Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high-grade multicentric lymphoma

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m² over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h⁻¹; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m².     

Identification and validation of cold responsive microRNAs of <Emphasis Type="Italic">Hevea brasiliensis</Emphasis> using high throughput sequencing

Cold stress is one of the major abiotic factors that influence the productivity and geographical distribution of many agriculturally important crops like Hevea brasiliensis. Cultivation of H. brasiliensis in India is being extended to northeastern regions, where low temperature during winter adversely affects its survival, growth, and productivity. Developing cold-tolerant genotypes is a primary requisite to maximize the productivity under such challenging environmental conditions. However, lack of methods for early evaluation of cold tolerance in the newly developed clones and the extensive time required for assessing their tolerance in the field are major constraints for clonal selection. The present study was initiated with an objective to identify and characterize cold stress responsive miRNAs from H. brasiliensis that show stronger association with cold tolerance. Next generation sequencing using Illumina HiSeq method revealed the expression of 21 and 29 conserved miRNA (from clone RRIM 600) families in cold-stressed and control samples, respectively. Forty-two novel miRNAs were identified from this study. Upon differential expression analysis, eight conserved miRNAs were found commonly expressed in both the samples. When expression analyses were performed subsequently with six selected miRNAs in two Hevea clones (viz. RRII 105 and RRIM 600), miR169 showed a strong association with cold tolerance. miRNAs such as miR482 and miR159 also exhibited association with cold tolerance. This study suggests the possibility of employing these miRNAs as markers for cold tolerance after validation in more number of genotypes with varying levels of cold tolerance.     

Using webinars to extend the reach of soil learning in New South Wales: A first look

Increasingly knowledge is shared using new web‐based channels. The use of these channels is relatively new in the realm of soil science. However, they may prove to be very useful for connecting time‐poor, geographically dispersed audiences in an efficient and cost‐effective way. There has been limited study of this form of knowledge sharing for natural science (let alone soil science). In New South Wales (NSW), Australia, the NSW Department of Primary Industries (NSW DPI) has coordinated the Soil Network of Knowledge (SNoK) monthly webinar over 3 years, with over 40 webinars targeting an audience of next users of soil information. Aggregated data collected from these webinars indicated that the majority of information is used for professional development by participants. Whether this will eventually lead to on‐ground practice change because of the improved professional and technical knowledge of participants is still a moot point and will require further investigation over time. The information collected on attendance and participation showed that webinars are a good way to connect with some target audiences such as other government bodies that have a historical relationship with NSW DPI. However, other target audiences that NSW DPI has always found difficulty in engaging, such as private advisers, require more active overtures to drive participation. The growing subscriber base is encouraging.     

Thunderstorms: an important mechanism in the transport of air pollutants

Acid deposition and photochemical smog are urban air pollution problems, and they remain localized as long as the sulfur, nitrogen, and hydrocarbon pollutants are confined to the lower troposphere (below about 1-kilometer altitude) where they are short-lived. If, however, the contaminants are rapidly transported to the upper troposphere, then their atmospheric residence times grow and their range of influence expands dramatically. Although this vertical transport ameliorates some of the effects of acid rain by diluting atmospheric acids, it exacerbates global tropospheric ozone production by redistributing the necessary nitrogen catalysts. Results of recent computer simulations suggest that thunderstorms are one means of rapid vertical transport. To test this hypothesis, several research aircraft near a midwestern thunderstrom measured carbon monoxide, hydrocarbons, ozone, and reactive nitrogen compounds. Their concentrations were much greater in the outflow region of the storm, up to 11 kilometers in altitude, than in surrounding air. Trace gas measurements can thus be used to track the motion of air in and around a cloud. Thunderstorms may transform local air pollution problems into regional or global atmospheric chemistry problems.     

Migration‐affected change and vulnerability in rural Vanuatu

Migration is increasingly being promoted as a possible adaptive response to risks associated with climate change and other stresses. While migration may present an adaptation pathway in certain contexts, existing research fails to consider the ways in which migration could contribute to vulnerability in sending communities. This paper examines the impact of migration‐affected change on local vulnerability in Lamen Bay, Vanuatu. Qualitative methods, including interviews and focus groups with 58 individuals, were used to determine how migration interacts with the multiple stressors faced by the community. The results show that migration is likely to contribute to vulnerability in already vulnerable communities. In Lamen Bay, migration affects a number of contextual factors that influence exposure and the capacity to respond to change, including labour supply, food security, migrant attitudes, underdevelopment and institutional viability. These results suggest that development policy in Vanuatu needs to address existing vulnerabilities while offering the opportunity to migrate.     

