Neurological complications of immune checkpoint inhibitors: a practical guide.

Immune checkpoint inhibition unleashes the power of the immune system against tumour cells. Immune checkpoint inhibitors (ICIs) block the inhibitory effects of cytotoxic T-lymphocyte associated protein 4, programmed death protein 1, programmed death ligand 1 and lymphocyte activation gene 3 molecules on T-cells, and so enhance physiological cytotoxic effects. ICIs can significantly improve survival from cancers, including those previously associated with poor treatment response, such as metastatic melanoma.

Late Archaic large-scale fisheries in the wetlands of the pre-Columbian Maya Lowlands.

Multiproxy data collected from the largest inland wetland in Belize, Central America, demonstrate the presence of large-scale pre-Columbian fish-trapping facilities built by Late Archaic hunter-gatherer-fishers, which continued to be used by their Maya descendants during Formative times (approximately 2000 BCE to 200 CE). This is the earliest large-scale Archaic fish-trapping facility recorded in ancient Mesoamerica. We suggest that such landscape-scale intensification may have been a response to long-term climate disturbance recorded between 2200 and 1900 BCE.

Cerebral cortical encephalitis in adults with myelin oligodendrocyte glycoprotein antibody-associated disease: A national case series.

Background And Purpose: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a relatively recently described disease, most commonly presenting with optic neuritis and longitudinally extensive transverse myelitis. Cerebral cortical encephalitis is a rare manifestation of MOGAD.

Methods: We identified patients presenting with cerebral cortical encephalitis with positive MOG antibodies in serum across a large specialized service.

Microscale Thermophoresis (MST) as a Tool to Study Binding Interactions of Oxygen-Sensitive Biohybrids.

Microscale thermophoresis (MST) is a technique used to measure the strength of molecular interactions. MST is a -based technique that monitors the change in fluorescence associated with the movement of fluorescent-labeled molecules in response to a temperature gradient triggered by an IR LASER. MST has advantages over other approaches for examining molecular interactions, such as isothermal titration calorimetry, nuclear magnetic resonance, biolayer interferometry, and surface plasmon resonance, requiring a small sample size that does not need to be immobilized and a high-sensitivity fluorescence detection.

Oligoclonal bands.

Oligoclonal bands (OCBs) represent the presence of intrathecal immunoglobulin G (IgG) as detected by isoelectric focusing and immunofixation. Cerebrospinal fluid (CSF) analysed alongside a paired serum sample gives five different immunofixation patterns. These are: type 1-the normal physiological state with no intrathecal IgG synthesis; type 2-evidence for intrathecal IgG synthesis, with CSF-restricted OCBs; type 3-evidence for intrathecal IgG synthesis, with CSF-restricted OCBs, but with additional, identical bands in the CSF and serum; type 4-absence of intrathecal IgG synthesis, but with identical OCBs in CSF and serum; and type 5-absence of intrathecal IgG synthesis, with a monoclonal band in CSF and serum.

Lack of reinforcement is hard to "bear": Assessing judgment bias in grizzly bears ().

Cognitive biases reveal underlying affective state by indicating optimism and pessimism. This methodology may permit assessment of positive welfare in animals that have few validated positive welfare indicators, such as bears. Our goal was to validate a judgment bias test for assessing optimism in brown bears, using a touchscreen.

Numerical Investigation of Odor-Guided Navigation in Flying Insects: Impact of Turbulence, Wingbeat-Induced Flow, and Schmidt Number on Odor Plume Structures.

Odor-guided navigation is fundamental to the survival and reproductive success of many flying insects. Despite its biological importance, the mechanics of how insects sense and interpret odor plumes in the presence of complex flow fields remain poorly understood. This study employs numerical simulations to investigate the influence of turbulence, wingbeat-induced flow, and Schmidt number on the structure and perception of odor plumes by flying insects.

Relevance of Multiple Sclerosis Severity Genotype in Predicting Disease Course: A Real-World Cohort.

Objective: Currently, 233 genetic loci are known to be associated with susceptibility to multiple sclerosis (MS). Two independent pivotal severity genome-wide association studies recently found the first genome-wide significant single-nucleotide variant (SNV; rs10191329 ) and several other suggestive loci associated with overall disability outcomes. It is now important to understand if these findings can influence individual patient management.

Cryo-annealing of Photoreduced CdS Quantum Dot-Nitrogenase MoFe Protein Complexes Reveals the Kinetic Stability of the E(2N2H) Intermediate.

A critical step in the mechanism of N reduction to 2NH catalyzed by the enzyme nitrogenase is the reaction of the four-electron/four-proton reduced intermediate state of the active-site FeMo-cofactor (E(4H)). This state is a junction in the catalytic mechanism, either relaxing by the reaction of a metal bound Fe-hydride with a proton forming H or going forward with N binding coupled to the reductive elimination () of two Fe-hydrides as H to form the E(2N2H) state. E(2N2H) can relax to E(4H) by the oxidative addition () of H and release of N or can be further reduced in a series of catalytic steps to release 2NH.

Differential gene expression of Asian citrus psyllids infected with ' Liberibacter asiaticus' reveals hyper-susceptibility to invasion by instar fourth-fifth and teneral adult stages.

The bacterial pathogen Liberibacter asiaticus (CLas) is the causal agent of citrus greening disease. This unusual plant pathogenic bacterium also infects its psyllid host, the Asian citrus psyllid (ACP). To investigate gene expression profiles with a focus on genes involved in infection and circulation within the psyllid host of CLas, RNA-seq libraries were constructed from CLas-infected and CLas-free ACP representing the five different developmental stages, namely, nymphal instars 1-2, 3, and 4-5, and teneral and mature adults.

