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OBJECTIVES: To develop and determine the accuracy of a rapid manual technique for the detection of pre-treatment neutropenia (<1.50 × 109/L) in dogs receiving chemotherapy. MATERIALS AND METHODS: Twenty canine blood smears with known neutrophil counts between 1.00 × 109/L and 3.00 × 109/L were reviewed by two internal medicine clinicians and linear regressions performed to determine a cut-off value for a manual neutrophil count equating to >1.50 × 109/L. Consecutive blood samples from dogs undergoing chemotherapy were processed through an automated haematology analyser (VetScan HM5, Abaxis), and prospective blinded manual review by the same two observers assessed whether the manual technique could accurately detect dogs with neutropenia. RESULTS: Linear regression analysis found a cut-off of >26 neutrophils per 10 low power fields at the monolayer to be equivalent to a neutrophil count of >1.5 × 109/L. A total of 183 blood samples from 43 dogs were reviewed. Automated techniques detected neutropenia in 16 of 183 (9%) blood samples. Using the manual cut-off technique, 13 of 16 (81%) and 11 of 16 (69%) of neutropenic samples were correctly identified by observer 1 and observer 2, respectively. Twenty-three of 167 non-neutropenic dogs (14%) were incorrectly classified as neutropenic by observer 1, and 27 (16%) by observer 2. Inter-observer agreement was 92%. Sensitivity was 81% (95% confidence interval 54% to 96%) for observer 1 and 69% (95% confidence interval 41% to 89%) for observer 2. Specificity was 86% (95% confidence interval 80% to 91%) for observer 1 and 84% (95% confidence interval 77% to 89%) for observer 2. CLINICAL SIGNIFICANCE: Manual estimation resulted in up to five of 16 (31%) neutropenic samples being incorrectly classified. A full automated differential cell count remains preferable.
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Obesity is a chronic disease, and while weight loss is achievable, long-term weight loss maintenance is difficult and relapse common for people living with obesity. Aiming to meet the need for innovative approaches, digital behavior change interventions show promise in supporting health behavior change to maintain weight after initial weight loss. Implementation of such interventions should however be part of the design and development processes from project initiation to facilitate uptake and impact. Based on the development and implementation process of eCHANGE, an evidence-informed application-based self-management intervention for weight loss maintenance, this manuscript provides suggestions and guidance into; (1) How a service design approach can be used from initiation to implementation of digital interventions, and (2) How a technology transfer process can accelerate implementation of research-based innovation from idea to market.
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The increase in social media mental health (MH) campaigns provides an opportunity to improve awareness and attitudes toward MH. However, racial disparities remain in these social media campaigns. Black youth who participated in MH social media campaigns reported lower levels of improvement in stigma and help-seeking than their White peers. We employed a youth participatory action research (YPAR) process to expand on a previous community-wide MH social media campaign (A. Thompson et al., 2021), focusing on a Central Midwest community. We studied Black adolescents' perceptions of MH stigma and help-seeking to determine essential features of a culturally responsive MH social media campaign for Black youth. With a lead youth-research collaborator, the research team designed the following two-staged study. The first stage consisted of four semistructured focus group interviews (FGIs) (N = 20), analyzed by using a rapid analysis strategy to obtain results for the development of the campaign. In the second stage, using YPAR's iterative and action-based process, five youth researchers collaborated with the research team on the campaign's design. Following the two stages, the researcher's thematic analysis resulted in three themes: (a) broadening horizons for campaign designers and MH professionals; (b) considering mistrust of schools and school personnel; and (c) diverse experiences, sustainability, and accessibility in a campaign. Findings indicated that while culturally responsive social media campaigns to promote MH can be designed, mistrust of adults in schools is likely to hinder the impact of such campaigns. Implications for school psychology practice and research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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INTRODUCTION: Return to theatre for arrest of post-tonsillectomy haemorrhage represents a significant complication of a commonly performed Ear, Nose and Throat procedure. We used Hospital Episode Statistics data to quantify this risk. This method has been used previously for data from 2002-2004 and again for 2010-2016. In this article, coblation tonsillectomy was considered separately as it had not been analysed in previous studies. METHODS: We used Hospital Episode Statistics data provided by the Department of Health to determine the risk of return to theatre for patients undergoing tonsillectomy between 2016 and 2022. Adults and children were analysed separately. RESULTS: Between 1 April 2016 and 30 April 2022, 179,172 tonsillectomies were performed (not including coblation tonsillectomy), 4,311 (2.41%) of which returned to theatre for control of postoperative bleeding. In children, 1.16% returned to theatre, whereas in adults, 3.80% returned (p<0.05). When including coblation tonsillectomy, the return to theatre rate was 0.82% in children, 3.46% in adults and 1.92% overall. CONCLUSIONS: This study shows that adults remain more than three times more likely than children to require a return to theatre for arrest of haemorrhage following tonsillectomy. The rates of post-tonsillectomy haemorrhage decrease when coblation tonsillectomies are added to the analysis. The rate of return to theatre for post-tonsillectomy haemorrhage seems to have stabilised compared with previous work carried out. The authors recommend further work to assess the complication rate of tonsillectomy in the UK and to compare coblation tonsillectomy with other techniques.
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OBJECTIVES: To assess the prevalence of emergency medical incidents wherein naloxone was administered but overdose was not described as the chief complaint during the 9-1-1 call, including differences by overdose victim race/ethnicity and sex. METHODS: We computed the percentage of 9-1-1 calls in Marion County, Indiana, from 2011 to 2020, wherein naloxone was administered but the caller did not describe overdose as the chief complaint. We estimated a logistic regression to examine the associations between reporting of overdose as the chief complaint and race and sex of the overdose victim. RESULTS: Almost one-fifth of 9-1-1 calls preceding naloxone administration did not describe overdose as the chief complaint. 9-1-1 callers were more likely to describe a non-overdose as the chief complaint when the overdose victim was Black or female. CONCLUSION: 9-1-1 callers are less likely to use terminology describing overdose when the overdose victim is female or Black, than when the victim is male or White. Inaccurate terminology when calling 9-1-1 could delay naloxone administration, thereby increasing risk of overdose death and hypoxic brain injury. Some 9-1-1 callers may be avoiding overdose terminology to prevent a police response, or due to lack of knowledge about overdose identification, but further research is needed to determine the mechanisms underlying these findings.
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Antibody effector functions including antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) are mediated through the interaction of the antibody Fc region with Fcγ receptors present on immune cells. Several approaches have been used to modulate antibody Fc-Fcγ interactions with the goal of driving an effective antitumor immune response, including Fc point mutations and glycan modifications. However, robust antibody-Fcγ engagement and immune cell binding of Fc-enhanced antibodies in the periphery can lead to the unwanted induction of systemic cytokine release and other dose-limiting infusion-related reactions. Creating a balance between effective engagement of Fcγ receptors that can induce antitumor activity without incurring systemic immune activation is an ongoing challenge in the field of antibody and immuno-oncology therapeutics. Herein, we describe a method for the reversible chemical modulation of antibody-Fcγ interactions using simple poly(ethylene glycol) (PEG) linkers conjugated to antibody interchain disulfides with maleimide attachments. This method enables dosing of a therapeutic with muted Fcγ engagement that is restored in vivo in a time-dependent manner. The technology was applied to an effector function enhanced agonist CD40 antibody, SEA-CD40, and experiments demonstrate significant reductions in Fc-induced immune activation in vitro and in mice and nonhuman primates despite showing retained efficacy and improved pharmacokinetics compared to the parent antibody. We foresee that this simple, modular system can be rapidly applied to antibodies that suffer from systemic immune activation due to peripheral FcγR binding immediately upon infusion.
