Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Lipnicki, Darren M.,Crawford, John D.,Dutta, Rajib,Thalamuthu, Anbupalam,Kochan, Nicole A.,Andrews, Gavin,Lima-Costa, M. Fernanda,Castro-Costa, Erico,Brayne, Carol,Matthews, Fiona E.,Stephan, Blossom Public Library of Science 2017 PLoS medicine Vol.14 No.3

<▼1><P><B>Background</B></P><P>The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (<I>APOE*4</I>) carrier status were associated with decline.</P><P><B>Methods and findings</B></P><P>We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], <I>p</I> < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], <I>p</I> = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (<I>p</I> = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], <I>p</I> < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], <I>p</I> = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], <I>p</I> < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], <I>p</I> = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], <I>p</I> = 0.001). <I>APOE*4</I> carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], <I>p</I> = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China.</P><P><B>Conclusions</B></P><P>Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and <I>APOE</I> genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.</P></▼1><▼2><P>In a collaborative cohort study, Darren Lipnicki and colleagues investigate associations between age-related cognitive decline and sex, education, and apoli

Global prevalence of depression and anxiety in patients with hepatocellular carcinoma: Systematic review and meta-analysis

Darren Jun Hao Tan,Sabrina Xin Zi Quek,Jie Ning Yong,Adithya Suresh,Kaiser Xuan Ming Koh,Wen Hui Lim,Jingxuan Quek,Ansel Tang,Caitlyn Tan,Benjamin Nah,Eunice Tan,Taisei Keitoku,Mark D. Muthiah,Nichola 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.4

Background/Aims: Depression and anxiety are associated with poorer outcomes in patients with hepatocellular carcinoma (HCC). However, the prevalence of depression and anxiety in HCC are unclear. We aimed to establish the prevalence of depression and anxiety in patients with HCC. Methods: MEDLINE and Embase were searched and original articles reporting prevalence of anxiety or depression in patients with HCC were included. A generalized linear mixed model with Clopper-Pearson intervals was used to obtain the pooled prevalence of depression and anxiety in patients with HCC. Risk factors were analyzed via a fractional-logistic regression model. Results: Seventeen articles involving 64,247 patients with HCC were included. The pooled prevalence of depression and anxiety in patients with HCC was 24.04% (95% confidence interval [CI], 13.99–38.11%) and 22.20% (95% CI, 10.07–42.09%) respectively. Subgroup analysis determined that the prevalence of depression was lowest in studies where depression was diagnosed via clinician-administered scales (16.07%;95% CI, 4.42–44.20%) and highest in self-reported scales (30.03%; 95% CI, 17.19–47.01%). Depression in patients with HCC was lowest in the Americas (16.44%; 95% CI, 6.37–36.27%) and highest in South-East Asia (66.67%; 95% CI, 56.68–75.35%). Alcohol consumption, cirrhosis, and college education significantly increased risk of depression in patients with HCC. Conclusions: One in four patients with HCC have depression, while one in five have anxiety. Further studies are required to validate these findings, as seen from the wide CIs in certain subgroup analyses. Screening strategies for depression and anxiety should also be developed for patients with HCC.

Korean Copyright Act Article 30

Darren QX Bean 조선대학교 법학연구원 2012 法學論叢 Vol.19 No.1

「한국 저작권법」 제30조는 저작물을 “한정된 범위” 안에서 이용하는 경우 사적복제를 허용하고 있다. 위 조항은 매우 흔하게 일어나는 “일상적인 복제” 즉, 친구나 지인이 소유하는 저작물을 비영리 목적으로 하는 복제를 사실상 적법하게 한다. 그러나 위 조항에 국제법에 의거할 때에도 합법적인지는 의문이다. TRIPs에 따르면 권리에 대한 모든 제한은 통상적인 이용과 충돌하지 아니하고 권리자의 권리를 불합리하게 침해하지 않는 구체적이고 특별한 경우에 한한다고 한다. 이 논문은 제30조의 적법성에 대한 문제점을 지적하고 조항의 타당성을 제고할 수 있는 두 가지 대안을 다루고자 한다. Article 30 of the Copyright Act allows for "private" reproduction of a work for use in a "limited circle." This effectively legalizes the very common practice of "casual copying," or not paying for copies of works owned by friends and acquaintances. But is this provision legal under international law? TRIPS states that all limitations to rights must be "certain special cases" that do not "conflict with a normal exploitation of" nor "unreasonably prejudice" the rights of the rightholder. The World Trade Organization Dispute Settlement Body ("DSB") has analyzed the TRIPS three-step test only once, in the context of a statutory exemption allowing certain businesses to play music without licenses. In the course of that arbitration, the DSB focused on the quantity of users exempted as well as evidence concerning the total losses (including potential losses) to rightholders. Currently there is only minimal evidence concerning the effect of casual copying on revenue, and that data suggests that casual copying does no harm to rightholders. This conclusion, however, is very tentative and could easily change based on new data. Therefore, although this paper concludes that article 30 would not currently run afoul of the TRIPS test, two amendments are suggested to ensure that "private" reproduction remains in compliance. Both approaches can already be seen in other aspects of Korean copyright law. First, article 30 could be amended to grant the President the power to decree uses outside the scope of "private" use if an international body finds a certain use would violate international obligations. In the alternative, TRIPS-like language(borrowed from the three-part test) could be added to article 30. As the former is more predictable yet still allows for a fair degree of responsiveness, a "Presidential Decree" amendment should be integrated into article 30.

