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Children with intersex variations continue to be subject to elective, irreversible, "sex-normalising" surgical interventions, despite multiple human rights and legislative bodies calling for their prohibition. Our systematic review aims to understand how medical literature reports rationales for "sex-normalising" surgical interventions conducted in childhood, and how they are contextualised within the medical and social controversy surrounding such interventions. PubMed, EMBASE and CINAHL were searched for English language, peer-reviewed articles reporting primary data on elective, genital, "sex-normalising" surgical interventions conducted on individuals <10 years, published 01/07/2006-30/06/2023 (PROSPERO ID: CRD42023460871). Data on outcomes reported, rationale for the conduct and timing of interventions and acknowledgement of controversy were extracted. Narrative synthesis described rationales and controversy. Risk of bias was assessed using Johanna Briggs Institute Tools. 11,042 records were retrieved, with 71 articles included for analysis. One of the most common outcomes collected in included literature were cosmetic outcomes, primarily reported by surgeons or parents. 62.0% of studies reported no rationale for intervention timing, 39.4% reported no rationale for conduct and 52.1% acknowledged no controversy in intervention conduct. Rationales included parental desire for intervention, anatomical/functional/cosmetic reasons, and a perceived goal of aligning with sex assigned by surgical teams or parents. Controversies addressed included concerns about the quality of interventions, the ethics of intervention conduct and gendered and social considerations. "Sex-normalising" interventions are conducted based largely on rationales that were not adequately supported by evidence, a desire from parents and surgeons to match genital cosmesis typically ascribed to male and female bodies, and a parental desire for intervention conduct. Legislating and medical regulatory bodies should advocate for ending the conduct of irreversible, elective, "sex-normalising" interventions conducted without the full, free and informed consent of the person concerned, to promote and protect the highest attainable standard of health for people with intersex variations.
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Single cell CRISPR screens such as Perturb-seq enable transcriptomic profiling of genetic perturbations at scale. However, the data produced by these screens are often noisy due to cost and technical constraints, limiting power to detect true effects with conventional differential expression analyses. Here, we introduce TRanscriptome-wide Analysis of Differential Expression (TRADE), a statistical framework which estimates the transcriptome-wide distribution of true differential expression effects from noisy gene-level measurements. Within TRADE, we derive multiple novel, interpretable statistical metrics, including the "transcriptome-wide impact", an estimator of the overall transcriptional effect of a perturbation which is stable across sampling depths. We analyze new and published large-scale Perturb-seq datasets to show that many true transcriptional effects are not statistically significant, but detectable in aggregate with TRADE. In a genome-scale Perturb-seq screen, we find that a typical gene perturbation affects an estimated 45 genes, whereas a typical essential gene perturbation affects over 500 genes. An advantage of our approach is its ability to compare the transcriptomic effects of genetic perturbations across contexts and dosages despite differences in power. We use this ability to identify perturbations with cell-type dependent effects and to find examples of perturbations where transcriptional responses are not only larger in magnitude, but also qualitatively different, as a function of dosage. Lastly, we expand our analysis to case/control comparison of gene expression for neuropsychiatric conditions, finding that transcriptomic effect correlations are greater than genetic correlations for these diagnoses. TRADE lays an analytic foundation for the systematic comparison of genetic perturbation atlases, as well as differential expression experiments more broadly.
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Background and Objective: Male stress urinary incontinence (SUI) and erectile dysfunction (ED) are well established diagnoses within Men's Health, often more specifically within the prostate cancer survivorship cohort. Taken individually, well defined treatment algorithms exist with which many surgeons are comfortable; however, treatment of both in a single setting or staged fashion introduces complexity. Emerging treatment options also exist, and there is immature or minimal data when these are combined with inflatable penile prosthesis (IPP) insertion, radiation history, and/or variable degrees of incontinence. Our objective was to describe and summarize the currently available treatment options for SUI particularly at the time of IPP insertion. Methods: A literature review was performed to summarize contemporary treatment of SUI at time of IPP placement. Anecdotal experience was added from high volume, subspecialty trained Men's Health and Reconstructive Urologists. Key Content and Findings: Non-invasive approaches such as pelvic floor muscle training (PFMT), behavioral modification, and external compression devices play some limited role in treatment and/or management of SUI, particularly in the early post operative period, or for those unwilling or unable to undergo more definitive intervention. More invasive options such as artificial urinary sphincter (AUS) implantation, male sling, or other implantable devices are more appropriate for good surgical candidates with higher bother and/or more severe incontinence. These options can be concomitant or staged relative to IPP placement. Climacturia, particularly with mild or no bothersome SUI, can successfully be addressed at the time of penile prosthesis placement with the utilization of the Mini-Jupette suburethral sling. Conclusions: A variety of treatment options exist for concomitant treatment of SUI at time of IPP, and both safety and efficacy have been demonstrated for many in the same operative setting. As with treatment of ED or SUI in isolation, patient selection, careful counseling, and management of expectations can lead to high patient satisfaction.
