Multidisciplinary Care for Moebius Syndrome and Related Disorders: Building a Management Protocol.

Moebius syndrome is a collection of orofacial anomalies with highly variable features affecting many different systems but characterised by bilateral facial palsy and absent eye abduction. We largely regard Moebius syndrome as a diagnosis of exclusion. Lack of awareness and knowledge means that children often fall between services, leading to treatment delays and difficulty interfacing with social care and schools, with long-term impact on physical health and psychosocial development. We developed a multidisciplinary team comprising core clinicians (lead physician, geneticist, speech and language therapist, psychologist and specialist nurse) and an expanded group to encompass the other affected systems. The interactions between our specialties lead to the development of a treatment protocol, which we present. The protocol harnesses the aspects of care of children with a range of other rare diseases at a specialised paediatric centre and synthesises them into a holistic approach for MBS and related conditions. Management is sequenced on an "ABC-style" basis, with airway, feeding, vision and speech taking priority in the early years. We define management priorities as airway stabilisation with swallow assessment, ocular surface protection and maintenance of nutritional support. Management principles for issues such as speech, reflux, drooling and sleep issues are outlined. In later years, psychological support has a prominent role geared towards monitoring and interventions for low mood, self-esteem and bullying.

Beyond the Neonate: A Delayed Presentation of Congenital Diaphragmatic Hernia in a 17-Year-Old.

Congenital diaphragmatic hernia (CDH) is a rare anomaly resulting from incomplete closure of pleuroperitoneal canals during fetal development, often presenting with acute respiratory distress in neonates. This case report highlights a 17-year-old female with recurrent episodes of acute left upper quadrant (LUQ) pain and no history of trauma or dietary change. A computerized tomography (CT) scan taken during her second presentation to the emergency department led to a diagnosis of left-sided CDH. She later had a successful laparoscopic diaphragmatic repair surgery and has remained symptom-free for over a year. Late-presenting CDH indicates a rare subset of cases diagnosed after one month of age. Late presentations comprise 5-25% of cases and become increasingly rare with age. Unlike neonatal CDH, which is associated with several comorbidities, late presentations often manifest as a standalone anomaly. When the correct diagnosis is made, uncomplicated surgical repair yields excellent long-term outcomes. However, delayed and incorrect diagnoses can result in serious morbidity. Late-presenting CDH has diverse clinical presentations and can elude diagnostic imaging. As a result, there is a need for heightened clinical suspicion. This report aims to enhance awareness of late-presenting CDH and explore challenges to prompt, accurate diagnosis. Ultimately, this study implores clinicians to consider this condition in patients with unexplained respiratory or gastrointestinal symptoms.

Tanzania's first Marburg Viral Disease outbreak response: Describing the roles of FELTP graduates and residents.

Viral Haemorrhagic Fever Outbreak presents a significant public health threat, requiring a timely, robust, and well-coordinated response. This paper aims to describe the roles of the Tanzania Field Epidemiology and Laboratory Training Program (TFELTP) graduates and residents in responding to Tanzania's first Marburg Viral Disease (MVD) outbreak. We performed a secondary data analysis using a range of documents, such as rosters of deployed responders and the TFELTP graduate and resident database, to count and describe them. Additionally, we conducted an exploratory textual analysis of field deployment reports and outbreak situational reports to delineate the roles played by the residents and graduates within each response pillar. A total of 70 TFELTP graduates and residents from different regions were involved in supporting the response efforts. TFELTP graduates and residents actively participated in several interventions, including contact tracing and follow up, sensitising clinicians on surveillance tools such as standard case definitions, alert management, supporting the National and Kagera Regional Public Health Emergency Operations Centres, active case search, risk communication, and community engagement, coordination of logistics, passenger screening at points of entry, and conducting Infection Prevention and Control (IPC) assessments and orientations in 144 Health Facilities. The successes achieved and lessons learned from the MVD response lay a foundation for sustained investment in skilled workforce development. FELTP Training is a key strategy for enhancing global health security and strengthening outbreak response capabilities in Tanzania and beyond.

A preliminary investigation of epigenome-wide DNA methylation and temperament during infancy.

