Occurrence of anticancer drugs in the aquatic environment : a systematic review

Water contamination with pharmaceutical products is a well-studied problem. Numerous studies have demonstrated the presence of anticancer drugs in different water resources that failed to be eliminated by conventional wastewater treatment plants. The purpose of this report was to conduct a systematic review of anticancer drugs in the aquatic environment. The methodology adopted was carried out in compliance with the PRISMA guidelines. From the 75 studies that met the specific requirements for inclusion, data extracted showed that the most common anticancer drugs studied are cyclophosphamide, tamoxifen, ifosfamide and methotrexate with concentrations measured ranging between 0.01 and 86,200 ng/L. There was significant variation in the methodologies employed due to lack of available guidelines to address sampling techniques, seasonal variability and analytical strategy. The most routinely used technique for quantitative determination was found to be solid-phase extraction followed by LC-MS analysis. The lowest reported recovery percentage was 11%, and the highest limit of detection was 1700 ng/L. This indicated the inadequacy of some methods to analyse anticancer drugs and the failure to obtain reliable results. The significant heterogeneity within methodologies made it difficult to compare results and draw conclusions, nevertheless, this study aids in the extrapolation of proposed recommendations to guide future studies and reviews

CBT for difficult-to-treat depression: self-regulation model

Background:Cognitive behavioural therapy (CBT) is an effective treatment for depression but a significant minority of clients do not complete therapy, do not respond to it, or subsequently relapse. Non-responders, and those at risk of relapse, are more likely to have adverse childhood experiences, early-onset depression, co-morbidities, interpersonal problems and heightened risk. This is a heterogeneous group of clients who are currently difficult to treat.Aim:The aim was to develop a CBT model of depression that will be effective for difficult-to-treat clients who have not responded to standard CBT.Method:The method was to unify theory, evidence and clinical strategies within the field of CBT to develop an integrated CBT model. Single case methods were used to develop the treatment components.Results:A self-regulation model of depression has been developed. It proposes that depression is maintained by repeated interactions of self-identity disruption, impaired motivation, disengagement, rumination, intrusive memories and passive life goals. Depression is more difficult to treat when these processes become interlocked. Treatment based on the model builds self-regulation skills and restructures self-identity, rather than target negative beliefs. A bespoke therapy plan is formed out of ten treatment components, based on an individual case formulation.Conclusions:A self-regulation model of depression is proposed that integrates theory, evidence and practice within the field of CBT. It has been developed with difficult-to-treat cases as its primary purpose. A case example is described in a concurrent article (Barton et al., 2022) and further empirical tests are on-going

Diet Composition: A Proximate Mechanism Explaining Stream Salamander Declines in Surface Waters with Elevated Specific Conductivity

Changes in land use, such as mountaintop removal mining with valley fills (MTR-VF), often results in headwater streams with elevated specific conductivity (SC). Stream salamanders appear to be particularly sensitive to elevated SC, as previous studies have shown occupancy and abundance decline consistently among all species and life stages as SC increases. Yet, the proximate mechanism responsible for the population declines in streams with elevated SC have eluded researchers. We sampled salamander assemblages across a continuous SC gradient (30–1966 μS/cm) in southeastern Kentucky and examined the diet of larval and adult salamanders to determine if the ratio of aquatic to terrestrial prey (autochthony), total prey volume, aquatic prey importance (Ix), and body condition are influenced by SC. Further, we asked if threshold points for each diet component were present along a gradient of SC. Larval salamanders experienced a 12–fold decline in autochthony at 153 μS/cm, a 4.2–fold decline in total prey volume at 100 μS/cm, a 2.2-fold decline in aquatic Ix at 135 μS/cm, and a rapid decline in body condition as SC increased. Adult salamanders experienced a 3–fold decline in autochthony at 382 μS/cm, no change in prey volumes, a 2-fold decline in aquatic Ix at 163 μS/cm, and a decline in body condition as SC increased. Our results indicate that SC indirectly affects stream salamander populations by changing the composition of diet, which suggests that food availability is a proximate mechanism that leads to reduced population occupancy, abundance, and persistence in streams with elevated SC

