wrist. Quadriceps and hamstrings activation was assessed using surface electromyography during walking at self-selected and fast paces. Muscle co-contraction indices for vastus medialis-medial hamstrings and vastus lateralis-lateral hamstrings muscle pairs were calculated during stance phases. Co-contraction outcomes were compared between people with and without mechanical temporal summation at each site, adjusting for age, sex, and body mass index. People with mechanical temporal summation at the knee had greater vastus lateralis-lateral hamstrings co-contraction while walking at a fast pace (P = 0.04). None of the other differences was statistically significant, but the overall trends and effect sizes indicated greater co-contraction in people with temporal summation at the knee irrespective of gait phase, walking speed, or muscle pairs. Central pain sensitization, assessed as mechanical temporal summation at the knee, is related to greater knee muscle co-contraction during fast walking in people with knee osteoarthritis. Thus, mitigating central sensitization may be an interventional target to reduce muscle co-contraction for people with knee osteoarthritis. • Greater temporal summation of pain is related to greater muscular co-contraction during walking. • Central sensitization could be one mechanism altering motor function in knee osteoarthritis. • Reducing pain sensitization may potentially help normalizing motor function. [ABSTRACT FROM AUTHOR]

This paper explores ways in which Roland Barthes' discussion of the encyclopaedia provides us with resources for thinking about education and research practice today. What Barthes addresses in his essay 'The Plates of the Encyclopedia' is a particular encyclopaedia, the Encyclopédie produced by Denis Diderot and Jean le Rond d'Alembert, which was published in France between 1751 and 1772. This is commonly referred as the first of a form that we recognise as the encyclopaedia today. I begin with Barthes' analysis and critique of the Encyclopédie. Barthes, writing in 1964, engages with the Encyclopédie as an iconic product of its time, seeing it as conditioned by and, in effect, reinforcing a particular way of experiencing the world. Next, I consider ways in which a parallel critique is pertinent today. I explore some current examples of encyclopaedic form in relation to education and educational research. The purpose of this is to examine the interplay between particular cultural products and their society, in which not only certain types of knowledge but also a certain conception of knowledge are produced and reinforced. So, it will not be the purpose of this paper to provide direct analysis or critique of the Enlightenment, or to provide a historical account of knowledge. Rather, what I am interested in is problematising a particular understanding of language and knowledge that arises through these cultural products, particularly with regard to educational inquiry. This lays the way for thoughts expressed by Gilles Deleuze and Félix Guattari in What is Philosophy? which, as I shall try to show, are of help in furthering the analysis of the dominant research culture's use of such products and in imagining the task of education and research differently. [ABSTRACT FROM AUTHOR]

Asthma is a common allergic airway inflammatory disease, characterized by abnormal breathing due to bronchial inflammation. Asthma aggravates the patient's quality of life and needs continuous pharmacological treatment. Therefore, discovery of drugs for the treatment of asthma is an important area of human health. The aim of the present study was to evaluate whether Cynanchum atratum extract (CAE) modulates the asthma-like allergic airway inflammation and to study its possible mechanism of action using ovalbumin (OVA)-induced airway inflammation and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice, as well as a mast cell-based in vitro model. The histological analysis showed that CAE reduced the airway constriction and immune cell infiltration. CAE also inhibited release of β -hexosaminidase and expression of inflammatory cytokines such as tumor necrosis factor (TNF)- α , interleukin (IL)-4, and IL-5 in bronchoalveolar lavage fluid and lung tissues. In addition, CAE reduced the OVA-specific immunoglobulin (Ig) E, total IgE, IgG1, and IgG2a levels in the serum. In the LPS-induced ALI model, CAE suppressed the LPS-induced lung barrier dysfunction and the release of proinflammatory cytokines. Because allergic airway inflammatory responses are associated with the activation of mast cells, RBL-2H3 cells were used to evaluate the underlying mechanism of CAE effects. In RBL-2H3 cells, CAE down-regulated release of β -hexosaminidase and histamine by reducing the intracellular calcium influx. In addition, CAE suppressed the expression of proinflammatory cytokines by inhibiting nuclear translocation of nuclear factor- κ B. Taken together, our findings suggest that CAE may help in the prevention or treatment of airway inflammatory diseases. [ABSTRACT FROM AUTHOR]

The development of place attachment is an important learning objective in geography education because it plays a significant role in people's behaviors toward protecting and acting on behalf of places. This study demonstrates the effects of selecting and presenting favorite places (SPFP) strategy in enhancing students' place attachment. The SPFP activity was expected to establish the participants' positive stance toward their chosen places and promote the consistent maintenance of their initial attitude. It builds on the preference for consistency, or the desire and tendency to behave predictably by acting similarly across diverse situations. We asked the participants to select their favorite places in a city, to visualize them using Google Earth, and to present their activities. As a result, the participants increased their place attachment, which is composed of place identity and place dependence. [ABSTRACT FROM AUTHOR]