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The morphology of cells is dynamic and mediated by genetic and environmental factors. Characterizing how genetic variation impacts cell morphology can provide an important link between disease association and cellular function. Here, we combine genomic sequencing and high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship between genetic variants and cellular morphology to map what we term cell morphological quantitative trait loci (cmQTLs). We identify novel associations between rare protein altering variants in WASF2, TSPAN15, and PRLR with several morphological traits related to cell shape, nucleic granularity, and mitochondrial distribution. Knockdown of these genes by CRISPRi confirms their role in cell morphology. Analysis of common variants yields one significant association and nominate over 300 variants with suggestive evidence (P < 10-6) of association with one or more morphology traits. We then use these data to make predictions about sample size requirements for increasing discovery in cellular genetic studies. We conclude that, similar to molecular phenotypes, morphological profiling can yield insight about the function of genes and variants.
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Células-Tronco Pluripotentes Induzidas , Locos de Características Quantitativas , Mapeamento Cromossômico , Locos de Características Quantitativas/genética , Núcleo Celular , Forma Celular , Proteínas MutantesRESUMO
Artificial light harvesting, a process that involves converting sunlight into chemical potential energy, is considered to be a promising part of the overall solution to address urgent global energy challenges. Conjugated polyelectrolyte complexes (CPECs) are particularly attractive for this purpose due to their extended electronic states, tunable assembly thermodynamics, and sensitivity to their local environment. Importantly, ionically assembled complexes of conjugated polyelectrolytes can act as efficient donor-acceptor pairs for electronic energy transfer (EET). However, to be of use in material applications, we must understand how modifying the chemical structure of the CPE backbone alters the EET rate beyond spectral overlap considerations. In this report we investigate the dependence of the EET efficiency and rate on the electronic structure and excitonic wave function of the CPE backbone. To do so, we synthesized a series of alternating copolymers where the electronic states are systematically altered by introducing comonomers with electron withdrawing and electron-rich character while keeping the linear ionic charge density nearly fixed. We find evidence that the excitonic coupling may be significantly affected by the exciton delocalization radius, in accordance with analytical models based on the line-dipole approximation and quantum chemistry calculations. Our results imply that care should be taken when selecting CPE components for optimal CPEC EET. These results have implications for using CPECs as key components in water-based light-harvesting materials, either as standalone assemblies or as adsorbates on nanoparticles and thin films.
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MOTIVATION: Existing methods for simulating synthetic genotype and phenotype datasets have limited scalability, constraining their usability for large-scale analyses. Moreover, a systematic approach for evaluating synthetic data quality and a benchmark synthetic dataset for developing and evaluating methods for polygenic risk scores are lacking. RESULTS: We present HAPNEST, a novel approach for efficiently generating diverse individual-level genotypic and phenotypic data. In comparison to alternative methods, HAPNEST shows faster computational speed and a lower degree of relatedness with reference panels, while generating datasets that preserve key statistical properties of real data. These desirable synthetic data properties enabled us to generate 6.8 million common variants and nine phenotypes with varying degrees of heritability and polygenicity across 1 million individuals. We demonstrate how HAPNEST can facilitate biobank-scale analyses through the comparison of seven methods to generate polygenic risk scoring across multiple ancestry groups and different genetic architectures. AVAILABILITY AND IMPLEMENTATION: A synthetic dataset of 1 008 000 individuals and nine traits for 6.8 million common variants is available at https://www.ebi.ac.uk/biostudies/studies/S-BSST936. The HAPNEST software for generating synthetic datasets is available as Docker/Singularity containers and open source Julia and C code at https://github.com/intervene-EU-H2020/synthetic_data.
