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Purpose: The purpose of this guideline is to provide evidence-based guidance to clinicians of all specialties on the evaluation, management, and treatment of idiopathic overactive bladder (OAB). The guideline informs the reader on valid diagnostic processes and provides an approach to selecting treatment options for patients with OAB through the shared decision-making process, which will maximize symptom control and quality of life, while minimizing adverse events and burden of disease., Methods: An electronic search employing OVID was used to systematically search the MEDLINE and EMBASE databases, as well as the Cochrane Library, for systematic reviews and primary studies evaluating diagnosis and treatment of OAB from January 2013 to November 2023. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. Following the study selection process, 159 studies were included and were used to inform evidence-based recommendation statements., Results: This guideline produced 33 statements that cover the evaluation and diagnosis of the patient with symptoms suggestive of OAB; the treatment options for patients with OAB, including Noninvasive therapies, pharmacotherapy, minimally invasive therapies, invasive therapies, and indwelling catheters; and the management of patients with BPH and OAB., Conclusion: Once the diagnosis of OAB is made, the clinician and the patient with OAB have a variety of treatment options to choose from and should, through shared decision-making, formulate a personalized treatment approach taking into account evidence-based recommendations as well as patient values and preferences., (© 2024 by American Urological Association Education and Research, Inc.)

When tablets are manufactured on a rotary tablet press and the throughput is increased, it leads to changes in powder dynamics during die filling due to formulation characteristics and changing powder flow in the feed frame. This may result, a.o. in increased tablet weight variability, poorer content uniformity, capping and lamination. This research focuses on explaining the die filling performance depending on material properties and process settings, including throughput for small and large tablets. It was concluded that throughput had a negative impact on die filling variability, which is related to reduced residence time and lower fill fraction of the feed frame and dies. Furthermore, the die filling mechanism was inherently different for large tablets in comparison to small tablets. Higher die filling consistency was observed for dense, less porous, less compressible and better flowing powders. As a result of this work, a model was developed to predict the impact of formulation properties and process settings on die filling variability and its dependency on changes in throughput. This model will benefit formulation development at an early stage when active ingredient availability may be challenging as it will avoid the need to conduct experiments at high throughputs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigated the added value of combining both near-infrared (NIR) and Raman spectroscopy into a single NIRaman Combi Fiber Probe for in-line blend potency determination in the feed frame of a rotary tablet press. A five-component platform formulation was used, containing acetylsalicylic acid as the Active Pharmaceutical Ingredient (API). Calibration models for the determination of 1 and 5% w/w label claim tablets were developed using NIR and Raman spectra of powder blends ranging from 0.75 to 1.25% w/w and 3.75 to 6.25% w/w API, respectively. Step-change experiments with deliberate 10% deviation steps from the label claims were performed, from which the collected spectra were used for model validation. For model development and validation, low-level data fusion was explored through concatenation of preprocessed NIR and Raman spectra. Mid-level data fusion was also evaluated, based on extracted features of the preprocessed data. Herewith, score vectors were extracted by transforming preprocessed spectra through Principal Component Analysis, followed by critical feature selection through Elastic Net Regression. Partial Least Squares regression was applied to regress singular, low-level or mid-level fused data versus blend potency. It could be concluded that irrespective of the data fusion technique, an increase in Step-Change Sensitivity (SCS) and decrease in Root Mean Squared Error (RMSE) was observed when predicting the 5% w/w step-change experiment. For the prediction of the 1% w/w step-change experiment, no added benefit with regard to SCS and RMSE was observed due to the addition of the noisy NIR spectra.

Purpose: The purpose of this guideline is to provide evidence-based guidance to clinicians of all specialties on the evaluation, management, and treatment of idiopathic overactive bladder (OAB). The guideline informs the reader on valid diagnostic processes and provides an approach to selecting treatment options for patients with OAB through the shared decision-making process, which will maximize symptom control and quality of life, while minimizing adverse events and burden of disease., Methods: An electronic search employing OVID was used to systematically search the MEDLINE and EMBASE databases, as well as the Cochrane Library, for systematic reviews and primary studies evaluating diagnosis and treatment of OAB from January 2013 to November 2023. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. Following the study selection process, 159 studies were included and were used to inform evidence-based recommendation statements., Results: This guideline produced 33 statements that cover the evaluation and diagnosis of the patient with symptoms suggestive of OAB; the treatment options for patients with OAB, including non-invasive therapies, pharmacotherapy, minimally invasive therapies, invasive therapies, and indwelling catheters; and the management of patients with BPH and OAB., Conclusion: Once the diagnosis of OAB is made, the clinician and the patient with OAB have a variety of treatment options to choose from and should, through shared decision-making, formulate a personalized treatment approach taking into account evidence-based recommendations as well as patient values and preferences.