• Variations in patients' breathing characteristics during treatment were presented. • Limitation in the use of the ABC related to airflow rate was addressed. • Interfraction variation in breath-hold volume was investigated for the whole course. • Intrafraction variation in breath-hold volume was investigated for the whole course. • Target locations correlated to breath-hold volume were statistically analyzed. Conventionally fractionated and stereotactic body radiation therapy (SBRT) for thoracoabdominal tumors may utilize breath-hold techniques. However, there are concerns that differential amounts of inspired airflow may result in unplanned tumor dislocation and underdosing. Thus, we investigated tumor localization accuracy associated with lung volume variations during breath-hold treatment via an automated-gating interface. Twelve patients received breath-hold treatment with the active breathing coordinator (ABC) through an automated-gating interface. All breath-hold volumes were recorded at CT simulation, setup imaging, and during treatment, and analyzed as a function of airflow rate into the ABC. The variation of breath-hold volumes was calculated for each fraction over entire course. Intrafraction target motion related to the breathing variation was investigated based on daily imaging acquired before the breath-hold treatment. Correlation between target location and breath-hold variation was statistically analyzed. The air volume held by the ABC increased as the airflow rate increased on inhalation and decreased on exhalation. The mean range of airflow rate was 0.77 L/s and 0.29 L/s in the conventionally fractionated and SBRT patients, respectively. The maximum air volume difference with respect to the reference volume at the CT simulation was 1.0 L for conventional fractionation and 0.16 L for SBRT. The target dislocation caused by 0.25 L of air volume difference was 6 mm for SBRT. Three patients showed significant correlation between the target location and breath-hold variations. This investigation shows that because variations in the breath-hold volume may cause target dislocation, patient-specific breath-hold setting is required to improve tumor localization accuracy. [ABSTRACT FROM AUTHOR]

• FMs in "Tumor volume, Prescription & dose objectives" and "Treatment planning" had longer delay. • FMs in "CT simulation" and "Treatment planning" had high RPN indicating high improvement priority. • "Tumor volume, Prescription & Objectives" and "Treatment planning" had more FMs of higher RPN SE-EE. • "Delay in providing contours for treatment planning" had high RPN and RPN SE-EE. This study identified and evaluated the factors that are responsible for delay in the clinical workflow of radiation therapy, starting from the CT simulation (CT-Sim) to the first fraction of treatment delivery using the Failure Mode and Effects Analysis (FMEA) methodology. A total of 1106 patient cases were retrospectively analyzed using FMEA methodology. For each failure mode (FM), the following factors were rated and discussed by the group: occurrence (O), severity (S), detectability (D), and methods of improvement or mitigation. In addition, two new factors, namely social effect (SE) and economic effect (EE), were introduced to evaluate the impact of FM on the department or hospital. Risk priority number (RPN) and the product of RPN, SE, and EE (i.e. RPN SE-EE) were calculated for each FM. Average delay caused by identified FM was 8 days while 76% of the FMs resulted in delay of less than 5 days. The RPN of all the FMs ranged from 4 to 60 with an average value of 18. "Tumor volume, prescription and objective" had the highest average RPN of 23. The majority of FMs with high RPN were identified in "CT-Sim" (RPN: 21.5 ± 11.1; RPN SE-EE : 97.0 ± 46.4) and "treatment planning" (RPN: 20.1 ± 8.1, RPN SE-EE : 152.9 ± 76.5) stages. The FMEA enabled identification of the factors that caused delay in the pre-treatment process of radiation therapy. "CT-Sim" and "treatment planning" stages had more FMs with high RPN values which have higher priority for future improvement. Two new factors, SE and EE, were introduced and appeared to be valuable in evaluating the impact of FMs on radiation oncology department or hospital in general. [ABSTRACT FROM AUTHOR]

Ursodeoxycholic acid (UDCA) is a secondary bile acid component used for treating primary biliary cirrhosis. This study evaluated and compared the pharmacokinetic (PK) profiles of UDCA and its conjugates glyco‐UDCA (G‐UDCA) and tauro‐UDCA (T‐UDCA) in healthy elderly subjects and younger adults. In this randomized, open‐label, 2‐treatment, 1‐sequence, and parallel study, subjects received 400 or 800 mg UDCA on day 1, followed by 200 mg UDCA twice daily for 2 weeks. Blood samples were obtained up to 24 hours after the first UDCA dose. Changes in miRNA‐122, γ‐glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase levels from baseline were assessed to determine the safety and pharmacological effects of UDCA. This study examined the outcomes of 16 elderly subjects and 16 younger adults. Dose‐normalized peak concentration of and systemic exposure to UDCA were 2 to 4 times higher, and the corresponding values of G‐UDCA and T‐UDCA were 1.7 times higher in the elderly subjects than in the younger adults. The subjects in both groups showed multiple peak profiles of UDCA and its conjugates. The miRNA‐122 levels and hepatic enzyme test results were within the normal range in the elderly subjects after multiple administration of UDCA. This study is the first to confirm that the PK measurements of UDCA were higher in elderly subjects than in younger adults, which may improve the clinical outcomes of elderly subjects. [ABSTRACT FROM AUTHOR]

In exploring why American mothers spend more time on care work compared to prior decades while increasingly engaging in paid work, Hays (1997) attributed women's actions to intensive motherhood (IM) ideology. Hays also asserted that women purposedly adhere to IM to resist an increasingly neoliberal market-based society by dedicating time and effort to nurturing children and family life. Here, we undertake a content analysis to take stock of IM literature's evolution in recent decades. Specifically, we examine scholars' treatment of how women adhere to IM, and why and whether women do so in resistance to neoliberalism. We found that while scholars consistently cite and echo Hays (1997) on how women adhere to IM, most depart from Hays (1997) by positing women adhere to live up to an ideal of being a perfect mother due to the pervasive nature of IM. We also found many scholars focus on the possibility of resisting IM ideology itself rather than Hays's (1997) perspective that women employ the ideology to resist neoliberalism. These findings raise questions about how women's agency manifests in the IM context, and concerns about embedded assumptions that limit our understanding of women's realities. Implications are discussed. [ABSTRACT FROM AUTHOR]

