Read-Across for Rat Oral Gavage Repeated-Dose Toxicity for Short-Chain Mono-Alkylphenols: A Case Study

Short-chain mono-alkylphenols provide an example of where a category-approach to read-across may be used to estimate the repeated-dose endpoint for a number of derivatives. Specifically, the NOAELs of 50 mg/kg bw/d for mono-methylphenols based on a LOAEL of very low systemic toxicity can be read across with confidence to untested mono-alkylphenols in the category. These simple alkylphenols are non-reactive and exhibit an unspecific, reversible polar narcosis mode of toxic action. Briefly, polar narcotics act via unspecific, reversible interactions with biological membranes in a manner similar to cataleptic anaesthetics. The read-across premise includes rapid and complete absorption via the gastrointestinal tract, distribution in the circulatory system, first-pass Phase 2 metabolism in the liver, and elimination of sulphates and glucuronides in the urine. Thus, toxicokinetic parameters are considered to be similar and have the same toxicological significance. Five analogues have high quality experimental oral repeated-dose toxicity data (i.e., OECD TG 408 or OECD TG 422). These repeated-dose toxicity test results exhibit qualitative consistency in symptoms. Typical findings include decreased body weight and slightly increased liver and kidney weights which are generally without concurrent histopathological effects. The sub-chronic findings are quantitatively consistent with the No Observed Adverse Effect Level (NOAEL) of ≥ 50 mg/kg bw/d. Chemical similarity between the analogues is readily defined, and data uncertainty associated with the similarities in toxicokinetic properties, as well as toxicodynamic properties, are low. Uncertainty associated with mechanistic relevance and completeness of the read-across is low-to-moderate, largely because there is no adverse outcome pathway or intermediate event data. Uncertainty associated with mechanistic relevance and completeness of the read-across is reduced by the concordance of in vivo, in vitro, USEPA toxicity forecaster (ToxCast) results, as well as the in silico data. The rat oral repeated-dose NOAEL values for the source substances can be read across to fill the data gaps of the untested analogues in this category with uncertainty deemed equivalent to results from a TG 408 assessment

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

The underestimated biodiversity of tropical grassy biomes

For decades, there has been enormous scientific interest in tropical savannahs and grasslands, fuelled by the recognition that they are a dynamic and potentially unstable biome, requiring periodic disturbance for their maintenance. However, that scientific interest has not translated into widespread appreciation of, and concern about threats to, their biodiversity. In terms of biodiversity, grassy biomes are considered poor cousins of the other dominant biome of the tropics—forests. Simple notions of grassy biomes being species-poor cannot be supported; for some key taxa, such as vascular plants, this may be valid, but for others it is not. Here, we use an analysis of existing data to demonstrate that high-rainfall tropical grassy biomes (TGBs) have vertebrate species richness comparable with that of forests, despite having lower plant diversity. The Neotropics stand out in terms of both overall vertebrate species richness and number of range-restricted vertebrate species in TGBs. Given high rates of land-cover conversion in Neotropical grassy biomes, they should be a high priority for conservation and greater inclusion in protected areas. Fire needs to be actively maintained in these systems, and in many cases re-introduced after decades of inappropriate fire exclusion. The relative intactness of TGBs in Africa and Australia make them the least vulnerable to biodiversity loss in the immediate future. We argue that, like forests, TGBs should be recognized as a critical—but increasingly threatened—store of global biodiversity

Apports des méthodes statistiques et hydrochimiques à la caractérisation des eaux des aquifères fissurés de la région du N’zi-Comoé (Centre-Est de la Côte d’Ivoire)

La région du N’zi-Comoé est située au Centre-Est de la Côte d’Ivoire et appartient du point de vue géologique au socle cristallin. La végétation est constituée de lambeaux de forêt mésophile, de savanesséparées par des forêts-galeries et de jachères, résultat de la déforestation. L’appauvrissement des sols, issu de cette déforestation a eu pour conséquence l’utilisation d’engrais. La déforestation et l’usage des engrais suscitent des interrogations sur la qualité des eaux souterraines du N’zi-Comoé et leur aptitude à la consommation humaine. C’est pour répondre à cette problématique que ce présent travail a été initié. Ainsi,l’objectif de cette étude est la caractérisation hydrogéochimique des eaux et l’analyse de leur aptitude à la consommation humaine. Ce travail a été mené à partir des résultats d’analyses de paramètres physicochimiquesdes eaux et s’est appuyé sur un échantillon de 193 forages. La méthodologie appliquée est basée sur une approche pluridisciplinaire intégrant l’hydrochimie (diagramme triangulaire de piper, indicateur de temps de séjour) et des analyses statistiques univariées, bivariées et multivariées (ACPN). Du point de vue hydrofaciès, la majorité des eaux des aquifères fissurés du N’zi-Comoé est du faciès bicarbonaté calcique etmagnésien. La région du N’zi-Comoé est dominée par deux phénomènes hydrochimiques majeurs : la minéralisation couplée au temps de séjour et l’oxydo-réduction qui sont à l’origine de l’acquisition de la minéralisation des eaux souterraines du N’zi-Comoé. L’étude de la potabilité révèle que les eaux souterraines sont physico-chimiquement conformes dans l’ensemble aux normes recommandées par l’OMS et ne présententpas de danger majeur pour la consommation humaine

Using global datasets to estimate flood exposure at the city scale: an evaluation in Addis Ababa