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Benchmarking , Confiabilidade dos Dados , Humanos , Genótipo , Fenótipo , Herança MultifatorialRESUMO
Linkage disequilibrium (LD) is the correlation among nearby genetic variants. In genetic association studies, LD is often modeled using large correlation matrices, but this approach is inefficient, especially in ancestrally diverse studies. In the present study, we introduce LD graphical models (LDGMs), which are an extremely sparse and efficient representation of LD. LDGMs are derived from genome-wide genealogies; statistical relationships among alleles in the LDGM correspond to genealogical relationships among haplotypes. We published LDGMs and ancestry-specific LDGM precision matrices for 18 million common variants (minor allele frequency >1%) in five ancestry groups, validated their accuracy and demonstrated order-of-magnitude improvements in runtime for commonly used LD matrix computations. We implemented an extremely fast multiancestry polygenic prediction method, BLUPx-ldgm, which performs better than a similar method based on the reference LD correlation matrix. LDGMs will enable sophisticated methods that scale to ancestrally diverse genetic association data across millions of variants and individuals.
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Desequilíbrio de Ligação , Humanos , Alelos , Frequência do Gene/genética , Estudos de Associação Genética , Haplótipos/genéticaRESUMO
INTRODUCTION: Unintentional injury is a leading cause of mortality and morbidity in children. There is no consensus on the ideal, discrete management of pediatric renal trauma (PRT). Therefore, management protocols tend to be institution-specific. OBJECTIVE: This study aimed to characterize PRT at a rural level-1 trauma center and subsequently develop a standardized protocol. STUDY DESIGN: A retrospective review of a prospectively maintained database of PRT at a rural level 1 trauma center between 2009 and 2019 was conducted. Injuries were characterized regarding renal trauma grade, associated multi-organ involvement and the need for intervention. The benefit of patient transfer from regional hospitals and length and cost of stay were evaluated. RESULTS: Of 250 patients admitted with renal trauma diagnosis 50 patients <18 years were analyzed. Of those, the majority (32/50, 64%) had low-grade (grade I-III) injuries. Conservative management was successful in all low-grade injuries. Of 18 high-grade PRT, 10 (55.6%) required intervention, one prior to transfer. Among patients with low-grade trauma, 23/32 (72%) were transferred from an outside facility. A total of 13 (26%) patients with isolated low-grade renal trauma were transferred from regional hospitals. All isolated, transferred low-grade renal trauma had diagnostic imaging before transfer and none required invasive intervention. Interventional management of renal injury was associated with a longer median LOS [7 (IQR = 4-16.5) vs 4 (IQR = 2-6) days for conservative management, p = 0.019)] and an increased median total cost of $57,986 vs. $18,042 for conservative management (p = 0.002). DISCUSSION: The majority of PRT, particularly low-grade, can be managed conservatively. A significant proportion of children with low-grade trauma are unnecessarily transferred to higher level centers. Review of pediatric renal trauma at our institution over a decade has allowed us to develop an institutional protocol which we believe allows for safe and effective patient monitoring. CONCLUSION: Isolated, low-grade PRT can be managed conservatively at regional hospitals without needing transfer to a level 1 trauma center. Children with high-grade injuries should be closely monitored and are more likely to need invasive intervention. Development of a PRT protocol will help to safely triage this population and identify those who may benefit from transfer to a tertiary care center.
