After 50 Years of Hepatic Clearance Models, Where Should We Go from Here? Improvements and Implications for Physiologically Based Pharmacokinetic Modeling.

There is overwhelming preference for application of the unphysiologic, well-stirred model (WSM) over the parallel tube model (PTM) and dispersion model (DM) to predict hepatic drug clearance, , despite that liver blood flow is dispersive and closer to the DM in nature. The reasoning is the ease in computation relating the hepatic intrinsic clearance ( ), hepatic blood flow ( ), unbound fraction in blood ( ) and the transmembrane clearances ( and ) to for the WSM. However, the WSM, being the least efficient liver model, predicts a lower that is associated with the in vitro ( / ), therefore requiring scale-up to predict in vivo.

SARS-CoV-2 Surveillance of Wild Mice and Rats in North American Cities.

From July 2020 to June 2021, 248 wild house mice (Mus musculus), deer mice (Peromyscus maniculatus), brown rats (Rattus norvegicus), and black rats (Rattus rattus) from Texas and Washington, USA, and British Columbia, Canada, were tested for SARS-CoV-2 exposure and infection. Two brown rats and 11 house mice were positive for neutralizing antibodies using a surrogate virus neutralization test, but negative or indeterminate with the Multiplexed Fluorometric ImmunoAssay COVID-Plex, which targets full-length spike and nuclear proteins. Oro-nasopharyngeal swabs and fecal samples tested negative by RT-qPCR, with an indeterminate fecal sample in one house mouse.

Pathogen Prevalence Estimates and Diagnostic Methodology Trends in Laboratory Mice and Rats from 2003 to 2020.

Rodents used in biomedical research are maintained as specific pathogen-free (SPF) by employing biosecurity measures that eliminate and exclude adventitious infectious agents known to confound research. The efficacy of these practices is assessed by routine laboratory testing referred to as health monitoring (HM). This study summarizes the results of HM performed at Charles River Research Animal Diagnostic Services (CR-RADS) on samples submitted by external (non-Charles River) clients between 2003 and 2020.

Improving rowing performance by adjusting oar blade size and angle.

The principal aim of the work presented here is to investigate and demonstrate that a forward tilted rowing blade would result in a more efficient and effective motion of the blade through the water that would result in a higher boat speed when an equal input power is provided. A 1:5 scaled rowing boat is used to determine the performance of rowing blades with different sizes and blade angles. This is used to validate the results of a previous study where the optimal blade angle of 15 with respect to the oar shaft was determined ( 1).

Strontium isotopes and concentrations in cremated bones suggest an increased salt consumption in Gallo-Roman diet.

The high temperatures reached during cremation lead to the destruction of organic matter preventing the use of traditional isotopic methods for dietary reconstructions. Still, strontium isotope (Sr/Sr) and concentration ([Sr]) analyses of cremated human remains offer a novel way to assess changing consumption patterns in past populations that practiced cremation, as evidenced by a large amount of new data obtained from Metal Ages and Gallo-Roman human remains from Destelbergen, Belgium. The Gallo-Roman results show significantly higher [Sr] and a narrower interquartile range in Sr/Sr (0.

These boots are made for burnin': Inferring the position of the corpse and the presence of leather footwears during cremation through isotope (δ13C, δ18O) and infrared (FTIR) analyses of experimentally burnt skeletal remains.

Cremation is a complex mortuary practice, involving a number of activities of the living towards the dead before, during, and after the destruction of the bodily soft tissues by fire. The limiting information concerning these behavioral patterns obtained from the pyre remains and/or cremation deposits prevents the reconstruction of the handling of the corpse during the burning process. This pioneering study tries to determine the initial positioning of the corpse in the pyre and assess whether the deceased was wearing closed leather shoes during cremation through isotopic (δ13C, δ18O) and infrared (ATR-FTIR) analyses of experimentally burnt pig remains, used as a proxy for humans.

Revisiting metric sex estimation of burnt human remains via supervised learning using a reference collection of modern identified cremated individuals (Knoxville, USA).

Objectives: This study aims to increase the rate of correctly sexed calcined individuals from archaeological and forensic contexts. This is achieved by evaluating sexual dimorphism of commonly used and new skeletal elements via uni- and multi-variate metric trait analyses.

Materials And Methods: Twenty-two skeletal traits were evaluated in 86 individuals from the William M.

Repeated outbreaks drive the evolution of bacteriophage communication.

Recently, a small-molecule communication mechanism was discovered in a range of -infecting bacteriophages, which these temperate phages use to inform their lysis-lysogeny decision. We present a mathematical model of the ecological and evolutionary dynamics of such viral communication and show that a communication strategy in which phages use the lytic cycle early in an outbreak (when susceptible host cells are abundant) but switch to the lysogenic cycle later (when susceptible cells become scarce) is favoured over a bet-hedging strategy in which cells are lysogenised with constant probability. However, such phage communication can evolve only if phage-bacteria populations are regularly perturbed away from their equilibrium state, so that acute outbreaks of phage infections in pools of susceptible cells continue to occur.

Estimating age-at-death in burnt adult human remains using the Falys-Prangle method.

Objectives: The Falys-Prangle-method assesses age-related morphological changes to the sternal clavicle end (SCE), enabling the observation of mature adults from the 5th decade onwards in unburnt human skeletal remains. The aim of this study is to investigate the applicability of the Falys-Prangle-method on burnt human remains.

Materials And Methods: Fifty-two SCE of 40 cremated individuals (out of 86) from the William M.

Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study.

Background: Patients with idiopathic pulmonary fibrosis (IPF) treated with PRM-151, a recombinant human pentraxin 2 protein, in a phase 2 double-blind, randomised controlled trial had significantly reduced decline in percentage of predicted forced vital capacity (FVC) and stabilised 6-min walking distance compared with placebo over a 28-week period. Here we report the 76-week results of an open-label extension study.

Methods: Patients who completed the 28-week double-blind period of the PRM-151-202 trial were eligible to participate in the open-label extension study.

An island of wildlife in a human-dominated landscape: The last fragment of primary forest on the Osa Peninsula's Golfo Dulce coastline, Costa Rica.

Habitat loss and fragmentation, together with related edge effects, are the primary cause of global biodiversity decline. Despite a large amount of research quantifying and demonstrating the degree of these effects, particularly in top predators and their prey, most fragmented patches are lost before their conservation value is recognized. This study evaluates terrestrial vertebrates in Playa Sandalo, in the Osa Peninsula of Costa Rica, which represents the last patch of "primary" forest in the most developed part of this region.

Scientific Opinion of Flavouring Group Evaluation 411 (FGE.411): 2-(4-methylphenoxy)--(1-pyrazol-3-yl)--(thiophen-2-ylmethyl)acetamide from chemical group 30 (miscellaneous substances).

EFSA was requested to deliver a scientific opinion on the implications for human health of the flavouring substance 2-(4-methylphenoxy)--(1-pyrazol-3-yl)--(thiophen-2-ylmethyl)acetamide [FL-no: 16.133], in the Flavouring Group Evaluation 411 (FGE.411), according to Regulation (EC) No 1331/2008 of the European Parliament and of the Council.

Using Hysterectomy Rederivation to Produce Guinea Pigs () Free of Guinea Pig Cytomegalovirus.

Due to similarities in placentation, guinea pigs can be used as models of human cytomegalovirus infection, but they must be free of guinea pig cytomegalovirus. Many commercial guinea pig colonies are enzootically infected with guinea pig cytomegalovirus, which can be transmitted vertically as well as horizontally through saliva, vaginal secretions, and milk. These characteristics make its eradication in a commercial setting challenging.

Effect of Recombinant Human Pentraxin 2 vs Placebo on Change in Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis: A Randomized Clinical Trial.

Importance: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Approved therapies do not halt disease progression.

Objective: To determine the effect of recombinant human pentraxin 2 vs placebo on change from baseline to week 28 in mean forced vital capacity (FVC) percentage of predicted value.

Scientific opinion on flavouring group evaluation 77, revision 3 (FGE.77Rev3): consideration of pyridine, pyrrole and quinoline derivatives evaluated by JECFA (63rd meeting) structurally related to pyridine, pyrrole, indole and quinoline derivatives evaluated by EFSA in FGE.24Rev2.

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the EFSA was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of 22 pyridine, pyrrole and quinoline derivatives evaluated by JECFA (63rd meeting). The revision of this consideration is made since additional genotoxicity data have become available for 6-methylquinoline [FL-no: 14.

Scientific Opinion on Flavouring Group Evaluation 74, Revision 4 (FGE.74Rev4): Consideration of aliphatic sulphides and thiols evaluated by JECFA (53rd and 61st meeting) structurally related to aliphatic and alicyclic mono-, di-, tri- and polysulphides with or without additional oxygenated functional groups from chemical group 20 evaluated by EFSA in FGE.08Rev5.

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present revision of this FGE is on the assessment of recently submitted toxicity data on methyl propyl trisulfide [FL-no: 12.020], being the representative for a group of seven additional flavouring substances: diallyl trisulfide [FL-no: 12.

Scientific Opinion of Flavouring Group Evaluation 406 (FGE.406): ()-1-(3-(((4-amino-2,2-dioxido-1-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)-3-methylbutan-1-one.

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) of EFSA was requested to deliver a scientific opinion on the safety of the use of the substance ()-1-(3-(((4-amino-2,2-dioxido-1-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)-3-methylbutan-1-one [FL-no: 16.129], as a flavouring substance. The substance is intended to be used in the form of its sodium salt as a flavour modifier in beverages.

Infection-free Clinical Response Among Patients With Hidradenitis Suppurativa Who Were Treated With Adalimumab: Results from Two Phase 3 Studies.

Objective: The objective of this study is to assess the rates of infection-free achievement of hidradenitis suppurativa clinical response (HiSCR) using integrated data from 2 phase 3, placebo-controlled trials, PIONEER I and II.

Materials And Methods: Analyses from the first 12 weeks of both studies were examined. Patients were randomized to receive adalimumab (ADA) or placebo, and they then were assessed in the clinic at weeks 0, 2, 4, 8, and 12.

Scientific Opinion of Flavouring Group Evaluation 410 (FGE.410): 4',5,7-trihydroxyflavanone from chemical group 25 (phenol derivatives containing ring-alkyl, ring-alkoxy, and side-chains with an oxygenated functional group).

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) of EFSA was requested to deliver a scientific opinion on the implications for human health of the flavouring substance 4',5,7-trihydroxyflavanone or naringenin [FL-no: 16.132], in the Flavouring Group Evaluation 410 (FGE.410), according to Regulation (EC) No 1331/2008 of the European Parliament and of the Council.

Safety of benzophenone to be used as flavouring.

Benzophenone [FL-no: 07.032] has been evaluated as a flavouring substance, in FGE.69, by the EFSA Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food in 2008.