Purpose: The symptoms of urethral stricture are non-specific and may overlap with other common conditions that can confound diagnosis. Urologists play a key role in the initial evaluation of urethral stricture, currently provide all accepted treatments, and must be familiar with the evaluation, diagnostic tests, and surgical treatments for urethral stricture., Materials and Methods: A systematic review of the literature using the Pubmed, Embase, and Cochrane databases (search dates January 1, 1990 to January 12, 2015) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of urethral stricture in men. The review yielded an evidence base of 250 articles after application of inclusion/exclusion criteria. The search for the 2023 Amendment was modified to included females and males (search dates December 2015-October 2022 for males; January 1990-October 2022 for females) and a new Key Question on sexual dysfunction was added (search dates: January 1990-10/2022). After inclusion and exclusion criteria were applied, 81 studies were added to the existing evidence base., Results: Once a urethral stricture is diagnosed, clinicians should determine the length and location of the stricture in order to inform treatment. After a period of urethral rest, patients with short (<2cm) bulbar urethral stricture may be treated endoscopically. Urethroplasty may be performed by an experienced surgeon in patients with first time or recurrent anterior and posterior urethral strictures. The best treatment option for urethral stricture in female patients is urethroplasty using oral mucosa grafts or vaginal flaps rather than endoscopic treatment., Conclusion: This guideline provides evidence-based guidance to clinicians and patients regarding how to recognize symptoms and signs of a urethral stricture/stenosis, carry out appropriate testing to determine the location and severity of the stricture, and recommend the best options for treatment. The most effective approach for a particular patient is best determined by the individual clinician and patient in the context of that patient's history, values, and goals for treatment.

Purpose: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part II of a two-part series focusing on initial and repeat biopsies, and biopsy technique. Please refer to Part I for discussion of initial prostate cancer screening recommendations., Materials and Methods: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles., Results: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsies, and biopsy technique., Conclusions: The evaluation of prostate cancer risk should be focused on the detection of clinically significant prostate cancer (Grade Group 2 or higher [GG2+]). The use of laboratory biomarkers, prostate MRI, and biopsy techniques described herein may improve detection and safety when a prostate biopsy is deemed necessary following prostate cancer screening.

Purpose: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part I of a two-part series that focuses on prostate cancer screening. Please refer to Part II for discussion of initial and repeat biopsies as well as biopsy technique., Materials and Methods: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles., Results: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsy, and biopsy technique., Conclusions: Prostate-specific antigen (PSA)-based prostate cancer screening in combination with shared decision-making (SDM) is recommended. Current data regarding risk from population-based cohorts provide a basis for longer screening intervals and tailored screening, and the use of available online risk calculators is encouraged.

