Association of ABO blood group with severe falciparum malaria in adults: case control study and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Erythrocyte-associated antigenic polymorphisms or their absence have perhaps evolved in the human population to protect against malarial infection. Studies in various populations consistently demonstrate that blood group 'O' confers resistance against severe falciparum infection. In India, Odisha state has one of the highest incidences of <it>Plasmodium falciparum </it>infection and contributes to the highest number of deaths by falciparum malaria. This study aims to evaluate the relationship between ABO blood group and severe malaria in an adult population at the tertiary care centre in Odisha.</p> <p>Methods</p> <p>A total of 353 <it>P. falciparum </it>infected subjects and 174 healthy controls were screened for ABO blood group. Falciparum-infected individuals were categorized as severe malaria and uncomplicated malaria. Severe malaria was further clinically phenotyped into cerebral malaria, non-cerebral severe malaria and multi-organ dysfunction. A meta-analysis was performed to assess the role of ABO blood group in severe malaria.</p> <p>Results</p> <p>Frequency of blood group 'B' was significantly higher in patients with severe malaria compared to the uncomplicated cases (P < 0.0001; OR = 4.09) and healthy controls (P < 0.0001; OR = 2.79). Irrespective of the level of clinical severity, blood group 'B' was significantly associated with cerebral malaria (P < 0.0001; OR = 5.95), multi-organ dysfunction (P < 0.0001; OR = 4.81) and non-cerebral severe malaria patients (P = 0.001; OR = 3.02) compared to the uncomplicated category. Prevalence of 'O' group in uncomplicated malaria (P < 0.0001; OR = 2.81) and healthy controls (P = 0.0003; OR = 2.16) was significantly high compared to severe malaria. Meta-analysis of previous studies, including the current one, highlighted the protective nature of blood group 'O' to severe malaria (P = 0.01). On the other hand, carriers of blood group 'A' (P = 0.04) and 'AB' (P = 0.04) were susceptible to malaria severity.</p> <p>Conclusions</p> <p>Results of the current study indicate that blood group 'O' is associated with reduced and 'B' blood group with increased risk of development of severe malaria in Odisha, India. Meta-analysis also supports the protective nature of blood group 'O' from severe falciparum infection.</p

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Helical and Nonhelical Structures of Vinylene- and Azomethine-Linked Heterocyclic Oligomers: A Computational Study of Conformation-Dependent Optoelectronic Properties

A systematic computational investigation has been carried out at the density functional level of theory to characterize various conformational isomers of furan, pyrrole, and thiophene based oligomers and consequently study their stabilities and electronic properties, especially in the cases of long oligomers. In these oligomers, adjacent heterocyclic rings are connected by either vinylene or azomethine linkages. B3LYP and B3LYP-D3 functionals are used to observe the effect of dispersion energy. Our results show that a combination of the B3LYP-D3 functional and the 6-31G­(d,p) basis set is suitable for ground-state studies of these systems. For long vinylene-linked oligomers, folding isomers are comparatively more stable than their respective linearly conjugated isomers, due to intramolecular noncovalent interactions. In the case of azomethine-linked oligomers, geometries and stabilities of conformers depend on the type of heterocyclic ring in the repeating unit. For vinylene-linked heterocyclic oligomers, first optically allowed electronic transitions of linearly conjugated oligomers have the largest oscillator strengths, and these absorption bands are dominated by HOMO to LUMO transitions. In the case of a few linear azomethine-linked oligomers, two major electronic transitions, S₀ → S₁ and S₀ →S₂, are noticed. However, transitions from S₀ to higher electronic states are the most prominent transitions in cases of foldamers, except azomethine-linked thiophene foldamers. Major absorption bands of these helical oligomers are dominated by transitions from HOMO–<i>N</i> to LUMO+<i>N</i> orbitals. All the helical conformers are found to be circular dichroism active

Static and Dynamic Characterization and Control of a High-Performance Electro-Hydraulic Actuator

This paper characterizes the static, dynamic, and controlled behavior of a high-performance electro-hydraulic actuator to assess its suitability for use in evaluating machine tool behavior. The actuator consists of a double-acting piston and cylinder arrangement controlled by a servo valve and a separate rear chamber controlled by a separate valve, designed to work in conjunction to generate static forces of up to 7000 N that can be superposed with dynamic forces of up to &plusmn;1500 N. This superposition of periodic forces with a non-zero mean makes the actuator capable of applying realistic loading conditions like those experienced by machines during cutting processes. To characterize the performance of this actuator, linearized static and dynamic models are described. Since experiments with the actuator exhibit nonlinear characteristics, the linearized static model is expanded to include the influence of nonlinearities due to flow, leakages, saturations, and due to friction and hysteresis. Since all major nonlinearities are accounted for in the expanded static model, the dynamical model remains linear. Unknown static and dynamical model parameters are calibrated from experiments, and the updated models are observed to capture experimentally observed behavior very well. Validated models are used to tune the proportional and integral gains for the closed-loop control strategy, and the model-based tuning in turn guides appropriate closed-loop control of the actuator to increase its bandwidth to 200 Hz. The statically and dynamically characterized actuator can aid machine tool structural testing. Moreover, the validated models can instruct the design and development of other higher-performance electro-hydraulic actuators, guide the conversion of the actuator into a damper, and also test other advanced control strategies to further improve actuator performance

Enhancing Cloud Communication Security: A Blockchain-Powered Framework with Attribute-Aware Encryption

The global production of information continuously increases in quantity and variety. However, the tools and technologies developed to handle such large volumes of data have not adequately met the security and privacy requirements. Existing cloud security systems, often managed by a trusted third party, are susceptible to various security risks. To address these challenges and ensure the protection of personal information, blockchain technology emerges as a crucial solution with substantial potential. This research uses the blockchain-powered attribute-aware encryption method to establish a real-time secure communication approach over the cloud. By employing attribute-based encryption technology, data owners can implement fine-grained search permissions for data users. The proposed solution incorporates accessible encryption technology to enable secure access to encrypted data and facilitate keyword searches on the blockchain. This study provides a functional comparison of recently developed attribute-based encryption algorithms. The access control strategy comprises two access tree types and a linear secret-sharing system, serving as the main components. The elliptic curve’s base field was set to 512b, and the bilinear pairing parameter type used was Type-A. This approach involves storing keywords on a remote server and encrypting them using attribute-based encryption. Furthermore, the encrypted data blockchain and the corresponding ciphertext are stored in the blockchain. Numerical experiments were conducted to evaluate the system’s key generation, trapdoor building, and keyword retrieval capabilities