Copyright \ua9 2024 Carr, Trigg, Haile, Bernhofen, Alemu, Bekele and Walsh.Introduction: Cities located in lower income countries are global flood risk hotspots. Assessment and management of these risks forms a key part of global climate adaptation efforts. City scale flood risk assessments necessitate flood hazard information, which is challenging to obtain in these localities because of data quality/scarcity issues, and the complex multi-source nature of urban flood dynamics. A growing array of global datasets provide an attractive means of closing these data gaps, but their suitability for this context remains relatively unknown. Methods: Here, we test the use of relevant global terrain, rainfall, and flood hazard data products in a flood hazard and exposure assessment framework covering Addis Ababa, Ethiopia. To conduct the tests, we first developed a city scale rain-on-grid hydrodynamic flood model based on local data and used the model results to identify buildings exposed to flooding. We then observed how the results of this flood exposure assessment changed when each of the global datasets are used in turn to drive the hydrodynamic model in place of its local counterpart. Results and discussion: Results are evaluated in terms of both the total number of exposed buildings, and the spatial distribution of exposure across Addis Ababa. Our results show that of the datasets tested, the FABDEM global terrain and the PXR global rainfall data products provide the most promise for use at the city scale in lower income countries

Tube-Gel: A Fast and Effective Sample Preparation Method for High-Throughput Quantitative Proteomics

International audienceSample preparation is a key step in proteomics workflows. Tube-gel (TG) is a fast and repeatable sample preparation method that consists in the instantaneous trapping of the sample in a polyacrylamide gel matrix. It takes advantage of in-gel sample preparations by allowing the use of high concentrations of sodium-dodecyl sulfate but avoids the time-consuming step of electrophoresis. Therefore, TG limits the sample handling and is thus particularly suitable for high-throughput quantitative proteomics when large sample numbers have to be processed, as it is often the case in biomarker research and clinical proteomics projects

Evolution of context dependent regulation by expansion of feast/famine regulatory proteins

BACKGROUND: Expansion of transcription factors is believed to have played a crucial role in evolution of all organisms by enabling them to deal with dynamic environments and colonize new environments. We investigated how the expansion of the Feast/Famine Regulatory Protein (FFRP) or Lrp-like proteins into an eight-member family in Halobacterium salinarum NRC-1 has aided in niche-adaptation of this archaeon to a complex and dynamically changing hypersaline environment.RESULTS: We mapped genome-wide binding locations for all eight FFRPs, investigated their preference for binding different effector molecules, and identified the contexts in which they act by analyzing transcriptional responses across 35 growth conditions that mimic different environmental and nutritional conditions this organism is likely to encounter in the wild. Integrative analysis of these data constructed an FFRP regulatory network with conditionally active states that reveal how interrelated variations in DNA-binding domains, effector-molecule preferences, and binding sites in target gene promoters have tuned the functions of each FFRP to the environments in which they act. We demonstrate how conditional regulation of similar genes by two FFRPs, AsnC (an activator) and VNG1237C (a repressor), have striking environment-specific fitness consequences for oxidative stress management and growth, respectively.CONCLUSIONS: This study provides a systems perspective into the evolutionary process by which gene duplication within a transcription factor family contributes to environment-specific adaptation of an organism

Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.

BACKGROUND\ud \ud Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud \ud METHODS\ud \ud Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud \ud RESULTS\ud \ud The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud \ud CONCLUSIONS\ud \ud The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended

The Architectural Design Rules of Solar Systems based on the New Perspective

On the basis of the Lunar Laser Ranging Data released by NASA on the Silver Jubilee Celebration of Man Landing on Moon on 21st July 1969-1994, theoretical formulation of Earth-Moon tidal interaction was carried out and Planetary Satellite Dynamics was established. It was found that this mathematical analysis could as well be applied to Star and Planets system and since every star could potentially contain an extra-solar system, hence we have a large ensemble of exoplanets to test our new perspective on the birth and evolution of solar systems. Till date 403 exoplanets have been discovered in 390 extra-solar systems. I have taken 12 single planet systems, 4 Brown Dwarf - Star systems and 2 Brown Dwarf pairs. Following architectural design rules are corroborated through this study of exoplanets. All planets are born at inner Clarke Orbit what we refer to as inner geo-synchronous orbit in case of Earth-Moon System. By any perturbative force such as cosmic particles or radiation pressure, the planet gets tipped long of aG1 or short of aG1. Here aG1 is inner Clarke Orbit. The exoplanet can either be launched on death spiral as CLOSE HOT JUPITERS or can be launched on an expanding spiral path as the planets in our Solar System are. It was also found that if the exo-planet are significant fraction of the host star then those exo-planets rapidly migrate from aG1 to aG2 and have very short Time Constant of Evolution as Brown Dwarfs have. This vindicates our basic premise that planets are always born at inner Clarke Orbit. This study vindicates the design rules which had been postulated at 35th COSPAR Scientific Assembly in 2004 at Paris, France, under the title ,New Perspective on the Birth & Evolution of Solar Systems.Comment: This paper has been reported to Earth,Moon and Planets Journal as MOON-S-09-0007

Outcome reporting bias in trials: a methodological approach for assessment and adjustment in systematic reviews

Systematic reviews of clinical trials aim to include all relevant studies conducted on a particular topic and to provide an unbiased summary of their results, producing the best evidence about the benefits and harms of medical treatments. Relevant studies, however, may not provide the results for all measured outcomes or may selectively report only some of the analyses undertaken, leading to unnecessary waste in the production and reporting of research, and potentially biasing the conclusions to systematic reviews. In this article, Kirkham and colleagues provide a methodological approach, with an example of how to identify missing outcome data and how to assess and adjust for outcome reporting bias in systematic reviews