The importance of residence time distribution modeling is acknowledged as a tool for enabling material tracking and control within a continuous manufacturing line in order to safeguard both product quality and production efficiency. One of the first unit-operations into a continuous direct compression line (i.e. CDC-line) worthwhile doing extensive RTD-analysis upon are the LIW-feeders since they dose the ingredients in a controlled way following the label claim and hence can directly influence critical quality attributes like content uniformity. An NIR measurement method was developed determining the RTD of selected powders at specific feeder settings. Step-change experiments using sodium saccharin as a tracer were conducted. In order to gain and in depth understanding of the material flow, spatial samples throughout the hopper were taken at predefined timepoints during the step change experiments. This revealed the presence of a bypass trajectory along the edges of the agitator, while in the center of the agitator an inner mixing volume in which the tracer concentration lags behind seemed to be present. Finally, a model based on a plug flow and continuous stirred tank reactor was evaluated. The fitted model was not able to capture this complex flow behavior and shows the need for an extended compartmental model distinguishing between a bypass trajectory formed by the agitator and an inner mixing volume., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Residence time distributions (RTDs) are a valuable tool for product tracking in the unit operations of a continuous line for manufacturing pharmaceutical oral solid dosage (OSD) and the integrated system itself. The first unit operation in such a continuous line in which extended intermixing can occur, is typically a feeder. The RTD of a feeder can be obtained by performing tracer experiments with a tracer material. A physical interpretation can be given to the observed tracer concentration responses by fitting a tanks-in-series (TIS) or compartmental model to it. Consequently, the internal mixing behaviour inside the feeder hopper can be rationalized. However, typically, a constant volume is assumed for the tanks or compartments in these models. This has led to several publications where the experimental set-up does not violate the constant volume assumption, i.e. one performs refills at a high hopper fill level. Here, we step away from this assumption and develop a set of differential equations for a 3-compartment model in order to account for a non-constant volume of the compartments. Moreover, the model distinguishes between a bypass trajectory formed by the agitator inside the feeder and an inner mixing volume, in which the tracer concentration lags on the tracer concentration in the bypass volume. This compartmentalization was inspired by the results obtained in a previous study using a spatial sampling method to assess the tracer concentration throughout the feeder hopper for different experimental runtimes. The developed model successfully describes the step responses for different refill regimes: the standard smooth first order plus dead time response (FOPDT) for a high refill regime and the more complex step response, including dips in the rising phase of the curve, for the low refill regime. As a consequence, a more thorough understanding of the complex mixing behaviour inside the feeder is obtained, which allows for an improved traceability. Next to that, the model delivers enhanced knowledge on the interaction between the residence time and the refill regime. The developed model was fitted to a data set, containing step change experiments for different pharmaceutical materials (Tablettose 80 (T80), Microcelac 100 (MCL), and Avicel PH101 (MCC)), different mass flow rates, and refill regimes. The experimentally observed phenomena could be reliably described by the proposed model. The model showed an improved transferability compared to typical TIS models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Context.—: The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status., Objective.—: To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy., Design.—: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Using the National Academy of Medicine-endorsed Grading of Recommendations Assessment, Development and Evaluation approach, the recommendations were derived from available evidence, strength of that evidence, open comment feedback, and expert panel consensus. Mismatch repair immunohistochemistry, microsatellite instability derived from both polymerase chain reaction and next-generation sequencing, and tumor mutation burden derived from large panel next-generation sequencing were within scope., Results.—: Six recommendations and 3 good practice statements were developed. More evidence and evidence of higher quality were identified for colorectal cancer and other cancers of the gastrointestinal (GI) tract than for cancers arising outside the GI tract., Conclusions.—: An optimal assay depends on cancer type. For most cancer types outside of the GI tract and the endometrium, there was insufficient published evidence to recommend a specific clinical assay. Absent published evidence, immunohistochemistry is an acceptable approach readily available in most clinical laboratories., Competing Interests: Authors' disclosures of potential conflicts of interest and author contributions are found in the Appendix at the end of this article.

Hyaluronan (HA) is a major component of peri- and extra-cellular matrices and plays important roles in many biological processes such as cell adhesion, proliferation and migration. The abundance, size distribution and presentation of HA dictate its biological effects and are also useful indicators of pathologies and disease progression. Methods to assess the molecular mass of free-floating HA and other glycosaminoglycans (GAGs) are well established. In many biological and technological settings, however, GAGs are displayed on surfaces, and methods to obtain the size of surface-attached GAGs are lacking. Here, we present a method to size HA that is end-attached to surfaces. The method is based on the quartz crystal microbalance with dissipation monitoring (QCM-D) and exploits that the softness and thickness of films of grafted HA increase with HA size. These two quantities are sensitively reflected by the ratio of the dissipation shift (ΔD) and the negative frequency shift (- Δf) measured by QCM-D upon the formation of HA films. Using a series of size-defined HA preparations, ranging in size from ~ 2 kDa tetrasaccharides to ~ 1 MDa polysaccharides, we establish a monotonic yet non-linear standard curve of the ΔD/ - Δf ratio as a function of HA size, which reflects the distinct conformations adopted by grafted HA chains depending on their size and surface coverage. We demonstrate that the standard curve can be used to determine the mean size of HA, as well as other GAGs, such as chondroitin sulfate and heparan sulfate, of preparations of previously unknown size in the range from 1 to 500 kDa, with a resolution of better than 10%. For polydisperse samples, our analysis shows that the process of surface-grafting preferentially selects smaller GAG chains, and thus reduces the average size of GAGs that are immobilised on surfaces comparative to the original solution sample. Our results establish a quantitative method to size HA and other GAGs grafted on surfaces, and also highlight the importance of sizing GAGs directly on surfaces. The method should be useful for the development and quality control of GAG-based surface coatings in a wide range of research areas, from molecular interaction analysis to biomaterials coatings., (© 2022. The Author(s).)

Context.—: The process for identifying patients with monoclonal gammopathies is complex. Initial detection of a monoclonal immunoglobulin protein (M protein) in the serum or urine often requires compilation of analytical data from several areas of the laboratory. The detection of M proteins depends on adequacy of the sample provided, available clinical information, and the laboratory tests used., Objective.—: To develop an evidence-based guideline for the initial laboratory detection of M proteins., Design.—: To develop evidence-based recommendations, the College of American Pathologists convened a panel of experts in the diagnosis and treatment of monoclonal gammopathies and the laboratory procedures used for the initial detection of M proteins. The panel conducted a systematic literature review to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were created based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework., Results.—: Nine guideline statements were established to optimize sample selection and testing for the initial detection and quantitative measurement of M proteins used to diagnose monoclonal gammopathies., Conclusions.—: This guideline was constructed to harmonize and strengthen the initial detection of an M protein in patients displaying symptoms or laboratory features of a monoclonal gammopathy. It endorses more comprehensive initial testing when there is suspicion of amyloid light chain amyloidosis or neuropathies, such as POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome, associated with an M protein., Competing Interests: Authors' disclosures of potential conflicts of interest and author contributions are found in the Appendix at the end of this article.

Introduction: The 2020 AUA microhematuria (MH) guideline stratifies patients into low, intermediate and high-risk for urologic malignancy based on established risk-factors for urothelial carcinoma. Notably, urine-based tumor markers (UBTMs) were not included in the risk classification. We evaluated the impact of incorporating UBTMs (cytology and multiple commercially available UBTMs) into this risk stratification., Methods: We performed a systematic review of performance characteristics of UBTMs for the detection of bladder cancer during hematuria evaluation, pooled the reported sensitivity and specificity, and calculated positive and negative likelihood ratios (LR). These were then applied to the estimated pre-test probability for the diagnosis for each AUA risk strata: low-risk 0.5%, intermediate-risk 1.0%, and high-risk (2%-3%) in order to calculate a post-test probability of bladder cancer in the event of a positive or negative test., Results: The pooled sensitivity for urinary cytology and commercially available UBTMs was 68% and 58%-95%, respectively while the specificity was estimated at 91% and 34%-90%, respectively. The positive LRs of UBTMs ranged from 2.1-7.67 and negative LRs ranged from 0.07-0.48. A negative UBTM was associated with a post-test probability of cancer for low, intermediate, and high-risk patients of 0-0.2%, 0.2%-0.5%, and 0.4%-1.1%, respectively. In the setting of a positive UBTM, the post-test probability of cancer for low, intermediate, and high-risk patients was 1.1%-3.7%, 2.1%-7.8%, 4.2%-19.2%, respectively., Conclusion: Pending prospective validation, UBTMs may be able to enhance risk stratification and inform shared decision-making over clinical factors alone and allow for re-classification of patients into higher or lower risk categories., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions., Materials/methods: The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text])., Results: Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article., Conclusion: Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.

Purpose: This AUA Guideline focuses on active surveillance (AS) and follow-up after intervention for adult patients with clinically-localized renal masses suspicious for cancer, including solid enhancing tumors and Bosniak 3/4 complex cystic lesions., Materials and Methods: In January 2021, the Renal Mass and Localized Renal Cancer guideline underwent additional amendment based on a current literature-search. This literature search retrieved additional studies published between July 2016 to October 2020 using the same Key Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. When sufficient evidence existed, the body of evidence was assigned strength-rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text])., Results: AS with potential delayed intervention should be considered for patients with solid, enhancing renal masses <2cm or Bosniak 3-4 lesions that are predominantly-cystic. Shared decision-making about AS should consider risks of intervention/competing mortality versus the potential oncologic benefits of intervention. Recommendations for renal mass biopsy and considerations for periodic clinical/imaging-based surveillance are discussed. After intervention, risk-based surveillance protocols are defined incorporating clinical/laboratory evaluation and abdominal/chest imaging designed to detect local/systemic recurrences and possible treatment-related sequelae, such as progressive renal-insufficiency., Conclusion: AS is a potential management strategy for some patients with clinically-localized renal masses that requires careful risk-assessment, shared decision-making and periodic-reassessment. Follow-up after intervention is designed to identify local/systemic recurrences and potential treatment-related sequelae. A risk-based approach should be prioritized with selective use of laboratory/imaging resources.

A key prediction of motivational theories of automatic imitation is that people imitate in-group over out-group members. However, research on this topic has provided mixed results. Here, we investigate the possibility that social group modulations emerge only when people can directly compare in- and out-group. To this end, we conducted three experiments in which we measured automatic imitation of two simultaneously shown hands: one in-group and one out-group hand. Our general hypothesis was that the in-group hand would be imitated more than the out-group hand. However, even though both explicit and implicit manipulation checks showed that we succeeded in manipulating participants' feelings of group membership, we did not find support for the predicted influence of group membership on automatic imitation. In contrast to motivational theories, this suggests that group membership does not influence who we do or do not imitate, not even in a contrastive multi-agent paradigm.

Context.—: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings., Objective.—: To develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma., Design.—: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were derived based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework., Results.—: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma., Conclusions.—: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions on specimen suitability, diagnostic capabilities, and correct use of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment., Competing Interests: Authors' disclosures of potential conflicts of interest and author contributions are found in the Appendix at the end of this article., (© 2021 College of American Pathologists.)

Objectives: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery lead to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings., The Aim of This Review Is to: develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma., Methods: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of the literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were derived based on the available evidence, the strength of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework., Results: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma., Conclusions: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions about specimen suitability, diagnostic capabilities, and correct utilization of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The authors of this guideline reviewed the urologic trauma literature to guide clinicians in the appropriate methods of evaluation and management of genitourinary injuries., Materials and Methods: The Panel amended the Guideline in 2020 to reflect additional literature published through February 2020. When sufficient evidence existed, the Panel assigned the body of evidence a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, the Panel provided additional information as Clinical Principles and Expert Opinions (See table 1[Table: see text])., Results: The Panel updated a total of six existing statements on renal, ureteral, bladder, urethra, and genital trauma. Additionally, four new statements were added based on literature released since the 2017 amendment. Statement 5b was added based on new evidence for treatment of hemodynamically unstable patients with renal trauma. Statement 20b was added based on new literature for percutaneous or open suprapubic tube placement following pelvic fracture urethral injury. Statements 30a and 30b were also added to provide guidance on ultrasonography for blunt scrotal injuries suggestive of testicular rupture and for performing surgical exploration with repair or orchiectomy for penetrating scrotal injuries respectively., Conclusions: These evidence-based updates to the AUA Guidelines further inform the treatment of urotrauma.

Context.—: The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples., Objective.—: To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies., Methods.—: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered., Results.—: Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples., Conclusions.—: Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens.

The perineuronal net (PNN) is a specialized extracellular matrix structure that surrounds subpopulations of neurons in the central nervous system (CNS). The appearance of PNNs on the cell surface marks the closure of the critical period during development and has been observed to reduce synaptic plasticity. Perineuronal nets comprise hyaluronan, chondroitin sulfate proteoglycans (CSPGs), link proteins, tenascin-R, and other components, some of which are substrates for a disintegrin-like and metalloprotease domain with thrombospondin type 1 motifs (ADAMTS) proteases. There is a high heterogeneity of PNNs in the CNS. Depending on which part of the CNS is studied, the PNNs may be observed surrounding the soma, or both the soma and proximal dendrites. The most robust marker for PNN is a lectin called Wisteria floribunda agglutinin. Here, we describe a method for preparing tissue for visualization of PNNs in CNS.

