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A truly global bioethics involves cooperation and collaboration among countries. Most of the articles published in bioethics journals address a problem that exists in one or more countries, but the articles typically do not discuss solutions that require collaboration or cooperation. COVAX is one example of proposed international cooperation related to the current COVID-19. pandemic. Yet it is evident that nations have been proceeding on their own with little, if any collaboration. Despite international research ethics guidance from the World Health Organization (WHO), an article published under WHO auspices violates an ethical principle rejecting “double standards” in the conduct of global research. The COVID pandemic provides an opportunity for countries to learn from the recent lack of international cooperation and employ a multi-national strategy in future global health crises.

B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and [CD68.sup.+] phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Abs against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients, but not in inflammatory and noninflammatory neurologic controls. CSF PLP1 complex Abs provide a pathogenic autoantibody biomarker specific for MS., Introduction Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disease of the CNS. Multiple molecular mechanisms have been posited as driving lesion pathology (1-3), but the failure to identify [...]

The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) throughout many countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating [...]

BackgroundChronic pain and early cognitive decline, which are costly to treat and highly prevalent among older adults, commonly co-occur, exacerbate one another over time, and can accelerate the development and progression of Alzheimer disease and related dementias. We developed the first mind-body activity program (Active Brains [AB]) tailored to the needs of older adults with chronic pain and early cognitive decline. Results from our previous study strongly supported the feasibility of conducting AB remotely and provided evidence for improvements in outcomes. ObjectiveWe are conducting a single-blinded, National Institutes of Health stage-2, randomized clinical trial to establish the efficacy of AB versus a time-matched and dose-matched education control (Health Enhancement Program [HEP]) in improving self-reported and objective outcomes of physical, cognitive, and emotional functions in 260 participants. The methodology described in this paper was informed by the lessons learned from the first year of the trial. MethodsParticipants are identified and recruited through multidisciplinary clinician–referred individuals (eg, pain psychologists and geriatricians), the Rally Research platform, social media, and community partnerships. Interested participants complete eligibility screening and electronic informed consent. Baseline assessments include self-report, performance-based measures (eg, 6-min walk test) and objective measures (eg, Repeatable Battery for the Assessment of Neuropsychological Status). Participants are mailed a wrist-worn ActiGraph device (ActiGraph LLC) to passively monitor objective function (eg, steps) during the week between the baseline assessment and the beginning of the programs, which they continue to wear throughout the programs. After baseline assessments, participants are randomized to either AB or HEP and complete 8 weekly, remote, group sessions with a Massachusetts General Hospital psychologist. The AB group receives a Fitbit (Fitbit Inc) to help reinforce increased activity. Assessments are repeated after the intervention and at the 6-month follow-up. Coprimary outcomes include multimodal physical function (self-report, performance based, and objective). Secondary outcomes are cognitive function (self-report and objective), emotional function, and pain. ResultsWe began recruitment in July 2022 and recruited 37 participants across 4 cohorts. Of them, all (n=37, 100%) have completed the baseline assessment, 26 (70%) have completed the posttest assessment, and 9 (24%) are actively enrolled in the intervention (total dropout: n=2, 5%). In the three cohorts (26/37, 70%) that have completed the AB or HEP, 26 (100%) participants completed all 8 group sessions (including minimal makeups), and watch adherence (1937/2072, 93.48%, average across ActiGraph and Fitbit devices) has been excellent. The fourth cohort is ongoing (9/37, 24%), and we plan to complete enrollment by March 2026. ConclusionsWe aim to establish the efficacy of the AB program over a time-matched and dose-matched control in a live video-based trial and test the mechanisms through theoretically driven mediators and moderators. Findings will inform the development of a future multisite effectiveness-implementation trial. Trial RegistrationClinicalTrials.gov NCT05373745; https://classic.clinicaltrials.gov/ct2/show/NCT05373745 International Registered Report Identifier (IRRID)DERR1-10.2196/47319

ABSTRACT: A successful hatch has a considerable economic impact on all poultry companies. The aim of the current study was to describe the possible effects of shell translucency (T score) and coloration lightness (L* value) on shell thickness, hatchability, and chick weight. A total of 4,320 eggs from 4 commercial Ross 708 breeder flocks (50–55-wk old) were used. Eggs were selected for T score and L* value. A 3-point subjective scoring system was used for T score (1 = low, 2 = medium, 3 = high), and an electronic colorimeter for L* value, sorting the eggs as light (avg. L* = 80.7) or dark (avg. L* = 76.0). Data were analyzed using the GLIMMIX procedure of SAS (V9.4) and Tukey's HSD test was performed to separate means, a significant difference was considered when P ≤ 0.05. Results suggest that the color of the eggshell was related to the egg weight on the day of collection (P = 0.0056) and at transfer (P = 0.0211), in both cases dark eggs were 0.6 g heavier than light eggs. Dark eggs had a 3.8% increased hatchability of egg set (P = 0.0481) and yielded 6 µm thicker shells (P = 0.0019) when compared to light eggs. Regarding translucency, egg weight at transfer was 0.8 g heavier for T score 1 eggs compared to T score 3 (P = 0.0358). The translucency score of 1 had a 6.9% higher hatchability of eggs set (P = 0.0127) and 0.7 g heavier chick weight (P = 0.0385) compared to T score 3. However, T score 1 eggs had shells 28 µm thinner than the T score 2 and 34 µm thinner than T score 3 (P < 0.0001). An interaction effect was observed for eggshell thickness, L* value, and T score, where eggs classified as light with T score 1 had thinner eggshells compared to those that were dark with T score 3 (P = 0.0292). These results suggest that eggshell translucency and coloration lightness can be good noninvasive indicators of eggshell thickness, hatchability, and chick weight in broiler breeder flocks.

