Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions.

ObjectiveTo determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.MethodsBreast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion.ResultsThe median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.ConclusionsWe determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding

Trusted Source Alignment in Large Language Models

Large language models (LLMs) are trained on web-scale corpora that inevitably include contradictory factual information from sources of varying reliability. In this paper, we propose measuring an LLM property called trusted source alignment (TSA): the model's propensity to align with content produced by trusted publishers in the face of uncertainty or controversy. We present FactCheckQA, a TSA evaluation dataset based on a corpus of fact checking articles. We describe a simple protocol for evaluating TSA and offer a detailed analysis of design considerations including response extraction, claim contextualization, and bias in prompt formulation. Applying the protocol to PaLM-2, we find that as we scale up the model size, the model performance on FactCheckQA improves from near-random to up to 80% balanced accuracy in aligning with trusted sources

The impact of streetlights on an aquatic invasive species: artificial light at night alters signal crayfish behaviour

Artificial light at night (ALAN) can significantly alter the behaviour, communication and orientation of animals, and will potentially interact with other stressors to affect biodiversity. Invasive, non-native species are one of the largest threats to freshwater biodiversity; however, the impact of ALAN on such species is unknown. This study assessed the effects of ALAN at ecologically relevant levels on the behaviour of a globally widespread invasive species, the signal crayfish (Pacifastacus leniusculus). In experimental aquaria, crayfish were exposed to periods of daylight, control (<0.1 lx) and street-lit nights to test two hypotheses: (1) signal crayfish under natural conditions are nocturnal animals, spending more time in shelter during the day, whilst active and interacting during the night, and (2) ALAN reduces crayfish activity and intraspecific interactions, whilst increasing their propensity to use shelter. Our results confirm that signal crayfish are largely nocturnal, showing peak activity and interaction levels during control nights, whilst taking refuge during daylight hours. When exposed to short-term simulated light pollution from a streetlight at night however, activity and interactions with conspecifics were significantly reduced compared to control nights, whilst time spent in shelters increased. By altering crayfish behaviour, ALAN may change the ecosystem impacts of invasive crayfish in the wild. This study is the first to show an impact of ALAN on the behaviour of an invasive, non-native species, and provides information for the management of invasive crayfish in areas where ALAN is prevalent

Does relatedness influence migratory timing and behaviour in Atlantic salmon smolts?

Aggregating and moving with relatives may enable animals to increase opportunities for kin selection to occur. To gain group-living benefits, animals must coordinate their behaviour. Atlantic salmon, Salmo salar, demonstrate both territoriality and schooling: the two key social behaviours performed by fish. In this investigation we compared the migratory timing and behaviour of six distinct full-sibling groups of tagged S. salar smolts with a large control sample from the same wild population. The results clearly demonstrate that the incidence of schooling and diel migratory timing is not significantly influenced by relatedness, and this adds further support to the hypothesis that S. salar smolt migration is primarily an adaptive response to environmental conditions, rather than a behaviour based solely on genetics or kin-biased behaviour. Used in conjunction with the results of two previous investigations, this is the first study to illustrate that kin discrimination among full-sibling groups of parr does not lead to kin-biased schooling in smolts. Thus, even within the same full-sibling groups, the extent of kin-biased behaviour in fish can both differ within a life history stage under varying ecological conditions and shift from one life history stage to the next

Sensory Impact of Extended Maceration and Regulated Deficit Irrigation on Washington State Cabernet Sauvignon Wines