This study provides preliminary evidence for an epigenetic architecture of infant temperament. At 12 months of age, blood was collected and assayed for DNA methylation and maternally reported infant temperament was assessed using the Infant Behavior Questionnaire in 67 mother-infant dyads. Epigenome-wide analyses showed that the higher order temperament dimensions Surgency and Negative Affect were associated with DNA methylation. The epigenetic signatures of Surgency and Negative Affect were situated at genes involved in synaptic signaling and plasticity. Although replication is required, these results are consistent with a biologically based model of temperament, create new avenues for hypothesis-driven research into epigenetic pathways that underlie individual differences in temperament, and demonstrate that infant temperament has a widespread epigenetic signature in the methylome.

Searching for Structure: Characterizing the Protein Conformational Landscape with Clustering-Based Algorithms.

The identification and characterization of the main conformations from a protein population are a challenging and inherently high-dimensional problem. Here, we evaluate the performance of the Secondary sTructural Ensembles with machine LeArning (StELa) double-clustering method, which clusters protein structures based on the relationship between the φ and ψ dihedral angles in a protein backbone and the secondary structure of the protein, thus focusing on the local properties of protein structures. The classification of states as vectors composed of the clusters' indices arising naturally from the Ramachandran plot is followed by the hierarchical clustering of the vectors to allow for the identification of the main features of the corresponding free energy landscape (FEL). We compare the performance of StELa with the established root-mean-squared-deviation (RMSD)-based clustering algorithm, which focuses on global properties of protein structures and with Combinatorial Averaged Transient Structure (CATS), the combinatorial averaged transient structure clustering method based on distributions of the φ and ψ dihedral angle coordinates. Using ensembles of conformations from molecular dynamics simulations of intrinsically disordered proteins (IDPs) of various lengths (tau protein fragments) or short fragments from a globular protein, we show that StELa is the clustering method that identifies many of the minima and relevant energy states around the minima from the corresponding FELs. In contrast, the RMSD-based algorithm yields a large number of clusters that usually cover most of the FEL, thus being unable to distinguish between states, while CATS does not sample well the FELs for long IDPs and fragments from globular proteins.

Relationship Between Celiac Disease and Dental Caries in Children and Adolescents: A Systematic Review and Meta-Analysis

ABSTRACT Objective: To assess the relationship between celiac disease and the prevalence of dental caries in children and adolescents and also evaluate if dental enamel defects in celiac children predispose to dental caries. Material and Methods: Searches were performed in the following databases: PubMed, Scopus, Cochrane Library, Latin American and Caribbean Literature on Health Sciences, and OpenGrey. The risk of bias was assessed using the Newcastle-Ottawa Scale. DMFT/dmft and DMFS/dmfs data of observational studies that compared the prevalence of caries between children and adolescents with celiac disease and healthy individuals. Meta-analysis was performed using a random effects model. Heterogeneity between studies was estimated using Cochran's Q test, and inconsistency was measured using I2 statistics. Results: Of the 121 studies retrieved, 17 were selected, and 12 were included in the meta-analysis. The prevalence of caries in the primary dentition (dmft) did not differ between celiac patients and controls [SMD = -0.35; 95% CI (-0.83; 0.13); p = 0,15; I2 = 89%]. There was also no difference in the prevalence of caries in permanent teeth (DMFT) between groups [SMD = -0.44; 95% CI (-1.02; 0.14); p = 0.14; I2 = 95%]. Conclusion: Celiac disease is not a determinant factor in the development of dental caries in children and adolescents compared to the control group.

The East African Community mobile laboratory network prepares for monkeypox outbreaks.

In response to the largest recorded monkeypox virus outbreak outside of endemic Central and Western Africa, the East African Community (EAC), in cooperation with the Bernhard-Nocht- Institute for Tropical Medicine, coordinated an emergency monkeypox diagnostic training for the East African Region. As of June 2022, the Democratic Republic of Congo reported a steady increase of suspected monkeypox cases, increasing the risk of spill-over into the remaining six EAC Partner States. Within the existing EAC Mobile Laboratories project, laboratory experts of the National Public Health Laboratories of the remaining six EAC Partner States (Burundi, Rwanda, Tanzania, Kenya, Uganda, and South Sudan) participated in the workshop and were trained in the reception of suspect samples, DNA extraction and diagnosis using real-time polymerase chain reaction (RT-PCR). The EAC region is now equipped with the tools to prepare and rapidly respond to any emerging monkeypox outbreak.