Purpose: The purpose of this guideline is to provide a clinical framework for the diagnosis and treatment of non-neurogenic overactive bladder (OAB)., Materials & Methods: The primary source of evidence for the original version of this guideline was the systematic review and data extraction conducted as part of the Agency for Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assessment Number 187 titled Treatment of Overactive Bladder in Women (2009). That report was supplemented with additional searches capturing literature published through December 2011. Following initial publication, this guideline underwent amendment in 2014 and 2018. The current document reflects relevant literature published through October 2018., Results: When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low). Such statements are provided as Standards, Recommendations, or Options. In instances of insufficient evidence, additional guidance information is provided as Clinical Principles and Expert Opinions., Conclusions: The evidence-based statements are provided for diagnosis and overall management of OAB, as well as for the various treatments. Diagnosis and treatment methodologies can be expected to change as the evidence base grows and as new treatment strategies become obtainable.

Background: For patients who are diagnosed with early-stage cutaneous melanoma, the principal therapy is wide surgical excision of the primary tumour and assessment of lymph nodes. The purpose of the present guideline was to update the 2010 Cancer Care Ontario guideline on wide local excision margins and sentinel lymph node biopsy (slnb), including treatment of the positive sentinel node, for melanomas of the trunk, extremities, and head and neck., Methods: Using Ovid, the medline and embase electronic databases were systematically searched for systematic reviews and primary literature evaluating narrow compared with wide excision margins and the use of slnb for melanoma of the truck and extremities and of the head and neck. Search timelines ran from 2010 through week 25 of 2017., Results: Four systematic reviews were chosen for inclusion in the evidence base. Where systematic reviews were available, the search of the primary literature was conducted starting from the end date of the search in the reviews. Where systematic reviews were absent, the search for primary literature ran from 2010 forward. Of 1213 primary studies identified, 8 met the inclusion criteria. Two randomized controlled trials were used to inform the recommendation on completion lymph node dissection.Key updated recommendations include:■ Wide local excision margins should be 2 cm for melanomas of the trunk, extremities, and head and neck that exceed 2 mm in depth.■ slnb should be offered to patients with melanomas of the trunk, extremities, and head and neck that exceed 0.8 mm in depth.■ Patients with sentinel node metastasis should be considered for nodal observation with ultrasonography rather than for completion lymph node dissection., Conclusions: Recommendations for primary excision margins, sentinel lymph node biopsy, and completion lymph node dissection in patients with cutaneous melanoma have been updated based on the current literature., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

Slag piles from mining activities are common worldwide, but in contrast to mine tailings the environmental impact of runoff from slag piles is less documented. This study was designed to assess the geochemistry and potential toxicity of water draining a large, 62.2ha slag pile in Sudbury, Ontario. The Coniston slag pile contains 12-20Mt of slag from smelting local Ni-Cu ore between 1913 and 1972. Slag leaching experiments confirmed slag is a source of sulphate (SO 4 ), heavy metals (including Fe, Al, Ni, Co, Cu, Zn, Pb, Cr, Mn) and base cations (Ca, K, Mg, Na). Concentrations of some metals draining through slag in column experiments were similar to concentrations measured at the base of the slag pile, although base cations, SO 4 and pH were much higher, possibly because of water inputs interacting with the surrounding basic glaciolacustrine landscape. The high pH rapidly precipitates metals, leading to high accumulations in surface sediments in the pond-wetland complex draining from the pile. Away from the pile's base, vegetation cover increases, which increases dissolved organic carbon (DOC) and nutrient concentrations in runoff along with metals with strong binding affinities (e.g. Cu). Total metal concentration in water and sediment exceed provincial guidelines, particularly near the slag pile, however WHAM7 modeling indicated the free metal ion concentration in water is very low. Nevertheless, 48-h toxicity experiments showed that water with greater concentrations of solutes collected close to the slag negatively impacts D. magna, suggesting water draining the slag pile can adversely impact biota in nearby drainage areas., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: This study aims to identify geographical disparities in perinatal mortality and morbidity in the province of Antwerp, Belgium. We performed a retrospective cohort study from an existing database. Data included from 1 January , 2000 to 31 December, 2009 and including all deliveries in the Province of Antwerp, Belgium. Collected outcome measures : fetal death, early and late neonatal death, preterm birth, low birth weight. Outcomes were analyzed according to postal code of the pregnant women's address., Results: A total of 167.246 deliveries in sixty postal codes were analyzed and statistically significant differences (p<0.001) between postal codes for all outcome measures except for early and late neonatal death were detected. Generally postal codes tend to have either high or low prevalences for all perinatal outcomes and two postal code zones had a significantly worse perinatal outcome on all fields. Major differences in perinatal outcome exist within the well-defined area of the relatively small province of Antwerp, Belgium., Conclusion: Perinatal outcome is strongly influenced by maternal postal code even within a relatively affluent European region demonstrating persistent health inequalities and suggesting further research is necessary to explain these differences and create interventions to diminish inequalities.

