B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence ...protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna's mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was ~4- to 5-log
reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log
reduction in nasal swabs in the 100-µg group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.
Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 μg of the mRNA-1273 ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti–S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273–induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine–induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.
Neutralizing antibody responses gradually wane against several variants of concern (VOCs) after vaccination with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine messenger ...RNA-1273 (mRNA-1273). We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted about 6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.β, which encompasses the spike sequence of the B.1.351 Beta variant. After boost, animals had increased neutralizing antibody responses across all VOCs, which was sustained for at least 8 weeks after boost. Nine weeks after boost, animals were challenged with the SARS-CoV-2 Beta variant. Viral replication was low to undetectable in bronchoalveolar lavage and significantly reduced in nasal swabs in all boosted animals, suggesting that booster vaccinations may be required to sustain immunity and protection.
In "Small Teaching K-8," a team of veteran educators bridges the gap between cognitive theory and the K-8 classroom environment, applying the same foundational research found in author James Lang's ...bestselling "Small Teaching: Everyday Lessons from the Science of Learning" to the elementary and middle school setting. Via clear descriptions and step-by-step methods, the book demonstrates how to integrate simple interventions into pre-existing pedagogical techniques to dramatically improve student outcomes. The interventions consist of classroom or online learning activities, one-time additions, or small modifications in course design or communication. Regardless of their form, they all deliver powerful, positive consequences. In this book, readers will also find: (1) Foundational concepts from up-to-date cognitive research that has implications for classroom teaching and the rationales for using them in a K-8 classroom; (2) Concrete examples of how interventions have been used by faculty in various disciplines; and (3) Directions on the specific timing of each intervention, backed by evidence-based reasons An essential resource for K-8 educators seeking ways to improve their efficacy in the classroom, "Small Teaching K-8" offers teachers intuitive and actionable advice on helping students absorb and retain knowledge for the long-term.
The invention and development of next or second generation sequencing methods has resulted in a dramatic transformation of ancient DNA research and allowed shotgun sequencing of entire genomes from ...fossil specimens. However, although there are exceptions, most fossil specimens contain only low (~ 1% or less) percentages of endogenous DNA. The only skeletal element for which a systematically higher endogenous DNA content compared to other skeletal elements has been shown is the petrous part of the temporal bone. In this study we investigate whether (a) different parts of the petrous bone of archaeological human specimens give different percentages of endogenous DNA yields, (b) there are significant differences in average DNA read lengths, damage patterns and total DNA concentration, and (c) it is possible to obtain endogenous ancient DNA from petrous bones from hot environments. We carried out intra-petrous comparisons for ten petrous bones from specimens from Holocene archaeological contexts across Eurasia dated between 10,000-1,800 calibrated years before present (cal. BP). We obtained shotgun DNA sequences from three distinct areas within the petrous: a spongy part of trabecular bone (part A), the dense part of cortical bone encircling the osseous inner ear, or otic capsule (part B), and the dense part within the otic capsule (part C). Our results confirm that dense bone parts of the petrous bone can provide high endogenous aDNA yields and indicate that endogenous DNA fractions for part C can exceed those obtained for part B by up to 65-fold and those from part A by up to 177-fold, while total endogenous DNA concentrations are up to 126-fold and 109-fold higher for these comparisons. Our results also show that while endogenous yields from part C were lower than 1% for samples from hot (both arid and humid) parts, the DNA damage patterns indicate that at least some of the reads originate from ancient DNA molecules, potentially enabling ancient DNA analyses of samples from hot regions that are otherwise not amenable to ancient DNA analyses.
The UK's Improving Access to Psychological Therapies (IAPT) program is a stepped-care model treating individuals with depression and anxiety disorders. Internet-delivered cognitive behavioral therapy ...(iCBT) is routinely offered to individuals with mild to moderate symptoms, but its applicability to individuals with severe clinical symptoms and requiring a high-intensity intervention is relatively unknown. The current study sought to investigate the potential impacts of using iCBT as a prequel for patients requiring high-intensity treatment (HIT; face-to-face) for depression and anxiety in IAPT.
The study utilized an open study design. One hundred and twenty-four participants who were on a waiting list for high-intensity, face-to-face psychological treatment were offered iCBT. Psychometric data on symptoms of depression, anxiety, and functioning were collected from participants before starting and on finishing iCBT and at the point of service exit. Therapeutic alliance data were collected from patients and clinicians during treatment. Patient pathway data, such as number of treatment sessions and time in treatment, was also collected and incorporated into the analysis.
Significant reductions across primary outcome measures of depression and anxiety, as well as improved functioning, were observed from baseline to iCBT treatment exit, and from iCBT exit to service exit. Analysis of the therapeutic alliance data for patients and clinicians illustrated differences in outcome for those who dropped out and those who completed treatment.
This study illustrates the potential for using iCBT as a prequel to high-intensity therapy for depression and anxiety disorders and is the first of its kind to do so within IAPT stepped care. The results show that iCBT is a valuable option reducing waiting times and enhancing clinical efficiency. The study contributes to the well-established evidence on online psychological treatments worldwide, but further clinical and service development research is necessary to scale these treatments appropriately.