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Centros de Traumatologia , Ferimentos não Penetrantes , Criança , Humanos , Bases de Dados Factuais , Rim/lesões , Estudos Retrospectivos , Ferimentos não Penetrantes/diagnósticoRESUMO
Both common and rare genetic variants influence complex traits and common diseases. Genome-wide association studies have identified thousands of common-variant associations, and more recently, large-scale exome sequencing studies have identified rare-variant associations in hundreds of genes1-3. However, rare-variant genetic architecture is not well characterized, and the relationship between common-variant and rare-variant architecture is unclear4. Here we quantify the heritability explained by the gene-wise burden of rare coding variants across 22 common traits and diseases in 394,783 UK Biobank exomes5. Rare coding variants (allele frequency < 1 × 10-3) explain 1.3% (s.e. = 0.03%) of phenotypic variance on average-much less than common variants-and most burden heritability is explained by ultrarare loss-of-function variants (allele frequency < 1 × 10-5). Common and rare variants implicate the same cell types, with similar enrichments, and they have pleiotropic effects on the same pairs of traits, with similar genetic correlations. They partially colocalize at individual genes and loci, but not to the same extent: burden heritability is strongly concentrated in significant genes, while common-variant heritability is more polygenic, and burden heritability is also more strongly concentrated in constrained genes. Finally, we find that burden heritability for schizophrenia and bipolar disorder6,7 is approximately 2%. Our results indicate that rare coding variants will implicate a tractable number of large-effect genes, that common and rare associations are mechanistically convergent, and that rare coding variants will contribute only modestly to missing heritability and population risk stratification.
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Exoma , Frequência do Gene , Variação Genética , Herança Multifatorial , Humanos , Exoma/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Herança Multifatorial/genética , Fatores de Risco , Reino Unido , Loci Gênicos/genética , Esquizofrenia/genética , Transtorno Bipolar/genéticaRESUMO
BACKGROUND: The Improving Access to Psychological Therapies (IAPT) programme aims to provide equitable access to therapy for common mental disorders. In the UK, inequalities by ethnicity exist in accessing and receiving mental health treatment. However, limited research examines IAPT pathways to understand whether and at which points such inequalities may arise. METHODS: This study examined variation by ethnicity in (i) source of referral to IAPT services, (ii) receipt of assessment session, (iii) receipt of at least one treatment session. Routine data were collected on service user characteristics, referral source, assessment and treatment receipt from 85 800 individuals referred to South London and Maudsley NHS Foundation Trust IAPT services between 1st January 2013 and 31st December 2016. Multinomial and logistic regression analysis was used to assess associations between ethnicity and referral source, assessment and treatment receipt. Missing ethnicity data (18.5%) were imputed using census data and reported alongside a complete case analysis. RESULTS: Compared to the White British group, Black African, Asian and Mixed ethnic groups were less likely to self-refer to IAPT services. Black Caribbean, Black Other and White Other groups are more likely to be referred through community services. Almost all racial and minority ethnic groups were less likely to receive an assessment compared to the White British group, and of those who were assessed, all racial and ethnic minority groups were less likely to be treated. CONCLUSIONS: Racial and ethnic minority service users appear to experience barriers to IAPT care at different pathway stages. Services should address potential cultural, practical and structural barriers.
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Etnicidade , Grupos Minoritários , Humanos , Etnicidade/psicologia , Londres , Encaminhamento e Consulta , Acessibilidade aos Serviços de SaúdeRESUMO
The canonical paradigm for converting genetic association to mechanism involves iteratively mapping individual associations to the proximal genes through which they act. In contrast, in the present study we demonstrate the feasibility of extracting biological insights from a very large region of the genome and leverage this strategy to study the genetic influences on autism. Using a new statistical approach, we identified the 33-Mb p-arm of chromosome 16 (16p) as harboring the greatest excess of autism's common polygenic influences. The region also includes the mechanistically cryptic and autism-associated 16p11.2 copy number variant. Analysis of RNA-sequencing data revealed that both the common polygenic influences within 16p and the 16p11.2 deletion were associated with decreased average gene expression across 16p. The transcriptional effects of the rare deletion and diffuse common variation were correlated at the level of individual genes and analysis of Hi-C data revealed patterns of chromatin contact that may explain this transcriptional convergence. These results reflect a new approach for extracting biological insight from genetic association data and suggest convergence of common and rare genetic influences on autism at 16p.
