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BackgroundIncorporating cognitive testing into routine clinical practice is a challenge in multiple sclerosis (MS), given the wide spectrum of both cognitive and physical impairments people can have and the time that testing requires. Shortened paper and verbal assessments predominate but still are not used routinely. Computer-based tests are becoming more widespread; however, changes in how a paper test is implemented can impact what exactly is being assessed in an individual. The Symbol Digit Modalities Test (SDMT) is one validated test that forms part of the cognitive batteries used in MS and has some computer-based versions. We developed a tablet-based SDMT variant that has the potential to be ultimately deployed to patients’ own devices. ObjectiveThis paper aims to develop, validate, and deploy a computer-based SDMT variant, the Cognition Reaction (CoRe) test, that can reliably replicate the characteristics of the paper-based SDMT. MethodsWe carried out analysis using Pearson and intraclass correlations, as well as a Bland-Altman comparison, to examine consistency between the SDMT and CoRe tests and for test-retest reliability. The SDMT and CoRe tests were evaluated for sensitivity to disability levels and age. A novel metric in CoRe was found: question answering velocity could be calculated. This was evaluated in relation to disability levels and age for people with MS and compared with a group of healthy control volunteers. ResultsSDMT and CoRe test scores were highly correlated and consistent with 1-month retest values. Lower scores were seen in patients with higher age and some effect was seen with increasing disability. There was no learning effect evident. Question answering velocity demonstrated a small increase in speed over the 90-second duration of the test in people with MS and healthy controls. ConclusionsThis study validates a computer-based alternative to the SDMT that can be used in clinics and beyond. It enables accurate recording of elements of cognition relevant in MS but offers additional metrics that may offer further value to clinicians and people with MS.

This article explores the history of vagrancy laws in England, the British Empire, and the British colonial world, the significance of those laws, the various challenges that were made to vagrancy laws in the twentieth century, and the limits of those challenges to date. While vagrancy laws preceded the nineteenth century, the 1824 Vagrancy Act in England set a new model, which proved extremely influential around the world over the following centuries. Between the early nineteenth and the early twentieth centuries, vagrancy laws were adopted or reformulated almost everywhere the British left a footprint. The laws that were adopted covered a broad range of (what the authorities considered) offenses and offensive ways of being, including impoverishment, idleness, begging, hawking, public gambling, sex work, public indecency, fortune-telling, traditional religious practices, drunkenness, homosexuality, cross-dressing, socializing across racial groups, being suspicious, and many other activities as well. They were adopted for a range of purposes: to control labor and limit workers' bargaining positions, including after the abolition of slavery; to define the boundaries of civilized, industrious, and moral society; and to 'clean up the streets' and reinforce urban boundaries. Most overarchingly, vagrancy laws served as a practical and rhetorical means through which the discretionary power of the authorities, as enforced through the police and magistracy, was expanded. Far from constituting an object of challenge for 'rule of law' advocates, expansion in such discretionary authority was closely bound up with the expansion of the rule of law in theory and practice. While vagrancy laws began to be challenged in the mid-twentieth century, including through a decades-long anti-vagrancy law campaign in the United States that had significant success, they remain part of the law of numerous states around the world. In addition, even where explicit vagrancy laws have been abolished, vagrancy-type laws--laws that have granted the police discretionary authority to commit arbitrary detention, of the poor in particular--remain deeply embedded in the criminal law regimes of all former British jurisdictions. Overcoming the vagrancy law legacy will require recognizing and taking measures to reform the arbitrary, class-discriminatory police power vagrancy laws have helped entrench in common law legal orders., I. INTRODUCTION 183 II. VAGRANCY AND VAGRANCY-TYPE LAWS IN ENGLAND, THE BRITISH EMPIRE AND THE BRITISH COLONIAL WORLD, C. 18000- 1938 190 A. Vagrancy Laws in England 190 B. Vagrancy [...]

Future changes in tropical cyclone properties are an important component of climate change impacts and risk for many tropical and midlatitude countries. In this study we assess the performance of a multimodel ensemble of climate models, at resolutions ranging from 250 to 25 km. We use a common experimental design including both atmosphere-only and coupled simulations run over the period 1950-2050, with two tracking algorithms applied uniformly across the models. There are overall improvements in tropical cyclone frequency, spatial distribution, and intensity in models at 25 km resolution, with several of them able to represent very intense storms. Projected tropical cyclone activity by 2050 generally declines in the South Indian Ocean, while changes in other ocean basins are more uncertain and sensitive to both tracking algorithm and imposed forcings. Coupled models with smaller biases suggest a slight increase in average TC 10 m wind speeds by 2050.

