Maximum tolerable dose of cyclophosphamide and azathioprine in Pakistani patients with primary renal disease

Objective: The immunosuppressive regimens, at present, mainly rely on western guidelines that were derived from studies conducted in western populations. No such study exists for South Asian population, which is home to almost two billion people different in both genetics and environment from west. Locally derived thresholds for side effects markedly different from western figures may warrant re-adjustment of current local immunosuppressive regimens that are at present based largely on western guidelines. In order to define optimum dose for Cyclophosphamide (CYC) and Azathioprine (AZA) based immunosuppressive therapy, we conducted this study to find out maximum tolerable doses of azathioprine (AZA) and cyclophosphamide (CYC) beyond which neutropenia and thrombocytepenia are most likely to occur in patients with primary renal pathology.METHOD: Patients with systemic vasculitis and idiopathic glomerulonephritis who were on CYC and AZA were identified through review of medical records at a tertiary care hospital in Pakistan (The Aga Khan University Hospital, Karachi). Patients were categorized under three principal diagnosis i.e. systemic lupus erythematosus (SLE), primary (idiopathic) glomerulonephritis (GN) and Wegener\u27s granulomatosis (WG). The Receiver Operating Curve (ROC) was used to calculate the maximum tolerable dose for both CYC and AZA.Results: We identified 94 patients aged 6-82 years (median 44.5 years) with primary renal disease (Wegener\u27s granulomatosis n=13, Systemic lupus erythematosis n=62 and idiopathic glomerulonephritis n=19) who received CYC or AZA. Of these 94 patients, 36.2% (n=34) received CYC and 63.8% (n=60) received AZA. The mean dose of CYC was 1.54 +/- 0.50 mg/kg of body weight (range: 0.77-2.93). The mean dose of AZA was 1.64 +/- 0.59 mg/kg of body weight (range: 0.47-2.97). The maximum tolerable doses calculated for CYC and AZA were 1.25 mg/kg and 1.30 mg/kg of body weight respectively. The maximum tolerable dose for CYC and AZA among males could not be calculated, because of insufficient number of patients who developed neutropenia and thrombocytopenia. The maximum tolerable doses for CYC and AZA among females were 1.34 mg/kg and 1.03 mg/kg of body weight respectively. Also we found out that AZA was relatively more likely to cause neutropenia and thrombocytopenia (p=0.07).CONCLUSION: We thereby recommend that CYC should be initiated at a dose no more than 1 mg/kg of body weight and AZA at an initial dose of 0.75-1.0 mg/kg of body weight. The dose may be adjusted later on the basis of clinical response and laboratory reports

Mathematical Modelling of the Relationship between Two Different Temperament Classifications: During the Covid-19 Pandemic

In medicine, it is well known that healthy individuals have different physical and mental characteristics. Ancient Indian medicine, Ayurveda and the Persian-Arabic traditional Unani medicine has two distinct approaches for the classification of human subjects according to their temperaments. The individual temperament is an important foundation for personalized medicine, which can help in the prevention and treatment of many diseases including COVID-19. This paper attempts to explore the relationship of the utmost important concepts of these systems called individual temperament named as Prakruti in Ayurveda and Mizaj in Unani practice using mathematical modelling. The results of mathematical modelling can be adopted expediently for the development of algorithms that can be applied in medical informatics. For this, a significant literature review has been carried out. Based on the previous researchers' reviews the essential parameters have been identified for making the relationship and hypothesis were framed. The mathematical modelling was adopted to propose the existence of the relationship between the parameters of such an ancient and rich medicine systems. The hypotheses are validated through the mathematic driven model. Doi: 10.28991/esj-2021-01258 Full Text: PD

Boundary spanning at the science–policy interface: the practitioners’ perspectives

