Numerical study of radiative Maxwell viscoelastic magnetized flow from a stretching permeable sheet with the Cattaneo–Christov heat flux model

In this article, the Cattaneo-Christov heat flux model is implemented to study non-Fourier heat and mass transfer in the magnetohydrodynamic (MHD) flow of an upper convected Maxwell (UCM) fluid over a permeable stretching sheet under a transverse constant magnetic field. Thermal radiation and chemical reaction effects are also considered. The nonlinear partial differential conservation equations for mass, momentum, energy and species conservation are transformed with appropriate similarity variables into a system of coupled, highly nonlinear ordinary differential equations with appropriate boundary conditions. Numerical solutions have been presented for the influence of elasticity parameter (), magnetic parameter (M2), suction/injection parameter (λ), Prandtl number (Pr), conduction-radiation parameter (Rd), sheet stretching parameter (A), Schmidt number (Sc), chemical reaction parameter (γ_c), modified Deborah number with respect to relaxation time of heat flux (i.e. non-Fourier Deborah number) on velocity components, temperature and concentration profiles using the successive Taylor series linearization method (STSLM) utilizing Chebyshev interpolating polynomials and Gauss-Lobatto collocation. The effects of selected parameters on skin friction coefficient, Nusselt number and Sherwood number are also presented with the help of tables. Verification of the STSLM solutions is achieved with existing published results demonstrating close agreement. Further validation of skin friction coefficient, Nusselt number and Sherwood number values computed with STSLM is included using Mathematica software shooting quadrature

Does Sleep Improve Your Grammar? : Preferential Consolidation of Arbitrary Components of New Linguistic Knowledge

We examined the role of sleep-related memory consolidation processes in learning new form-meaning mappings. Specifically, we examined a Complementary Learning Systems account, which implies that sleep-related consolidation should be more beneficial for new hippocampally dependent arbitrary mappings (e.g. new vocabulary items) relative to new systematic mappings (e.g. grammatical regularities), which can be better encoded neocortically. The hypothesis was tested using a novel language with an artificial grammatical gender system. Stem-referent mappings implemented arbitrary aspects of the new language, and determiner/suffix+natural gender mappings implemented systematic aspects (e.g. tib scoiffesh + ballerina, tib mofeem + bride; ked jorool + cowboy, ked heefaff + priest). Importantly, the determiner-gender and the suffix-gender mappings varied in complexity and salience, thus providing a range of opportunities to detect beneficial effects of sleep for this type of mapping. Participants were trained on the new language using a word-picture matching task, and were tested after a 2-hour delay which included sleep or wakefulness. Participants in the sleep group outperformed participants in the wake group on tests assessing memory for the arbitrary aspects of the new mappings (individual vocabulary items), whereas we saw no evidence of a sleep benefit in any of the tests assessing memory for the systematic aspects of the new mappings: Participants in both groups extracted the salient determiner-natural gender mapping, but not the more complex suffix-natural gender mapping. The data support the predictions of the complementary systems account and highlight the importance of the arbitrariness/systematicity dimension in the consolidation process for declarative memories

Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1

To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols

Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.

The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis

Background Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive—despite the region’s long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 569,000 deaths (95% UI 406,000–771,000) associated with bacterial AMR and 141,000 deaths (99,900–196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000–241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200–278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600–168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000–608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen–drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen–drug combination in 15 countries for deaths associated with AMR. Interpretation Given the burden across different countries, infectious syndromes, and pathogen–drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund