Dental anomalies in cleft lip and/or palate children at age 10 years: A retrospective review across three cleft centres (Part A)

Introduction Children with oral clefts often present with dental anomalies which can impact function, aesthetics and complicate the patient's dental treatment and needs. An understanding of potential anomalies, along with early recognition and planning, is thus essential for effective care. Aim This paper is the first in a two-part three-centre series. This paper will assess the dental anomalies identified in 10-year-old patients attending three cleft centres in the UK. Method Retrospective review was undertaken of the clinical notes of 10-year-old patients attending South Wales (SW), Cleft NET East (CNE) and West Midlands (WM) cleft units, for their ten-year audit record appointment in 2016/2017. Results In total, 144 patients were reviewed (SW = 42; CNE = 52; WM = 50). Dental anomalies were recorded for 80.6% of patients (n = 116). Discussion The review gives insight into the dental complexities of UK oral cleft patients. These patients require specialist paediatric dental input and intensive preventive regimes. Conclusion Shared care between cleft team specialists and general dental practitioners is important when providing holistic care for cleft patient

High-Efficiency Transduction of Liver Cancer Cells by Recombinant Adeno-Associated Virus Serotype 3 Vectors

Recombinant vectors based on a non-pathogenic human parvovirus, the adeno-associated virus 2 (AAV2) have been developed, and are currently in use in a number of gene therapy clinical trials. More recently, a number of additional AAV serotypes have also been isolated, which have been shown to exhibit selective tissue-tropism in various small and large animal models1. Of the 10 most commonly used AAV serotypes, AAV3 is by far the least efficient in transducing cells and tissues in vitro as well as in vivo

Quantitative Three-dimensional Assessment of Knee Joint Space Width from Weight-bearing CT.

Background Imaging of structural disease in osteoarthritis has traditionally relied on MRI and radiography. Joint space mapping (JSM) can be used to quantitatively map joint space width (JSW) in three dimensions from CT images. Purpose To demonstrate the reproducibility, repeatability, and feasibility of JSM of the knee using weight-bearing CT images. Materials and Methods Two convenience samples of weight-bearing CT images of left and right knees with radiographic Kellgren-Lawrence grades (KLGs) less than or equal to 2 were acquired from 2014 to 2018 and were analyzed retrospectively with JSM to deliver three-dimensional JSW maps. For reproducibility, images of three sets of knees were used for novice training, and then the JSM output was compared against an expert's assessment. JSM was also performed on 2-week follow-up images in the second cohort, yielding three-dimensional JSW difference maps for repeatability. Statistical parametric mapping was performed on all knee imaging data (KLG, 0-4) to show the feasibility of a surface-based analysis in three dimensions. Results Reproducibility (in 20 individuals; mean age, 58 years ± 7 [standard deviation]; mean body mass index, 28 kg/m2 ± 6; 14 women) and repeatability (in nine individuals; mean age, 53 years ± 6; mean body mass index, 26 kg/m2 ± 4; seven women) reached their lowest performance at a smallest detectable difference less than ±0.1 mm in the central medial tibiofemoral joint space for individuals without radiographically demonstrated disease. The average root mean square coefficient of variation was less than 5% across all groups. Statistical parametric mapping (33 individuals; mean age, 57 years ± 7; mean body mass index, 27 kg/m2 ± 6; 23 women) showed that the central-to-posterior medial joint space was significantly narrower by 0.5 mm for each incremental increase in the KLG (threshold P < .05). One knee (KLG, 2) demonstrated a baseline versus 24-month change in its three-dimensional JSW distribution that was beyond the smallest detectable difference across the lateral joint space. Conclusion Joint space mapping of the knee using weight-bearing CT images is feasible, demonstrating a relationship between the three-dimensional joint space width distribution and structural joint disease. It is reliably learned by novice users, can be personalized for disease phenotypes, and can be used to achieve a smallest detectable difference that is at least 50% smaller than that reported to be achieved at the highest performance level in radiography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Roemer in this issue

Solidarity and Strife After the Atlanta Spa Shootings: A Mixed Methods Study Characterizing Twitter Discussions by Qualitative Analysis and Machine Learning

Background: On March 16, 2021, a white man shot and killed eight victims, six of whom were Asian women at Atlanta-area spa and massage parlors. The aims of the study were to: (1) qualitatively summarize themes of tweets related to race, ethnicity, and racism immediately following the Atlanta spa shootings, and (2) examine temporal trends in expressions hate speech and solidarity before and after the Atlanta spa shootings using a new methodology for hate speech analysis. Methods: A random 1% sample of publicly available tweets was collected from January to April 2021. The analytic sample included 708,933 tweets using race-related keywords. This sample was analyzed for hate speech using a newly developed method for combining faceted item response theory with deep learning to measure a continuum of hate speech, from solidarity race-related speech to use of violent, racist language. A qualitative content analysis was conducted on random samples of 1,000 tweets referencing Asians before the Atlanta spa shootings from January to March 15, 2021 and 2,000 tweets referencing Asians after the shooting from March 17 to 28 to capture the immediate reactions and discussions following the shootings. Results: Qualitative themes that emerged included solidarity (4% before the shootings vs. 17% after), condemnation of the shootings (9% after), racism (10% before vs. 18% after), role of racist language during the pandemic (2 vs. 6%), intersectional vulnerabilities (4 vs. 6%), relationship between Asian and Black struggles against racism (5 vs. 7%), and discussions not related (74 vs. 37%). The quantitative hate speech model showed a decrease in the proportion of tweets referencing Asians that expressed racism (from 1.4% 7 days prior to the event from to 1.0% in the 3 days after). The percent of tweets referencing Asians that expressed solidarity speech increased by 20% (from 22.7 to 27.2% during the same time period) (p \u3c 0.001) and returned to its earlier rate within about 2 weeks. Discussion: Our analysis highlights some complexities of discrimination and the importance of nuanced evaluation of online speech. Findings suggest the importance of tracking hate and solidarity speech. By understanding the conversations emerging from social media, we may learn about possible ways to produce solidarity promoting messages and dampen hate messages