Detection of O,O-diethyl-O-(2,5-dichlorophenyl) phosphorothioate and O,O-diethyl-O-(3,6-dichloro-2-pyridyl) phosphorothioate in meat fat.

Two previously unreported organophosphorus residues have been detected in meat fat. The first, O,O-diethyl-O-(2,5-dichlorophenyl) phosphorothioate, apparently results from the debromination of bromophos-ethyl, while the other, O,O-diethy-O-(3,6-dichloro-2-pyridyl) phosphorothioate, presumably arises by the monodechlorination of chlorpyriphos. Mass spectral evidence is presented in support of the assigned structures and gas-liquid chromatographic retention data for the residues and their oxygen analogs are provided.     

Segregation distortion in doubled haploid lines of barley (Hordeum vulgare L.) detected by simple sequence repeat (SSR) markers

A total of 147 simple sequence repeat (SSR) markers (including86 barley and 61 wheat microsatellite markers) were tested for their segregation in a doubled haploid (DH) and an F₂ population of barley. The DH population consisted of 71 doubled haploid lines, developed from F₁ plants of a cross between Tadmor and WI2291using isolated microspore culture technique. A genetic linkage map consisting of 43 microsatellite markers was constructed using the DH population. Particularly on chromosome 4H microsatellite markers showed distorted segregation ratios. Segregation of DH lines based on molecular markers were compared with segregation of 92 F₂ lines from the same cross. The proportion of loci deviating from the expected monogenic segregation ratios in the DH population was significantly higher (19/43loci, 44%) than in the F₂ population (7/43 loci, 16%). The deviation was biased towards the WI2291 parent alleles. In line with this observation, WI2291 was found to perform better than Tadmor in regenerating green plantlets with the isolated microspore-culture technique. This revised version was published online in July 2006 with corrections to the Cover Date.     

Detection of antibiotic residues and association of cefquinome residues with the occurrence of Extended-Spectrum β-Lactamase (ESBL)-producing bacteria in waste milk samples from dairy farms in England and Wales in 2011

Waste milk samples from 103 farms in England and Wales were examined for the presence of β-lactam antibiotics and ESBL-producing Enterobacteriaceae. Approximately 10 months after the initial sampling, further waste milk, environmental and faecal samples from farms shown to be positive for CTX-M Escherichia coli were investigated further. Isolates with an ESBL phenotype were tested by PCR for the presence of bla_CTX-M, bla_OXA, bla_SHV and bla_TEM genes. Isolates positive for bla_CTX-M were sequenced to determine CTX-M type. Representative isolates were further examined by PFGE, plasmid replicon typing and serotyping. Of particular interest, 21.4% of waste milk samples contained residues of the cephalosporin cefquinome, which was significantly associated with CTX-M bacteria. Such bacteria occurred in 5.8% of the waste milk samples (including 3.9% CTX-M E. coli). CTX-M types identified were 1, 14, 14b and 15, but none of the E. coli were serotype O25, the serotype of the human pandemic strain.     

Effects of salinity on growth characteristics and osmoregulation of juvenile cobia,Rachycentron canadum (Linnaeus 1766), reared in potassium‐amended inland saline groundwater

The suitability of inland saline groundwater as a medium to culture juvenile cobia, Rachycentron canadum, was assessed. In the first experiment, juvenile cobia stocked in raw (unamended) saline groundwater at salinities of 5, 10, and 15 g/L exhibited complete mortality after 108, 176, and 195 hr, respectively. The second experiment evaluated the rearing of juvenile cobia (mean weight ~9.23 ± 0.12 g) in potassium (K⁺)‐amended saline groundwater (100% K⁺ fortified) and reconstituted seawater at salinities of 5, 10, and 15 g/L to assess growth and osmoregulation in distinct culture media. Following 60 days of culture, all fish survived the experimental period. Final mean bodyweight of cobia reared in K⁺‐amended saline groundwater (103.2–115.8 g) and seawater (111.2–113.8 g) of different salinities did not vary significantly (p > .05). No differences (p > .05) were observed in specific growth rate, weight gain (%), and feed conversion ratio between treatment groups. Serum osmolality increased with salinity and was significantly higher (p < .05) for fish in K⁺‐amended saline groundwater (353–361 mOsmol/Kg) than in reconstituted seawater (319–332 mOsmol/Kg), although differences were not observed between salinities by water type. Cobia stocked in saline groundwater of different salinities were osmoregulating normally, and the higher values observed may be because of variations in ionic composition and other interfering ions in saline groundwater. Trial results suggest that juvenile cobia can achieve optimal growth in K⁺‐amended saline groundwater of low and intermediate salinities.     

Habitat use of a coastal delphinid population investigated using passive acoustic monitoring

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