Cache-Oblivious Iterated Predecessor Queries via Range Coalescing

In this paper we develop an optimal cache-oblivious data structure that solves the iterated predecessor problem. Given k static sorted lists L[subscript 1],L[subscript 2],…,L[subscript k] of average length n and a query value q, the iterated predecessor problem is to find the largest element in each list which is less than q. Our solution to this problem, called “range coalescing”, requires O(log[subscript B+1]n+k/B) memory transfers for a query on a cache of block size B, which is information-theoretically optimal. The range-coalescing data structure consumes O(kn) space, and preprocessing requires only O(kn / B) memory transfers with high probability, given a tall cache of size M=Ω(B[superscript 2])

CIFKAS A Measurer of Functional Disability Status in Knee Osteoarthritis

Knee osteoarthritis (OA) results in structural and functional abnormalities and reduced functional performance abilities. In developing countries majority of population lives in rural areas having limited resources and socio-cultural biodiversity. Their personal, socio-cultural and occupational habits vary and need to be addressed. So a culturally relevant and contextually appropriate, Composite Indian Functional Knee Assessment Scale (CIFKAS) for measuring the functional status in knee osteoarthritis was formulated. 128 participants from various geographical regions of India of age range 40 to 60 years using convenient sampling were included and informed consent signed by the participants. Each participant was assigned to one of the two groups. 39 participants in group A reported no episode of knee pain while 89 participants in group B reported at least one episode of knee pain in the last two months. Each participant was assessed on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and CIFKAS and statistical analysis was done. The Pearson correlation coefficient calculated for all 128 subjects for pain, physical functional abilities and total functional disability score were 0.878, 0.925 and 0.945 respectively. Between group analysis was done using Independent t test and p value was found to be not significant for pain (≤178), highly significant for physical functional abilities (p≤0001) and very significant for total functional disability status score (p≤004). The results indicate that both WOMAC and CIFKAS are highly correlated and there is no difference between the two for measuring pain, but for functional ability and overall functional disability status within their functional context, CIFKAS is a better tool than WOMAC.KEYWORDS: Knee osteoarthritis; Functional disability; Socio-cultural biodiversities; Functional contextInternet Journal of Medical Update 2012 January;7(1):47-5

Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses

Background. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs

A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant

ABSTRACT Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.IMPORTANCEThe 2012 outbreak of MERS-CoV raises the specter of another global epidemic, similar to the 2003 SARS-CoV epidemic. MERS-CoV is related to BtCoV HKU5 in target regions that are essential for drug and vaccine testing. Because no small animal model exists to evaluate MERS-CoV pathogenesis or to test vaccines, we constructed a recombinant BtCoV HKU5 that expressed a region of the SARS-CoV spike (S) glycoprotein, thereby allowing the recombinant virus to grow in cell culture and in mice. We show that this recombinant virus targets airway epithelial cells and causes disease in aged mice. We use this platform to (i) identify a broad-spectrum antiviral that can potentially inhibit viruses closely related to MERS-CoV, (ii) demonstrate the absence of increased eosinophilic immune pathology for MERS-CoV N protein-based vaccines, and (iii) mouse adapt this virus to identify viral genetic determinants of cross-species transmission and virulence. This study holds significance as a strategy to control newly emerging viruses

Predictors of mortality among hospitalized COVID-19 patients and risk score formulation for prioritizing tertiary care—An experience from South India

BACKGROUND: We retrospectively data-mined the case records of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients hospitalized to a tertiary care centre to derive mortality predictors and formulate a risk score, for prioritizing admission. METHODS AND FINDINGS: Data on clinical manifestations, comorbidities, vital signs, and basic lab investigations collected as part of routine medical management at admission to a COVID-19 tertiary care centre in Chengalpattu, South India between May and November 2020 were retrospectively analysed to ascertain predictors of mortality in the univariate analysis using their relative difference in distribution among ‘survivors’ and ‘non-survivors’. The regression coefficients of those factors remaining significant in the multivariable logistic regression were utilised for risk score formulation and validated in 1000 bootstrap datasets. Among 746 COVID-19 patients hospitalised [487 “survivors” and 259 “non-survivors” (deaths)], there was a slight male predilection [62.5%, (466/746)], with a higher mortality rate observed among 40–70 years age group [59.1%, (441/746)] and highest among diabetic patients with elevated urea levels [65.4% (68/104)]. The adjusted odds ratios of factors [OR (95% CI)] significant in the multivariable logistic regression were SaO(2)3; 3.01 (1.61–5.83), Age ≥50 years;2.52 (1.45–4.43), Pulse Rate ≥100/min: 2.02 (1.19–3.47) and coexisting Diabetes Mellitus; 1.73 (1.02–2.95) with hypertension and gender not retaining their significance. The individual risk scores for SaO(2)3–11, Age ≥50 years-9, Pulse Rate ≥100/min-7 and coexisting diabetes mellitus-6, acronymed collectively as ‘OUR-ARDs score’ showed that the sum of scores ≥ 25 predicted mortality with a sensitivity-90%, specificity-64% and AUC of 0.85. CONCLUSIONS: The ‘OUR ARDs’ risk score, derived from easily assessable factors predicting mortality, offered a tangible solution for prioritizing admission to COVID-19 tertiary care centre, that enhanced patient care but without unduly straining the health system