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Receptores de IgG , Animais , Camundongos , Receptores de IgG/imunologia , Humanos , Polietilenoglicóis/química , Citotoxicidade Celular Dependente de Anticorpos , Fagocitose/efeitos dos fármacosRESUMO
During the COVID-19 pandemic, problem-solving courts adopted virtual hearings. We conducted an online nationwide survey with a convenience sample of court staff to elicit their perceptions of court participants' attendance, engagement, willingness to talk, and ability to form connection with judges during in-person versus virtual hearings. Sign tests compared ordinal ratings for perceptions of court participant outcomes during in-person versus virtual hearing modalities, and for audiovisual technology versus audio-only technology. The final analysis included 146 staff. Staff felt that during in-person hearings judges could form closer relationships with participants, quality of information exchanged was higher, and participants were more willing to talk. Staff rated attendance as high regardless of the modality. Staff felt participant engagement was higher with audiovisual technology than audio-only technology. Our results suggest that staff have concerns about effects of virtual hearings on court participant engagement and ability to form relationships with judges. Courts should address these potential negative effects of virtual hearings. We are concerned that staff perceived participants more negatively when participants used audio-only versus audiovisual technology, because technology access could be associated with participant demographic characteristics. Further research is needed to examine court participant perceptions and outcomes.
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Pandemias , Resolução de Problemas , Humanos , Projetos de Pesquisa , Direito Penal , Função JurisdicionalRESUMO
With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}âν_{a}. We report new limits on fermionic dark matter absorption (χ+Aâν+A) and sub-GeV DM-nucleus 3â2 scattering (χ+χ+AâÏ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.
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BACKGROUND: Physical activity (PA) improves outcomes, but disadvantaged children typically experience more sedentary behavior (SB). This study explored movement, executive function (EF) health, and academic achievement (AA) for economically disadvantaged kindergarteners. METHODS: Children in 2 classrooms (n = 16; n = 7) wore wrist-based accelerometers to assess PA/SB during the school day. Independent t-tests and analysis of variance analyzed mean group differences in PA/SB and EF/AA, and correlations explored AA and EF associations. RESULTS: The movement-based class spent significantly less time in SB compared to the contemporary class (t = 2.552, g = 1.115), made greater reading (t = -2.611) and math (t = .967) gains, and had better EF (t = .012). There were significant negative correlations between SB and math (r = -.534) and reading (r = -.592), but no significant relationships with EF. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Schools should consider methods to decrease time spent in SB at lower-SES schools, which is financially feasible and less time-consuming than programs to increase PA. CONCLUSION: Decreased SB time was associated with better AA. More research is needed to determine whether interventions to decrease time spent in SB at school improve academic outcomes in disadvantaged children.
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Comportamento Sedentário , Postura Sentada , Humanos , Escolaridade , Exercício Físico , Atividade Motora , Pré-EscolarRESUMO
Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss 'omics' approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.
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Ecossistema , Multiômica , Biodiversidade , PrevisõesRESUMO
^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known ß and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19} yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single ß and electron capture decay ever achieved. Over all channels, the decay can be excluded for T_{1/2}<0.29×10^{18} yr.
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Purpose: To quantify the cumulative oral implant survival rates and changes in radiographic bone levels based on the configuration of the implant-abutment connection type over time. Materials and Methods: An electronic literature search was conducted in four databases (PubMed/MEDLINE, Cochrane Library, Web of Science, and Embase), and records were refereed by two independent reviewers based on the inclusion criteria. Data from included articles were grouped by implant-abutment connection type into four categories ([1] external hex; [2] bone level, internal, narrow cone < 45 degrees; [3] bone level, internal wide cone ≥ 45 degrees or flat; and [4] tissue level) and duration of follow-up (short-term 1 to 2 years, mid-term 2 to 5 years, and long-term > 5 years). Meta-analyses were performed for cumulative survival rate (CSR) and changes