Root Resorption of the Permanent Central Incisor through Ectopic Eruption of the Maxillary Canine.

Although ectopic eruption of the maxillary canine has a low prevalence, a late diagnosis can have serious consequences. A careful clinical examination, assisted with radiographic examination, ensures early diagnosis, facilitates planning, and minimizes possible adverse consequences. This study reports a case of ectopic eruption of the permanent maxillary canine, with complete root resorption of the central permanent incisor, the consequences of which caused functional, aesthetic, and psychological harms to the patient. The procedures used included canine ectopic remodeling of the ectopic canine in the central incisor and orthodontic correction, which treated the anomaly and rebuilt the patient's self-esteem.

Ophthalmia nodosa secondary to intraocular, white-marked tussock caterpillar setae (Orgyia leucostigma) in a 15-year-old.

A 15-year-old female presented to the emergency department with a 1-day history of pain and swelling of her right eye following ocular contact with a caterpillar. Caterpillars of the white-marked tussock moth and other related species possess hairlike structures called setae, with angled barbs along their length, allowing them to travel linearly upon penetration of an enemy, resisting backward movement and becoming very difficult to extract once imbedded. When these fine, pointed hairs contact the surface of the eye, they can easily migrate in, eliciting movement of the globe, blinking, and rubbing of the eye in an attempt to remove the offending agent, potentially leading to ophthalmia nodosa. One of the most important aspects of ophthalmia nodosa diagnosis is a thorough history and prompt slit-lamp examination to identify the presence of foreign bodies and where they are located; this will help guide clinical management decisions. This case demonstrates that, depending on the number and location, more than one attempt may be required to remove all of the barbed setae. If ophthalmia nodosa is suspected, it is important to promptly refer to ophthalmology for a thorough eye exam, keep the eye clean, prescribe prophylactic topical antibiotics and/or steroids to reduce the potential for infection and inflammation, and emphasize the importance of keeping the eye protected during the healing process with an eye shield.

Acute Visual Disturbances and Ataxia Secondary to Attempted COVID-19 Prophylaxis With Ivermectin in a Nine-Year-Old.

Ivermectin is an antiparasitic agent listed as an essential medication by the World Health Organization. Ivermectin utilization has increased due to the popular, though inaccurate, perception of its use in COVID-19 management. Poison Control Central calls regarding ivermectin toxicity have increased 245% since pre-pandemic baselines. This case study illustrates the clinical presentation of ivermectin toxicity in a nine-year-old child with acute vision changes and ataxia. The child was given 60 mg (1 mg/kg) of veterinary-grade ivermectin by a parent, 10 times the clinically recommended dose of 0.1 mg/kg, as prophylaxis after household exposure to COVID-19. Ten hours later, the child developed new-onset blurry vision, a perception of red dots in the peripheral vision, dizziness, and balance issues. Physical examination was notable for pulsating pupils, ataxia, and dysmetria. Symptoms resolved completely after 10 hours. Ivermectin ingestion is an important diagnostic consideration in children presenting with similar symptoms. We hope our case aids in the identification of ivermectin toxicity and hastens necessary supportive measures.

Regional Evaluation of Two SARS-CoV-2 Antigen Rapid Diagnostic Tests in East Africa.

The clinical performance of two rapid antigen tests for the diagnosis of Severe Acute Respiratory Coronavirus (SARS-CoV-2) were regionally evaluated in East African populations. Swabs were collected from 1,432 individuals from five Partner States of the East African Community (Tanzania, Uganda, Burundi, Rwanda and South Sudan). The two rapid antigen tests (Bionote NowCheck COVID-19 Ag and SD Biosensor STANDARD Q COVID-19 Ag) were evaluated against the detection of SARS-CoV-2 RNA by the Reverse Transcription PCR (RT-PCR) gold standard. Of the concordant results with both RT-PCR and rapid antigen test data (862 for Bionote and 852 for SD Biosensor), overall clinical sensitivity was 60% and 50% for the Bionote NowCheck and the SD Biosensor STANDARD Q, respectively. Stratification by viral load, including samples with RT-PCR cycle thresholds (Ct) of <25, improved sensitivity to 90% for both rapid diagnostic tests (RDTs). Overall specificity was good at 99% for both antigen tests. Taken together, the clinical performance of both Ag-RDTs in real world settings within the East African target population was lower than has been reported elsewhere and below the acceptable levels for sensitivity of >80%, as defined by the WHO. Therefore, the rapid antigen test alone should not be used for diagnosis but could be used as part of an algorithm to identify potentially infectious individuals with high viral load. IMPORTANCE Accurate diagnostic tests are essential to both support the management and containment of outbreaks, as well as inform appropriate patient care. In the case of the SARS-CoV-2 pandemic, antigen Rapid Diagnostic Tests (Ag-RDTs) played a major role in this function, enabling widespread testing by untrained individuals, both at home and within health facilities. In East Africa, a number of SARS-CoV-2 Ag-RDTs are available; however, there remains little information on their true test performance within the region, in the hands of the health workers routinely carrying out SARS-CoV-2 diagnostics. This study contributes test performance data for two commonly used SARS-CoV-2 Ag-RDTs in East Africa, which will help inform the use of these RDTs within the region.

