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Context.— Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized. Objective.— To investigate their morphologic, immunohistochemical, and molecular features. Design.— Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing. Results.— The mean age at diagnosis was 69 years (42–81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%). Conclusions.— Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous.

Optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) are imaging technologies invented in the 1980s that have revolutionized the field of in vivo retinal diagnostics and are now commonly used in ophthalmology clinics as well as in vision science research. Adaptive optics (AO) technology enables high-fidelity correction of ocular aberrations, resulting in improved resolution and sensitivity for both SLO and OCT systems. The potential of gathering multi-modal cellular-resolution information in a single instrument is of great interest to the ophthalmic imaging community. Although similar instruments have been developed for imaging the human retina, developing such a system for mice will benefit basic science research and should help with further dissemination of AO technology. Here, we present our work integrating OCT into an existing mouse retinal AO-SLO system, resulting in a multi-modal AO-enhanced imaging system of the living mouse eye. The new system allows either independent or simultaneous data acquisition of AO-SLO and AO-OCT, depending on the requirements of specific scientific experiments. The system allows a data acquisition speed of 200 kHz A-scans/pixel rate for OCT and SLO, respectively. It offers ∼6 µm axial resolution for AO-OCT and a ∼1 µm lateral resolution for AO-SLO-OCT imaging.

Introduction The purpose of this study is to determine which patient factors predict two-year postoperative met expectations in a cohort of patients undergoing knee surgery. Additionally, this study aims to measure the association between met expectations and postoperative outcomes. Methods 319 patients undergoing knee surgery at one institution were studied. Patients completed patient-reported outcome questionnaires prior to surgery and again two years postoperatively. Preoperative Expectations and postoperative Met Expectations were measured using the Musculoskeletal Outcomes and Data Evaluation Management System (MODEMS) Expectations domain. Results The mean Met Expectations score was significantly lower than the preoperative Expectations Score. Worse two-year Met Expectations were associated with older age, higher BMI, greater comorbidities, more previous surgeries, black race, unemployment, lower income, government insurance, Worker's Compensation, smoking, and no injury prior to surgery. Greater Met Expectations were correlated with better scores on all two-year outcome measures as well as greater improvement on most outcome measures. Race, insurance status, function, mental health, and knee pain were found to be independent predictors of Met Expectations. Conclusion This study identified multiple patient factors and outcome measures that were associated with Met Expectations two years after knee surgery.

BACKGROUND Endometriosis-associated deep dyspareunia is associated with reduced sexual quality of life, lower self-esteem, and impaired sexual function. OBJECTIVE The primary objective is to assess the acceptability of a phallus length reducer (brand name: Ohnut [OhnutCo]), which is a buffer worn over the penis or a penetrating object to reduce endometriosis-associated deep dyspareunia, and the feasibility of a definitive randomized controlled trial (RCT). The secondary objective is to obtain estimates of the effectiveness of the buffer. An embedded substudy will explore the acceptability and the preliminary validity and reliability of a vaginal insert for the self-assessment of deep dyspareunia. METHODS Ours is an investigator-initiated, 2-arm RCT. We will recruit 40 patient participants with diagnosed endometriosis between the ages of 19 and 49 years, as well as their sexual partners. The participating couples will be randomized in a 1:1 ratio into the experimental arm or the waitlist control arm. The length of the study period will be 10 weeks, during which time all participants will record deep dyspareunia severity following each episode of sexual intercourse. In weeks 1 to 4, all patient participants will record deep dyspareunia severity at each sexual encounter. In weeks 5 to 10, participants in the experimental arm will use the buffer during vaginal penetration; participants in the waitlist control arm will continue engaging in vaginal penetration as usual. Participants will complete questionnaires for assessing measures of anxiety, depression, and sexual function at baseline, at 4 weeks, and at 10 weeks. In the substudy, patient participants will self-assess dyspareunia by using a vaginal insert on 2 occasions, at least 1 week apart. The primary outcomes—the acceptability and feasibility of the buffer—will be assessed with descriptive statistics, and the secondary outcome—phallus length reducer effectiveness—will be assessed by using an analysis of covariance–based approach. For the vaginal insert, we will assess acceptability, test-retest reliability, and convergent validity via correlation analyses comparing the use of the insert to clinical examination in terms of dyspareunia assessment outcomes. RESULTS Our pilot will provide initial data on the acceptability and effectiveness of the buffer and the feasibility of the study methodology. The results from our study are expected to be submitted for publication by the spring of 2023. As of September 2021, we have consented 31 couples into the study. CONCLUSIONS Our study will provide preliminary evidence for the self-assessment and management of endometriosis-associated deep dyspareunia. The findings will inform the decision to proceed to a definitive RCT. CLINICALTRIAL ClinicalTrials.gov NCT04370444; https://clinicaltrials.gov/ct2/show/NCT04370444 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/39834

