Modelling impacts of seasonal wastewater treatment plant effluent permits and biosolid substitution for phosphorus management in catchments and river systems

The issues of diffuse and point source phosphorus (P) pollution in river systems are presented using a catchment model to assess nutrient behaviour, seasonal effluent standards and biosolid substitution. A process-based, dynamic water quality model (INCA-P) has been applied to four UK catchments, namely, the Rivers Tywi, Wensum, Lunan and Hampshire Avon, to simulate water fluxes, sediments, total phosphorus and soluble reactive phosphorus (SRP) concentrations. The model has been used to assess impacts of both agricultural runoff and point P sources from wastewater treatment plants (WWTPs) on water quality. With increasing costs for P fertilizer and P reduction at WWTPs, a strategy of recycling P from WWTPs as biosolids to substitute for fertilizers in vulnerable catchments has been investigated. Significant reductions in P concentrations are achieved if this substitution were implemented on a large scale. Reductions in SRP of between 6% and 41% can be achieved using this strategy. The effects of implementing new WWTP standards are shown to reduce SRP by 30%. Seasonal consent standards applied in only summer months could reduce SRP by 53% and achieve a substantial reduction in treatment costs year round

Monoclonal antibody levels and protection from COVID-19

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies (mAb) in preventing symptomatic SARS-CoV-2 infection. We use data on the in vivo concentration of mAb and the associated protection from COVID-19 over time to model the dose-response relationship of mAb for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a mAb concentration of 96-fold of the in vitro IC50 (95% CI: 32—285). This relationship provides a tool for predicting the prophylactic efficacy of new mAb and against SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either mAb treatment or vaccination. We find no significant difference between the 50% protective titer for mAb and vaccination, although sample sizes limited the power to detect a difference

Robotic assisted Laparoscopic partial Nephrectomy for suspected Renal Cell Carcinoma: Retrospective review of surgical outcomes of 35 Cases

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Representing 3D Space in Working Memory: Spatial Images from Vision, Hearing, Touch, and Language

The chapter deals with a form of transient spatial representation referred to as a spatial image. Like a percept, it is externalized, scaled to the environment, and can appear in any direction about the observer. It transcends the concept of modality, as it can be based on inputs from the three spatial senses, from language, and from long-term memory. Evidence is presented that supports each of the claimed properties of the spatial image, showing that it is quite different from a visual image. Much of the evidence presented is based on spatial updating. A major concern is whether spatial images from different input modalities are functionally equivalent— that once instantiated in working memory, the spatial images from different modalities have the same functional characteristics with respect to subsequent processing, such as that involved in spatial updating. Going further, the research provides some evidence that spatial images are amodal (i.e., do not retain modality-specific features)

SUMO-Targeted Ubiquitin Ligase, Rad60, and Nse2 SUMO Ligase Suppress Spontaneous Top1–Mediated DNA Damage and Genome Instability

Through as yet undefined proteins and pathways, the SUMO-targeted ubiquitin ligase (STUbL) suppresses genomic instability by ubiquitinating SUMO conjugated proteins and driving their proteasomal destruction. Here, we identify a critical function for fission yeast STUbL in suppressing spontaneous and chemically induced topoisomerase I (Top1)–mediated DNA damage. Strikingly, cells with reduced STUbL activity are dependent on tyrosyl–DNA phosphodiesterase 1 (Tdp1). This is notable, as cells lacking Tdp1 are largely aphenotypic in the vegetative cell cycle due to the existence of alternative pathways for the removal of covalent Top1–DNA adducts (Top1cc). We further identify Rad60, a SUMO mimetic and STUbL-interacting protein, and the SUMO E3 ligase Nse2 as critical Top1cc repair factors in cells lacking Tdp1. Detection of Top1ccs using chromatin immunoprecipitation and quantitative PCR shows that they are elevated in cells lacking Tdp1 and STUbL, Rad60, or Nse2 SUMO ligase activity. These unrepaired Top1ccs are shown to cause DNA damage, hyper-recombination, and checkpoint-mediated cell cycle arrest. We further determine that Tdp1 and the nucleotide excision repair endonuclease Rad16-Swi10 initiate the major Top1cc repair pathways of fission yeast. Tdp1-based repair is the predominant activity outside S phase, likely acting on transcription-coupled Top1cc. Epistasis analyses suggest that STUbL, Rad60, and Nse2 facilitate the Rad16-Swi10 pathway, parallel to Tdp1. Collectively, these results reveal a unified role for STUbL, Rad60, and Nse2 in protecting genome stability against spontaneous Top1-mediated DNA damage

Adaptive Sampling of Information in Perceptual Decision-Making

In many perceptual and cognitive decision-making problems, humans sample multiple noisy information sources serially, and integrate the sampled information to make an overall decision. We derive the optimal decision procedure for two-alternative choice tasks in which the different options are sampled one at a time, sources vary in the quality of the information they provide, and the available time is fixed. To maximize accuracy, the optimal observer allocates time to sampling different information sources in proportion to their noise levels. We tested human observers in a corresponding perceptual decision-making task. Observers compared the direction of two random dot motion patterns that were triggered only when fixated. Observers allocated more time to the noisier pattern, in a manner that correlated with their sensory uncertainty about the direction of the patterns. There were several differences between the optimal observer predictions and human behaviour. These differences point to a number of other factors, beyond the quality of the currently available sources of information, that influences the sampling strategy

Accurate path integration in continuous attractor network models of grid cells

Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal's position in 2-D space and have been hypothesized to form the neural substrate for dead-reckoning. However, errors accumulate rapidly when velocity inputs are integrated in existing models of grid cell activity. To produce grid-cell-like responses, these models would require frequent resets triggered by external sensory cues. Such inadequacies, shared by various models, cast doubt on the dead-reckoning potential of the grid cell system. Here we focus on the question of accurate path integration, specifically in continuous attractor models of grid cell activity. We show, in contrast to previous models, that continuous attractor models can generate regular triangular grid responses, based on inputs that encode only the rat's velocity and heading direction. We consider the role of the network boundary in the integration performance of the network and show that both periodic and aperiodic networks are capable of accurate path integration, despite important differences in their attractor manifolds. We quantify the rate at which errors in the velocity integration accumulate as a function of network size and intrinsic noise within the network. With a plausible range of parameters and the inclusion of spike variability, our model networks can accurately integrate velocity inputs over a maximum of ~10–100 meters and ~1–10 minutes. These findings form a proof-of-concept that continuous attractor dynamics may underlie velocity integration in the dorsolateral medial entorhinal cortex. The simulations also generate pertinent upper bounds on the accuracy of integration that may be achieved by continuous attractor dynamics in the grid cell network. We suggest experiments to test the continuous attractor model and differentiate it from models in which single cells establish their responses independently of each other