Velufenacin (DA‐8010) is a new muscarinic receptor antagonist under development for the treatment of overactive bladder. This study aimed to evaluate the effect of food on the pharmacokinetics (PK) and safety of velufenacin in healthy subjects. A randomized, open‐label, single‐dose, 4‐sequence, 4‐treatment, 4‐period crossover study was conducted. Subjects received a single oral dose of velufenacin 2.5 or 5 mg in a fasted or fed (high‐fat meal) state in each period with a 7‐day washout. PK parameters including maximum plasma concentration (Cmax) and area under the concentration‐time curve from time 0 to the last measurable point were compared between the fed and fasted states. Twenty‐seven subjects completed the study. The mean area under the concentration‐time curve from time 0 to the last measurable point of the velufenacin 2.5 and 5 mg doses under the fed condition showed a 1.5‐ and 1.3‐fold increase, respectively, compared to the fasted condition. The corresponding values for Cmax were a 2.3‐ and 2.0‐fold increase, respectively. The time to reach Cmax was comparable regardless of the dose or food intake, showing median values of 4.5‐5.0 hours. These results suggest a modest increase of velufenacin absorption by food intake. Velufenacin was generally safe and well tolerated at the 2.5 and 5 mg doses regardless of food. [ABSTRACT FROM AUTHOR]

While the wheel and the rail are in contact, the stress on the wheel affects the safety of the vehicle and causes ride discomfort and noise. Therefore, the design of the wheel to reduce the damage is needed. To solve these problems, the shape optimization on the railway wheel web was carried out using the finite-element analysis and shape-morphing technique. First, thermo-mechanical analysis, with consideration to mechanical and thermal loads under tread braking, was developed and the contact pressure and stress generated on the wheel were obtained. Then, the integrated shape-morphing design process was proposed to improve the efficiency of the shape optimization. It made it possible to parameterize the finite-element models and modify them directly without returning to the computer-aided design model. Based on the analysis results, we performed the metamodel and genetic algorithm based optimization by using response surface method, Kriging and Gaussian process, then compared their optimal solutions. Optimization proceeded in two stages, two-dimensional optimization under axisymmetric conditions and three-dimensional optimization in which the shape changed in the period of 60°. For the post-optimization work, fatigue evaluation for the verifications on initial and optimal wheel models was performed and the results were discussed. [ABSTRACT FROM AUTHOR]

This paper explores the concept of Gelassenheit as developed in the later thought of Martin Heidegger. It seeks to show the relevance of this to aspects of education, especially to the ways that teaching can be enhanced in order to do better justice both to the learners and to what is studied. Thinking in this way helps to overcome the dominance of representational thought, a kind of thinking that imposes barriers on the understanding and restrictions on how the world can come to be. In the end the thinking illustrated by Gelassenheit constitutes a more responsible and more responsive relationship to the truth. My paper provides examples of ways that this can enhance education. In the end, with a caveat, I revisit and re‐examine aspects of Heidegger's work about which I think there is reason to be cautious. This is to encourage a degree of vigilance in relation to Heidegger's thought, but in a way that does not deny its powerful insights. [ABSTRACT FROM AUTHOR]

Background: Maternal depression and suicidal ideation (SI) predict adolescent SI. However, the influence of paternal psychopathology is less clear. This study examines how parental psychopathology contributes to adolescent SI.Methods: Data from a cross-sectional, nationwide, population-based survey was used. It assessed 4,073 adolescents (12-18 years) and their parents identified through random sampling of the non-institutionalized population in Korea. Stress, depressed mood, and SI of parents and adolescents were assessed using multivariate logistic regression to determine the association of adolescents' SI with parental stress, depressed mood, and SI.Results: Adolescents who reported SI were more likely to be girls, have shorter sleep duration, more stress, and a depressed mood than were adolescents without SI. Logistic regression analysis showed estimated odds ratios for SI of 1.444 (p < .05), 1.485 (p < .05) and 1.801 (p < .05) for girls who had mothers with stress, depressed mood, and SI, respectively, and 2.113 (p < .05) and 3.091 (p < .05) for girls who had fathers with depressed mood and SI, respectively. Boys' SI was associated with father's depressed mood (OR: 2.608, p < .05).Limitations: Cross-sectional design and use of self-report measures.Conclusions: Girls' SI was related to both parents' stress, depressed mood, and SI except for father's stress, and boys' SI was related to father's depressed mood. Evaluations and therapeutic interventions for adolescents with SI should consider both adolescents and their parents, and family-based interventions could be one method for adolescent suicide prevention. [ABSTRACT FROM AUTHOR]