This paper uses a 30 m record of valley alluviation in the Lockyer Creek, a major tributary of the mid-Brisbane River in Southeast Queensland, to document the timing and nature of Quaternary fluvial response. A combination of radiocarbon and optically stimulated luminescence dating reveals a sequence of major cut and fill episodes. The earliest aggradation phase is represented by a basal gravel unit, dating to ~220 ka (marine isotope sub-stage 7d), and although little evidence supports higher fluvial discharges during MIS 5, a MIS 3 fluvial episode characterised by incision and aggradation dates to ~60 ka. A penultimate phase of incision to a depth of 30 m prior to ~14 ka saw the lower Lockyer occupy its current position within the valley floor. The Lockyer Creek shows evidence of only minor fluvial activity during MIS 2, suggesting a drier LGM climate. The appearance of alternating fine- and coarse-grained units at about 2 ka is notable and may represent higher-energy flood conditions associated with a strengthening of El Niño Southern Oscillation activity as observed in the flood of 2011. The aggradation rate for this Holocene floodplain unit is ~11 times higher than the long-term rate.

Whether the nom de guerre is Mathematical Oncology, Computational or Systems Biology, Theoretical Biology, Evolutionary Oncology, Bioinformatics, or simply Basic Science, there is no denying that mathematics continues to play an increasingly prominent role in cancer research. Mathematical Oncology-defined here simply as the use of mathematics in cancer research-complements and overlaps with a number of other fields that rely on mathematics as a core methodology. As a result, Mathematical Oncology has a broad scope, ranging from theoretical studies to clinical trials designed with mathematical models. This Roadmap differentiates Mathematical Oncology from related fields and demonstrates specific areas of focus within this unique field of research. The dominant theme of this Roadmap is the personalization of medicine through mathematics, modelling, and simulation. This is achieved through the use of patient-specific clinical data to: develop individualized screening strategies to detect cancer earlier; make predictions of response to therapy; design adaptive, patient-specific treatment plans to overcome therapy resistance; and establish domain-specific standards to share model predictions and to make models and simulations reproducible. The cover art for this Roadmap was chosen as an apt metaphor for the beautiful, strange, and evolving relationship between mathematics and cancer.

OBJECTIVE: To revise the 1999 Airlie House consensus guidelines for the design and implementation of preclinical therapeutic studies and clinical trials in amyotrophic lateral sclerosis (ALS). METHODS: A consensus committee comprising 140 key members of the international ALS community (ALS researchers, clinicians, patient representatives, research funding representatives, industry, and regulatory agencies) addressed 9 areas of need within ALS research: (1) preclinical studies; (2) biological and phenotypic heterogeneity; (3) outcome measures; (4) disease-modifying and symptomatic interventions; (5) recruitment and retention; (6) biomarkers; (7) clinical trial phases; (8) beyond traditional trial designs; and (9) statistical considerations. Assigned to 1 of 8 sections, committee members generated a draft set of guidelines based on a background of developing a (pre)clinical question and a rationale outlining the evidence and expert opinion. Following a 2-day, face-to-face workshop at the Airlie House Conference Center, a modified Delphi process was used to develop draft consensus research guidelines, which were subsequently reviewed and modified based on comments from the public. Statistical experts drafted a separate document of statistical considerations (section 9). RESULTS: In this report, we summarize 112 guidelines and their associated backgrounds and rationales. The full list of guidelines, the statistical considerations, and a glossary of terms can be found in data available from Dryad (appendices e-3-e-5, doi.org/10.5061/dryad.32q9q5d). The authors prioritized 15 guidelines with the greatest potential to improve ALS clinical research. CONCLUSION: The revised Airlie House ALS Clinical Trials Consensus Guidelines should serve to improve clinical trial design and accelerate the development of effective treatments for patients with ALS.

