In 2018, North Korean Leader Kim Jong-un expressed his desire to write a new history of Korean reunification. South Korean President Moon Jae-in reciprocated Kim’s desire in August 2019 when Moon set ...the ambitious deadline of the year 2045 for a peaceful reunification of the Koreas. The rhetoric of the two Koreas placed a renewed spotlight on the reunification of the Korean Peninsula. While contemporary literature on Korean reunification primarily focuses on the differences between the two Koreas, little attention has been paid to how a unified Korean identity can play a crucial rule in sustaining the reunification effort. This article seeks to bridge that gap by arguing that a unified Korea should be understood as a reimagined community of two distinct nations joined by a shared identity. To support this argument, this article looks first to the theoretical framework of Benedict Anderson’s Imagined Communities: Reflections on the Origin and Spread of Nationalism and applies the framework to the history of Korea’s shared identity. Second, the article analyzes the evolution of the national identities of both South Korea and North Korea since 1945, when the Koreas were divided along the thirty-eighth parallel. Third, the obstacles to reunification are examined. Finally, suggestions on how reunification of the two Koreas could be sustained through shared national identities are explored.
The aim of the investigation was to search the current literature (from April 2005 to December 2012) and determine the effectiveness of orthodontic tooth movement using the Invisalign system. With ...changes in attachments implemented within the past few years, a more recent appraisal of the available literature is of value. It is expected that this systematic review will provide a more up-to-date understanding of the treatment effects (efficacy in tooth movement and stability) of the Invisalign system. Additionally, an evaluation of the indications and case selection using Invisalign will be conducted. A computerized search was conducted using PubMed, Evidence Based Medicine (EBM) Reviews Database (Cochrane Database of Systematic Reviews), Database of Abstracts of Reviews of Effects and Cochrane Central Register of Controlled Trials, Science Direct, and Thomsen's ISI Web of Science. Inclusion criteria that were to be satisfied by the literature search results were publications in English and human clinical trials. Studies not pertaining to the question of clinical effectiveness of Invisalign were selected for exclusion. Case reports, book chapters, and review papers were considered separately for analysis and contribution to the general information gathering in the systematic review. Book chapters were excluded. Quality assessment was performed on the studies that fulfilled the inclusion criteria. The quality and design of the study was considered. Of the studies that passed the quality assessment stage, a thorough evaluation was completed. Summaries of the included articles were prepared and information regarding study design, subjects, treatment times, and outcomes were organized in tabulated form. Appraisal of the included studies was performed using the 2010 CONSORT statement and 2009 ADA Clinical Recommendations Handbook. Overall, of the 271 studies reviewed (Stage I), 23 were selected for further review (Stage II). Ultimately, 10 studies were included in the systematic review (Stage III). In summary, after thorough analysis of the studies, it has been shown that Invisalign is an effective appliance for minor space closure, lingual constriction, and correction of anterior rotations and marginal ridge height discrepancies. However, Invisalign lacks the ability to correct anteroposterior discrepancies, occlusal contacts, extrusion, and rotations greater than 15 degrees. While the achieved and predicted tooth movement discrepancy was very minimal, it was found that overbite must be overcorrected.
The JAK pathway is a potential therapeutic target in ankylosing spondylitis. This study assessed the efficacy and safety of upadacitinib, a selective JAK1 inhibitor, in patients with ankylosing ...spondylitis.
This multicentre, randomised, double-blind, placebo-controlled, two-period, parallel-group, phase 2/3 study, SELECT-AXIS 1, enrolled adults in 62 sites in 20 countries. Eligible patients had active ankylosing spondylitis, fulfilled modified New York criteria, were previously untreated with biological disease-modifying antirheumatic drugs, and had inadequate response to at least two or intolerance or contraindication to non-steroidal anti-inflammatory drugs. Patients were randomly assigned 1:1 using interactive response technology to take oral upadacitinib 15 mg once daily or oral placebo for the 14-week period 1; only period 1 data are reported here. The primary endpoint was the composite outcome measure of the Assessment of SpondyloArthritis international Society 40 response at week 14. Analyses were done in the full analysis set of patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03178487.
Between Nov 30, 2017, and Oct 15, 2018, 187 patients were randomly assigned to upadacitinib 15 mg (93 patients) or to placebo (94 patients), and 178 (95%) patients (89 in the upadacitinib group and 89 in the placebo group) completed period 1 on study drug (by the completion date of Jan 21, 2019). Significantly more patients had an Assessment of SpondyloArthritis international Society 40 response in the upadacitinib group versus in the placebo group at week 14 (48 52% of 93 patients vs 24 26% of 94 patients; p=0·0003; treatment difference 26% 95% CI 13–40). Adverse events were reported in 58 (62%) of 93 patients in the upadacitinib group versus 52 (55%) of 94 in the placebo group. The most common adverse event in the upadacitinib group was increased creatine phosphokinase (eight 9% of 93 patients in the upadacitinib group vs two 2% of 94 patients with placebo). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported; one serious adverse event was reported in each group.