HPLC estimation of iothalamate to measure glomerular filtration rate in humans

Glomerular filtration rate (GFR) is usually determined by estimation of iothalamate (IOT) clearance. We have developed and validated an accurate and robust method for the analysis of IOT in human plasma and urine. The mobile phase consisted of methanol and 50 mM sodium phosphate (10:90; v/v). Flow rate was 1.2 mL/min on a C18 reverse phase column, Synergi-hydro (250 × 4.6 mm) 4 µm 80 Å, with an ultraviolet detector set to 254 nm. Acetonitrile was used for the deproteination and extraction of IOT from human plasma and urine. Precision and accuracy were within 15% for IOT in both plasma and urine. The recoveries of IOT in urine and plasma ranged between 93.14% and 114.74 and 96.04–118.38%, respectively. The linear range for urine and plasma assays were 25–1500 and 1–150 µg/mL respectively. The lower limits of detection were 0.5 µg/mL for both urine and plasma, with no interference from plasma and urine matices. This method has been fully validated according to FDA guidelines and the new HPLC assay has been applied to a new formulation of IOT (Conray™ 43), to calculate GFR in healthy volunteers. The new method is simple, less expensive and it would be instrumental in future clinical and pharmacokinetic studies of iothalamate in kidney patients

Determination of diclofenac concentrations in human plasma using a sensitive gas chromatography mass spectrometry method

Background A gas chromatography mass spectrometry (GCMS) method for the determination of diclofenac in human plasma has been developed and validated. Results This method utilizes hexane which is a relatively less toxic extraction solvent compared to heptane and benzene. In addition, phosphoric acid and acetone were added to the samples as deproteination agents, which increased the recovery of diclofenac. These revised processes allow clean extraction and near-quantitative recovery of analyte (approx. 89–95 %). Separation was achieved on a BP-1 column with helium as carrier gas. The molecular ion peaks of the indolinone derivatives of diclofenac ion (m/z 277) and the internal standard, 4-hydroxydiclofenac ion (m/z 439) were monitored by a mass-selective detector using selected ion monitoring (SIM) mode. The linear range for the newly developed and highly sensitive assay was between 0.25–50 ng/mL. The detection and lower quantifiable limits were 0.125 and 0.25 ng/mL, respectively. The inter-day and intra-day coefficients of variation for high, medium and low quality control concentrations were less than 9 %. The robustness and efficacy of this sensitive GCMS method was further demonstrated by using it for a pharmacokinetic study of an oral dosage form of diclofenac, 100 mg of modified-release capsules (Rhumalgan XL), in human plasma. Conclusions This method is rapid, sensitive, specific, reproducible and robust, and offers improved sensitivity over previous methods. This method has considerable potential to be used for detailed pharmacokinetics, pharmacodynamics and bioequivalence studies of diclofenac in humans

Occupancy and Abundance of Stream Salamanders along a Specific Conductance Gradient

In the Central Appalachians (USA), mountaintop-removal mining accompanied by valley fills often leads to streams with elevated specific conductivity (SC). Thus, the ionic composition of freshwaters in this region is hypothesized to be a driver of the distribution and abundance of freshwater taxa, including stream salamanders. We examined the association between SC and stream salamander populations by conducting salamander counts in 30 southeastern Kentucky streams across a continuous gradient of SC that ranged from 30 to 1966 μS/cm. We counted 2319 salamanders across 5 species and, using a hierarchical Bayesian version of the N-mixture model, found a negative association between SC and salamander occupancy rates. This finding was consistent across adults and larvae of the 5 species we examined. Furthermore, we found that most salamander species and life stages showed reduced abundances given occupancy at greater SC levels. For example, estimated mean abundance given occupancy of larval Southern Two-lined Salamanders (Eurycea cirrigera) was 67.69 (95% credible interval 48.31–98.25) ind/10 m at 250 μS/cm and 2.30 (95% credible interval 1.46–3.93) ind/10 m at 2000 μS/cm. The consistent negative association across all species and life stages supports the hypothesis that salamander distributions and abundances are negatively associated with elevated SC of streams in southeastern Kentucky, even though physical and chemical environmental attributes, such as forest cover within stream catchments, were correlated with SC. Restoration of streams affected by mountaintop-removal mining should focus on restoring the ionic compositions that naturally occur in this region

The SISO CSPI PDG standard for commercial off-the-shelf simulation package interoperability reference models

For many years discrete-event simulation has been used to analyze production and logistics problems in manufactur-ing and defense. Commercial-off-the-shelf Simulation Packages (CSPs), visual interactive modelling environ-ments such as Arena, Anylogic, Flexsim, Simul8, Witness, etc., support the development, experimentation and visua-lization of simulation models. There have been various attempts to create distributed simulations with these CSPs and their tools, some with the High Level Architecture (HLA). These are complex and it is quite difficult to assess how a set of models/CSP are actually interoperating. As the first in a series of standards aimed at standardizing how the HLA is used to support CSP distributed simula-tions, the Simulation Interoperability Standards Organiza-tion’s (SISO) CSP Interoperability Product Development Group (CSPI PDG) has developed and standardized a set of Interoperability Reference Models (IRM) that are in-tended to clearly identify the interoperability capabilities of CSP distributed simulations