The quaternary question: Determining allostery in spastin through dynamics classification learning and bioinformatics.

The nanomachine from the ATPases associated with various cellular activities superfamily, called spastin, severs microtubules during cellular processes. To characterize the functionally important allostery in spastin, we employed methods from evolutionary information, to graph-based networks, to machine learning applied to atomistic molecular dynamics simulations of spastin in its monomeric and the functional hexameric forms, in the presence or absence of ligands. Feature selection, using machine learning approaches, for transitions between spastin states recognizes all the regions that have been proposed as allosteric or functional in the literature. The analysis of the composition of the Markov State Model macrostates in the spastin monomer, and the analysis of the direction of change in the top machine learning features for the transitions, indicate that the monomer favors the binding of ATP, which primes the regions involved in the formation of the inter-protomer interfaces for binding to other protomer(s). Allosteric path analysis of graph networks, built based on the cross-correlations between residues in simulations, shows that perturbations to a hub specific for the pre-hydrolysis hexamer propagate throughout the structure by passing through two obligatory regions: the ATP binding pocket, and pore loop 3, which connects the substrate binding site to the ATP binding site. Our findings support a model where the changes in the terminal protomers due to the binding of ligands play an active role in the force generation in spastin. The secondary structures in spastin, which are found to be highly degenerative within the network paths, are also critical for feature transitions of the classification models, which can guide the design of allosteric effectors to enhance or block allosteric signaling.

Molecular Characterization and Phylogenetic Analysis of Dengue Fever Viruses in Three Outbreaks in Tanzania Between 2017 and 2019.

BACKGROUND: Dengue is a disease of public health interest, and Tanzania experienced major outbreaks in 2014 and 2019. Here, we report our findings on the molecular characterization of dengue viruses (DENV) that circulated during two smaller outbreaks (2017 and 2018) and one major epidemic (2019) in Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: We tested archived serum samples from 1,381 suspected dengue fever patients, with a median age of 29 (IQR:22-40) years, referred to the National Public Health Laboratory for confirmation of DENV infection. DENV serotypes were identified by reverse transcription polymerase chain reaction (RT-PCR), and specific genotypes were identified by sequencing the envelope glycoprotein gene and phylogenetic inference methods. DENV was confirmed in 823 (59.6%) cases. More than half (54.7%) of patients with dengue fever infection were males, and nearly three-quarters (73%) of the infected individuals were living in Kinondoni district, Dar es Salaam. DENV-3 Genotype III caused the two smaller outbreaks in 2017 and 2018, while DENV-1 Genotype V caused the 2019 epidemic. DENV-1 Genotype I was also detected in one patient in 2019. CONCLUSION/SIGNIFICANCE: This study has demonstrated the molecular diversity of dengue viruses circulating in Tanzania. We found that contemporary circulating serotypes did not cause the major epidemic of 2019 but rather due to a serotype shift from DENV-3 (2017/2018) to DENV-1 in 2019. Such a change increases the risk for patients previously infected with a particular serotype to develop severe symptoms upon potential re-infection with a heterologous serotype due to antibody-dependent enhancement of infection. Therefore, the circulation of serotypes emphasizes the need to strengthen the country's dengue surveillance system for better management of patients, early detection of outbreaks, and vaccine development.