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination.

Background: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear.

Objective: To report COVID-19 rates in pwMS according to vaccine serology.

Methods: PwMS with available (1) serology 2-12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included.

Reconstructing archaeological palaeolandscapes using geophysical and geomatic survey techniques: An example from Red Lily Lagoon, Arnhem Land, Australia.

Arnhem Land is a key region for understanding the Pleistocene colonisation of Australia, due to the presence of the oldest sites in the continent. Despite this, conventional archaeological survey has not been effective at locating additional pre-Holocene sites in the region due to a complex distribution of geomorphic units caused by sea level rise and coastal aggradation. This research uses geophysical and geomatic techniques to map the subsurface distribution of the geomorphic units in the Red Lily Lagoon region in eastern Arnhem Land.

Urinary oxytocin and cortisol concentrations vary by group type in male western lowland gorillas (Gorilla gorilla gorilla) in North American zoos.

Evaluating how primates in human care function within their social environment is important for understanding and optimizing their management and welfare. The neuroendocrine hormone oxytocin is associated with affiliation and bonding, suggesting it can be used to evaluate the affiliative nature of social groupings. When paired with cortisol concentrations, social stressors can simultaneously be assessed, providing a more complete picture of primate social environments than if measuring either hormone independently.

A comparison of odor plume-tracking behavior of walking and flying insects in different turbulent environments.

Many animals locate food, mates and territories by following plumes of attractive odors. There are clear differences in the structure of this plume-tracking behavior depending on whether an animal is flying, swimming, walking or crawling. These differences could arise from different control rules used by the central nervous system during these different modes of locomotion or one set of rules interacting with the different environments while walking on the surface versus flying or swimming.

Contemporary study of multiple sclerosis disability in South East Wales.

Background: A contemporary understanding of disability evolution in multiple sclerosis (MS) is an essential tool for individual disease management and planning of interventional studies. We have used prospectively collected longitudinal data to analyse disability progression and variation in a British MS cohort.

Methods: Cox proportional hazards regression was used to estimate hazard of Expanded Disability Status Scale (EDSS) 4.

Challenging the 50-50 rule for the basal-bolus insulin ratio in patients with type 2 diabetes who maintain stable glycaemic control.

Background: For patients using basal-bolus insulin therapy, it is widespread clinical practice to aim for a 50-50 ratio between basal and total daily bolus. However, this practice was based on a small study of individuals without diabetes. To assess the rule in real-world practice, we retrospectively analyzed patients on basal-bolus therapy that was adjusted at least weekly by an artificial intelligence-driven titration within the d-Nav® Insulin Management Technology.

Multiple sclerosis and the risk of infection: Association of British Neurologists consensus guideline.

Infection in people with multiple sclerosis (MS) is of major concern, particularly for those receiving disease-modifying therapies. This article explores the risk of infection in people with MS and provides guidance-developed by Delphi consensus by specialists involved in their management-on how to screen for, prevent and manage infection in this population.

Response to COVID-19 booster vaccinations in seronegative people with multiple sclerosis.

Background: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group.

Methods: PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate.

Factors Driving Resistance to Clinical Decision Support: Finding Inspiration in Radiology 3.0.

Purpose: The effectiveness of evidence-based guidelines (EBGs) and clinical decision support (CDS) is significantly hampered by widespread clinician resistance to it. Our study was designed to better understand the reasons for this resistance to CDS and explore the factors that drive it.

Methods: We used a mixed-methods approach to explore and identify the drivers of resistance for CDS among clinicians, including a web-based multispecialty survey exploring clinicians' impressions of the strengths and weaknesses of CDS, two clinician focus groups, and several one-on-one focused clinician interviews in which individual participants were asked to comment on their rationale for choosing imaging utilization that might not be supported by EBGs.

COVID-19 Vaccine Response in People with Multiple Sclerosis.

Objective: The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines in people with multiple sclerosis (MS).

Methods: Four hundred seventy-three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID-19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records.

An automated computational approach to kinetic model discrimination and parameter estimation.

We herein report experimental applications of a novel, automated computational approach to chemical reaction network (CRN) identification. This report shows the first chemical applications of an autonomous tool to identify the kinetic model and parameters of a process, when considering both catalytic species and various integer and non-integer orders in the model's rate laws. This kinetic analysis methodology requires only the input of the species within the chemical system (starting materials, intermediates, products, ) and corresponding time-series concentration data to determine the kinetic information of the chemistry of interest.

Development of a biogas distribution model for a wastewater treatment plant: a mixed integer linear programming approach.

In this paper, we propose a realistic model for gas distribution of an advanced municipal wastewater treatment works and through minimisation of the total cost of gas distribution we perform retrospective optimisation (RO) using historical plant data. This site is the first in the UK with a mixed operational strategy for biomethane produced on site: to burn in combined heat and power (CHP) engines to create electricity, burn in steam boilers for onsite steam use or inject the biomethane into the National Grid. In addition, natural gas can be imported to make up shortfalls in biomethane if required.

COVID-19: Mechanistic model calibration subject to active and varying non-pharmaceutical interventions.

Mathematical models are useful in epidemiology to understand COVID-19 contagion dynamics. We aim to demonstrate the effectiveness of parameter regression methods to calibrate an established epidemiological model describing infection rates subject to active, varying non-pharmaceutical interventions (NPIs). We assess the potential of established chemical engineering modelling principles and practice applied to epidemiological systems.