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Transtorno Autístico , Humanos , Transtorno Autístico/genética , Variações do Número de Cópias de DNA , Cromossomos , Deleção Cromossômica , Cromossomos Humanos Par 16/genéticaRESUMO
The blue-crowned laughingthrush (BCLT) (Pterorhinus courtoisi) is a species of critically endangered passerine that is part of a Global Species Management Plan and experiences high mortality rates in some collections. Complete necropsy and medical records from 15 European institutions that housed BCLT between 1998 and 2018 were assessed to evaluate morbidity and mortality in the captive population. Medical records for 407 BCLT were received; a total of 191 morbidity events were recorded from 111 individual BCLT. The most common cause of morbidity was coccidial disease, including systemic isosporosis (30.4%, n = 58). Age was a significant factor contributing to mortality, with 53% of deaths occurring between 0 and 14 d old and 78% by 1 yr of age. The most common cause of death was trauma (22.8%, n = 31), followed by systemic isosporosis (22%, n = 30). Of the 343 deceased birds for which records were provided, 50.4% had a necropsy performed and 40.5% had histopathology carried out postmortem. Based on these findings, BCLT should be managed carefully to mitigate risk of trauma, and screening for isosporosis should be performed. Institutions should carry out standardized necropsies and histopathology on every BCLT that dies in their collection to elucidate the etiology of disease in this critically endangered species.
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Isosporíase , Aves Canoras , Animais , Animais de Zoológico , Isosporíase/veterinária , Morbidade , Estudos RetrospectivosRESUMO
Disease-associated single-nucleotide polymorphisms (SNPs) generally do not implicate target genes, as most disease SNPs are regulatory. Many SNP-to-gene (S2G) linking strategies have been developed to link regulatory SNPs to the genes that they regulate in cis. Here, we developed a heritability-based framework for evaluating and combining different S2G strategies to optimize their informativeness for common disease risk. Our optimal combined S2G strategy (cS2G) included seven constituent S2G strategies and achieved a precision of 0.75 and a recall of 0.33, more than doubling the recall of any individual strategy. We applied cS2G to fine-mapping results for 49 UK Biobank diseases/traits to predict 5,095 causal SNP-gene-disease triplets (with S2G-derived functional interpretation) with high confidence. We further applied cS2G to provide an empirical assessment of disease omnigenicity; we determined that the top 1% of genes explained roughly half of the SNP heritability linked to all genes and that gene-level architectures vary with variant allele frequency.
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Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla/métodos , Fenótipo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Most disease-associated genetic variants are pleiotropic, affecting multiple genetically correlated traits. Their pleiotropic associations can be mechanistically informative: if many variants have similar patterns of association, they may act via similar pleiotropic mechanisms, forming a shared component of heritability. We developed pleiotropic decomposition regression (PDR) to identify shared components and their underlying genetic variants. We validated PDR on simulated data and identified limitations of existing methods in recovering the true components. We applied PDR to three clusters of five to six traits genetically correlated with coronary artery disease (CAD), asthma, and type II diabetes (T2D), producing biologically interpretable components. For CAD, PDR identified components related to BMI, hypertension, and cholesterol, and it clarified the relationship among these highly correlated risk factors. We assigned variants to components, calculated their posterior-mean effect sizes, and performed out-of-sample validation. Our posterior-mean effect sizes pool statistical power across traits and substantially boost the correlation (r2) between true and estimated effect sizes (compared with the original summary statistics) by 94% and 70% for asthma and T2D out of sample, respectively, and by a predicted 300% for CAD.
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Asma , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Asma/genética , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Humanos , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Unknown SNP-to-gene regulatory architecture complicates efforts to link noncoding GWAS associations with genes implicated by sequencing or functional studies. eQTLs are often used to link SNPs to genes, but expression in bulk tissue explains a small fraction of disease heritability. A simple but successful approach has been to link SNPs with nearby genes via base pair windows, but genes may often be regulated by SNPs outside their window. We propose the abstract mediation model (AMM) to estimate (1) the fraction of heritability mediated by the closest or kth-closest gene to each SNP and (2) the mediated heritability enrichment of a gene set (e.g., genes with rare-variant associations). AMM jointly estimates these quantities by matching the decay in SNP enrichment with distance from genes in the gene set. Across 47 complex traits and diseases, we estimate that the closest gene to each SNP mediates 27% (SE: 6%) of heritability and that a substantial fraction is mediated by genes outside the ten closest. Mendelian disease genes are strongly enriched for common-variant heritability; for example, just 21 dyslipidemia genes mediate 25% of LDL heritability (211× enrichment, p = 0.01). Among brain-related traits, genes involved in neurodevelopmental disorders are only about 4× enriched, but gene expression patterns are highly informative, as they have detectable differences in per-gene heritability even among weakly brain-expressed genes.
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Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Regulação da Expressão Gênica/genética , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
PURPOSE: The underlying premise of prostate cancer active surveillance (AS) is that cancers likely to metastasize will be recognized and eliminated before cancer-related disease can ensue. Our study was designed to determine the prostate cancer upgrading rate when biopsy guided by magnetic resonance imaging (MRGBx) is used before entry and during AS. MATERIALS AND METHODS: The cohort included 519 men with low- or intermediate-risk prostate cancer who enrolled in prospective studies (NCT00949819 and NCT00102544) between February 2008 and February 2020. Subjects were preliminarily diagnosed with Gleason Grade Group (GG) 1 cancer; AS began when subsequent MRGBx confirmed GG1 or GG2. Participants underwent confirmatory MRGBx (targeted and systematic) followed by surveillance MRGBx approximately every 12 to 24 months. The primary outcome was tumor upgrading to ≥GG3. RESULTS: Upgrading to ≥GG3 was found in 92 men after a median followup of 4.8 years (IQR 3.1-6.5) after confirmatory MRGBx. Upgrade-free probability after 5 years was 0.85 (95% CI 0.81-0.88). Cancer detected in a magnetic resonance imaging lesion at confirmatory MRGBx increased risk of subsequent upgrading during AS (HR 2.8; 95% CI 1.3-6.0), as did presence of GG2 (HR 2.9; 95% CI 1.1-8.2) In men who upgraded ≥GG3 during AS, upgrading was detected by targeted cores only in 27%, systematic cores only in 25% and both in 47%. In 63 men undergoing prostatectomy, upgrading from MRGBx was found in only 5 (8%). CONCLUSIONS: When AS begins and follows with MRGBx (targeted and systematic), upgrading rate (≥GG3) is greater when tumor is initially present within a magnetic resonance imaging lesion or when pathology is GG2 than when these features are absent.
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Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Conduta Expectante/métodos , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Prostatectomia , Neoplasias da Próstata/cirurgia , Fatores de RiscoRESUMO
BACKGROUND: While magnetic resonance imaging (MRI)-targeted biopsy (TBx) results in better prostate cancer (PCa) detection relative to systematic biopsy (SBx), the combination of both methods increases clinically significant PCa detection relative to either Bx method alone. However, combined Bx subjects patients to higher number of Bx cores and greater detection of clinically insignificant PCa. OBJECTIVE: To determine if prebiopsy prostate MRI can identify men who could forgo combined Bx without a substantial risk of missing clinically significant PCa (csPC). DESIGN, SETTING, AND PARTICIPANTS: Men with MRI-visible prostate lesions underwent combined TBx plus SBx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcomes were detection rates for grade group (GG) ≥2 and GG ≥3 PCa by TBx and SBx, stratified by Prostate Imaging-Reporting and Data System (PI-RADS) score. RESULTS AND LIMITATIONS: Among PI-RADS 5 cases, nearly all csPCs were detected by TBx, as adding SBx resulted in detection of only 2.5% more GG ≥2 cancers. Among PI-RADS 3-4 cases, however, SBx addition resulted in detection of substantially more csPCs than TBx alone (8% vs 7.5%). Conversely, TBx added little to detection of csPC among men with PI-RADS 2 lesions (2%) relative to SBx (7.8%). CONCLUSIONS: While combined Bx increases the detection of csPC among men with MRI-visible prostate lesions, this benefit was largely restricted to PI-RADS 3-4 lesions. Using a strategy of TBx only for PI-RADS 5 and combined Bx only for PI-RADS 3-4 would avoid excess biopsies for men with PI-RADS 5 lesions while resulting in a low risk of missing csPC (1%). PATIENT SUMMARY: Our study investigated an optimized strategy to diagnose aggressive prostate cancer in men with an abnormal prostate MRI (magnetic resonance imaging) scan while minimizing the risk of excess biopsies. We used a scoring system for MRI scan images called PI-RADS. The results show that MRI-targeted biopsies alone could be used for men with a PI-RADS score of 5, while men with a PI-RADS score of 3 or 4 would benefit from a combination of MRI-targeted biopsy and systematic biopsy. This trial is registered at ClinicalTrials.gov as NCT00102544.