Design, Rationalization, and Automation of a Catalytic Sensing Mechanism for Homogeneous SERS Biosensors.

The current pandemic has shown that we need sensitive and deployable diagnostic technologies. Surface-enhanced Raman scattering (SERS) sensors can be an ideal solution for developing such advanced point-of-need (PON) diagnostic tests. Homogeneous (reagentless) SERS sensors work by directly responding to the target without any processing step, making them capable for simple one-pot assays, but their limitation is the achievable sensitivity, insufficient compared to what is needed for sensing of viral biomarkers. Noncovalent DNA catalysis mechanisms have been recently exploited for catalytic amplification in SERS assays. These advances used catalytic hairpin assembly (CHA) and other DNA self-assembly processes to develop sensing mechanisms with improved sensitivities. However, these mechanisms have not been used in OFF-to-ON homogeneous sensors, and they often target the same biomarker, likely due to the complexity of the mechanism design. There is still a strong need for a catalytic SERS sensor with a homogeneous mechanism and a rationalization of the catalytic sensing mechanism to translate this sensing strategy to different targets and applications. We developed and investigated a homogeneous SERS sensing mechanism that uses catalytic amplification based on DNA self-assembly. We systematically investigated the role of three domains in the fuel strand (internal loop, stem, and toehold), which drives the catalytic mechanism. The thermodynamic parameters determined in our studies were used to build an algorithm for automated design of catalytic sensors that we validated on target sequences associated with malaria and SARS-CoV-2 strains. With our mechanism, we were able to achieve an amplification level of 20-fold for conventional DNA and of 36-fold using locked nucleic acids (LNAs), with corresponding improvements observed in the sensor limit of detection (LOD). We also show a single-base sequence specificity for a sensor targeting a sequence associated with the omicron variant, tested against a delta variant target. This work on catalytic amplification of homogeneous SERS sensors has the potential to enable the use of this sensing modality in new applications, such as infectious disease surveillance, by improving the LOD while conserving the sensor's homogeneous character.

Consensus Quality Measures and Dose Constraints for Lung Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and ASTRO Expert Panel.

PURPOSE: For patients with lung cancer, it is critical to provide evidence-based radiation therapy to ensure high-quality care. The US Department of Veterans Affairs (VA) National Radiation Oncology Program partnered with the American Society for Radiation Oncology (ASTRO) as part of the VA Radiation Oncology Quality Surveillance to develop lung cancer quality metrics and assess quality of care as a pilot program in 2016. This article presents recently updated consensus quality measures and dose-volume histogram (DVH) constraints. METHODS AND MATERIALS: A series of measures and performance standards were reviewed and developed by a Blue-Ribbon Panel of lung cancer experts in conjunction with ASTRO in 2022. As part of this initiative, quality, surveillance, and aspirational metrics were developed for (1) initial consultation and workup; (2) simulation, treatment planning, and treatment delivery; and (3) follow-up. The DVH metrics for target and organ-at-risk treatment planning dose constraints were also reviewed and defined. RESULTS: Altogether, a total of 19 lung cancer quality metrics were developed. There were 121 DVH constraints developed for various fractionation regimens, including ultrahypofractionated (1, 3, 4, or 5 fractions), hypofractionated (10 and 15 fractionations), and conventional fractionation (30-35 fractions). CONCLUSIONS: The devised measures will be implemented for quality surveillance for veterans both inside and outside of the VA system and will provide a resource for lung cancer-specific quality metrics. The recommended DVH constraints serve as a unique, comprehensive resource for evidence- and expert consensus-based constraints across multiple fractionation schemas.

Etiologies of influenza-like illness and severe acute respiratory infections in Tanzania, 2017-2019.