Understanding the predictability drivers for the North Atlantic Oscillation (NAO) during boreal winter at seasonal time scales remains challenging. This study uses large ensembles with the ECMWF seasonal forecasting system to investigate the relative impact of tropical Indian and Pacific heating on NAO predictability by examining the tropical forcing, teleconnection pathways, and sources of uncertainty. We select three case studies ‐ 1997/98, 2015/16 and 2019/20 ‐ with strong Indian Ocean heating anomalies, but with different El Niño conditions. We show that in 2019/20, with neutral ENSO conditions, Indian Ocean SSTs favor a positive NAO response via stratospheric and tropospheric pathways. In the cases with strong El Niño, we find contrasting results: in 1997/98, the Pacific forcing dominates, producing a negative NAO. In 2015/16, despite the strong El Niño, the Indian Ocean forcing dominates, leading to a positive NAO via intensification of the stratospheric polar vortex (SPV). While the stratospheric pathway exhibits varying responses to Indian Ocean forcing ‐ being weaker in 1997/98 and strongest in 2015/16, the Indian Ocean‐related tropospheric pathway remains robust along the Pacific subtropical jet across years. However, there is destructive interference between teleconnections from Indian and Pacific SST anomalies in both the tropospheric and stratospheric pathways. The competing effects of tropical heating in both basins, uncertainties in the Rossby wave response to tropical heating and SPV variability contribute to uncertainty in seasonal NAO predictions. The flow‐dependent nature of the stratospheric pathway underscores the complexity of seasonal forecast predictability, and the existence of windows of opportunity. Plain Language Summary: The NAO is a phenomenon that manifests as a pressure see‐saw in the North Atlantic, affecting the seasonal climate in many parts of the northern hemisphere. In this study, we demonstrate that the predictability of the phases of the NAO can be affected by the remote and opposing influence of surface temperatures in the tropical Indian and Pacific oceans, which propagate via the troposphere and stratosphere. This interplay, in turn, contributes to the uncertainty of seasonal forecasts of the NAO. Key Points: Large ensemble seasonal forecasts reveal a predictable link between tropical heating and the NAO via a flow‐dependent stratospheric pathwayThe impact of Indian Ocean heating on the NAO can be stronger than that of El Niño in the presence of an anomalously strong stratospheric pathwayCompetition between basins, flow‐dependent response, and intrinsic variability contribute to the uncertainty in seasonal forecasts of NAO [ABSTRACT FROM AUTHOR]

Microencapsulation of plant-beneficial bacteria, such as pink pigmented facultative methylotrophs (PPFM), may greatly extend the shelf life of these Gram-negative microorganisms and facilitate their application to crops for sustainable agriculture. A species of PPFM designated Methylobacterium radiotolerans was microencapsulated in cross-linked alginate microcapsules (CLAMs) prepared by an innovative and industrially scalable process that achieves polymer cross-linking during spray-drying. PPFM survived the spray-drying microencapsulation process with no significant loss in viable population, and the initial population of PPFM in CLAMs exceeded 1010 CFU/g powder. The PPFM population in CLAMs gradually declined by 4 to 5 log CFU/g over one year of storage. The extent of alginate cross-linking, modulated by adjusting the calcium phosphate content in the spray-dryer feed, did not influence cell viability after spray-drying, viability over storage, or dry particle size. However, particle size measurements and light microscopy of aqueous CLAMs suggest that enhanced crosslinking may limit the release of encapsulated bacteria. This work demonstrates an industrially scalable method for producing alginate-based inoculants that may be suitable for on-seed or foliar spray applications.

A family of macrodilactam natural products, the syrbactins, are known proteasome inhibitors. A small group of syrbactin analogs was prepared with a sulfur-for-carbon substitution to enhance synthetic accessibility and facilitate modulation of their solubility. Two of these compounds surprisingly proved to be inhibitors of the trypsin-like catalytic site, including of the immunoproteasome. Their bound and free conformations suggest special properties of the thiasyrbactin ring are responsible for this unusual preference, which may be exploited to develop drug-like immunoproteasome inhibitors. These compounds show greater selectivity than earlier compounds used to infer phenotypes of immunoproteasome inhibition, like ONX-0914.