Purification of Tannery Effluent by electrolytic corrosion of aluminium

Tannery Effluent is noxious because tanning process chemicals are preservatives, including chromium, and the pH is high. Electrolytic processing is feasible because the high salt content gives a high electrical conductivity. While research on the subject dates back to early in the 20th Century, commercialization has not occurred, perhaps due to excessive power consumption. Other researchers have produced promising results with rendering plant effluent (Tetrault 2003). During 2005 a specialised proprietary prototype with a novel anode design was trialed extensively at a Tannery site in New Zealand and produced good results during continuous inline operation despite wide variation in the inflow. Greater than 90% removal of chromium from solution with similar reductions in turbidity were achieved at lower operating cost, residual aluminum and total aluminum addition than by dosing with usual commercial aluminum based flocculants. Results from the field trials are shown and discussed

Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children

Background. Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5 - 10 µg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury. Objective. To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIVinfected children. Methods. A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose. Results. Median (25th - 75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5 - 1.5) µg/ml, 1.94 (1.4 - 2.2) µg/ml and 7.68 (6.1- 7.8) µg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4 - 8.8) µg/ml and 9.25 (8.2 - 10.3) µg/ml respectively. Conclusion. Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children

Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children

Background. Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5 - 10 µg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury. Objective. To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIVinfected children. Methods. A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose. Results. Median (25th - 75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5 - 1.5) µg/ml, 1.94 (1.4 - 2.2) µg/ml and 7.68 (6.1- 7.8) µg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4 - 8.8) µg/ml and 9.25 (8.2 - 10.3) µg/ml respectively. Conclusion. Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children. No Abstract. South African Medical Journal Vol. 96(7) 2006: 627-62

Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers.

MMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed. Additionally, a volunteer infection study investigated the antimalarial activity of MMV390048 using the Plasmodium falciparum induced blood-stage malaria (IBSM) model. Due to the high pharmacokinetic variability with the powder-in-bottle formulation used in both of these studies, a third study was undertaken to select a tablet formulation of MMV390048 to take forward into future studies. MMV390048 was generally well tolerated when administered as a single oral dose up to 120 mg, with rapid absorption and a long elimination half-life. Twelve adverse events were considered to be potentially related to MMV390048 in the first-in-human study but with no obvious correlation between these and MMV390048 dose or exposure. Although antimalarial activity was evident in the IBSM study, rapid recrudescence occurred in most subjects after treatment with 20 mg MMV390048, a dose expected to be subtherapeutic. Reformulation of MMV390048 into two tablet formulations (tartaric acid and Syloid) resulted in significantly reduced intersubject pharmacokinetic variability. Overall, the results of this study suggest that MMV390048 is well tolerated in humans, and the pharmacokinetic properties of the compound indicate that it has the potential to be used for antimalarial prophylaxis or inclusion in a single-dose cure. MMV390048 is currently being tested in a phase 2a study in Ethiopian adults with acute, uncomplicated falciparum or vivax malaria monoinfection. (The three clinical trials described here were each registered with ClinicalTrials.gov as follows: first-in-human study, registration no. NCT02230579; IBSM study, registration no. NCT02281344; and formulation optimization study, registration no. NCT02554799.)

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Management policies for invasive alien species: Adressing the impacts rather than the species

