A risk- and complexity-rating framework for investment products

Sim Kee Boon Institute for Financial Economics SKB

A randomized control trial comparing peginterferon-α-2a versus observation after stopping tyrosine kinase inhibitor in chronic myeloid leukemia with deep molecular response for at least two years

Background: There is much advancement in treatment of chronic myeloid leukemia (CML) since the approval of first tyrosine kinase inhibitor (TKI), imatinib, by US FDA in 2001. One of them is definitely the concept of stopping TKI, starting at the CML patients who have achieved deep molecular response (MR) of MR4.5 for a reasonable long period of at least two years, pioneered by the researchers from French and Australia. Meanwhile, interferon, the standard treatment of CML before the era of TKI, showed that interferon-responded patients may indeed retain the response once interferon was withdrawn via interferon-induced immunity towards the leukemic clone. This is further supported by stop trial in Japan, in which after stopping TKI, interferon was given for 2 years and it showed a higher drug-free rate compared to stop trial from French and Australia. Hence, it is logical to postulate the use of interferon after TKI was stopped when patients have attained deep MR for more than two years will increase the percentage of patients remain TKI-free on follow-up. Materials and Methods: This is a multi-center randomized controlled trial. Adult CML patients, diagnosed in chronic phase, treated with ongoing TKI for at least 3 years without previous history of TKI failure and have achieved stable deep MR on International Scale for ≥2 years with at least 2 readings of MR4.5 (including the latest before study entry), were randomized into 2 arms: (1) peginterferon-α-2a, subcutaneous weekly, starting at 180 mcg, or (2) observation. Disease is monitored by PCR (centralized in Ampang Hospital) at monthly for the first year, 2 monthly for the second year and 3 monthly for the third year. Relapse is defined as either (i) one reading of loss of major MR, i.e. reading of >0.1% IS and confirmed by second analysis taken 1 month later if the first analysis point reading is ≤1% IS, or (ii) positivity of BCR-ABL1 transcripts, as confirmed by a second analysis point, indicating the increase (at least 1 log) in relation to the first analysis point at two successive assessments. Quality of Life is assessed using EORTC QLO-C30. Results: At the time of writing, total of 8 patients were randomized, 5 into peginterferon arm, 3 into observation arm, all were on imatinib, M:F = 4:4, Malay: Chinese:Indian = 3:4:1, median age 49.5 (range 25-58), median follow-up 4 months (range 1-6) and none of them relapse. Two patients developed imatinib withdrawal syndrome, both female on observation arm, one was mild and resolved after 2 months but one was severe and needed termination after 2 months and restarted on imatinib. Two patients in peginterferon arm developed mild hepatitis with liver enzymes <2x of ULN. Four patients were able to tolerate peginterferon-α-2a at the dose of 180 mcg weekly, while one patient needed dose reduction to 90 mcg weekly. Quality of life score comparing two months after stopping TKI and baseline will be presented in the conference later. Conclusion: No conclusive date can be drawn so far because sample size is small and follow-up is short. Nonetheless, this trial provides Malaysian CML a platform to stop TKI safely

Fluctuation of BCR-ABL1 qPCRIS level beyond 0.1%IS after stopping tyrosine kinase inhibitor in chronic myeloid leukaemia patients with deep molecular response for at least two years

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS ) level below major molecular response (MMR) (0.1%IS ) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion – loss of MMR for one reading – aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding Bill & Melinda Gates Foundation

Determinants of higher learning institutions' websites towards student satisfaction

In this recent years, internet has been a necessities in searching for information. The growth rate of internet adoption in Asian country has been rapidly increasing over the years. This then highlighted the needs for higher learning institution to focus on their website in order to communicate their business to potential customer or student. Together with the booming use of World Wide Web, many institutions website have developed as fast as corporate website to reach their potential audiences and users begun to interact as well as interface with web application. Higher learning institution’s website is essential as it is the primary interface for users to search for information or products the university is offering. The World Wide Web also has brought to the introduction of several powerful search engines such as Google, Yahoo etc. These search engine plays an important role in bringing student to the higher learning institution website. However, in today’s internet world, matter of being the leader of internet competition is the most crucial factor. Higher learning institution can have a website, but if the website is deem unreliable and a waste of time to visit as this will then defeat the purpose of having website that originally aim to provide information. A successful website is the website that make users feel trustworthy, dependable, can be relied on and creates users satisfaction. Poorly designed website create frustration among users and lead them to leave the site as they unable to find information needed. It is importance for higher learning institution website to gain satisfaction from current students or prospective students. Research has shown that when satisfaction is formed, the purchase intention will follow and in some cases, the intention to recommend to others also will take place. This can be one of the most useful marketing channel for institute of higher learning to target their prospective students. Therefore, investigation on factors or variables on higher learning institution website that will bring toward student satisfaction are performed

Increased Bleeding Tendency from Interaction between Rivaroxaban and Topical Miconazole: Case Report

Novel oral anticoagulants (OAC) are being increasingly used. We describe a case of increased bleeding tendency resulting from probable drug interaction between rivaroxaban and topical miconazole. Recognition of this possible interaction is important during concomitant use to prevent adverse outcome arising from over-anticoagulation

Nonvolatile Memristive Materials and Physical Modeling for In‐Memory and In‐Sensor Computing

Publication status: PublishedSeparate memory and processing units are utilized in conventional von Neumann computational architectures. However, regarding the energy and the time, it is costly to shuffle data between the memory and the processing entity, and for data‐intensive applications associated with artificial intelligence, the demand is ever increasing. A paradigm shift in traditional architectures is required, and in‐memory computing is one of the non‐von‐Neumann computing strategies. By harnessing physical signatures of the memory, computing workloads are administered in the same memory element. For in‐memory computing, a wide range of memristive material (MM) systems have been examined. Moreover, developing computing schemes that perform in the same sensory network and that minimize the data shuffle between the processing unit and the sensing element is a requirement, to process large volumes of data efficiently and decrease the energy consumption. In this review, an overview of the switching character and system signature harnessed in three archetypal MM systems is rendered, along with an integrated application survey for developing in‐sensor and in‐memory computing, viz., brain‐inspired or analogue computing, physical unclonable functions, and random number generators. The recent progress in theoretical studies that reveal the structural origin of the fast‐switching ability of the MM system is further summarized.</jats:p

Nonvolatile Memristive Materials and Physical Modeling for In‐Memory and In‐Sensor Computing

Separate memory and processing units are utilized in conventional von Neumann computational architectures. However, regarding the energy and the time, it is costly to shuffle data between the memory and the processing entity, and for data‐intensive applications associated with artificial intelligence, the demand is ever increasing. A paradigm shift in traditional architectures is required, and in‐memory computing is one of the non‐von‐Neumann computing strategies. By harnessing physical signatures of the memory, computing workloads are administered in the same memory element. For in‐memory computing, a wide range of memristive material (MM) systems have been examined. Moreover, developing computing schemes that perform in the same sensory network and that minimize the data shuffle between the processing unit and the sensing element is a requirement, to process large volumes of data efficiently and decrease the energy consumption. In this review, an overview of the switching character and system signature harnessed in three archetypal MM systems is rendered, along with an integrated application survey for developing in‐sensor and in‐memory computing, viz., brain‐inspired or analogue computing, physical unclonable functions, and random number generators. The recent progress in theoretical studies that reveal the structural origin of the fast‐switching ability of the MM system is further summarized