Phase I dose-escalation and pharmacokinetic study of a novel folate analogue AG2034

The novel folate analogue AG2034, which was designed as an inhibitor of GARFT (glycinamide ribonucleotide formyltransferase), was evaluated in this phase I study under the auspices of The Cancer Research Campaign, UK. AG2034 blocks de novo purine synthesis through inhibition of GARFT. A total of 28 patients with histologically proven intractable cancers were enrolled. AG2034 was administered as a short intravenous infusion once every 3 weeks. 8 dose levels ranging from 1–11 mg/m2 were evaluated with patients receiving up to 6 cycles. Dose-limiting toxicities in the form of mucositis, diarrhoea and vomiting were observed at doses of 6 mg/m2 and above. Significant levels of thrombocytopenia, neutropenia and anaemia were also recorded. Other sporadic toxicities included fatigue and myalgia. The MTD with this schedule of AG2034 was 5 mg/m2. Most side effects occurred more frequently with cumulative dosing. In keeping with this, pharmacokinetic analysis revealed evidence of drug accumulation. The AG2034 AUC0–24 increased by a median of 184% (range 20–389%) from cycle 1 to 3 in all 10 patients examined. No objective antitumour responses were observed in the study. © 2001 Cancer Research Campaign http://www.bjcancer.co

Capnocytophaga ochracea Septicemia

A case report describing Capnocytophaga ochracea (Bacteroides ochraceus) septicemia in a 21-year-old male patient receiving chemotherapy for acute lymphocytic leukemia is presented. The unusual features of this organism are discussed together with a review of the literature

A microsensor for carbonate ions suitable for microprofiling in freshwater and saline environments

A novel carbonate microsensor, based on the ion‐selective ionophore N,N,‐dioctyl‐3a,12 a‐bis(4‐trifluoroacetylbenzoxy)‐5β‐cholan‐24‐amide, is presented. The sensor chemistry and filling electrolyte, used previously for macrosensors, was improved for use in microsensors, and a simple calibration procedure was designed. The sensor is highly selective for carbonate, having a similar selectivity as the macrosensor, and is so insensitive to Cl− interference that it can be used in seawater. The ability to measure accurate profiles with the carbonate sensor was verified in agar gels with artificial carbonate gradients. Several environmental applications are presented, including photosynthesis and calcification measurements in freshwater stromatolites (tufas) and foraminifera. Carbonate profiles in illuminated and darkened hypersaline microbial mats were qualitatively as expected and aligned with the oxygen and pH profiles. The dissolved inorganic carbon profiles calculated from local pH and carbonate values, however, did not follow the expected trends, both in the foraminifera and the hypersaline mat. Temporal and spatial heterogeneities make perfect alignment of pH and carbonate profiles, needed for DIC calculations, unrealistic. The calculation of dissolved inorganic carbon microprofiles from pH and carbonate microprofiles is not recommended. The microsensor is highly useful in studies on calcification and decalcification, where direct concentrations of carbonate and calcium ions are needed

The reintroduction of large carnivores to the Eastern Cape, South Africa: an assessment

Recently, conservation estate in South Africa's Eastern Cape Province has increased 10-fold resulting in large predators being increasingly reintroduced to restore ecological integrity and maximize tourism. We describe the reintroductions of large carnivores (>10 kg) that have occurred in the Eastern Cape and use various criteria to assess their success. Lion Panthera leo reintroduction has been highly successful with a population of 56 currently extant in the region and problems of overpopulation arising. The African wild dog Lycaon pictus population has increased to 24 from a founder population of 11. Preliminary results for spotted hyaenas Crocuta crocuta also indicate success. Wild populations of leopards Panthera pardus exist on several reserves and have been supplemented by translocated individuals, although deaths of known individuals have occurred and no estimate of reproduction is available. Cheetah Acinonyx jubatus reintroduction has also been less successful with 36 individuals reintroduced and 23 cubs being born but only 41 individuals surviving in 2005. Criteria for assessing the success of reintroductions of species that naturally occur in low densities, such as top predators, generally have limited value. Carrying capacity for large predators is unknown and continued monitoring and intensive management will be necessary in enclosed, and possibly all, conservation areas in the Eastern Cape to ensure conservation success

Spheroidisation of iron powder in a microwave plasma reactor

Plasma-assisted spheroidisation of metal powders offers several technical advantages with respect to both the ease of materials handling and powder-metallurgical item manufacturing. Advantages include improved flowability, increased powder packing density, elimination of internal component cavities and fractures, changes in morphology resulting in decreased friction between particles and contamination during pneumatic transport and enhanced particle purity. In this empirical study, spherical iron particles were produced using a microwave plasma operating at atmospheric pressure and characterized using optical microscopy and SEM techniques. Iron powders were fed into the system at fixed operating conditions, resulting in particles with spherical structures. The theoretical estimate of the time required for melting to occur is 1.6 ms, an order of magnitude smaller than the actual residence time.http://www.saimm.co.za/journal-papersam2016Chemical Engineerin

Wildfire impact : natural experiment reveals differential short-term changes in soil microbial communities