Royalties? Not Joseon Dynasty Kings - A Comparative Analysis of Copyright and Music Licensing Groups in the United States and Korea

( Darren Qx Bean ),( Yuna Lee ) 서울대학교 법학연구소 2014 Journal of Korean Law Vol.13 No.1

Media has been one of the United States’ premier exports for several years. Recently, the “Korean Wave” has garnered coverage in many international arenas, with “Big Bang” winning best international group at the 2011 MTV European Music Awards and “Gangnam Style” reaching number one on the Billboard Social 50 Chart. This Article compares and contrasts the copyright and music licensing regimes in the Republic of Korea and the United States, focusing on substantive copyright protection but also including discussion of the function of rights management societies. We address cultural, historical, and economic factors contributing to the distinctive treatment of musical regulation and offer our opinion as to which nation’s approach is more legally and logically sound in key areas of legal difference in order to encourage reconsideration of certain points within the legal regimes in both nations.

A retrospective review of correlative radiological assessment and surgical exploration for hilar cholangiocarcinoma

Darren Chua,Albert Low,Yexin Koh,Brian Goh,Peng Chung Cheow,Juinn Har Kam,Jin Yao Teo,Ek Khoon Tan,Alexander Chung,London Lucien Ooi,Chung Yip Chan,Ser Yee Lee 한국간담췌외과학회 2018 Annals of hepato-biliary-pancreatic surgery Vol.22 No.3

Backgrounds/Aims: Hilar cholangiocarcinomas (HCCAs) are tumors that involve the biliary confluence; at present, radical surgery offers the only chance of long-term survival, but this can be challenging given the complexity of the hilar anatomy. Blumgart and Jarnagin described a preoperative staging system that incorporates the effect of local tumor extent and its impact on adjacent structures and that has been demonstrated to correlate better with actual surgical resectability. The primary aim of this study is to describe the correlation between preoperative Blumgart-Jarnagin staging and its correlation with surgical resectability. Methods: Patients who underwent surgical resection for hilar cholangiocarcinoma at Singapore General Hospital between January 1, 2002, and January 1, 2013, were identified from a prospectively maintained institutional database. All patients were staged based on the criteria described by Blumgart and Jarnagin. Correlation with surgical resectability was then determined. Results: A total of 19 patients were identified. Overall resectability was 57.8% (n=11). Patients with Blumgart-Jarnagin stage T1 had the highest rates of respectability at 80%; patients with stage T2 and T3 disease had resectability rates of 25% and 40% respectively. Median overall survival was 13.6 months. Conclusions: The Blumgart-Jarnagin staging system is useful for predicting tumor respectability in HCCA.

A Disclosure Form for Work Submitted to Medical Journals: a Proposal from the International Committee of Medical Journal Editors

Darren B. Taichman,Joyce Backus,Christopher Baethge,Howard Bauchner,Annette Flanagin,Fernando Florenzano,Frank A. Frizelle,Fiona Godlee,Laragh Gollogly,Abraham Haileamlak,Sung-Tae Hong,Richard Horton 대한의학회 2020 Journal of Korean medical science Vol.35 No.4

Many factors, including professional and personal relationships and activities, can influence the design, conduct, and reporting of the clinical science that informs health care decision. The potential for conflict of interest exists when these relationships and activities may bias judgement.1 Many stakeholders—editors, peer reviewers, clinicians, educators, policymakers, patients, and the public—rely on the disclosure of authors' relationships and activities to inform their assessments. Trust in the transparency, consistency, and completeness of these disclosures is essential.

Is it time for a paradigm shift in first line treatment of EGFR mutant NSCLC?