The importance of Levinas's philosophy for education has been widely discussed. In 'Levinas: Ethics or Mystification?' however, Alistair Miller questions whether Levinas's work is of value at all, raising doubts about whether his philosophy can, in any way, be helpful when it comes to practical ethical decision‐making, especially within education. Levinas's ethics, he argues, in the light of its lack of rational argument, amounts only to poetic imagery and mystical incantation. The purpose of this paper is to read Levinas in relation to education against this indictment by Miller. This paper proceeds by investigating the basis of Miller's arguments, in the light of exegesis of relevant aspects of Levinas's work. My purpose is not the positing of a new system or the formulation of systematic ideas of ethics but rather achieving an understanding of human experience, especially in contexts of teaching and learning, under a different, more accurate description. In doing so I attempt to show that Levinas's philosophy indeed provides a ground for ethics—that is, a means of understanding the practicality of ethics differently, beyond systematic approaches. In the last section, where education is discussed more directly, ethics will be seen as its very condition. [ABSTRACT FROM AUTHOR]

This study was investigated to compare the natural variation of nutrients in rice variety by different environmental factors. Fifteen kinds of rices were used, which were cultivated in two locations for 2 years. All data were analyzed by the various statistical tools to identify the nutritional variations of nutrients. The results of variable importance in the prediction analysis were found to be consistent with the % variability. The nutrient compositions most affected by variety were fatty acids, and next were vitamins, proximate nutrients, minerals, and amino acids in order. The nutrient compositions most affected by location were proximate, followed by minerals, vitamins, fatty acids, and amino acids. For cultivation year, vitamins were most affected and then minerals, fatty acids, proximate nutrients, and amino acids in order. These findings could explain that each kind of nutrients can be naturally varied by different environmental factors. This study was investigated to compare the natural variation of nutrients in rice by different environmental factors. Fifteen kinds of rices were used, which were cultivated in two locations for 2 years. Through the multiple statistical tools, it was found that the natural variation of the nutrients varied depending on the environmental factors. [ABSTRACT FROM AUTHOR]

Purpose: Combination therapy of pregabalin and tramadol is used to treat chronic neuropathic pain; however, the pharmacokinetic (PK) interactions of these drugs has not been studied. This study aimed to evaluate PK interactions between pregabalin and tramadol and the safety of combination therapy.Methods: A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence cross-over study was conducted in healthy subjects. All subjects received the following three treatments for 4 days in each period: pregabalin 150 mg twice daily; tramadol extended-release (ER) 200 mg in the morning, and 100 mg in the evening; and co-administration of pregabalin 150 mg and tramadol ER 200 mg in the morning, and pregabalin 150 mg and tramadol ER 100 mg in the evening.Results: A total of 21 subjects completed the study with no clinically significant safety issues. For pregabalin, the geometric mean ratio (GMR) (90% CI; confidence interval) of combination therapy to monotherapy for maximum concentration at steady state (Cmax,ss) and area under the concentration curve from 0 to dosing interval time at steady state (AUCτ,ss) were 0.8801 (0.8043-0.9632) and 1.0830 (1.0569-1.1098), respectively. The corresponding values for tramadol were 1.0177 (0.9839-1.0526) and 1.0152 (0.9896-1.0414), respectively. The GMR (90% CI) of combination therapy to monotherapy of O-desmethyl-tramadol for Cmax,ss and AUCτ,ss was 1.0465 (1.0095-1.0848) and 1.0361 (1.0001-1.0734), respectively.Conclusions: There were no significant drug interactions between pregabalin and tramadol, considering that all of the 90% CI of PK measures were within the conventional bioequivalence range. Both drugs were well tolerated when administered concomitantly. [ABSTRACT FROM AUTHOR]

Highlights • Suggestion of a novel lift-generating disk type wind power system. • Integrated simulation of proposed system using Modelica. • Verification of Modelica simulation result by wind tunnel test data. • Prediction of power generation of actual scale model by similarity law. Abstract Wind power generation research and application technology have received much attention in the development of renewable energy. However, the traditional blade-rotating type wind power system has a number of drawbacks such as natural landscaping damage, flow-induced noise, and shadow flickering problems. In this paper, we propose a lift-generating disk-type blade power generation mechanism that can effectively generate wind power even with a simple structure considering the problems of the existing systems. Data on the lift force in relation to the shape of the designed blade were derived through a computational fluid dynamics simulation, and the Modelica language was used to model the integrated multi-physics wind power system. Then, a wind tunnel test was conducted using a small-scale model of the disk-type blade created to verify the simulation. The experimental results were in good agreement with the simulated results. Thus, we validated the modeling of the wind power system and applied the law of similarity to obtain the generator power output prediction results for the actual scale model. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

The ClC-K channels CLCNKA and CLCNKB are crucial for the transepithelial transport processes required for sufficient urinary concentrations and sensory mechanoelectrical transduction in the cochlea. Loss-of-function alleles in these channels are associated with various clinical phenotypes, ranging from hypokalemic alkalosis to sensorineural hearing loss (SNHL) accompanied by severe renal conditions, i.e., Bartter's syndrome. Using a stepwise genetic approach encompassing whole-genome sequencing (WGS), we identified one family with compound heterozygous variants in the ClC-K channels, specifically a truncating variant in CLCNKA in trans with a contiguous deletion of CLCNKA and CLCNKB. Breakpoint PCR and Sanger sequencing elucidated the breakpoint junctions derived from WGS, and allele-specific droplet digital PCR confirmed one copy loss of the CLCNKA_CLCNKB contiguous deletion. The proband that harbors the CLCNKA_CLCNKB variants is characterized by SNHL without hypokalemic alkalosis and renal anomalies, suggesting a distinct phenotype in the ClC-K channels in whom SNHL predominantly occurs. These results expanded genotypes and phenotypes associated with ClC-K channels, including the disease entities associated with non-syndromic hearing loss. Repeated identification of deletions across various extents of CLCNKA_CLCNKB suggests a mutational hotspot allele, highlighting the need for an in-depth analysis of the CLCNKA_CLCNKB intergenic region, especially in undiagnosed SNHL patients with a single hit in CLCNKA. [ABSTRACT FROM AUTHOR]

