GARCH Diagnosis with Portmanteau Bicorrelation Test: An Application on the Malaysia's Stock Market

This study employed the Hinich portmanteau bicorrelation test (Hinich and Patterson, 1995; Hinich, 1996) as a diagnostic tool to determine the adequacy of the GARCH model in describing the returns generating process of Malaysia’s stock market, specifically the Kuala Lumpur Stock Exchange Composite Index (KLSE CI). The bicorrelation results demonstrated that, while GARCH model is commonly applied to financial time series, this model cannot provide an adequate characterization for the underlying process of KLSE CI. Further investigation using the windowed test procedure revealed that this was due to the presence of episodic non- stationarity in the data, which could not be captured by any kind of ARCH or GARCH model, even after modifications to the specifications of the GARCH model. Thus, this study points to the need to continue the search for a parsimonious and congruent model capable of capturing the episodic features presence in the returns series of KLSE CI.GARCH; Non-linearity; Non-stationarity; Data generating process; Bicorrelation; Malaysian stock market.

Genetic Diversity Of Duabanga Moluccana Using Dominant Dna Markers Based On Inter-Simple Sequence Repeats In Sarawak

Duabanga moluccana or locally known as Sawih is a widely known forest tree species for its multipurpose timber and other natural products such as fibers. Genetic diversity investigation of this species can provide baseline information for indirect selection in tree improvement programme. This study has employed Inter Simple Sequence Repeat (ISSR) technique to assess the genetic diversity and relatedness within and between three populations of D. moluccana located in Sarawak, namely, Mukah, Tatau (Bintulu) and Niah. A total of 151 loci from 90 individuals were successfully amplified with 6 selected ISSR primers and the percentage of polymorphic loci was 90.1%. The Shannon’s diversity index showed that D. moluccana in Mukah natural forest (0.429) was the most diverse compared to Tatau (Bintulu) (0.362) and Niah natural forest (0.387). Neighbour joining tree were constructed to show relationship among the selected populations. The overall populations were completely clustered into three main groups, according to their corresponding population. Based on these results, it implies that D. moluccana trees are genetically diverse among populations

Genetic diversity of Kelampayan using dominant DNA markers based on inter-simple sequence repeats (ISSRs) in Sarawak

Neolamarckia cadamba (Roxb.) Bosser, or locally known as kelampayan, is a fast-growing timber species which produces one of the best sources of raw material for the plywood industry and also for the pulp and paper industry. It has been selected as one of the promising plantation tree species for large-scale planted forest development in Sarawak. Therefore, the molecular characterization of this indigenous tropical tree species is needed to maintain its high quality. Intersimple sequence repeats (ISSR) markers were used in this study to determine the genetic diversity of kelampayan in three progeny trial blocks at the Landeh Nature Reserve, Semengok, Sarawak. The seeds were collected from the selected mother trees located at the Pasai Bon, Niah and Lawas seed production areas (SPAs) in Sarawak. Three ISSR primers, namely (GTG)6, (AG)10 and (AC)10, that yielded reproducible, informative and scorable fragments were chosen for ISSR analysis. A total of 64 loci were generated of which 45.3–74.6% of the loci were identified as polymorphic bands with the size ranging from 500 bp to 2 kb among 247 kelampayan progenies selected in the present study. Molecular diversity based on Shannon’s diversity indices (I) among 247 trees ranged from 0.268 to 0.350. In general, the kelampayan trees in the three progeny trial blocks exhibited a high level of molecular diversity and DNA polymorphism compared with its natural populations. This preliminary information will form the base for kelampayan tree improvement and conservation programmes

Applications Of Genomics To Plantation Forestry With Kelampayan In Sarawak

Wood-based industries in Sarawak are increasingly encouraged to adapt to “new wood” from planted forests composed of fast-growing species such as Kelampayan with short rotation cycle (6-8 years). The rationale is that natural forests at the most produce about 3m3 /ha/yr of commercial timber, whereas plantations can produce annually from 10m3 /ha to 30m3 /ha of commercial timber. It is estimated at least 30 million seedlings are required for annual planting or reforestation programmes to meet the increasing global demand for raw materials. To date, several molecular genetics studies have been completed for Kelampayan. These include genetic diversity of Kelampayan, genetic marker (SSRs) development, ‘Touch-incubate-PCR’ approach for preparing plant tissues for high throughput genotyping, and transcriptomics and bioinformatics on wood formation of Kelampayan. This information provides a useful resource for genomic selection of Kelampayan aiming at the production of high value forests for maximum returns

Genomics studies on plantation tree species in Sarawak

Rapid socio-economic changes in the world are having profound impacts on all sectors, including forestry. The increase in global demand for wood requires increase in forest productivity. The alternative is to farm trees in plantations composed of fast-growing species with short rotation cycles (6–8 y). The rationale is that natural forests at the most produce about 3 m3 ha y-1 of commercial timber, whereas plantations can produce annually from 10 m3 ha y-1 of hardwoods to 30 m3 ha-1 of softwoods and thus, decrease the effects of human pressure on our ecosystems while increasing the competitiveness of Sarawak’s forest industry. This is in line with the state government’s aspiration to establish one million hectares of planted forests by year 2020 to meet the increasing demand from both domestic and international markets for raw materials. It is estimated at least 30 million seedlings are required for annual planting or reforestation programmes. In this regard, forest genomics research will help respond to the need to develop adequate tools that enable us to produce quality planting materials that are of faster growth, high yield and high wood quality, and also adapted to local conditions, so that we may achieve economic benefits of great significance. Realizing the need, we have centred our research on the development of tools via biotechnological innovations for tree breeders. Over the years, we have successfully developed: 1) simple sequence repeat (SSR) 173 DNA markers specific for identifying the genetic make-up of two fastgrowing indigenous tree species, i.e. kelampayan and sawih; 2) the ‘Touch-incubate-PCR’ approach for preparing plant tissues for high throughput genotyping, and 3) a kelampayan tree transcriptome database (NcdbEST aka CADAMOMICS) for wood formation. These tools will greatly facilitate the selection of quality planting materials for planted forest development in Sarawak as well as long-term tree improvement activities by integrating genomics into our breeding programme via association mapping. The overall benefit of genomics application to tree improvement programme will be in terms of greater certainty in the outcome of results, specifically the performance of the forest plantations, as well as the savings in time and cost in the production and supply of quality planting materials

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Optimization of a functional cookie formulation by using response surface methodology

A functional cookie formulation containing oligofructose, dietary fibre and lower calorie, fat and sugar contents than conventional cookies was optimized using Response Surface Methodology (RSM). Instant N-Oil II was used as a fat replacer, while Raftilose ®P95 was used as a sugar substitute with the addition of fructose to enhance sweetness. Selection of the optimal formulation was based on caloric content. An optimized formulation, V1, was obtained from the model Y = 4927.70 – 152.34X1 – 155.42X3 + 104.20X32 + 151.71X33 – 95.08X34, where Instant N-Oil II replaced 30% of butter and 24.4%, w/w (30.5g) fructose replaced 40.0%, w/w (50.0g) sucrose. Two additional optimized formulations, S1 and S2, were proposed which contained the same ingredients as V1, but both contained 19.0%, w/w (23.8g) Raftilose ®P95. Also, S2 had a higher fat replacement level (42%). A reference cookie prepared from a conventional recipe received significantly higher scores (P < 0.05) than the functional cookies V1, S1 and S2 in the sensory evaluation. However, when health benefits of the functional cookies were explained to the panel after the sensory evaluation had concluded, majority of the panelists stated that they would prefer S1, had they known of its health benefits. S1 contained 19.04% fat, 8.62% fructose and 0.74% sucrose, namely, significantly lower fat and sucrose levels and higher fructose content than the conventional cookie