( Darren Wan-teck Lim ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-

EGFR mutant NSCLC represents the majority of lung cancer in Asia. All generations of EGFR tyrosine kinase inhibitors have demonstrated excellent efficacy in advanced disease. Osimertinib was developed specifically to address T790M mutation, the dominant resistance mechanism following failure of 1st/2nd generation inhibitors. Moving the use of osimertinib to the first-line setting represents a paradigm shift in management of EGFR mt lung cancer, as it challenges current practice of sequencing EGFR inhibitors. The discussion will focus on recent overall survival data from FLAURA and its possible impact on existing practice in EGFR mutant NSCLC in Asia.

The effect of semantic categorization of episodic memory on encoding of subordinate details

Darren Sehjung Yi(이세중),Sanghoon Han(한상훈) 한국인지과학회 2017 인지과학 Vol.28 No.4

의미적 연관성을 지닌 일화들의 범주화는 기억을 더 효과적으로 구조화하는데 도움이 된다. 그러나 해당일화의 하위 세부 기억들에 대한 상기한 범주화의 영향은 아직 명확하게 알려져 있지 않다. 본 연구에서는 fMRI 실험을 통해 의미적 범주화가 이루어지는 동안 상위의 일화 기억에 주의를 기울이는 것이 하위 세부기억의 생성을 방해하는지, 혹은 강화하는지 실험하였다. 참가자들에게 한 사이클 내에서 각각 2개의 하위단어를 가지고 있는 5개의 목표 단어들이 순서대로 제시되었는데, 참가자들은 해당 사이클 내에서 제시된 목표 단어들을 포함할 수 있는 범주를 떠올릴 수 있는지 응답한 후 그 범주에 대한 주관적 확신도를 평정하였다. fMRI 내 과정이 끝난 후 참가자들은 스캐너 밖으로 이동하여 제시되었던 단서 단어의 하위 단어들에 대한 단서 회상과제를 수행하였다. 행동 실험 결과 매 사이클의 세 번째 시행에서 범주화 과제의 반응속도가 감소하였고 동시에 주관적 확신도 수준이 증가하였는데, 이는 해당 시행에서 의미적 범주화가 완성되었음을 의미한다. 주목할 점은 세 번째 시행 바로 직전에 제시되었던 하위 단어들의 회상 정확도가 그 다음 시행 직전에 제시된 단어들에 비해 유의미하게 낮았다는 점이며 이는 범주화가 완성될 때 일화 기억의 하위 세부 요소들이 손상되었음을 의미한다. 일반선형모델을 통한 분석 결과 의미적 범주화가 완성되기 직전의 시행에서 의미적 기억망과 관련이 있는 것으로 알려져 있는 측두회와 하전두회에서 유의미한 활성화가 나타났다. 또한 패턴 유사성 분석 결과 또한 측두회, 하전두회, 해마 영역에서 세 번째 시행 간의 활성화 패턴이 두 번째 시행의 활성화 패턴에 비해 더 일관적인 것으로 나타났다. 본 연구는 의미적 범주화가 하위 세부 일화 기억을 방해할 수 있다는 것을 보여주며, 이러한 범주화가 진행되는 동안 일어나는 의미적 인출 경험이 관련된 일화 기억의 흔적에 질적인 영향을 미칠 수 있음을 시사한다. Grouping episodes into semantically related categories is necessary for better mnemonic structure. However, the effect of grouping on memory of subordinate details was not clearly understood. In an fMRI study, we tested whether attending superordinate during semantic association disrupts or enhances subordinate episodic details. In each cycle of the experiment, five cue words were presented sequentially with two related detail words placed underneath for each cue. Participants were asked whether they could imagine a category that includes the previously shown cue words in each cycle, and their confidence on retrieval was rated. Participants were asked to perform cued recall tests on presented detail words after the session. Behavioral data showed that reaction times for categorization tasks decreased and confidence levels increased in the third trial of each cycle, thus this trial was considered to be an important insight where a semantic category was believed to be successfully established. Critically, the accuracy of recalling detail words presented immediately prior to third trials was lower than those of followed trials, indicating that subordinate details were disrupted during categorization. General linear model analysis of the trial immediately prior to the completion of categorization, specifically the second trial, revealed significant activation in the temporal gyrus and inferior frontal gyrus, areas of semantic memory networks. Representative Similarity Analysis revealed that the activation patterns of the third trials were more consistent than those of the second trials in the temporal gyrus, inferior frontal gyrus, and hippocampus. Our research demonstrates that semantic grouping can cause memories of subordinate details to fade, suggesting that semantic retrieval during categorization affects the quality of related episodic memory.

Molecularly Stretchable Electronics for Energy and Healthcare

Darren J. LIPOMI 한국고분자학회 2016 한국고분자학회 학술대회 연구논문 초록집 Vol.41 No.2

The US, China and ‘Technology War’

Darren Lim 동아시아재단 2019 Global Asia Vol.14 No.1