Abstract: Evidence‐based writing is a complex standard in the Common Core State Standards that has taken center stage in the writing curriculum. Students must demonstrate proficiency in making claims based on evidence and explain how the evidence supports their claim. This is a challenging task for all students, but for English learners, it can be especially overwhelming. The author describes a series of lessons that teachers can use to introduce evidence‐based writing in three steps to English learners. The author developed the three‐step lessons for use with English learners after observing teachers and students struggling with evidence‐based writing in linguistically diverse settings. The lessons incorporate literature on best practices in writing development for second‐language learners, and the descriptions of the lessons are supported with examples from a sixth‐grade English as a Second Language classroom. [ABSTRACT FROM AUTHOR]

Abstract: The tumor microenvironment (TME) plays a crucial role in tumorigenesis and cancer cell metastasis. Accordingly, a drug‐delivery system (DDS) that is capable of targeting tumor and releasing drugs in response to TME‐associated stimuli should lead to potent antitumor efficacy. Here, a cancer targeting, reactive oxygen species (ROS)‐responsive drug delivery vehicle as an example of a TME‐targeting DDS is reported. Tumor targeting is achieved using biotin as a ligand for “biotin transporter”–overexpressing malignant tumors, and bilirubin‐based nanoparticles (BRNPs) are used as a drug‐delivery carrier that enables ROS‐responsive drug release. Doxorubicin‐loaded, biotinylated BRNPs (Dox@bt‐BRNPs) with size of ≈100 nm are prepared by a one‐step self‐assembly process. Dox@bt‐BRNPs exhibit accelerated Dox‐release behavior in response to ROS and show specific binding as well as anticancer activity against biotin transporter–overexpressing HeLa cells in vitro. bt‐BRNPs labeled with cypate, near‐infrared dye, show much greater accumulation at tumor sites in HeLa tumor‐bearing mice than BRNPs lacking the biotin ligand. Finally, intravenous injection of Dox@bt‐BRNPs into HeLa tumor‐bearing mice results in greater antitumor efficacy compared with free Dox, bt‐BRNPs only, and Dox@BRNPs without causing any appreciable body weight loss. Collectively, these findings suggest that bt‐BRNPs hold potential as a new TME‐responsive DDS for effectively treating various tumors. [ABSTRACT FROM AUTHOR]

There are complex relationships among individual, family, community, and social factors related to breastfeeding. Immigrant mothers, specifically, face several unique challenges to practicing breastfeeding while negotiating these factors within two cultural worlds. Grounded in the theory of planned behavior and the ecological perspective, our qualitative study findings unveil a part of the complex and dynamic process of breastfeeding decision-making among Korean immigrant mothers in the United States. To elicit mothers’ underlying beliefs of attitude and intention toward breastfeeding as immigrants, we conducted in-person interviews with 13 pregnant and postpartum Korean immigrant mothers, ages ranging from 30 to 39. The findings revealed that Korean mothers held positive attitudes toward breastfeeding. However, translation of these positive attitudes toward breastfeeding into actual practice depended on the feasibility of actual breastfeeding by mothers. To overcome several barriers to breastfeeding, such as inadequate milk supply, health concerns, employment status, and the relationship with a firstborn child, many Korean mothers combined breastfeeding with formula feeding. The factors that shaped the development of beliefs and behavioral intentions toward breastfeeding among Korean immigrant mothers included the dynamic family interactions with their children, husbands, mothers, mothers-in-law, and sisters; support from friends and infant care experts; information available through various technology and media; and Korean-specific cultural traditions. Our findings suggest possible directions for future cross-cultural research on breastfeeding within diverse family contexts, and may inform the design of population specific intervention programs. [ABSTRACT FROM AUTHOR]

Purpose To investigate the dosimetric effects due to interfractional changes in catheter position and variation in patient's anatomy during the course of interstitial high-dose-rate (HDR) brachytherapy. Methods and Materials A total of 15 patients with either cervical or vaginal cancer underwent interstitial HDR brachytherapy. Interstitial catheters and fiducials were placed under fluoroscopy and intraoperative 3T MRI to confirm the desired catheter placement for adequate target volume coverage. Single plan was generated from first-fraction CT fused with the MRI and used for all fractions of treatment. CT image was acquired before each treatment and registered to the first-fraction CT. Displacement of fiducials and catheters was calculated for each fraction and its effects on dosimetric parameters such as dose covering 90% for high-risk clinical target volume and intermediate-risk clinical target volume and dose to the 2 cm 3 of the volume for bladder, rectum, sigmoid, and bowel were studied. Results Average movements of fiducials and catheters were 1.6 mm (range: 0.1–7.1 mm) and 1.7 mm (range: 0.1–4.5 mm), respectively. Overall, deviation of the delivered dose to the target in each fraction was insignificant for all patients ( p -value: 0.66 for high-risk clinical target volume and 0.87 for intermediate-risk clinical target volume). The mean dose to organs at risk showed maximum difference up to 0.9, 2.7, 1.6, and 2.1 Gy for bladder, rectum, sigmoid, and bowel, respectively ( p -value: 0.88, 0.34, 0.68, and 0.85 for bladder, rectum, sigmoid, and bowel, respectively). Conclusions The interfractional dosimetric variation for both target and organs at risk was within clinically acceptable limit throughout the entire course of interstitial HDR-Syed brachytherapy. Only 6% of cases performed replanning, which could be readily identified using CT imaging. [ABSTRACT FROM AUTHOR]