Upadacitinib 15 mg was efficacious and well tolerated in patients with active ankylosing spondylitis who had an inadequate response or contraindication to non-steroidal anti-inflammatory drugs. These data support the further investigation of upadacitinib for the treatment of axial spondyloarthritis.
AbbVie.
Membrane bioreactor (MBR) technology is a promising method for water and wastewater treatment because of its ability to produce high-quality effluent that meets water quality regulations. Due to the ...intrinsic complexity and uncertainty of MBR processes, basic models that can provide a holistic understanding of the technology at a fundamental level are of great necessity. Compared to experimental research and development, followed by commercialization of the technology, modeling studies for system design analysis and performance prediction are at a relatively rudimentary state. In this light, this review was conducted to provide an assessment of present efforts in modeling MBR systems, specifically for municipal wastewater treatment. Models considered in this review are classified into three categories: biomass kinetic models, membrane fouling models, and integrated models with (light) couplings to describe the complete MBR process. The specific features, unique advantages, and capturing capability of experimental observations of each model are discussed and assessed. Crucial components in MBR modeling studies are carefully selected and assessed, based on the importance of their roles in characterizing MBR performance, and future MBR modeling directions are suggested.
Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, and tyrosine kinase 2. We aimed to assess the efficacy and safety of upadacitinib ...compared with placebo for the treatment of moderate-to-severe atopic dermatitis.
Measure Up 1 and Measure Up 2 were replicate multicentre, randomised, double-blind, placebo-controlled, phase 3 trials; Measure Up 1 was done at 151 clinical centres in 24 countries across Europe, North and South America, Oceania, and the Asia-Pacific region; and Measure Up 2 was done at 154 clinical centres in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region. Eligible patients were adolescents (aged 12–17 years) and adults (aged 18–75 years) with moderate-to-severe atopic dermatitis (≥10% of body surface area affected by atopic dermatitis, Eczema Area and Severity Index EASI score of ≥16, validated Investigator's Global Assessment for Atopic Dermatitis vIGA-AD score of ≥3, and Worst Pruritus Numerical Rating Scale score of ≥4). Patients were randomly assigned (1:1:1) using an interactive response technology system to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks, stratified by baseline disease severity, geographical region, and age. Coprimary endpoints were the proportion of patients who had achieved at least a 75% improvement in EASI score from baseline (EASI-75) and the proportion of patients who had achieved a vIGA-AD response (defined as a vIGA-AD score of 0 clear or 1 almost clear with ≥2 grades of reduction from baseline) at week 16. Efficacy was analysed in the intention-to-treat population and safety was analysed in all randomly assigned patients who received at least one dose of study drug. These trials are registered with ClinicalTrials.gov, NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2), and are both active but not recruiting.
Between Aug 13, 2018, and Dec 23, 2019, 847 patients were randomly assigned to upadacitinib 15 mg (n=281), upadacitinib 30 mg (n=285), or placebo (n=281) in the Measure Up 1 study. Between July 27, 2018, and Jan 17, 2020, 836 patients were randomly assigned to upadacitinib 15 mg (n=276), upadacitinib 30 mg (n=282), or placebo (n=278) in the Measure Up 2 study. At week 16, the coprimary endpoints were met in both studies (all p<0·0001). The proportion of patients who had achieved EASI-75 at week 16 was significantly higher in the upadacitinib 15 mg (196 70% of 281 patients) and upadacitinib 30 mg (227 80% of 285 patients) groups than the placebo group (46 16% of 281 patients) in Measure Up 1 (adjusted difference in EASI-75 response rate vs placebo, 53·3% 95% CI 46·4–60·2 for the upadacitinib 15 mg group; 63·4% 57·1–69·8 for the upadacitinib 30 mg group) and Measure Up 2 (166 60% of 276 patients in the upadacitinib 15 mg group and 206 73% of 282 patients in the upadacitinib 30 mg group vs 37 13% of 278 patients in the placebo group; adjusted difference in EASI-75 response rate vs placebo, 46·9% 39·9–53·9 for the upadacitinib 15 mg group; 59·6% 53·1–66·2 for the upadacitinib 30 mg group). The proportion of patients who achieved a vIGA-AD response at week 16 was significantly higher in the upadacitinib 15 mg (135 48% patients) and upadacitinib 30 mg (177 62% patients) groups