Measuring vaccine hesitancy: The development of a survey tool.

In March 2012, the SAGE Working Group on Vaccine Hesitancy was convened to define the term "vaccine hesitancy", as well as to map the determinants of vaccine hesitancy and develop tools to measure and address the nature and scale of hesitancy in settings where it is becoming more evident. The definition of vaccine hesitancy and a matrix of determinants guided the development of a survey tool to assess the nature and scale of hesitancy issues. Additionally, vaccine hesitancy questions were piloted in the annual WHO-UNICEF joint reporting form, completed by National Immunization Managers globally. The objective of characterizing the nature and scale of vaccine hesitancy issues is to better inform the development of appropriate strategies and policies to address the concerns expressed, and to sustain confidence in vaccination. The Working Group developed a matrix of the determinants of vaccine hesitancy informed by a systematic review of peer reviewed and grey literature, and by the expertise of the working group. The matrix mapped the key factors influencing the decision to accept, delay or reject some or all vaccines under three categories: contextual, individual and group, and vaccine-specific. These categories framed the menu of survey questions presented in this paper to help diagnose and address vaccine hesitancy

Influence of sexual sensation-seeking on factors associated with risky sexual behaviour among African-American female adolescents

The identification of antecedents to sexual risk among youth is critical to the development and dissemination of multilevel interventions. Therefore, the aim of the present study was to examine the effect of sexual sensation-seeking on partner age, partner communication, and the sexual attitudes and behaviours of African-American female youth

Juvenile Justice—Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS): A Cluster Randomized Trial Targeting System-Wide Improvement in Substance Use Services

Background: The purpose of this paper is to describe the Juvenile Justice—Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) study, a cooperative implementation science initiative involving the National Institute on Drug Abuse, six research centers, a coordinating center, and Juvenile Justice Partners representing seven US states. While the pooling of resources across centers enables a robust implementation study design involving 36 juvenile justice agencies and their behavioral health partner agencies, co-producing a study protocol that has potential to advance implementation science, meets the needs of all constituencies (funding agency, researchers, partners, study sites), and can be implemented with fidelity across the cooperative can be challenging. This paper describes (a) the study background and rationale, including the juvenile justice context and best practices for substance use disorders, (b) the selection and use of an implementation science framework to guide study design and inform selection of implementation components, and (c) the specific study design elements, including research questions, implementation interventions, measurement, and analytic plan. Methods/design: The JJ-TRIALS primary study uses a head-to-head cluster randomized trial with a phased rollout to evaluate the differential effectiveness of two conditions (Core and Enhanced) in 36 sites located in seven states. A Core strategy for promoting change is compared to an Enhanced strategy that incorporates all core strategies plus active facilitation. Target outcomes include improvements in evidence-based screening, assessment, and linkage to substance use treatment. Discussion: Contributions to implementation science are discussed as well as challenges associated with designing and deploying a complex, collaborative project. Trial registration: NCT02672150

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The First Habitable Zone Earth-Sized Planet From TESS II: Spitzer Confirms TOI-700 d

We present Spitzer 4.5 μm observations of the transit of TOI-700 d, a habitable-zone Earth-sized planet in a multiplanet system transiting a nearby M-dwarf star (TIC 150428135, 2MASS J06282325–6534456). TOI-700 d has a radius of 1.144^(+0.062)_(-0.061) R⊕ and orbits within its host star's conservative habitable zone with a period of 37.42 days (T_(eq) ~ 269 K). TOI-700 also hosts two small inner planets (R_b = 1.037^(+0.0065)_(-0.064) R⊕ and R_c = 2.65^(+0.16)_(-0.15) R⊕) with periods of 9.98 and 16.05 days, respectively. Our Spitzer observations confirm the Transiting Exoplanet Survey Satellite (TESS) detection of TOI-700 d and remove any remaining doubt that it is a genuine planet. We analyze the Spitzer light curve combined with the 11 sectors of TESS observations and a transit of TOI-700 c from the LCOGT network to determine the full system parameters. Although studying the atmosphere of TOI-700 d is not likely feasible with upcoming facilities, it may be possible to measure the mass of TOI-700 d using state-of-the-art radial velocity (RV) instruments (expected RV semiamplitude of ~70 cm s⁻¹)

Global, regional, and national burden of meningitis and its aetiologies, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Although meningitis is largely preventable, it still causes hundreds of thousands of deaths globally each year. WHO set ambitious goals to reduce meningitis cases by 2030, and assessing trends in the global meningitis burden can help track progress and identify gaps in achieving these goals. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we aimed to assess incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990 to 2019, for 204 countries and territories. Methods We modelled meningitis mortality using vital registration, verbal autopsy, sample-based vital registration, and mortality surveillance data. Meningitis morbidity was modelled with a Bayesian compartmental model, using data from the published literature identified by a systematic review, as well as surveillance data, inpatient hospital admissions, health insurance claims, and cause-specific meningitis mortality estimates. For aetiology estimation, data from multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature studies were analysed by use of a network analysis model to estimate the proportion of meningitis deaths and cases attributable to the following aetiologies: Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococcus, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Staphylococcus aureus, viruses, and a residual other pathogen category. Findings In 2019, there were an estimated 236 000 deaths (95% uncertainty interval [UI] 204 000–277 000) and 2·51 million (2·11–2·99) incident cases due to meningitis globally. The burden was greatest in children younger than 5 years, with 112 000 deaths (87 400–145 000) and 1·28 million incident cases (0·947–1·71) in 2019. Age-standardised mortality rates decreased from 7·5 (6·6–8·4) per 100 000 population in 1990 to 3·3 (2·8–3·9) per 100 000 population in 2019. The highest proportion of total all-age meningitis deaths in 2019 was attributable to S pneumoniae (18·1% [17·1–19·2]), followed by N meningitidis (13·6% [12·7–14·4]) and K pneumoniae (12·2% [10·2–14·3]). Between 1990 and 2019, H influenzae showed the largest reduction in the number of deaths among children younger than 5 years (76·5% [69·5–81·8]), followed by N meningitidis (72·3% [64·4–78·5]) and viruses (58·2% [47·1–67·3]). Interpretation Substantial progress has been made in reducing meningitis mortality over the past three decades. However, more meningitis-related deaths might be prevented by quickly scaling up immunisation and expanding access to health services. Further reduction in the global meningitis burden should be possible through low-cost multivalent vaccines, increased access to accurate and rapid diagnostic assays, enhanced surveillance, and early treatment.publishedVersio