A wildfire which overran a sensor network site provided an opportunity (a natural experiment) to monitor short-term post-fire impacts (immediate and up to three months post-fire) in remnant eucalypt woodland and managed pasture plots. The magnitude of fire-induced changes in soil properties and soil microbial communities was determined by comparing (1) variation in fire-adapted eucalypt woodland vs. pasture grassland at the burnt site; (2) variation at the burnt woodland-pasture sites with variation at two unburnt woodland-pasture sites in the same locality; and (3) temporal variation pre- and post-fire. In the eucalypt woodland, soil ammonium, pH and ROC content increased post-fire, while in the pasture soil, soil nitrate increased post-fire and became the dominant soluble N pool. However, apart from distinct changes in N pools, the magnitude of change in most soil properties was small when compared to the unburnt sites. At the burnt site, bacterial and fungal community structure showed significant temporal shifts between pre- and post-fire periods which were associated with changes in soil nutrients, especially N pools. In contrast, microbial communities at the unburnt sites showed little temporal change over the same period. Bacterial community composition at the burnt site also changed dramatically post-fire in terms of abundance and diversity, with positive impacts on abundance of phyla such as Actinobacteria, Proteobacteria and Firmicutes. Large and rapid changes in soil bacterial community composition occurred in the fire-adapted woodland plot compared to the pasture soil, which may be a reflection of differences in vegetation composition and fuel loading. Given the rapid yet differential response in contrasting land uses, identification of key soil bacterial groups may be useful in assessing recovery of fire-adapted ecosystems, especially as wildfire frequency is predicted to increase with global climate change

Optimisation of the synthesis of ZrC coatings in a radio frequency induction-heating chemical vapour deposition system using response surface methodology

A chemical vapour deposition process using radio frequency induction heating operating at atmospheric pressure was developed for the deposition of ZrC coatings. The precursors utilised in this process were zirconium tetrachloride and methane as zirconium and carbon sources respectively, in an excess of hydrogen. Additionally, a stream of argon was used to, first, remove oxygen from the reactor and then to sweep the vapourised ZrCl4 at 300 °C to the reaction chamber. The ZrC coatings were deposited on graphite substrates at substrate temperatures in the range of 1200 °C–1600 °C. The molar ratio of CH4/ZrCl4 was varied from 6.04 to 24.44. Before the start of the deposition process, thermodynamic feasibility analysis for the growth of ZrC at atmospheric pressure was also carried out. Response surface methodology was applied to optimise the process parameters for the deposition of ZrC coatings. A central composite design was used to investigate the effects of temperature and molar ratio of CH4/ZrCl4 on the growth rate, atomic ratio of C/Zr and crystallite size of ZrC coatings. Quadratic statistical models for growth rate and crystallite size were established. The atomic ratio of C/Zr followed a linear trend. It was found that an increase in substrate temperature and CH4/ZrCl4 ratio resulted in increased growth rate of ZrC coatings. The carbon content (and concomitantly the atomic ratio of C/Zr) in the deposited coatings increased with temperature and molar ratio of CH4/ZrCl4. The substrate temperature of 1353.3 °C and the CH4/ZrCl4 molar ratio of 10.41 were determined as the optimal condition for growing near-stoichiometry ZrC coatings. The values were 1.03, 6.05 μm/h and 29.8 nm for C/Zr atomic percentage ratio, growth rate and average crystallite size respectively.University of Pretoria, Busitema University and African Union.http://www.elsevier.com/locate/tsf2018-02-28hb2017Chemical EngineeringPhysic

Cognitive tasks, anatomical MRI, and functional MRI data evaluating the construct of self-regulation

We describe the following shared data from N = 103 healthy adults who completed a broad set of cognitive tasks, surveys, and neuroimaging measurements to examine the construct of self-regulation. The neuroimaging acquisition involved task-based fMRI, resting state fMRI, and structural MRI. Each subject completed the following ten tasks in the scanner across two 90-minute scanning sessions: attention network test (ANT), cued task switching, Columbia card task, dot pattern expectancy (DPX), delay discounting, simple and motor selective stop signal, Stroop, a towers task, and a set of survey questions. The dataset is shared openly through the OpenNeuro project, and the dataset is formatted according to the Brain Imaging Data Structure (BIDS) standard

Using palaeoenvironmental DNA to reconstruct past environments: progress and prospects

Palaeoenvironmental DNA (PalEnDNA) is defined as ancient DNA (aDNA) originating from disseminated genetic material within palaeoenvironmental samples. Sources of PalEnDNA include marine and lake sediments, peat, loess, till, ice, permafrost, palaeosols, coprolites, preserved gut contents, dental calculus, tephras, and soils as well as deposits in caves/rockshelters and at archaeological sites. PalEnDNA analysis provides a relatively new tool for Quaternary and archaeological sciences and its applications have included palaeoenvironmental and palaeodietary reconstructions, testing hypotheses regarding megafaunal extinctions, human–environment interactions, taxonomic studies and studies of DNA damage. Because PalEnDNA samples comprise markedly different materials, and represent wide-ranging depositional and taphonomic contexts, various issues must be addressed to achieve robust, reproducible findings. Such issues include climatic and temporal limitations, the biological origin and state (free versus bound) of PalEnDNA, stratigraphic reliability, sterile sampling, ability to distinguish modern from aDNA signals, DNA damage and PCR amplification, DNA extraction methods, and taxonomic resolution. In this review, we provide a non-specialist introduction to the use of PalEnDNA for Quaternary and archaeological researchers, assess attributes and limitations of this palaeoenvironmental tool, and discuss future prospects of using PalEnDNA to reconstruct past environments