in marginal bone level (ΔMBL) from baseline (loading) to last reported follow-up. Studies were split or merged as appropriate based on the implants and follow-up duration in the study and trial design. The study was compiled under PRISMA 2020 guidelines and registered in the PROSPERO database. Results: A total of 3,082 articles were screened. Full-text review of 465 articles resulted in a total of 270 articles (representing 16,448 subjects with 45,347 implants) included for quantitative synthesis and analysis. Mean ΔMBL (95% CI) was as follows: short-term external hex = 0.68 mm (0.57, 0.79); short-term bone level, internal, narrow cone < 45 degrees = 0.34 mm (0.25, 0.43); short-term bone level, internal wide cone ≥ 45 degrees = 0.63 mm (0.52, 0.74); short-term tissue level = 0.42 mm (0.27, 0.56); mid-term external hex = 1.03 mm (0.72, 1.34); mid-term bone level, internal, narrow cone < 45 degrees = 0.45 mm (0.34, 0.56); mid-term bone level, internal wide cone ≥ 45 degrees = 0.73 mm (0.58, 0.88); mid-term tissue level = 0.4 mm (0.21, 0.61); long-term external hex = 0.98 mm, 0.70, 1.25); long-term bone level, internal, narrow cone < 45 degrees = 0.44 mm (0.31, 0.57); long-term bone level, internal wide cone ≥ 45 degrees = 0.95 mm (0.68, 1.22); and long-term tissue level = 0.43 mm (0.24, 0.61). CSRs (95% CI) were: short-term external hex = 97% (96%, 98%); short-term bone level, internal, narrow cone < 45 degrees = 99% (99%, 99%); short-term bone level, internal wide cone ≥ 45 degrees = 98% (98%, 99%); short-term tissue level = 99% (98%, 100%); mid-term external hex = 97% (96%, 98%); mid-term bone level, internal, narrow cone < 45 degrees = 98% (98%, 99%); mid-term bone level, internal wide cone ≥ 45 degrees = 99% (98%, 99%); mid-term tissue level = 98% (97%, 99%); long-term external hex = 96% (95%, 98%); long-term bone level, internal, narrow cone < 45 degrees = 98% (98%, 99%); long-term bone level, internal wide cone ≥ 45 degrees = 99% (98%, 100%); and long-term tissue level = 99% (98%, 100%). Conclusion: The configuration of the implant-abutment interface has a measurable effect on the ΔMBL over time. These changes can be observed over a period of at least 3 to 5 years. At all measured time intervals, similar ΔMBL was noted for external hex and internal wide cone ≥ 45-degree connections, as were internal, narrow cone < 45-degree and tissue-level connections.
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Implantes Dentários , Prótese Maxilofacial , Humanos , Taxa de SobrevidaRESUMO
Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from multiply interacting massive particles (MIMPs). Their unique track signature allows a targeted analysis with only 0.05 expected background events from muons. Following unblinding, we observe no signal candidate events. This Letter places strong constraints on spin-independent interactions of dark matter particles with a mass between 1×10^{12} and 2×10^{17} GeV/c^{2}. In addition, we present the first exclusion limits on spin-dependent MIMP-neutron and MIMP-proton cross sections for dark matter particles with masses close to the Planck scale.
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This corrects the article DOI: 10.1103/PhysRevLett.129.080401.
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PURPOSE: The objective of this study was to compare patient-reported outcomes (PROs) of periimplant soft tissue inflammation and aesthetics around single-tooth implants in the anterior maxillary region with three different implant-abutment interface designs. METHODS: Participants were randomized to one of three different types of implant-abutment interface designs [Conical (CI), flat-to-flat (FI), and Platform Switched (PS)]. Implants and provisional crowns with prefabricated titanium abutments were placed 5 months following extraction and/or ridge augmentation. Permanent ceramic crowns with zirconia abutments were placed after 12 weeks. To assess PROs, appearance and inflammation questionnaires were completed from provisional crown placement to the 3-year follow-up. RESULTS: Tooth appearance at the 3-year follow-up revealed a difference amongst CI, FI and PS implants (p=0.049; Kruskal-Wallis test). PS was rated better than FI (p=0.047) at 1 year for appearance of soft-tissue and satisfaction with colour. There were no differences for self-consciousness, smile and pain/discomfort while eating/hard food items. CONCLUSIONS: Although participants tended to rate the health of mucosa around PS implants as slighty better than the other two implant systems, the differences were minimal and inconsistent. Thus, patient satisfaction in terms self-perceived gingival health and esthetics was high for all 3 systems tested, suggesting that patients are unable to detect mucosal inflammation. CLINICAL SIGNIFICANCE: Patients find it difficult to perceive mucosal inflammation; hence, it is recommended that patients attend implant follow-up visits, even if they do not perceive inflammation. The study suggests that there is a relationship between the PROs and the clinical outcomes of tested implants.