Background The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for adults aged ≥65 years. To evaluate functional immune response against the additional 11 serotypes that are included in PPSV23, but not the 13-valent pneumococcal conjugate vaccine (PCV13), serotype-specific anti-pneumococcal antibodies were examined using an opsonophagocytic assay (OPA). Methods Participants ≥65 years of age that were naïve to the pneumococcal vaccine were enrolled. They were divided into two groups according to their age: group 1 (N = 30; aged 65–74 years) and group 2 (N = 32; aged ≥75 years). The functional antibody response prior to and 4 weeks post-immunization with PPSV23 was determined, using a multiplexed OPA (MOPA) for 11 pneumococcal serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F). Results Geometric mean OPA titers (GMTs) to 11 serotypes were significantly increased in both groups post-immunization compared to those prior to immunization. The GMTs for all serotypes were not significantly different between the two groups after immunization. The proportion of subjects with OPA titers post-immunization of ≥8 and ≥64 was 93–100% and 80–100% for the 11 serotypes, respectively, while subjects with a ≥4-fold increase in OPA titers ranged from 9 to 90% for the 11 serotypes. Conclusions This study revealed that PPSV23 vaccination induced significant functional immune responses to 11 non-PCV13 serotypes in older adults. The MOPA has been shown to be a useful tool for future application in evaluating new PCVs in older adults. The clinical trial registration number is KCT 0001963 (CRIS, https://cris.nih.go.kr/cris/en/ ). [ABSTRACT FROM AUTHOR]

• Hyperthermal erosion of nanocomposites by atomic oxygen and nitrogen molecule was compared for the first time. • Optimum reactive simulation condition to mimic disintegration under low earth orbital environment was provided. • Atomic oxygen bombardment showed reaction-assisted disintegration and desorption of nanocomposites. • Attack of nitrogen molecules showed comparable surface erosion to the atomic oxygen bombardment without active reaction. • Erosion yield of nanocomposites comparable to the in-flight experiment could be obtained. Against the hyperthermal atomic oxygen (AO) bombardment, mitigation of the surface recession has been the main issue in designing surface shielding materials in low earth orbital (LEO) environment. Meanwhile, the role of nitrogen molecules (N 2) in LEO and sub-LEO on disintegration of the shielding materials has rarely been studied despite their abundance and non-negligible colliding energy. This study for the first time compared the surface chemistry and disintegration of Kapton polyimide-based nanocomposites under AO and N 2 bombardment conditions using a reactive molecular dynamics (MD) simulation. The heat transfer from the surface to the behind layer and the associated boundary condition for the bombardment simulation were primarily discussed to provide the optimum bombardment simulation setup. Polyhedral oligomeric silsesquioxane (POSS), carbon nanotube (CNT) and graphene were respectively blended with Kapton to evaluate the damage mitigation efficacy. The addition of all types of additives to Kapton induced a notable thermo-protection effect. AO bombardment resulted in a sequential disintegration of oxidation and desorption, whereas the surface recession of nanocomposites by exposure to N 2 collision was mainly caused by physical desorption. It was also noteworthy that the surface recession caused by N 2 bombardment was comparable to that by AO attack at the same fluence. [Display omitted]. [ABSTRACT FROM AUTHOR]