Understanding and Creating Word Embeddings Blankenship, Avery; Connell, Sarah; Dombrowski, Quinn
The programming historian,
01/2024, Letnik:
13, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Word embeddings allow you to analyze the usage of different terms in a corpus of texts by capturing information about their contextual usage. Through a primarily theoretical lens, this lesson will ...teach you how to prepare a corpus and train a word embedding model. You will explore how word vectors work, how to interpret them, and how to answer humanities research questions using them.
We assessed three cochlear implant (CI) suppliers: Advanced Bionics, Cochlear Limited, and MED-EL, for implant revision requiring reoperation after CI placement.
Retrospective cohort study of ...integrated-health-system database between 2010 and 2021. Separate models were created for pediatric (age <18) and adult (age ≥18) cohorts.
Pediatric (age <18) and adult (age ≥18) patients undergoing cochlear implantation within our integrated healthcare system.
Revision after CI placement. Cox proportional hazard regression was used to evaluate revision risk and adjust for confounding factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) are presented.
A total of 2,347 patients underwent a primary CI placement, and Cochlear Limited was most implanted (51.5%), followed by Advanced Bionics (35.2%) and MED-EL (13.3%). In the pediatric cohort, the 7-year crude revision rate was 10.9% for Advanced Bionics and 4.8% for Cochlear Limited, whereas MED-EL had insufficient cases. In adults, the rates were 9.1%, 4.5%, and 3.3% for Advanced Bionics, MED-EL, and Cochlear Limited, respectively. After 2 years of postoperative follow-up, Advanced Bionics had a significantly higher revision risk (HR = 8.25, 95% CI = 2.91-23.46); MED-EL had no difference (HR = 2.07, 95% CI = 0.46-9.25).
We found an increased revision risk after 2 years of follow-up for adults with Advanced Bionics CI devices. Although we found no statistical difference between manufacturers in the pediatric cohort, after 2 years of follow-up, there were increasing trends in the revision probability for Advanced Bionics. Further research may determine whether patients are better suited for some CI devices.
Depression and anxiety are common mental health disorders worldwide. The UK's Improving Access to Psychological Therapies (IAPT) programme is part of the National Health Service (NHS) designed to ...provide a stepped care approach to treating people with anxiety and depressive disorders. Cognitive Behavioural Therapy (CBT) is widely used, with computerised and internet-delivered cognitive behavioural therapy (cCBT and iCBT, respectively) being a suitable IAPT approved treatment alternative for step 2, low- intensity treatment. iCBT has accumulated a large empirical base for treating depression and anxiety disorders. However, the cost-effectiveness and impact of these interventions in the longer-term is not routinely assessed by IAPT services. The current study aims to evaluate the clinical and cost-effectiveness of internet-delivered interventions for symptoms of depression and anxiety disorders in IAPT.
The study is a parallel-groups, randomised controlled trial examining the effectiveness and cost-effectiveness of iCBT interventions for depression and anxiety disorders, against a waitlist control group. The iCBT treatments are of 8 weeks duration and will be supported by regular post-session feedback by Psychological Wellbeing Practitioners. Assessments will be conducted at baseline, during, and at the end of the 8-week treatment and at 3, 6, 9, and 12-month follow-up. A diagnostic interview will be employed at baseline and 3-month follow-up. Participants in the waitlist control group will complete measures at baseline and week 8, at which point they will receive access to the treatment. All adult users of the Berkshire NHS Trust IAPT Talking Therapies Step 2 services will be approached to participate and measured against set eligibility criteria. Primary outcome measures will assess anxiety and depressive symptoms using the GAD-7 and PHQ-9, respectively. Secondary outcome measures will allow for the evaluation of long-term outcomes, mediators and moderators of outcome, and cost-effectiveness of treatment. Analysis will be conducted on a per protocol and intention-to-treat basis.
This study seeks to evaluate the immediate and longer-term impact, as well as the cost effectiveness of internet-delivered interventions for depression and anxiety. This study will contribute to the already established literature on internet-delivered interventions worldwide. The study has the potential to show how iCBT can enhance service provision, and the findings will likely be generalisable to other health services.
Current Controlled Trials ISRCTN ISRCTN91967124. DOI: https://doi.org/10.1186/ISRCTN91967124 . Web: http://www.isrctn.com/ISRCTN91967124 . Clinicaltrials.gov : NCT03188575. Trial registration date: June 8, 2017 (prospectively registered).
The Toll-Like receptor (TLR) pathway plays a core role in innate immunity and is maintained with remarkable consistency across all vertebrate species. Amidst this background of overall conservation, ...subtle differences in the components that make up this pathway may have important implications for species-specific defense against key pathogens. Here we employ a homology-based comparative method to characterize the TLR pathway in the recently sequenced chicken and zebra finch genomes, which represent two distantly related bird species. The key features of the TLR pathway are conserved in birds and mammals, although some clear differences exist. The TLR receptors show a pattern of gene duplication and gene loss in both avian species when compared to mammals. In particular, we observe avian specific duplication of both TLR1 and TLR2 as well and a recent duplication of the TLR7 gene in the zebra finch lineage. Both positive selection and gene conversion shape the evolution of the avian specific TLR2 genes. In addition, there are notable differences in the zebra finch repertoire of antimicrobial peptides (AMPs) when compared to those of the chicken. Bioinformatic analysis reveals no evidence of cathelicidins in the zebra finch genome but does identify a cluster of 12 novel defensins which map to the avian beta-defensin locus on chromosome 3. These findings contribute to the characterization of the differing immune response systems that have evolved in individual vertebrate species in response to their microbiological environment.
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