Ares-I-X Stability and Control Flight Test: Analysis and Plans

The flight test of the Ares I-X vehicle provides a unique opportunity to reduce risk of the design of the Ares I vehicle and test out design, math modeling, and analysis methods. One of the key features of the Ares I design is the significant static aerodynamic instability coupled with the relatively flexible vehicle - potentially resulting in a challenging controls problem to provide adequate flight path performance while also providing adequate structural mode damping and preventing adverse control coupling to the flexible structural modes. Another challenge is to obtain enough data from the single flight to be able to conduct analysis showing the effectiveness of the controls solutions and have data to inform design decisions for Ares I. This paper will outline the modeling approaches and control system design to conduct this flight test, and also the system identification techniques developed to extract key information such as control system performance (gain/phase margins, for example), structural dynamics responses, and aerodynamic model estimations

OXBench:a benchmark for evaluation of protein multiple sequence alignment accuracy

BACKGROUND: The alignment of two or more protein sequences provides a powerful guide in the prediction of the protein structure and in identifying key functional residues, however, the utility of any prediction is completely dependent on the accuracy of the alignment. In this paper we describe a suite of reference alignments derived from the comparison of protein three-dimensional structures together with evaluation measures and software that allow automatically generated alignments to be benchmarked. We test the OXBench benchmark suite on alignments generated by the AMPS multiple alignment method, then apply the suite to compare eight different multiple alignment algorithms. The benchmark shows the current state-of-the art for alignment accuracy and provides a baseline against which new alignment algorithms may be judged.RESULTS: The simple hierarchical multiple alignment algorithm, AMPS, performed as well as or better than more modern methods such as CLUSTALW once the PAM250 pair-score matrix was replaced by a BLOSUM series matrix. AMPS gave an accuracy in Structurally Conserved Regions (SCRs) of 89.9% over a set of 672 alignments. The T-COFFEE method on a data set of families with &lt;8 sequences gave 91.4% accuracy, significantly better than CLUSTALW (88.9%) and all other methods considered here. The complete suite is available from http://www.compbio.dundee.ac.uk.CONCLUSIONS: The OXBench suite of reference alignments, evaluation software and results database provide a convenient method to assess progress in sequence alignment techniques. Evaluation measures that were dependent on comparison to a reference alignment were found to give good discrimination between methods. The STAMP Sc Score which is independent of a reference alignment also gave good discrimination. Application of OXBench in this paper shows that with the exception of T-COFFEE, the majority of the improvement in alignment accuracy seen since 1985 stems from improved pair-score matrices rather than algorithmic refinements. The maximum theoretical alignment accuracy obtained by pooling results over all methods was 94.5% with 52.5% accuracy for alignments in the 0-10 percentage identity range. This suggests that further improvements in accuracy will be possible in the future.</p

Surface perfluoroalkyl chains segregation : a tool for reducing calcium deposits in medical grade poly(methyl methacrylate)

Intraocular lenses can be manufactured from a wide variety of polymers, but due to the lost cost associated with the use of Poly(methyl methacrylate) (PMMA), it is still the preferred material used in the developing countries. However, a major drawback to its use is the build-up of calcium containing deposits that are formed on the intraocular lens over a period of time. In an attempt to hinder this deposition, surface modification of medical grade PMMA has been carried out using perfluoroalkyl chain (1,2,4-trifluoro-3- (C10F21CH2O)-7-(N,N)-dimethylaminoacridine) segregation. The segregation was explored using a 1% 1,2,4-trifluoro-3-(C10F21CH2O)-7-(N,N)-dimethyla- minoacridine in two methods: film casting and spin-coating, a thin film onto preformed PMMA discs. Both methods were compared against control PMMA to determine which method provided the best hindrance against calcium containing deposits when immersed in a simulated aqueous humour solution. Characterisation of the surface using scanning electron microscopy coupled with energy; dispersive x-ray analysis indicated that the surface segregation of perfluoroalkyl chains had hindered calcification in both methods. This pleminary research shows promising results of employing perfluoroalkyl chains in the surface segregation of biomaterials that can be employed in intraocular lenses