Cultivating a more dynamic relationship between science and policy is essential for responding to complex social challenges such as sustainability. One approach to doing so is to “span the boundaries” between science and decision making and create a more comprehensive and inclusive knowledge exchange process. The exact definition and role of boundary spanning, however, can be nebulous. Indeed, boundary spanning often gets conflated and confused with other approaches to connecting science and policy, such as science communication, applied science, and advocacy, which can hinder progress in the field of boundary spanning. To help overcome this, in this perspective, we present the outcomes from a recent workshop of boundary-spanning practitioners gathered to (1) articulate a definition of what it means to work at this interface (“boundary spanning”) and the types of activities it encompasses; (2) present a value proposition of these efforts to build better relationships between science and policy; and (3) identify opportunities to more effectively mainstream boundary-spanning activities. Drawing on our collective experiences, we suggest that boundary spanning has the potential to increase the efficiency by which useful research is produced, foster the capacity to absorb new evidence and perspectives into sustainability decision-making, enhance research relevance for societal challenges, and open new policy windows. We provide examples from our work that illustrate this potential. By offering these propositions for the value of boundary spanning, we hope to encourage a more robust discussion of how to achieve evidence-informed decision-making for sustainability.Support for the workshop was provided by Margaret A. Cargill Philanthropies and The Pew Charitable Trusts. PFEA is supported by the U.K. Natural Environment Research Council (NE/N005457/1)

Enhancing the potential exploitation of food waste: Extraction, purification, and characterization of renewable specialty chemicals from blackcurrants (Ribes nigrum L.)

Natural colorants were extracted from renewable botanical sources, specifically waste epicarp from the blackcurrant fruit pressing industry. A process was developed which used acidified water extraction followed by a solid-phase extraction (SPE) purification stage which allowed the production of an anthocyanin-rich extract in good yields (ca. 2% w/w based on dry weight of raw material). The components in the extracts were extensively characterized by HPLC, mass spectrometry, IR, NMR and UV-Vis spectroscopy. HPLC confirmed presence of four anthocyanins: delphinidin-3-O-rutinoside (45%), cyanidin-3-O-rutinoside (31%) and the corresponding glucosides at 16% and 8%, respectively. On sequential liquid-liquid aqueous-organic partitioning of the post-SPE sample, monomeric anthocyanins (54.7%) and polymeric anthocyanins (18%) were found in the aqueous layer with 3-O-rutinosides of myricetin (3.1%) and quercetin (3.2%), whilst isopropylacetate achieved selective extraction of caffeic acid (3%), p-coumaric acid (5%), and myricetin (2.5%) and quercetin (3.2%) aglycons. 3-O-Glucosides of myricetin (3.1%) and quercetin (2%), along with nigrumin-p-coumarate (1%) and nigrumin ferulate (0.5%) were selectively extracted from the remaining aqueous fraction using ethylacetate. This allowed for near total quantification of the blackcurrant extract composition

Algorithm-driven activity-directed expansion of a series of antibacterial quinazolinones

Activity-directed synthesis (ADS) is a structure-blind, function driven approach that can drive the discovery of bioactive small molecules. In ADS, arrays of reactions are designed and executed, and the crude product mixtures are then directly screened to identify reactions that yield bioactive products. The design of subsequent reaction arrays is then informed by the hit reactions that are discovered. In this study, algorithms for reaction array design were developed in which the reactions to be executed were selected from a large set of virtual reactions; the reactions were selected on the basis of similarity to reactions known to yield bioactive products. The algorithms were harnessed to design arrays of photoredox-catalysed alkylation reactions whose crude products were then screened for inhibition of growth of S. aureus ATCC29213. It was demonstrated that the approach enabled expansion of a series of antibacterial quinazolinones. It is envisaged that such algorithms could ultimately enable fully autonomous activity-directed molecular discovery

Boundary spanning at the science–policy interface: the practitioners’ perspectives

Cultivating a more dynamic relationship between science and policy is essential for responding to complex social challenges such as sustainability. One approach to doing so is to “span the boundaries” between science and decision making and create a more comprehensive and inclusive knowledge exchange process. The exact definition and role of boundary spanning, however, can be nebulous. Indeed, boundary spanning often gets conflated and confused with other approaches to connecting science and policy, such as science communication, applied science, and advocacy, which can hinder progress in the field of boundary spanning. To help overcome this, in this perspective, we present the outcomes from a recent workshop of boundary-spanning practitioners gathered to (1) articulate a definition of what it means to work at this interface (“boundary spanning”) and the types of activities it encompasses; (2) present a value proposition of these efforts to build better relationships between science and policy; and (3) identify opportunities to more effectively mainstream boundary-spanning activities. Drawing on our collective experiences, we suggest that boundary spanning has the potential to increase the efficiency by which useful research is produced, foster the capacity to absorb new evidence and perspectives into sustainability decision-making, enhance research relevance for societal challenges, and open new policy windows. We provide examples from our work that illustrate this potential. By offering these propositions for the value of boundary spanning, we hope to encourage a more robust discussion of how to achieve evidence-informed decision-making for sustainability

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry