Muhammad Faisal

Adjusting for illness severity shows there is no difference in patient mortality at weekends or weekdays for emergency medical admissions

Background: Patients admitted to hospitals over the weekend appear to have a higher risk of death compared to weekday admissions, but the reasons remain unclear. Unlike previous studies, we use a standardised mandated vital signs physiological based measure of sickness known as the National Early Warning Score (NEWS) to investigate this “weekend effect” for emergency admissions. Aim: To determine if weekend admissions are (1) sicker as measured by their index NEWS, (2) have an increased risk of death and (3) have less favourable monitoring of their vital signs compared with weekday admissions. Methods Analysis of 58481 emergency adult medical admissions in three acute hospitals with electronic (index) NEWS recorded within 24 hours of admission. Results: Admissions over the weekend had higher index NEWS (weekend: 2.24 vs weekday: 2.05, p<0.001) with a higher risk of death (weekend: 260/3911 6.65% vs weekday: 696/12683 5.49%, Risk Ratio=1.10, 95%CI: 1.01 to 1.19, p=0.023) which was no longer seen after adjusting for the index NEWS (risk ratio=1.00, 95%CI 0.92 to 1.08, p=0.94). The time to index NEWS was earlier (-0.41 hours 95%CI -0.47 to -0.35, p<0.001) for weekend admissions whilst the number of NEWS recorded over their hospital stay was not dissimilar (-0.03 95%CI -0.39 to 0.34, p=0.892). Conclusions: Patients who have an acute admission over the weekend with a NEWS recorded within 24 hours are sicker, have earlier clinical assessments, and after adjusting for their illness severity do not appear to have a higher risk of death compared to weekday admissions.

Enzyme inhibitory activities an insight into the structure–Activity relationship of biscoumarin derivatives

Biscoumarin derivatives, a dimeric form of coumarin, are well known derivatives of coumarin, occurred in the bioactive metabolites of marine and terrestrial organisms. On account of pharmacological and biological applications, biscoumarins have long been the subject of innumerable enzyme inhibition studies. In this review the pros and cons of enzyme inhibition studies of biscoumarins as urease inhibitors, aromatase inhibitors, NPPs, α-glucosidase inhibitors, α-amylase inhibitors, HIV-1 integrase inhibition, steroid sulfatase inhibitors and c-Met inhibitors are discussed in a systematic way. Moreover, the review discusses the structure activity relationship of biscoumarin scaffold with enzyme inhibitory potency which would unleash new avenues for further development. The purpose of the current review is to disclose the value of biscoumarins as potent and efficient enzyme inhibitor. This review provides a guideline to elaborate the diversity of biscoumarin inhibitors by exploring the effects of electronic groups linked with biscoumarin nucleus.

A new approach to choose acceptance cutoff for approximate Bayesian computation

The approximate Bayesian computation (ABC) algorithm is used to estimate parameters from complicated phenomena, where likelihood is intractable. Here, we report the development of an algorithm to choose the tolerance level for ABC. We have illustrated the performance of our proposed method by simulating the estimation of scaled mutation and recombination rates. The result shows that the proposed algorithm performs well.

Forecasting Drought Using Multilayer Perceptron Artificial Neural Network Model

These days human beings are facing many environmental challenges due to frequently occurring drought hazards. It may have an effect on the countrys environment, the community, and industries. Several adverse impacts of drought hazard are continued in Pakistan, including other hazards. However, early measurement and detection of drought can provide guidance to water resources management for employing drought mitigation policies. In this paper, we used a multilayer perceptron neural network (MLPNN) algorithm for drought forecasting. We applied and tested MLPNN algorithm on monthly time series data of Standardized Precipitation Evapotranspiration Index (SPEI) for seventeen climatological stations located in Northern Area and KPK (Pakistan). We found that MLPNN has potential capability for SPEI drought forecasting based on performance measures (i.e., Mean Average Error (MAE), the coefficient of correlation R, and Root Mean Square Error (RMSE). Water resources and management planner can take necessary action in advance (e.g., in water scarcity areas) by using MLPNN model as part of their decision making.

Spatial Interpolation of Sulfate Concentration in Groundwater Including Covariates Using Bayesian Hierarchical Models

Sulfate is a key parameter for water quality and is commonly used in manufacturing of fertilizers, soaps, glass, papers, and common household items. If sulfate quantity is more than a threshold, it is hazardous for health. In the present paper, we use Bayesian kriging with external drift and Gaussian spatial predictive process model to analyze the spatial behavior of response variable (Sulfate). Different informative and non-informative priors are utilized to estimate the correlation parameters. The performance of these models are compared by means of twofold cross validation with deviance information criterion, and root mean square prediction as criterion. In summary, the inclusion of covariates plays an important role in minimizing the mean square prediction error. Bayesian kriging with external drift performs better than Gaussian spatial predictive process. The predictive distribution of Bayesian kriging with external drift is also applicable for interpolation of sulfate concentration at unobserved locations.