than the placebo group (24 8% patients) in Measure Up 1 (adjusted difference in vIGA-AD response rate vs placebo, 39·8% 33·2–46·4 for the upadacitinib 15 mg group; 53·6% 47·2–60·0 for the upadacitinib 30 mg group) and Measure Up 2 (107 39% patients in the upadacitinib 15 mg group and 147 52% patients in the upadacitinib 30 mg group vs 13 5% patients in the placebo group; adjusted difference in vIGA-AD response rate vs placebo, 34·0% 27·8–40·2 for the upadacitinib 15 mg group; 47·4% 41·0–53·7 for the upadacitinib 30 mg group). Both upadacitinib doses were well tolerated. The incidence of serious adverse events and adverse events leading to study drug discontinuation were similar among groups. The most frequently reported treatment-emergent adverse events were acne (19 7% of 281 patients in the upadacitinib 15 mg group, 49 17% of 285 patients in the upadacitinib 30 mg group, and six 2% of 281 patients in the placebo group in Measure Up 1; 35 13% of 276 patients in the upadacitinib 15 mg group, 41 15% of 282 patients in the upadacitinib 30 mg group, and six 2% of 278 patients in the placebo group in Measure Up 2), upper respiratory tract infection (25 9% patients, 38 13% patients, and 20 7% patients; 19 7% patients, 17 16% patients, and 12 4% patients), nasopharyngitis (22 8% patients, 33 12% patients, and 16 6% patients; 16 6% patients, 18 6% patients, and 13 5% patients), headache (14 5% patients, 19 7% patients, and 12 4% patients; 18 7% patients, 20 7% patients, and 11 4% patients), elevation in creatine phosphokinase levels (16 6% patients, 16 6% patients, and seven 3% patients; nine 3% patients, 12 4% patients, and five 2% patients), and atopic dermatitis (nine 3% patients, four 1% patients, and 26 9% patients; eight 3% patients, four 1% patients, and 26 9% patients).
Monotherapy with upadacitinib might be an effective treatment option and had a positive benefit–risk profile in adolescents and adults with moderate-to-severe atopic dermatitis.
AbbVie.
Atopic dermatitis is a chronic inflammatory skin disease characterized by pruritic skin lesions.
We sought to evaluate the safety and efficacy of multiple doses of the selective Janus kinase 1 ...inhibitor upadacitinib in patients with moderate to severe atopic dermatitis.
In the 16-week, double-blind, placebo-controlled, parallel-group, dose-ranging portion of this 88-week trial in 8 countries (ClinicalTrials.gov, NCT02925117; ongoing, not recruiting), adults with moderate to severe disease and inadequate control by topical treatment were randomized 1:1:1:1, using an interactive response system and stratified geographically, to once-daily upadacitinib oral monotherapy 7.5, 15, or 30 mg or placebo. The primary end point was percentage improvement in Eczema Area and Severity Index from baseline at week 16. Efficacy was analyzed by intention-to-treat in all randomized patients. Safety was analyzed in all randomized patients who received study medication, based on actual treatment.
Patients (N = 167) enrolled from November 21, 2016, to April 20, 2017. All were randomized and analyzed for efficacy (each upadacitinib group, n = 42; placebo, n = 41); 166 were analyzed for safety (each upadacitinib group, n = 42; placebo, n = 40). The mean (SE) primary efficacy end point was 39% (6.2%), 62% (6.1%), and 74% (6.1%) for the upadacitinib 7.5-, 15-, and 30-mg groups, respectively, versus 23% (6.4%) for placebo (P = .03, <.001, and <.001). Serious adverse events occurred in 4.8% (2 of 42), 2.4% (1 of 42), and 0% (0 of 42) of upadacitinib groups (vs 2.5% 1 of 40 for placebo).
A dose-response relationship was observed for upadacitinib efficacy; the 30-mg once-daily dose showed the greatest clinical benefit. Dose-limiting toxicity was not observed.
Implanting materials in the body to program host immune cells is a promising alternative to transplantation of cells manipulated ex vivo to direct an immune response, but doing so requires a surgical ...procedure. Here we demonstrate that high-aspect-ratio, mesoporous silica rods (MSRs) injected with a needle spontaneously assemble in vivo to form macroporous structures that provide a 3D cellular microenvironment for host immune cells. In mice, substantial numbers of dendritic cells are recruited to the pores between the scaffold rods. The recruitment of dendritic cells and their subsequent homing to lymph nodes can be modulated by sustained release of inflammatory signals and adjuvants from the scaffold. Moreover, injection of an MSR-based vaccine formulation enhances systemic helper T cells TH1 and TH2 serum antibody and cytotoxic T-cell levels compared to bolus controls. These findings suggest that injectable MSRs may serve as a multifunctional vaccine platform to modulate host immune cell function and provoke adaptive immune responses.