Background: Intravenous immunoglobulin G (IVIG) replacement therapy is used to prevent invasive infections in patients with primary antibody deficiency (PAD). However, few studies have functionally evaluated specific antibodies against encapsulated bacteria that cause invasive infection in patients with PAD. In this study, functional antibodies against Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococci), and Neisseria meningitidis (meningococci) in IVIG therapy were evaluated.Study Design and Methods: Sixteen lots of IVIG products prepared by two Korean manufacturers (Products A and B) were evaluated. The functional antibodies were measured by serum bactericidal assay for Hib and four meningococcal serogroups and by multiplexed opsonophagocytic assay for 26 pneumococcal serotypes. The estimated trough levels of antibodies against Hib, pneumococcus, and meningococcus were calculated to determine whether the usual IVIG dose is appropriate for protecting patients with PAD.Results: The functional antibody levels for Hib were similar in all of the IVIG products. In contrast, serum bacterial indices of meningococcal serogroups A and Y showed significant differences between products A and B. Opsonic indices to pneumococci varied depending on the serotype in each IVIG product. The estimated trough levels of antibodies against Hib, pneumococcus, and meningococcus exceeded the protective levels in most of the IVIG products except for the antibodies against two pneumococcal serotypes.Conclusion: Most of the tested commercial IVIG products had sufficient functional antibodies against Hib, pneumococcus, and meningococcus to protect patients with PAD receiving IVIG treatment. Regular and continuous evaluation of IVIG products is necessary to maintain an optimal therapeutic effect. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the use of local noise power spectrum (NPS) to characterize image noise and wavelet analysis to isolate defective pixels and inter-subpanel flat-fielding artifacts for quantitative quality assurance (QA) of electronic portal imaging devices (EPIDs). Methods: A total of 93 image sets including custom-made bar-pattern images and open exposure images were collected from four iViewGT a-Si EPID systems over three years. Global quantitative metrics such as modulation transform function (MTF), NPS, and detective quantum efficiency (DQE) were computed for each image set. Local NPS was also calculated for individual subpanels by sampling region of interests within each subpanel of the EPID. The 1D NPS, obtained by radially averaging the 2D NPS, was fitted to a power-law function. The r-square value of the linear regression analysis was used as a singular metric to characterize the noise properties of individual subpanels of the EPID. The sensitivity of the local NPS was first compared with the global quantitative metrics using historical image sets. It was then compared with two commonly used commercial QA systems with images collected after applying two different EPID calibration methods (single-level gain and multilevel gain). To detect isolated defective pixels and inter-subpanel flat-fielding artifacts, Haar wavelet transform was applied on the images. Results: Global quantitative metrics including MTF, NPS, and DQE showed little change over the period of data collection. On the contrary, a strong correlation between the local NPS (r-square values) and the variation of the EPID noise condition was observed. The local NPS analysis indicated image quality improvement with the r-square values increased from 0.80±0.03 (before calibration) to 0.85±0.03 (after single-level gain calibration) and to 0.96±0.03 (after multilevel gain calibration), while the commercial QA systems failed to distinguish the image quality improvement between the two calibration methods. With wavelet analysis, defective pixels and inter-subpanel flat-fielding artifacts were clearly identified as spikes after thresholding the inversely transformed images. Conclusions: The proposed local NPS (r-square values) showed superior sensitivity to the noise level variations of individual subpanels compared with global quantitative metrics such as MTF, NPS, and DQE. Wavelet analysis was effective in detecting isolated defective pixels and inter-subpanel flat-fielding artifacts. The proposed methods are promising for the early detection of imaging artifacts of EPIDs. [ABSTRACT FROM AUTHOR]

Although stimuli-responsive materials hold potential for use as drug-delivery carriers for treating cancers, their clinical translation has been limited. Ideally, materials used for the purpose should be biocompatible and nontoxic, provide 'on-demand' drug release in response to internal or external stimuli, allow large-scale manufacturing, and exhibit intrinsic anticancer efficacy. We present multistimuli-responsive nanoparticles formed from bilirubin, a potent endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory activity. Exposure of the bilirubin nanoparticles (BRNPs) to either reactive oxygen species (ROS) or external laser light causes rapid disruption of the BRNP nanostructure as a result of a switch in bilirubin solubility, thereby releasing encapsulated drugs. In a xenograft tumor model, BRNPs loaded with the anticancer drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm, significantly inhibited tumor growth. This study suggests that BRNPs may be used as a drug-delivery carrier as well as a companion medicine for effectively treating cancers. [ABSTRACT FROM AUTHOR]

Although stimuli-responsive materials hold potential for use as drug-delivery carriers for treating cancers, their clinical translation has been limited. Ideally, materials used for the purpose should be biocompatible and nontoxic, provide 'on-demand' drug release in response to internal or external stimuli, allow large-scale manufacturing, and exhibit intrinsic anticancer efficacy. We present multistimuli-responsive nanoparticles formed from bilirubin, a potent endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory activity. Exposure of the bilirubin nanoparticles (BRNPs) to either reactive oxygen species (ROS) or external laser light causes rapid disruption of the BRNP nanostructure as a result of a switch in bilirubin solubility, thereby releasing encapsulated drugs. In a xenograft tumor model, BRNPs loaded with the anticancer drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm, significantly inhibited tumor growth. This study suggests that BRNPs may be used as a drug-delivery carrier as well as a companion medicine for effectively treating cancers. [ABSTRACT FROM AUTHOR]

p38 mitogen-activated protein kinase (MAPK) is a promising target for the development of therapeutics for various immunological diseases. We designed and synthesized aminothiazole-based p38 MAPK inhibitors of with IC 50 values ranging from 0.1 to 2 μM by means of the structure-based de novo design of phenyl-(2-phenylamino-thiazol-5-yl)-methanone scaffold. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further investigation as anti-inflammatory drugs. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are discussed in detail. [ABSTRACT FROM AUTHOR]

(1) Background: This study aims to elucidate a novel non-transcriptional action of IRF3 in addition to its role as a transcription factor in mast cell activation and associated allergic inflammation; (2) Methods: For in vitro experiments, mouse bone-marrow-derived mast cells (mBMMCs) and a rat basophilic leukemia cell line (RBL-2H3) were used for investigating the underlying mechanism of IRF3 in mast-cell-mediated allergic inflammation. For in vivo experiments, wild-type and Irf3 knockout mice were used for evaluating IgE-mediated local and systemic anaphylaxis; (3) Results: Passive cutaneous anaphylaxis (PCA)-induced tissues showed highly increased IRF3 activity. In addition, the activation of IRF3 was observed in DNP-HSA-treated mast cells. Phosphorylated IRF3 by DNP-HSA was spatially co-localized with tryptase according to the mast cell activation process, and FcεRI-mediated signaling pathways directly regulated that activity. The alteration of IRF3 affected the production of granule contents in the mast cells and the anaphylaxis responses, including PCA- and ovalbumin-induced active systemic anaphylaxis. Furthermore, IRF3 influenced the post-translational processing of histidine decarboxylase (HDC), which is required for granule maturation; and (4) Conclusion: Through this study, we demonstrated the novel function of IRF3 as an important factor inducing mast cell activation and as an upstream molecule for HDC activity. [ABSTRACT FROM AUTHOR]