In 2016, Tanzania expanded sentinel surveillance for influenza-like illness (ILI) and severe acute respiratory infection (SARI) to include testing for non-influenza respiratory viruses (NIRVs) and additional respiratory pathogens at 9 sentinel sites. During 2017-2019, respiratory specimens from 2730 cases underwent expanded testing: 2475 specimens (90.7%) were tested using a U.S. Centers for Disease Control and Prevention (CDC)-developed assay covering 7 NIRVs (respiratory syncytial virus [RSV], rhinovirus, adenovirus, human metapneumovirus, parainfluenza virus 1, 2, and 3) and influenza A and B viruses. Additionally, 255 specimens (9.3%) were tested using the Fast-Track Diagnostics Respiratory Pathogens 33 (FTD-33) kit which covered the mentioned viruses and additional viral, bacterial, and fungal pathogens. Influenza viruses were identified in 7.5% of all specimens; however, use of the CDC assay and FTD-33 kit increased the number of specimens with a pathogen identified to 61.8% and 91.5%, respectively. Among the 9 common viruses between the CDC assay and FTD-33 kit, the most identified pathogens were RSV (22.9%), rhinovirus (21.8%), and adenovirus (14.0%); multi-pathogen co-detections were common. Odds of hospitalization (SARI vs. ILI) varied by sex, age, geographic zone, year of diagnosis, and pathogen identified; hospitalized illnesses were most common among children under the age of 5 years. The greatest number of specimens were submitted for testing during December-April, coinciding with rainy seasons in Tanzania, and several viral pathogens demonstrated seasonal variation (RSV, human metapneumovirus, influenza A and B, and parainfluenza viruses). This study demonstrates that expanding an existing influenza platform to include additional respiratory pathogens can provide valuable insight into the etiology, incidence, severity, and geographic/temporal patterns of respiratory illness. Continued respiratory surveillance in Tanzania, and globally, can provide valuable data, particularly in the context of emerging respiratory pathogens such as SARS-CoV-2, and guide public health interventions to reduce the burden of respiratory illnesses.

Zero-Gap Electrochemical CO2 Reduction Cells: Challenges and Operational Strategies for Prevention of Salt Precipitation.

Salt precipitation is a problem in electrochemical CO2 reduction electrolyzers that limits their long-term durability and industrial applicability by reducing the active area, causing flooding and hindering gas transport. Salt crystals form when hydroxide generation from electrochemical reactions interacts homogeneously with CO2 to generate substantial quantities of carbonate. In the presence of sufficient electrolyte cations, the solubility limits of these species are reached, resulting in "salting out" conditions in cathode compartments. Detrimental salt precipitation is regularly observed in zero-gap membrane electrode assemblies, especially when operated at high current densities. This Perspective briefly discusses the mechanisms for salt formation, and recently reported strategies for preventing or reversing salt formation in zero-gap CO2 reduction membrane electrode assemblies. We link these approaches to the solubility limit of potassium carbonate within the electrolyzer and describe how each strategy separately manipulates water, potassium, and carbonate concentrations to prevent (or mitigate) salt formation.

Consensus Quality Measures and Dose Constraints for Prostate Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel.

PURPOSE: There are no agreed upon measures to comprehensively determine the quality of radiation oncology (RO) care delivered for prostate cancer. Consequently, it is difficult to assess the implementation of scientific advances and adherence to best practices in routine clinical practice. To address this need, the US Department of Veterans Affairs (VA) National Radiation Oncology Program established the VA Radiation Oncology Quality Surveillance (VA ROQS) Program to develop clinical quality measures to assess the quality of RO care delivered to Veterans with cancer. This article reports the prostate cancer consensus measures. METHODS AND MATERIALS: The VA ROQS Program contracted with the American Society for Radiation Oncology to commission a Blue Ribbon Panel of prostate cancer experts to develop a set of evidence-based measures and performance expectations. From February to June 2021, the panel developed quality, aspirational, and surveillance measures for (1) initial consultation and workup, (2) simulation, treatment planning, and delivery, and (3) follow-up. Dose-volume histogram (DVH) constraints to be used as quality measures for definitive and post-prostatectomy radiation therapy were selected. The panel also identified the optimal Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE V5.0), toxicity terms to assess in follow-up. RESULTS: Eighteen prostate-specific measures were developed (13 quality, 2 aspirational, and 3 surveillance). DVH metrics tailored to conventional, moderately hypofractionated, and ultrahypofractionated regimens were identified. Decision trees to determine performance for each measure were developed. Eighteen CTCAE V5.0 terms were selected in the sexual, urinary, and gastrointestinal domains as highest priority for assessment during follow-up. CONCLUSIONS: This set of measures and DVH constraints serves as a tool for assessing the comprehensive quality of RO care for prostate cancer. These measures will be used for ongoing quality surveillance and improvement among veterans receiving care across VA and community sites. These measures can also be applied to clinical settings outside of those serving veterans.