COVID 19:Seroprevalence and vaccine responses in UK dental care professionals

Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction–proven infections occurred in individuals with a baseline anti–SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory

Multiparametric 3-D analysis of bone and joint space width at the knee from weight bearing computed tomography

Objective: Computed tomography (CT) can deliver multiple parameters relevant to osteoarthritis. In this study we demonstrate that a 3-D multiparametric approach at the weight-bearing knee with cone beam CT is feasible, can include multiple parameters from across the joint space, and can reveal stronger relationships with disease status when parameters are combined. Design: Weight-bearing (WBCT) images of the knees of 33 participants were analyzed with joint space mapping and cortical bone mapping to deliver joint space width (JSW), subchondral bone plate thickness, endocortical thickness, and trabecular attenuation on both sides of the joint. All data were co-localized to the same canonical surface. Statistical parametric mapping (SPM) was applied in uni- and multivariate models to demonstrate significant dependence of parameters on Kellgren & Lawrence grade (KLG). Correlations between JSW and bony parameters and 2-week test-retest repeatability were also calculated. Results: SPM revealed that the central-to-posterior medial tibiofemoral joint space was significantly narrowed by up to 0.5 mm with significantly higher tibial trabecular attenuation — up to 50 attenuation units for each increment in KLG as a single parameter — and in a wider distribution when combined with others (p<0.05). They were also more strongly correlated with worsening KLG grade category. Test-retest repeatability was subvoxel (0.37 mm) for nearly all thickness parameters. Conclusions: 3-D JSW and tibial trabecular attenuation are repeatable and significantly dependent on radiographic disease severity at the weight-bearing knee joint and even more so in combination. A quantitative multiparametric approach with WBCT may have potential for more sensitive investigation of disease progression in osteoarthritis

ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer.

We have previously shown that during pregnancy the E-twenty-six (ETS) transcription factor ELF5 directs the differentiation of mammary progenitor cells toward the estrogen receptor (ER)-negative and milk producing cell lineage, raising the possibility that ELF5 may suppress the estrogen sensitivity of breast cancers. To test this we constructed inducible models of ELF5 expression in ER positive luminal breast cancer cells and interrogated them using transcript profiling and chromatin immunoprecipitation of DNA followed by DNA sequencing (ChIP-Seq). ELF5 suppressed ER and FOXA1 expression and broadly suppressed ER-driven patterns of gene expression including sets of genes distinguishing the luminal molecular subtype. Direct transcriptional targets of ELF5, which included FOXA1, EGFR, and MYC, accurately classified a large cohort of breast cancers into their intrinsic molecular subtypes, predicted ER status with high precision, and defined groups with differential prognosis. Knockdown of ELF5 in basal breast cancer cell lines suppressed basal patterns of gene expression and produced a shift in molecular subtype toward the claudin-low and normal-like groups. Luminal breast cancer cells that acquired resistance to the antiestrogen Tamoxifen showed greatly elevated levels of ELF5 and its transcriptional signature, and became dependent on ELF5 for proliferation, compared to the parental cells. Thus ELF5 provides a key transcriptional determinant of breast cancer molecular subtype by suppression of estrogen sensitivity in luminal breast cancer cells and promotion of basal characteristics in basal breast cancer cells, an action that may be utilised to acquire antiestrogen resistance

Creating symbolic cultures of consumption: an analysis of the content of sports wagering advertisements in Australia

Background: Since 2008, Australia has seen the rapid emergence of marketing for online and mobile sports wagering. Previous research from other areas of public health, such as tobacco and alcohol, has identified the range of appeal strategies these industries used to align their products with culturally valued symbols. However, there is very limited research that has investigated the tactics the sports wagering industry uses within marketing to influence the consumption of its products and services. Method: This study consisted of a mixed method interpretive content analysis of 85 sports wagering advertisements from 11 Australian and multinational wagering companies. Advertisements were identified via internet searches and industry websites. A coding framework was applied to investigate the extent and nature of symbolic appeal strategies within advertisements. Results: Ten major appeal strategies emerged from this analysis. These included sports fan rituals and behaviours; mateship; gender stereotypes; winning; social status; adventure, thrill and risk; happiness; sexualised imagery; power and control; and patriotism. Symbols relating to sports fan rituals and behaviours, and mateship, were the most common strategies used within the advertisements. Discussion/Conclusions: This research suggests that the appeal strategies used by the sports wagering industry are similar to those strategies adopted by other unhealthy commodity industries. With respect to gambling, analysis revealed that strategies are clearly targeted to young male sports fans. Researchers and public health practitioners should seek to better understand the impact of marketing on the normalisation of sports wagering for this audience segment, and implement strategies to prevent gambling harm

Early ultrasound surveillance of newly-created haemodialysis arteriovenous fistula

IntroductionWe assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.MethodsConsenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.ResultsOf 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9–77.3]; elbow, 66.7% [48.9–84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan’s findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data.ConclusionEarly ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation