Forced decadal changes in the East Asian summer monsoon: the roles of greenhouse gases and anthropogenic aerosols

Since the mid-1990s precipitation trends over eastern China display a dipole pattern, characterized by positive anomalies in the south and negative anomalies in the north, named as the Southern-Flood-Northern-Drought (SFND) pattern. This work investigates the drivers of decadal changes of the East Asian summer monsoon (EASM), and the dynamical mechanisms involved, by using a coupled climate model (specifically an atmospheric general circulation model coupled to an ocean mixed layer model) forced by changes in (1) anthropogenic greenhouse gases (GHG), (2) anthropogenic aerosol (AA) and (3) the combined effects of both GHG and AA (All Forcing) between two periods across the mid-1990s. The model experiment forced by changes in All Forcing shows a dipole pattern of response in precipitation over China that is similar to the observed SFND pattern across the mid-1990s, which suggests that anthropogenic forcing changes played an important role in the observed decadal changes. Furthermore, the experiments with separate forcings indicate that GHG and AA forcing dominate different parts of the SFND pattern. In particular, changes in GHG increase precipitation over southern China, whilst changes in AA dominate in the drought conditions over northern China. Increases in GHG cause increased moisture transport convergence over eastern China, which leads to increased precipitation. The AA forcing changes weaken the EASM, which lead to divergent wind anomalies over northern China and reduced precipitation

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

Assessing Consumer Preference using Community Pharmacy Preference Evaluation Questionnaire (ComPETe): A Pilot Survey in a Malaysia City

Purpose: To assess the consumer preference for community pharmacy (CP) for filling prescription, and purchasing over-the-counter (OTC) and health products among customers frequenting eight departmental stores located in a Malaysian city.Method: A cross-sectional study was conducted in the city of Wakaf Bharu, Kelantan, Malaysia. A total of 400 respondents in the area were randomly selected to participate in the 14-item Community Pharmacy Preference Evaluation Questionnaire (ComPETe). The results were then subjected to data analysis.Results: A total of 198 respondents returned the questionnaire but only 120 respondents completely filled in them. Majority of the respondents was between the age of 18 and 30 years (42.4 %), female (55.0 %) and married (66.7 %). Most of them (90.8 %) agreed that location is an important criterion for choosing a CP. About 62 and 56 % of the respondents went to the same preferred CP and at least once a month, respectively. Interestingly, customers with a monthly income of <RM 1000 (equivalent to USD 280) and married were more likely to visit the same preferred CP (p < 0.05). More than half of the respondents preferred heavily subsidized medical treatment for minor ailments from government healthcare institutions. For OTC products, preference among consumers was almost the same among CPs and local stores. With regard to health supplements and screening test kits, most respondents preferred to go to CPs.Conclusion: The respondents showed variability in their preference for CPs. The findings about consumer preference for CPs and health products should facilitate the process of launching a successful CP establishment.Keywords: Consumer Satisfaction, Community Pharmacy Preference, Prescription Filling, Over-the-counter Products, Financial Managemen

Biophysics of Malarial Parasite Exit from Infected Erythrocytes

Upon infection and development within human erythrocytes, P. falciparum induces alterations to the infected RBC morphology and bio-mechanical properties to eventually rupture the host cells through parasitic and host derived proteases of cysteine and serine families. We used previously reported broad-spectrum inhibitors (E64d, EGTA-AM and chymostatin) to inhibit these proteases and impede rupture to analyze mechanical signatures associated with parasite escape. Treatment of late-stage iRBCs with E64d and EGTA-AM prevented rupture, resulted in no major RBC cytoskeletal reconfiguration but altered schizont morphology followed by dramatic re-distribution of three-dimensional refractive index (3D-RI) within the iRBC. These phenotypes demonstrated several-fold increased iRBC membrane flickering. In contrast, chymostatin treatment showed no 3D-RI changes and caused elevated fluctuations solely within the parasitophorous vacuole. We show that E64d and EGTA-AM supported PV breakdown and the resulting elevated fluctuations followed non-Gaussian pattern that resulted from direct merozoite impingement against the iRBC membrane. Optical trapping experiments highlighted reduced deformability of the iRBC membranes upon rupture-arrest, more specifically in the treatments that facilitated PV breakdown. Taken together, our experiments provide novel mechanistic interpretations on the role of parasitophorous vacuole in maintaining the spherical schizont morphology, the impact of PV breakdown on iRBC membrane fluctuations leading to eventual parasite escape and the evolution of membrane stiffness properties of host cells in which merozoites were irreversibly trapped, recourse to protease inhibitors. These findings provide a comprehensive, previously unavailable, body of information on the combined effects of biochemical and biophysical factors on parasite egress from iRBCs.Singapore. Agency for Science, Technology and ResearchSingapore-MIT AllianceGlobal Enterprise for Micro-Mechanics and Molecular MedicineNational University of SingaporeNational Institutes of Health (U.S.) (Grant R01 HL094270-01A1)National Institutes of Health (U.S.) (Grant 1-R01-GM076689-01)National Institutes of Health (U.S.) (P41-RR02594-18-24

Reported Adverse Drug Reactions in Infants: A Nationwide Analysis in Malaysia

Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia's national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia's National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% (n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash (n = 215), maculopapular rash (n = 206), urticaria (n = 169), erythematous rash (n = 76), and pruritus (n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens-Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial for systemic use, with most of the ADRs manifesting in skin reactions. This study also reveals rare cutaneous ADRs experienced by Malaysian children under the age of 2, which constitutes a crucial cause of harm among children

Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators