Polymer-Induced Drag Reduction in Dilute Newtonian and Semi-Dilute Non-Newtonian Fluids: An Assessment of the Double-Gap Concentric Cylinder Method.

Polymer-induced drag reduction (DR) in fluids was studied using a rotational rheometer with double-gap concentric cylinder geometry. Although both polymers (polyacrylamide (PAM) and 2-acrylamido-2-methylpropane sulfonic acid (SPAM)) had molecular weights of several MDa, the contrasting polymer charge, nonionic and anionic, led to different polymer overlap concentrations (c*), PAM ≫ SPAM, and fluid rheology, with PAM fluids mostly Newtonian and SPAM fluids non-Newtonian (shear-thinning). Based on these differences, it was important to account for the infinite shear viscosity and normalize the polymer concentration by the intrinsic concentration (c int) so that the DR performance of the two polymer fluids could be accurately compared. Both polymers induced DR, and the maximum DR by SPAM (DR% = 28) was slightly higher than that by PAM (DR% = 22) when Re p ∼ 1700. For PAM, the loss of DR with time diminished at higher polymer concentrations (≥100 ppm, at Re p = 3149) but was found to be sensitive to high Re p, with polymer chain scission the likely cause of the reduced performance. For the semi-dilute SPAM fluids, the shear stability contrasted that of PAM, showing negligible dependence on the polymer concentration and Re p. The apparent rapid loss of DR was predominantly attributed to a time-dependent effect and not polymer degradation. In pipe flow, the maximum DR for SPAM was higher than that measured by rheometry and was attributed to differences in the flow conditions. However, changes in the normalized DR/c with polymer concentration were found to be consistent between the two flow geometries. Furthermore, the high fluid stresses in pipe flow (at high Re p) led to drag reduction losses consistent with PAM, as the time-dependent effect was not seen.

Lessons identified from the 2017 Manchester and London terrorism incidents. Part 1: introduction and the prehospital phase.

This is the first article in a three-part series detailing the lessons identified during the NHS England clinical debrief meetings which followed the response to the 2017 Manchester and London terrorist incidents. It covers the prehospital phase including the overall key learning points, timeline information, scene challenges, resource utilisation, triage, distribution and helicopter emergency medical service feedback.

Lessons identified from the 2017 Manchester and London terrorism incidents. Part 3: the postincident and recovery phase.

This is the third paper in a three-part series detailing the lessons identified during the National Health Service (NHS) England clinical debrief meetings which followed the response to the 2017 Manchester and London terrorist incidents. It covers the postincident and recovery phases including rehabilitation, bereavement support, psychological support, network and regional lessons, NHS communications and supply organisations. It also summarises the military application of these lessons and outlines the next steps for further development.

Lessons identified from the 2017 Manchester and London terrorism incidents. Part two: the reception and definitive care (hospital) phases.

The provision of medical care during the reception and definitive care phases of a terrorist incident will likely take place in designated receiving hospitals such as Major Trauma Centres. There is a need for an enhanced capability in such units to receive, initially manage and hold casualties with more serious injuries. Also, even less severely injured casualties may require significant time and clinical input such as risk management in potential bloodborne viruses.The distribution of casualties from the incident scene requires advance consideration of the injury pattern and regional network organisation of specialist services, such as maxillofacial, neurosurgery or severe burns care. Paediatric centres are also more sparsely distributed and often only in large city networks which represents a significant challenge for planners and responders in other regions. An effective response relies on a coordinated multidisciplinary approach including emergency and front-of-house teams, surgical, medical and clinical support services.

Rapid identification of genes controlling virulence and immunity in malaria parasites.

Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.

Interpreting the International Right to Health in a Human Rights-Based Approach to Health.

This article tracks the shifting place of the international right to health, and human rights-based approaches to health, in the scholarly literature and United Nations (UN). From 1993 to 1994, the focus began to move from the right to health toward human rights-based approaches to health, including human rights guidance adopted by UN agencies in relation to specific health issues. There is a compelling case for a human rights-based approach to health, but it runs the risk of playing down the right to health, as evidenced by an examination of some UN human rights guidance. The right to health has important and distinctive qualities that are not provided by other rights-consequently, playing down the right to health can diminish rights-based approaches to health, as well as the right to health itself. Because general comments, the reports of UN Special Rapporteurs, and UN agencies' guidance are exercises in interpretation, I discuss methods of legal interpretation. I suggest that the International Covenant on Economic, Social and Cultural Rights permits distinctive interpretative methods within the boundaries established by the Vienna Convention on the Law of Treaties. I call for the right to health to be placed explicitly at the center of a rights-based approach and interpreted in accordance with public international law and international human rights law.

STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain.

OBJECTIVE: To evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma. METHODS: STOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12-17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses. RESULTS: A total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of -18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action. CONCLUSION: The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic. TRIAL REGISTRATION NUMBER: NCT01420159.

Declines in elevated blood lead levels among children, 1997-2011.

BACKGROUND: Early childhood lead exposure is associated with numerous adverse health effects. Eliminating blood lead poisoning is a national health objective for 2020. OBJECTIVE: To assess temporal trends in childhood elevated blood lead level (EBLL) rates. METHODS: Laboratory surveillance data were collected from 1997 to 2011 and analyzed in 2013 using linear regression to assess trends in confirmed EBLL rates among children aged <6 years in the U.S., New York State ([NYS], excluding New York City), and Monroe County NY. Monroe County was also examined as a case study of local public health efforts to reduce childhood lead exposures. Blood lead screening and home lead hazard inspection data were collected from 1990 to 2012 and analyzed in 2013. RESULTS: The prevalence of EBLL≥10 µg/dL per 100 tested children decreased from 13.4 to 1.1 in Monroe County, 6.3 to 1.0 in NYS, and 7.6 to 0.6 in the U.S. between 1997 and 2011. The absolute yearly rate of decline in Monroe County (slope=-0.0083, p<0.001) occurred 2.4-fold faster than that in NYS (slope=-0.0034, p<0.001) and 1.8-fold faster than that in the U.S. (slope=-0.0046, p<0.001). The childhood blood lead testing rate was consistently higher in Monroe County than in NYS and the U.S.; however, testing increased for all three areas (all slopes>0, p<0.05), with greater improvements observed for U.S. children overall (slope=0.0075, p<0.001). CONCLUSIONS: In addition to national and statewide policies, local efforts may be important drivers of population-based declines in childhood EBLL rates.

Artemisinin resistance in rodent malaria--mutation in the AP2 adaptor µ-chain suggests involvement of endocytosis and membrane protein trafficking.

BACKGROUND: The control of malaria, caused by Plasmodium falciparum, is hampered by the relentless evolution of drug resistance. Because artemisinin derivatives are now used in the most effective anti-malarial therapy, resistance to artemisinin would be catastrophic. Indeed, studies suggest that artemisinin resistance has already appeared in natural infections. Understanding the mechanisms of resistance would help to prolong the effective lifetime of these drugs. Genetic markers of resistance are therefore required urgently. Previously, a mutation in a de-ubiquitinating enzyme was shown to confer artemisinin resistance in the rodent malaria parasite Plasmodium chabaudi. METHODS: Here, for a mutant P. chabaudi malaria parasite and its immediate progenitor, the in vivo artemisinin resistance phenotypes and the mutations arising using Illumina whole-genome re-sequencing were compared. RESULTS: An increased artemisinin resistance phenotype is accompanied by one non-synonymous substitution. The mutated gene encodes the µ-chain of the AP2 adaptor complex, a component of the endocytic machinery. Homology models indicate that the mutated residue interacts with a cargo recognition sequence. In natural infections of the human malaria parasite P. falciparum, 12 polymorphisms (nine SNPs and three indels) were identified in the orthologous gene. CONCLUSION: An increased artemisinin-resistant phenotype occurs along with a mutation in a functional element of the AP2 adaptor protein complex. This suggests that endocytosis and trafficking of membrane proteins may be involved, generating new insights into possible mechanisms of resistance. The genotypes of this adaptor protein can be evaluated for its role in artemisinin responses in human infections of P. falciparum.

Human rights responsibilities of pharmaceutical companies in relation to access to medicines.

Although access to medicines is a vital feature of the right to the highest attainable standard of health ("right to health"), almost two billion people lack access to essential medicines, leading to immense avoidable suffering. While the human rights responsibility to provide access to medicines lies mainly with States, pharmaceutical companies also have human rights responsibilities in relation to access to medicines. This article provides an introduction to these responsibilities. It briefly outlines the new UN Guiding Principles on Business and Human Rights and places the human rights responsibilities of pharmaceutical companies in this context. The authors draw from the work of the first UN Special Rapporteur on the right to the highest attainable standard of health, in particular the Human Rights Guidelines for Pharmaceutical Companies in Relation to Access to Medicines that he presented to the UN General Assembly in 2008, and his UN report on GlaxoSmithKline (GSK). While the Guiding Principles on Business and Human Rights are general human rights standards applicable to all business entities, the Human Rights Guidelines for Pharmaceutical Companies consider the specific human rights responsibilities of one sector (pharmaceutical companies) in relation to one area of activity (access to medicines). The article signals the human rights responsibilities of all pharmaceutical companies, with particular attention to patent-holding pharmaceutical companies. Adopting a right-to-health "lens," the article discusses GSK and accountability. The authors argue that human rights should shape pharmaceutical companies' policies, and provide standards in relation to which pharmaceutical companies could, and should, be held accountable. They conclude that it is now crucial to devise independent, accessible, transparent, and effective mechanisms to monitor pharmaceutical companies and hold them publicly accountable for their human rights responsibilities.