British policy towards the Malays in the Federated Malay States, 1920-40

There are only a handful of studies on the political history of Malaya during the interwar years. This is mainly due to the fact that until 1966 the official records for the period were closed to researchers. Based mainly on information gleaned from these records, this dissertation studies an aspect of British policy in one limited area in Malaya during the period, 1920- 1940. The area referred to was the Federated Malay States (FMS) which comprised Perak, Selangor, Negri Sembilan and Pahang. Affairs in the other two regions in Malaya, namely the Straits Settlements and the Unfederated Malay States (UMS), have been omitted save when they had a bearing on the subject under discussion. This is a study of British efforts to uplift the Malays politically in the FMS with particular reference to a policy of decentralisation and of training Malays for the public service. The core of the thesis deals with the decentralisation movement which attempted to loosen the highly centralised federal administration in the FMS, restore powers to the states, and enable Malays to play a more active role in public affairs. This movement began in 1920 and in effect ended in 19*+0 » This explains the choice of dates for this dissertation

Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity

BACKGROUND Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 13 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors. FINDINGS Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity. INTERPRETATION IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs)

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

COVID-19 severity is associated with cytokine levels and lymphopenia, but the role of immune cell subsets is not well understood. Here the authors immunophenotype whole blood samples from 54 COVID-19 patients and find that the immature neutrophil-to-VD2 T-cell ratio is associated with severe COVID-19

Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of “long COVID-19”, and defines key cells and cytokines that delineate true and quasi-convalescent states

Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus

Early-onset systemic lupus erythematosus presents with a more severe disease and is associated with a greater genetic burden, especially in patients from Black, Asian or Hispanic ancestries. Next-generation sequencing techniques, notably whole exome sequencing, have been extensively used in genomic interrogation studies to identify causal disease variants that are increasingly implicated in the development of autoimmunity. This Review discusses the known casual variants of polygenic and monogenic systemic lupus erythematosus and its implications under certain genetic disparities while suggesting an age-based sequencing strategy to aid in clinical diagnostics and patient management for improved patient care