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Próstata , Neoplasias da Próstata , Humanos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Medição de RiscoRESUMO
OBJECTIVE: COVID-19-related inequities experienced by racial and ethnic minority groups including healthcare professionals mirror wider health inequities, which risk being perpetuated by lower uptake of vaccination. We aim to better understand lower uptake among racial and ethnic minority staff groups to inform initiatives to enhance uptake. DESIGN: Twenty-five semi-structured interviews were conducted (October 2020-January 2021) with UK-based healthcare staff. Data were inductively and thematically analysed. RESULTS: Vaccine decision-making processes were underpinned by an overarching theme, 'weighing up risks of harm against potential benefits to self and others'. Sub-themes included 'fear of harm', 'moral/ethical objections', 'potential benefits to self and others', 'information and misinformation', and 'institutional or workplace pressure'. We identified ways in which these were weighted more heavily towards vaccine hesitancy for racial and ethnic minority staff groups influenced by perceptions about institutional and structural discrimination. This included suspicions and fear around institutional pressure to be vaccinated, racial injustices in vaccine development and testing, religious or ethical concerns, and legitimacy and accessibility of vaccine messaging and communication. CONCLUSIONS: Drawing on a critical race perspective, we conclude that acknowledging historical and contemporary abuses of power is essential to avoid perpetuating and aggravating mistrust by de-contextualising hesitancy from the social processes affecting hesitancy, undermining efforts to increase vaccine uptake.
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COVID-19 , Vacinas , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Etnicidade , Humanos , Grupos Minoritários , Aceitação pelo Paciente de Cuidados de Saúde , Reino Unido , VacinaçãoRESUMO
OBJECTIVE: To summarize the recent literature discussing focal therapy for localized prostate cancer. METHODS: A thorough literature review was performed using PubMed to identify recent studies involving focal therapy for the treatment of localized prostate cancer. RESULTS: In an effort to decrease the morbidity associated with prostate cancer treatment, many urologists are turning to focal therapy as an alternative treatment option. With this approach, the cancer bearing portion of the prostate is targeted while leaving the benign tissue untouched. Multiparametric magnetic resonance imaging remains the gold standard for visualization during focal therapy, but new imaging modalities such as prostate specific membrane antigen/positron emission tomography and contrast enhanced ultrasound are being investigated. Furthermore, several biomarkers, such as prostate cancer antigen 3 and prostate health index, are used in conjunction with imaging to improve risk stratification prior to focal therapy. Lastly, there are several novel technologies such as nanoparticles and transurethral devices that are under investigation for use in focal therapy. CONCLUSION: Focal therapy is proving to be a promising option for the treatment of localized prostate cancer. However, further study is needed to determine the true efficacy of these exciting new technologies.
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BACKGROUND: We sought to determine if participating in a surgical training session using perfused fresh human cadavers (PFHC) had a positive effect on urology residents' confidence in performing open and endoscopic procedures. METHODS: Urology residents at our institution participated in a surgical training session in the West Virginia University Fresh Tissue Training Program, which utilized fresh cadavers with vascular perfusion. The session consisted of performing different urologic procedures (open and endoscopic) on the perfused fresh human cadavers (PFHC). Residents were given a survey to rate their confidence in different urologic procedures before, after, and 6 months after the session. Each procedure on the survey had 3-6 questions associated with it, with scores ranging from 0 (no confidence) to 4 (great confidence). Scores for each procedure before and after the session were compared. RESULTS: Six residents participated in the session. There was an increase in the score for every procedure performed after the session. Scores at 6 month follow up remained higher than the pre-session scores. CONCLUSION: PFHCs offer an excellent opportunity to teach a wide variety of urologic procedures to residents. Incorporation of PFHCs may be very useful in urologic training, and further studies on its use are warranted.