This study examined the levels of Latino mothers’ and fathers’ involvement in their school-age children’s care and the relationships between parents’ socio-economic status (SES) variables, sense of community, community provisions, and marital satisfaction with their involvement in children’s routine and demand care. Mothers and fathers from 159 intact Latino families participated in the study. Multivariate analyses revealed that mothers spent significantly more time in providing child care than fathers did. The gender of the child did not make a difference in the amount of time mothers and fathers invested in children’s care. Whereas community provisions and marital satisfaction predicted mothers’ involvement in routine care, sense of community and community provisions predicted mothers’ involvement in demand care. None of the predictors were related to fathers’ involvement in routine or demand care. Findings are discussed in light of gender role differences in parental involvement with children within Latino families. [ABSTRACT FROM AUTHOR]

Introduction This article aims to assess the efficacy and safety of atomoxetine in Korean adults with attention-deficit hyperactivity disorder ( ADHD). Methods This post hoc double-blind, placebo-controlled study of atomoxetine (40-120 mg/day) over 10 weeks in adults with ADHD at 45 Japanese, Korean, and Taiwanese study sites focused on patient data from Korea (atomoxetine, n = 37; placebo, n = 37). Primary efficacy outcome was change in baseline-to-endpoint Conners' Adult ADHD Rating Scale- Investigator-rated: Screening Version ( CAARS- Inv:SV) Total ADHD Symptoms score. Secondary efficacy outcomes included changes in Adult ADHD Quality of Life ( AAQoL) total, Behavior Rating Inventory of Executive Function- Adult Version Self- Report ( BRIEF-A: Self- Report), and Clinical Global Impression- ADHD- Severity ( CGI-ADHD-S) scale scores. Results Atomoxetine-treated patients demonstrated a mean 18.9-point reduction in CAARS-Inv: SV total ADHD Symptoms score, compared with the 7.45-point reduction in placebo-treated patients ( P ≤ 0.01). Significantly greater improvement was found for atomoxetine versus placebo in CGI-ADHD- S ( P ≤ 0.01), BRIEF-A: Self- Report global executive composite ( P ≤ 0.05), and metacognition index ( P ≤ 0.01) executive function scores. Nausea, decreased appetite, and dry mouth were reported with significantly greater frequency by atomoxetine-treated patients, and only one placebo-treated patient discontinued because of adverse event. A 2.1-kg reduction in weight and a 7.5-beat/minute increase in pulse rate were observed in atomoxetine-treated patients. Discussion These data support a significant benefit of 80- to 120-mg once daily atomoxetine versus placebo for treatment of ADHD in adult Korean patients. A high placebo response rate was observed in this adult Korean sample; a higher discontinuation rate was also observed in atomoxetine-treated patients. These observations warrant further investigation. [ABSTRACT FROM AUTHOR]

Thec-KIT tyrosine kinase has emerged as a potential therapeutictarget for an array of diseases. However, there exists a drug resistancethat is caused by mutations in c-KIT; therefore, c-KIT remains asa clinical challenge due to limited effective treatment options fortherapies. For example, the acquired activating point mutation D816Vsignificantly impairs the efficacy of targeted cancer therapies. Understandingthe mechanisms of drug resistance at the molecular level will aidin designing and developing particular inhibitors with the potentialto overcome these resistance mutations. We undertake a structure-basedde novo design of 7-azaindole as the molecular core using the modifiedscoring function. This approach led to an identification of new c-KITinhibitors over 100-fold specific for the D816V mutant relative tothe wild-type c-KIT with nanomolar inhibitory activity. More importantly,these compounds potently inhibit clinically relevant D816V mutationsof c-KIT in biochemical and cellular studies. [ABSTRACT FROM AUTHOR]

Using total suspended solid (TSS) removal efficiency and hydraulic retention time (HRT) as design parameters a design guideline of a settling basin in a constructed wetland (CW) was suggested; as well as management of sediment and particle in the settling basin. The CW was designed to treat the piggery wastewater effluent from a wastewater treatment plant during dry days and stormwater runoff from the surrounding paved area during wet days. The first settling basin (FSB) in the CW was theoretically designed with a total storage volume (TSV) of 453 m 3 and HRT of 5.5 hr. The amount of sediment and particles settled at the FSB was high due to the sedimentation and interception of plants in the CW. Dredging of sediments was performed when the retention rate at the FSB decreased to approximately 80%. Findings showed that the mean flow rate was 21.8 m 3 /hr less than the designed flow rate of 82.8 m 3 /hr indicating that the FSB was oversize and operated with longer HRT (20.7 hr) compared to the design HRT. An empirical model to estimate the length of the settling basin in the CW was developed as a function of HRT and desired TSS removal efficiency. Using the minimum tolerable TSS removal efficiency of 30%, the length of the FSB was estimated to be 31.2 m with 11.8 hr HRT. [ABSTRACT FROM AUTHOR]