Effective long-term management is needed to address the impacts of invasive alien species (IAS) that cannot be eradicated. We describe the fundamental characteristics of long-term management policies for IAS, diagnose a major shortcoming, and outline how to produce effective IAS management. Key international and transnational management policies conflate addressing IAS impacts with controlling IAS populations. This serious purpose–implementation gap can preclude the development of broader portfolios of interventions to tackle IAS impacts. We posit that IAS management strategies should directly address impacts via impact-based interventions, and we propose six criteria to inform the choice of these interventions. We review examples of interventions focused on tackling IAS impacts, including IAS control, which reveal the range of interventions available and their varying effectiveness in counteracting IAS impacts. As the impacts caused by IAS increase globally, stakeholders need to have access to a broader and more effective set of tools to respond.Fil: García Díaz, Pablo. University of Aberdeen; Reino UnidoFil: Cassey, Philip. University of Adelaide; AustraliaFil: Norbury, Grant. Crown Research Institutes. Landcare Research; Nueva ZelandaFil: Lambin, Xavier. University of Aberdeen; Reino UnidoFil: Montti, Lia Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Pizarro, J. Cristóbal. Universidad de Concepción; ChileFil: Powell, Priscila Ana. Universidad Nacional de Tucumán. Instituto de Ecología Regional. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Ecología Regional; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Burslem, David F. R. P.. University of Aberdeen; Reino UnidoFil: Cava, Mário. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Damasceno, Gabriella. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Fasola, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Asociación Ornitológica del Plata; ArgentinaFil: Fidelis, Alessandra. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Huerta, Magdalena F.. Universidad Austral de Chile; Chile. Universidad de Concepción; ChileFil: Langdon, Bárbara. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede San Martín de Los Andes-inibioma | Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede San Martín de Los Andes-inibioma.; ArgentinaFil: Linardaki, Eirini. University of Aberdeen; Reino UnidoFil: Moyano, Jaime. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede San Martín de Los Andes-inibioma | Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede San Martín de Los Andes-inibioma.; ArgentinaFil: Nuñez, Martin Andres. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede San Martín de Los Andes-inibioma | Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede San Martín de Los Andes-inibioma.; ArgentinaFil: Pauchard, Aníbal. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede San Martín de Los Andes-inibioma | Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede San Martín de Los Andes-inibioma.; ArgentinaFil: Phimister, Euan. University of Aberdeen; Reino UnidoFil: Raffo, Eduardo. Gobierno de Chile. Servicio Agrícola y Ganadero; ChileFil: Roesler, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Rodríguez Jorquera, Ignacio. Universidad Austral de Chile; Chile. Universidad de Concepción; ChileFil: Tomasevic, Jorge A.. Universidad Austral de Chile; Chile. Universidad de Concepción; Chil

Clark's Malthus delusion: response to ‘Farming in England 1200-1800’

Clark's claims about the scale of English agricultural output from the 1200s to the 1860s flout historical and geographical reality. His income-based estimates start with the daily real wages of adult males and assume that days worked per year were constant. Those advanced in British economic growth make no such assumption and instead are built up from the output side. They correlate better with population trends and are consistent with an economy slowly growing and becoming richer. Clark's denial that such growth occurred, his assertion that substantially more land must have been under arable cultivation, his belief that conditions of full employment invariably prevailed in the countryside at harvest time, his concern that the wage bill would have exceeded the value of output in British economic growth, his refusal to consider the possibility that the working year was of variable length, and his assertion that output per acre must have been equalized across arable and pasture are all shown to be figments of his ‘Malthus delusion’

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Interventions to reduce the time to diagnosis of brain tumours

BACKGROUND: Brain tumours are recognised as one of the most difficult cancers to diagnose because presenting symptoms, such as headache, cognitive symptoms, and seizures, may be more commonly attributable to other, more benign conditions. Interventions to reduce the time to diagnosis of brain tumours include national awareness initiatives, expedited pathways, and protocols to diagnose brain tumours, based on a person's presenting symptoms and signs; and interventions to reduce waiting times for brain imaging pathways. If such interventions reduce the time to diagnosis, it may make it less likely that people experience clinical deterioration, and different treatment options may be available. OBJECTIVES: To systematically evaluate evidence on the effectiveness of interventions that may influence: symptomatic participants to present early (shortening the patient interval), thresholds for primary care referral (shortening the primary care interval), and time to imaging diagnosis (shortening the secondary care interval and diagnostic interval). To produce a brief economic commentary, summarising the economic evaluations relevant to these interventions. SEARCH METHODS: For evidence on effectiveness, we searched CENTRAL, MEDLINE, and Embase from January 2000 to January 2020; Clinicaltrials.gov to May 2020, and conference proceedings from 2014 to 2018. For economic evidence, we searched the UK National Health Services Economic Evaluation Database from 2000 to December 2014. SELECTION CRITERIA: We planned to include studies evaluating any active intervention that may influence the diagnostic pathway, e.g. clinical guidelines, direct access imaging, public health campaigns, educational initiatives, and other interventions that might lead to early identification of primary brain tumours. We planned to include randomised and non-randomised comparative studies. Included studies would include people of any age, with a presentation that might suggest a brain tumour. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles identified by the search strategy, and the full texts of potentially eligible studies. We resolved discrepancies through discussion or, if required, by consulting another review author. MAIN RESULTS: We did not identify any studies for inclusion in this review. We excluded 115 studies. The main reason for exclusion of potentially eligible intervention studies was their study design, due to a lack of control groups. We found no economic evidence to inform a brief economic commentary on this topic. AUTHORS' CONCLUSIONS: In this version of the review, we did not identify any studies that met the review inclusion criteria for either effectiveness or cost-effectiveness. Therefore, there is no evidence from good quality studies on the best strategies to reduce the time to diagnosis of brain tumours, despite the prioritisation of research on early diagnosis by the James Lind Alliance in 2015. This review highlights the need for research in this area