ABSTRACT Current supervised phylogeny-based methods fall short on recognizing species assembled from metagenomic datasets from under-investigated habitats, as they are often incomplete or lack closely known relatives. Here, we report an efficient software suite, “Genome Constellation”, that estimates similarities between genomes based on their k-mer matches, and subsequently uses these similarities for classification, clustering, and visualization. The clusters of reference genomes formed by Genome Constellation closely resemble known phylogenetic relationships while simultaneously revealing unexpected connections. In a dataset containing 1,693 draft genomes assembled from the Antarctic lake communities where only 40% could be placed in a phylogenetic tree, Genome Constellation improves taxa assignment to 61%. It revealed six clusters derived from new bacterial phyla and 63 new giant viruses, 3 of which missed by the traditional marker-based approach. In summary, we demonstrate that Genome Constellation can tackle the computational and algorithmic challenges in large-scale taxonomy analyses in metagenomics.

Abstract Background Pathogenic variants in AXIN2 have been associated with tooth agenesis, colon polyps, and colon cancer. Given the rare nature of this phenotype, we set out to collect additional genotypic and phenotypic information. Methods Data were collected via a structured questionnaire. Sequencing was performed in these patients mostly due to diagnostic purpose. A little more than half of the AXIN2 variant carriers were identified by NGS; other six were family members. Results Here, we report 13 individuals with a heterozygous AXIN2 pathogenic/likely pathogenic variant who have a variable expression of oligodontia‐colorectal cancer syndrome (OMIM 608615) or oligodontia‐cancer predisposition syndrome (ORPHA 300576). Three individuals from one family also had cleft palate, which might represent a new clinical feature of AXIN2 phenotype, also given the fact that AXIN2 polymorphisms have been found in association with oral clefting in population studies. AXIN2 has already been added to multigene cancer panel tests; further research should be conducted to determine whether it should be added to cleft lip/palate multigene panels. Conclusion More clarity about oligodontia‐colorectal cancer syndrome, about the variable expression, and associated cancer risks is needed to improve clinical management and to establish guidelines for surveillance. We collected information about the surveillance that was advised, which might support clinical management of these patients.

Recent advances in extended reality (XR) technologies make seeing and hearing virtual objects commonplace, yet strategies for synthesizing haptic interactions with virtual objects continue to be limited. Two design principles govern the rendering of believable and intuitive haptic feedback: movement through open space must feel “free” while contact with virtual objects must feel stiff. Herein, a novel multisensory approach that conveys proprioception and effort through illusory visual feedback and refers to the wrist, via a bracelet interface, discrete and continuous interaction forces that would otherwise occur at the hands and fingertips, is presented. Results demonstrate that users reliably discriminate the stiffness of virtual buttons when provided with multisensory pseudohaptic feedback, comprising tactile pseudohaptic feedback (discrete vibrotactile feedback and continuous squeeze cues in a bracelet interface) and visual pseudohaptic illusions of touch interactions. Compared to the use of tactile or visual pseudohaptic feedback alone, multisensory pseudohaptic feedback expands the range of physical stiffnesses that are intuitively associated with the rendered virtual interactions and reduces individual differences in physical‐to‐virtual stiffness mappings. This multisensory approach, which leaves users' hands unencumbered, provides a flexible framework for synthesizing a wide array of touch‐enabled interactions in XR, with great potential for enhancing user experiences.

ABSTRACT: A study was conducted to assess the effects of a dietary yeast cell wall (YCW) with and without a Campylobacter jejuni (CJ) challenge. A total of 2,240-day-old Ross 708 males were randomly assigned within 8 treatments with a 4 × 2 factorial design, with 4 diets (negative control, positive control, YCW constant dose (400 g/ton), and YCW step-down dose (800/400/200 g/ton in the starter/grower/finisher diets, respectively) and with and without d 21 CJ oral gavage challenge at 5.2 × 107 CFU/mL. At d 0, 14, 28, and 41 body weights and feed consumption were measured to determine performance. At d 14, 28, and 42, 8 jejunal and ileal histology samples per treatment were collected for villi morphology measurements. At d 22 and 28 (1- and 7-days postinoculation), 24 ileal tissue samples per treatment were collected for relative gene expression analysis. At d 42, 24 cecal content samples per treatment were collected for CJ enumeration. Finally, on d 44, 96 birds per treatment were processed to determine carcass yield and 16 carcass rinses per treatment were collected to determine CJ prevalence after processing. Diet or inoculation did not impact broiler performance (P > 0.05). Limited differences were observed in intestinal morphology, and villus height and crypt depth were different only in the ileum at d 42 (P = 0.0280 and P = 0.0162, respectively). At d 1 postinoculation, differences between treatments inoculated with CJ and PBS were observed in the expression of avian beta defensin 10 (AvBD10), interleukin 1ß (IL-1ß), and interleukin 10 (IL-10) (P < 0.05). At d 7 postinoculation, expression of AvBD10, IL-1ß, and IL-10 was similar among all treatments (P > 0.05). At d 42, all birds, regardless the inoculation, had similar levels of CJ recovered from cecal contents (P > 0.05). After processing, carcass yield and CJ prevalence postchilling was similar in all treatments (P > 0.05). Overall, under the conditions of this study, the addition of YCW during a CJ challenge did not have an impact in growth performance, innate immune response, cecal colonization, carcass yield, or CJ prevalence after processing.