Irrigation practices such as regulated deficit irrigation (RDI) and winemaking practices such as extended maceration have been experimentally evaluated from a chemical perspective but their impacts on sensory composition and interactive effects merit scientific attention. This study evaluated the sensory impact of extended maceration applied to Cabernet Sauvignon grapes sourced from a vineyard subjected to four RDI treatments: replenishment of 100%, 70%, and 25% of full-vine crop evapotranspiration (ETc) from fruit set until veraison followed by 100% ETc until harvest (labeled 100% ETc, 70% ETc, and 25% ETc, respectively) and 25% ETc from fruit set to veraison followed by 100% ETc from veraison to harvest (labeled 25/100% ETc). Each RDI treatment was replicated four times (n = 4) and made into wine, with two replicates designated as controls (10 day skin contact) and two as extended maceration (30 day skin contact). Wines were evaluated by descriptive analysis with a trained panel (n = 15) and chemical and sensory data were correlated using canonical correlation analysis. Wine-perceived saturation and purple component ratings were highest in 25% ETc wines and were highly correlated with the concentration of flavonols, malvidin- and delphinidin-derivatives, and small polymeric pigments. Fruit-based aroma descriptors were highest in the 25/100% ETc and 70% ETc wines. Extended maceration increased perceived astringency and bitterness, which were in turn correlated with the concentration of flavan-3-ol and oligomeric proanthocyanidins. These results suggest that moderate RDI protocols such as 70% ETc and 25/100% ETc impact positively the fruity aroma component (black and red fruit), whereas extended maceration lowered fruity aromas, possibly due to the masking effect of the oxidized character perceived in these wines.EEA MendozaFil: Casassa, Luis Federico. Washington State University. Irrigated Agriculture Research and Extension Center. School of Food Science; Estados Unidos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza. Centro de Estudios de Enología; Argentina.Fil: Larsen, Richard C. Washington State University. Viticulture and Enology Program; Estados UnidosFil: Beaver, Christopher W. Washington State University. Irrigated Agriculture Research and Extension Center. School of Food Science; Estados UnidosFil: Mireles, María S. Washington State University. Irrigated Agriculture Research and Extension Center. School of Food Science; Estados UnidosFil: Keller, Markus. Washington State University. Department of Horticulture; Estados UnidosFil: Riley, William R. Ste. Michelle Wine Estates; Estados UnidosFil: Smithyman, Russell. Ste. Michelle Wine Estates; Estados UnidosFil: Harbertson, James F. Washington State University. Irrigated Agriculture Research and Extension Center. School of Food Science; Estados Unido

Does social environment influence learning ability in a family-living lizard?

Financial support for this research was provided by the Australian Research Council (DP130102998, awarded to MJW and RWB), Natural Sciences and Engineering Research Council of Canada (scholarship to JLR), the Australasian Society for the Study of Animal Behaviour, the Australian Museum, and Macquarie University. DWAN was supported by an ARC Discovery Early Career Research Award (DE150101774) and UNSW Vice Chancellors Fellowship.Early developmental environment can have profound effects on individual physiology, behaviour, and learning. In birds and mammals social isolation during development is known to negatively affect learning ability; yet in other taxa, like reptiles, the effect of social isolation during development on learning ability is unknown. We investigated how social environment affects learning ability in the family-living tree skink (Egernia striolata). We hypothesized that early social environment shapes cognitive development in skinks, and predicted that skinks raised in social isolation would have reduced learning ability compared to skinks raised socially. Offspring were separated at birth into two treatments: (1) raised alone, or (2) in a pair. After one year we quantified spatial learning ability of skinks in these treatments (N = 14 solitary, 14 social). We found no effect of treatment on learning ability. The number of skinks to successfully learn the task, the number of trials taken to learn the task, the latency to perform the task, and the number of errors in each trial did not differ between isolated and socially-reared skinks. Our results were unexpected, yet the facultative nature of this species’ social system may result in a reduced effect of social isolation on behaviour when compared to species with obligate sociality. Overall, our findings do not provide evidence that social environment affects development of spatial learning ability in this family-living lizard.PostprintPostprintPeer reviewe

Criteria for the diagnosis of corticobasal degeneration

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed

A Mechanistic Treatment of the Dominant Soil Nitrogen Cycling Processes: Model Development, Testing, and Application

The development and initial application of a mechanistic model (TOUGHREACT-N) designed to characterize soil nitrogen (N) cycling and losses are described. The model couples advective and diffusive nutrient transport, multiple microbial biomass dynamics, and equilibrium and kinetic chemical reactions. TOUGHREACT-N was calibrated and tested against field measurements to assess pathways of N loss as either gas emission or solute leachate following fertilization and irrigation in a Central Valley, California, agricultural field as functions of fertilizer application rate and depth, and irrigation water volume. Our results, relative to the period before plants emerge, show that an increase in fertilizer rate produced a nonlinear response in terms of N losses. An increase of irrigation volume produced NO{sub 2}{sup -} and NO{sub 3}{sup -} leaching, whereas an increase in fertilization depth mainly increased leaching of all N solutes. In addition, nitrifying bacteria largely increased in mass with increasing fertilizer rate. Increases in water application caused nitrifiers and denitrifiers to decrease and increase their mass, respectively, while nitrifiers and denitrifiers reversed their spatial stratification when fertilizer was applied below 15 cm depth. Coupling aqueous advection and diffusion, and gaseous diffusion with biological processes, closely captured actual conditions and, in the system explored here, significantly clarified interpretation of field measurements