Aims: This clinical practice guideline was developed to provide evidence-based guidance on the frequency by which prostate-specific antigen (PSA) levels should be tested in men after curative-intent treatment for prostate cancer and to define the most appropriate diagnostic testing if biochemical recurrence occurs., Materials and Methods: An electronic search using OVID was used to systematically search the MEDLINE and EMBASE databases for systematic reviews and primary literature. A systematic review and practice guideline was written, reviewed and approved by the Guideline Development Group (GDG) and Program in Evidence-Based Care Report Approval Panel. External review by three prostate experts was completed, as well as an online consultation with healthcare professionals who were intended users of the guideline., Results: Three systematic reviews and seven primary studies were included in the evidence base. All identified literature reported on diagnostic imaging properties of diagnostic tests following biochemical recurrence., Conclusions: Due to a lack of empirical research, few evidenced-based recommendations could be made with respect to a follow-up schedule of PSA testing for prostate cancer survivors following curative-intent treatment, or detailing diagnostic testing upon detection of biochemical recurrence. Accordingly, the GDG focused substantial effort on critical examination of the identified evidence, existing clinical practice guidelines and on obtaining clinical expertise consensus using a modified Delphi method. Overall, the recommendations embedded in this guideline reflect the best practice to date for the efficient and effective clinical follow-up care of prostate cancer survivors., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: This clinical practice guideline was developed to determine the level of evidence supporting the clinical utility of commercially available multigene profiling assays and to provide guidance about whether certain breast cancer patient populations in Ontario would benefit from alternative tests in addition to Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.)., Methods: A systematic electronic Ovid search of the medline and embase databases sought out systematic reviews and primary literature. A systematic review and practice guideline was written by a working group and was then reviewed and approved by Cancer Care Ontario's Molecular Oncology Advisory Committee., Results: Twenty-four studies assessing the clinical utility of Oncotype dx, Prosigna (NanoString Technologies, Seattle, WA, U.S.A.), EndoPredict (Myriad Genetics, Salt Lake City, U.S.A.), and MammaPrint (Agendia, Irvine, CA, U.S.A.) were included in the evidence base., Conclusions: The clinical utility of multigene profiling assays is currently established for an appropriate subset of patients with estrogen receptor-positive, her2-negative, node-negative breast cancer for whom a decision to give chemotherapy is difficult to make. For patients with estrogen receptor-positive tumours who receive tamoxifen alone, Oncotype dx, Prosigna, and EndoPredict validly identify a low-risk population with favourable outcomes, indicating that a low-risk assay result is actionable and the decision to withhold chemotherapy is supported. Clinical evidence indicates that a high Oncotype dx recurrence score can predict for chemotherapy benefit, but a high Prosigna or EndoPredict score, although prognostic, is not, based on clinical trial evidence, directly actionable. Prosigna and EndoPredict are statistically more likely to identify a population at risk for recurrence beyond 5 years, but that information is currently not actionable because of a lack of interventional studies.