Summary Background Upadacitinib, a Janus kinase inhibitor, has been shown to be effective in patients with ankylosing spondylitis. We aimed to assess the efficacy and safety of upadacitinib in ...non-radiographic axial spondyloarthritis. Methods The SELECT-AXIS 2 non-radiographic axial spondyloarthritis study was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 113 sites across 23 countries (Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Japan, Mexico, Poland, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey, Ukraine, and the USA). Eligible adults had active non-radiographic axial spondyloarthritis, with objective signs of inflammation based on MRI or elevated C-reactive protein and an inadequate response to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1) to receive oral upadacitinib 15 mg once daily or placebo using interactive response technology. Random treatment assignment was stratified by MRI inflammation in the sacroiliac joints and screening high-sensitivity C-reactive protein status (MRI-positive and C-reactive protein-positive, MRI-positive and C-reactive protein-negative, and MRI-negative and C-reactive protein-positive) and previous exposure to biologic disease-modifying antirheumatic drugs (yes vs no). Treatment assignment was masked from patients, investigators, study site personnel, and the study sponsor. The primary endpoint was the proportion of patients with an Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Analyses were performed on the full analysis set of patients, who underwent random allocation and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04169373. Findings Between Nov 26, 2019, and May 20, 2021, 314 patients with active non-radiographic axial spondyloarthritis were enrolled into the study, and 313 received study drug (156 in the upadacitinib group and 157 in the placebo group); 295 (94%) patients (145 in the upadacitinib group and 150 in the placebo group) received treatment for the full 14 weeks. A significantly higher ASAS40 response rate was achieved with upadacitinib compared with placebo at week 14 (70 45% of 156 patients vs 35 23% of 157 patients; p<0·0001; treatment difference 22%, 95% CI 12–32). The rate of adverse events up to week 14 was similar in the upadacitinib group (75 48% of 156 patients) and placebo group (72 46% of 157 patients). Serious adverse events and adverse events leading to discontinuation of study drug occurred in four (3%) of 156 patients in the upadacitinib group and two (1%) of 157 patients in the placebo group. Few patients had serious infections or herpes zoster in either treatment group (each event occurred in two 1% of 156 patients in the upadacitinib group and one 1% of 157 patients in the placebo group). Five (3%) of 156 patients in the upadacitinib group had neutropenia; no events of neutropenia occurred in the placebo group. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, or deaths were reported with upadacitinib treatment. Interpretation Upadacitinib significantly improved the signs and symptoms of non-radiographic axial spondyloarthritis compared with placebo at week 14. These findings support the potential of upadacitinib as a new therapeutic option in patients with active non-radiographic axial spondyloarthritis. Funding AbbVie.
Breast cancer (BrC) and its treatments impair health-related quality of life (HRQoL). Utility is a measure of HRQoL that includes preferences for health outcomes, used in treatment decision-making. ...Generic preference-based instruments lack BrC-specific concerns, indicating the need for a BrC-specific preference-based instrument. Our objective was to determine dimensions of the European Organisation for Research and Treatment of Cancer (EORTC) general cancer (QLQ-C30) and breast module (BR45) instruments, the first step in our development of the novel Breast Utility Instrument (BUI).
Patients (n = 408) attending outpatient BrC clinics at an urban cancer centre, and representing a spectrum of BrC health states, completed the QLQ-C30 and BR45. We performed confirmatory factor analysis of the combined QLQ-C30 and BR45 using mean-and variance-adjusted unweighted least squares estimation. The hypothesized factor model was based on clinical relevance, item distributions, missing data, item-importance, and internal reliability of dimensions. Models were evaluated based on global and item fit, local areas of strain, and likelihood ratio tests of nested models.
Our final model had 10 dimensions: physical and role functioning, emotional functioning, social functioning, body image, pain, fatigue, systemic therapy side effects, sexual functioning and enjoyment, arm and breast symptoms, and endocrine therapy symptoms. Good overall model fit was achieved: χ2/df: 1.45, Tucker-Lewis index: 0.946, comparative fit index: 0.951, standardized root-mean-square residual: 0.069, root-mean-square error of approximation: 0.033 (0.030-0.037). All items had salient factor loadings (λ>0.4, p<0.001).
We identified important BrC HRQoL dimensions to develop the BUI, a BrC-specific preference-based instrument.
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