DABCO–PEG ionic liquid-based synthesis of acridine analogous and its inhibitory activity on alkaline phosphatase

ABSTRACT In world, many people struggle with viral, parasitic, bacterial, cancer, and other diseases. Therefore, numerous chemists seek to develop less toxic, more selective, and effective medicines. Most therapeutic medicines are based on inhibition of specific enzymes. Acridines are interesting heterocyclic structures that are much sought after targets attributed to their wide biological activities and feature to display potent enzymes inhibitory effects. Their approach of action is owing to DNA interaction and subsequent effects on the biological functions linked to DNA and associated enzymes. In this regards, we synthesized acridine analogous through 1,4-diazabicyclo[2.2.2]octane (DABCO)–polyethylene glycol-400 (PEG-400) mediated ionic liquid approach. DABCO–PEG-400-mediated IL was prepared through the DABCO alkylation using 1-bromopentane followed by mixing with PEG-400. The synthesized analogous were investigated as inhibitors of alkaline phosphatase, which is a nonspecific phosphomonoester hydrolase that catalyzes the hydrolysis of broad spectrum of organic monophosphates. Analogue viz. 3,3,6,6-tetramethyl-9-(4-nitrophenyl)-2,3,4,5,6,7,9,10-octahydroacridine-1,8-dione was found to be potent alkaline phosphatase inhibitor. GRAPHICAL ABSTRACT

Metal-free and azide-free synthesis of 1,2,3-triazoles derivatives

ABSTRACT 1,2,3-Triazoles, significant five-membered ring N-heterocycles, are main structural moieties in well-designed materials, pharmaceutical agents, bioactive products, and synthetic intermediates. In the research of life sciences and pharmaceuticals, by seeing the spacious applications of 1,2,3-triazoles, the progress of metal-free method is exceedingly desirable to evade the heterocyclic product metal contamination. Moreover, on a larger scale, the toxicity and explosiveness of azides makes azides discommode and hard to hold, to synthesize 1,2,3-triazoles. The need to steer the development of the synthesis of 1,2,3-triazoles toward more maintainable synthesis is a pressing issue. There are rare methods to construct 1,2,3-triazoles under azide-free and metal-free environments. These rare methods are compiled in this review. The afford of the collection and compilation of azide-free and metal-free synthesis methodologies of 1,2,3-triazole in single podium is supportive and crucial for synthetic chemist to extend the diversity of the synthesis of 1,2,3-trizoles through green protocol. GRAPHICAL ABSTRACT

Synthetic approaches towards the multi target drug spironolactone and its potent analogues/derivatives

HIGHLIGHTSSynthetic approaches to the versatile mutitarget drug spironolactone have been reviewed.Aims to provide a comprehensive insight to the synthetic endeavors devoted to drug and its analogues/derivatives.It will help the synthetic chemist to design and prepare new more effective derivatives.The efficacy and limitations of the drug have also been discussed. ABSTRACT Spironolactone is a well‐known multi‐target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment of edema, cirrhosis of the liver, malignant, pediatric, nephrosis and primary hyperaldosteronism. Spironolactone in association with thiazide diuretics treats hypertension and in association with furosemide treats bronchopulmonary dyspepsia. The therapeutic mechanism of action of spironolactone involves binding to intracellular mineralocorticoids receptors (MRs) in kidney epithelial cells, thereby inhibiting the binding of aldosterone. Since its first synthesis in 1957 there are several synthetic approaches have been reported throughout the years, Synthetic community has devoted efforts to improve the synthesis of spironolactone and to synthesize its analogues and derivatives. This review aims to provide comprehensive insight for the synthetic endeavors devoted towards the synthesis of a versatile drug spironolactone and its analogues/derivatives.

Developments in the synthesis of the antiplatelet and antithrombotic drug (S)-clopidogrel

S-(+)-Methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate, also known as (S)-clopidogrel, is marketed under the trade names Plavix and Iscover. It is a potent thienopyridine-class of antithrombotic and antiplatelet drug (antiaggregant). Among the two available stereoisomers of clopidogrel, for pharmaceutical activities only the S-enantiomer is applicable, as no antithrombotic activity is observed in the R-enantiomer and causes political upheavals and social turmoil in animal experiments. Worldwide sales of Plavix amounted to

Comparison of Two New Robust Parameter Estimation Methods for the Power Function Distribution.

6.4 billion yearly, which ranks second. Attributed to the increased demand of (S)-clopidogrel drug, it provoked the synthetic community to devise facile synthetic approaches. This review aims to summarize the synthetic methods of (S)-clopidogrel drug reported in the literature. The present review discusses the pros and cons of each synthetic methodology, which would be beneficial to the scientific community for further developments in the synthetic methodologies for (S)-clopidogrel. In addition, the compilation approach of literature-reported synthetic strategies of (S)-clopidogrel in one platform is advantageous, supportive, and crucial for the synthetic community to elect the best synthetic methodology of (S)-clopidogrel and to create new synthesis ideas.