Peat cores have long been used to reconstruct atmospheric metal deposition; however, debate remains regarding how well historical depositional patterns are preserved in peat. This study examined peat cores sampled from 14 peatlands in the Sudbury region of Ontario, Canada, which has a well-documented history of acid and metal deposition. Copper (Cu) and lead (Pb) concentrations within individual peat cores were strongly correlated and were elevated in the upper 10 cm, especially in the sites closest to the main Copper Cliff smelter. In contrast, nickel (Ni) and cobalt (Co) concentrations were often elevated at depths greater than 10 cm, indicating much greater post-depositional movement of these metals compared with Cu and Pb. Post-depositional movement of metals is supported by the observation that Ni and Co concentrations in peat pore water increased by approximately 530 and 960% for Ni and Co, respectively between spring and summer due to drought-induced acidification, but there was much less change in Cu concentration. Sphagnum cover and (210)Pb activity measured at 10 cm at the 14 sites significantly increased with distance from Copper Cliff, and the surface peat von Post score decreased with distance from Copper Cliff, indicating the rate of peat formation increases with distance from Sudbury presumably as a result of improved Sphagnum survival. This study shows that the ability of peat to preserve deposition histories of some metals is strongly affected by drought-induced post-depositional movement and that loss of Sphagnum due to air pollution impairs the rate of peat formation, further affecting metal profiles in peatlands., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Knowledge of the expression profile of a gene is a critical piece of information required to build an understanding of the normal and essential functions of that gene and any role it may play in the development or progression of disease. High-throughput, large-scale efforts are on-going internationally to characterise reporter-tagged knockout mouse lines. As part of that effort, we report an open access adult mouse expression resource, in which the expression profile of 424 genes has been assessed in up to 47 different organs, tissues and sub-structures using a lacZ reporter gene. Many specific and informative expression patterns were noted. Expression was most commonly observed in the testis and brain and was most restricted in white adipose tissue and mammary gland. Over half of the assessed genes presented with an absent or localised expression pattern (categorised as 0-10 positive structures). A link between complexity of expression profile and viability of homozygous null animals was observed; inactivation of genes expressed in ≥ 21 structures was more likely to result in reduced viability by postnatal day 14 compared with more restricted expression profiles. For validation purposes, this mouse expression resource was compared with Bgee, a federated composite of RNA-based expression data sets. Strong agreement was observed, indicating a high degree of specificity in our data. Furthermore, there were 1207 observations of expression of a particular gene in an anatomical structure where Bgee had no data, indicating a large amount of novelty in our data set. Examples of expression data corroborating and extending genotype-phenotype associations and supporting disease gene candidacy are presented to demonstrate the potential of this powerful resource., (© 2015. Published by The Company of Biologists Ltd.)

Recent evidence indicates that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that breast carcinoma and tumorigenic breast cell lines have higher 5alpha-reductase and lower 3alpha-hydroxysteroid oxidoreductase (3alpha-HSO) and 20alpha-HSO activities and mRNA expression levels than normal tissue and non-tumorigenic cell lines. The 5alpha-reduced progesterone metabolites such as 5alpha-dihydroprogesterone (5alphaP) promote both mitogenic and metastatic activity in breast cell lines in culture, whereas the 4-pregnene metabolites, 4-pregnen-3alpha-ol-20-one (3alphaHP) and 4-pregnen-20alpha-ol-3-one (20alphaHP) have the opposite (anti-cancer-like) effects. The 5alpha-reductase inhibitor dutasteride has been shown to inhibit 5alpha-reduction of testosterone to 5alpha-dihydrotestosterone in prostate tissue, resulting in decreased prostate volume. The aim of this study was to determine if dutasteride is an effective inhibitor of progesterone 5alpha-reduction in human breast cell lines and if such inhibition reduces mammary cell proliferation and detachment. The effect of dutasteride on progesterone metabolizing enzyme activities and mRNA expression were examined in tumorigenic MCF-7 and non-tumorigenic MCF-10A human breast cell lines. Dutasteride (10(-6)M) inhibited progesterone conversion to 5alpha-pregnanes by >95% and increased 4-pregnene production. The results indicated that effects of dutasteride on the progesterone metabolizing enzymes are due to direct inhibition of 5alpha-reductase activity and to altered levels of expression of 5alpha-reductase and HSO mRNAs. Treatment of cells with progesterone without medium change for 72 h resulted in significant conversion to 5alpha-pregnanes and increases in cell proliferation and detachment. The increases in proliferation and detachment were blocked by dutasteride and were reinstated by concomitant treatment with 5alphaP, providing proof-of-principle that the effects were due not to progesterone but to the 5alpha-reduced metabolites. This study provides the first evidence that dutasteride is a potent progesterone 5alpha-reductase inhibitor and that such inhibition may be beneficial in breast cancer.