The medial collateral ligament (MCL) is a major contributor to knee joint stability and is the most common ligament involved in knee injuries. When conservative management for high-grade MCL injuries fails, operative treatment is indicated. Various reconstruction techniques are described in the literature. The following report describes a reconstruction technique based on the modified Bosworth. We present a step-by-step technique for using autograft semitendinosus tendon as a double limb to reconstruct the MCL and if necessary, the posterior oblique ligament. The technique is versatile with respect to a spectrum of MCL injury patterns, isometric, incorporates techniques that are common to other knee reconstructions, and uses readily available autograft. It has been used extensively by the senior authors as an adjunct/augmentation to the repair of acute MCL injuries as well as in the reconstruction of chronic MCL laxity. The technique restores stability to rotation and valgus stress while maintaining the distal insertion of the semitendinosus intact.

There have been conflicting data on the relative frequency of common forms of primary nephrotic syndrome (PNS). We undertook this study to look at the causes of PNS in the latest decade from our biopsy population, with a special attention to breakdown by race. Retrospective chart review of all cases of adult PNS extracted from a database of 1388 cases for the last 10 years. We were careful to exclude patients with secondary disease and without the full nephrotic syndrome. There were 115 cases of PNS. Overall, MN was the most common lesion (40.0%), followed by minimal change disease (MCD) (34.0%), focal segmental glomerulosclerosis (FSGS) (13.0%), and IgA nephropathy (IgAN) (11.3%). Among whites, MN was the most common cause of NS (41.7%), followed by MCD (33.3%), IgAN (16.7%), and FSGS (6.3%). Among blacks, FSGS was the most common lesion (33.3%) followed closely by MN (29.6%), and MCD (26.0%). IgAN was present in 7.4%. Among multiracial patients (MR), MGN was the most common (50%) followed by MCD (45.5%) and FSGS (4.5%). In Asians, MCD (50.1%) and MGN (33.3%) were the most common, followed by FSGS and IgAN with 8.3% each. MN and MCD were the most common causes of PNS in our population, with FSGS much less common overall. This is especially the case among whites and MR. Among blacks, MN and FSGS were almost codominant causes. The apparent decreased prevalence of FSGS may be related to more effective exclusion of secondary and maladaptive causes.

Objectives This literature review was performed to assess the risk of bleeding in dental implantation procedures in patients taking antiplatelet drugs (APs), oral anticoagulants (OACs) and direct oral anticoagulants (DOACs). Study Design MEDLINE and SCOPUS databases were searched for English language publications through October 2019, using the keywords “dental implants,” “dental implantation,” “anticoagulants,” “platelet aggregation inhibitors,” and “hemorrhage.” Reference lists of relevant articles were also hand searched. Collected data regarding dental implantation procedures, type of medications (APs, OACs and DOAC), and postoperative bleeding episodes were analyzed. Results Nine studies were included in the review. Postoperative bleeding occurred in 10 (2.2%) of 456 of cases involving dental implant placements; in all of those cases, bleeding was controlled with the use of local hemostatic agents. The bleeding incidence in patients on antiplatelet medications was 0.4% (range 1 of 253 to 1 of 261). Among those taking oral anticoagulants, the bleeding incidence was 5.7% (range 6 of 105 to 6 of 113), and among those on direct oral anticoagulants, the bleeding incidence was 3.3% (3 of 90). The numbers of more extensive surgical procedures (i.e., sinus lift and bone augmentation procedures) were small, and additional information regarding the surgery, the specific antithrombotic used, or bleeding was often not provided, so further analysis was not possible. Conclusions Evidence supports continuing OACs, DOACs, or APs during dental implant surgery.

The purpose of this study was to evaluate Patient-Reported Outcomes Measurement Information System physical function (PROMIS PF) 2 years following knee surgery, and identify preoperative factors associated with postoperative PROMIS PF. Three hundred and sixty-five patients, age 17 years and older, undergoing knee surgery at one institution were studied. Patients completed multiple questionnaires prior to surgery and again 2 years postoperatively including PROMIS PF, International Knee Documentation Committee (IKDC), joint and body numeric pain scales (NPS), Tegner's activity scale (TAS), and Marx's activity rating scale (MARS). Mean PROMIS PF improved from 41.4 to 50.9 at 2 years postoperatively (p

Tribocorrosion involves mechanical wear in a corrosive environment, damaging the protective oxide layer of passivating alloys and increasing material loss rates. Here, we develop a nanoscale, in situ technique using scanning probe microscopy in an electrochemical cell to explore the phase-by-phase tribocorrosion behavior of a heat-treated duplex stainless-steel alloy with secondary phases. We found that under anodic potentials well within the passive oxide region, sliding mechanical contact initiated pitting corrosion and increased electrochemical cell current localized to regions undergoing pitting. Secondary phases were most vulnerable to pitting corrosion during sliding, particularly secondary austenite which is chromium-depleted relative to the matrix steel phases. Under certain conditions, even sigma phases of high nobility were damaged from pits that originate from chromium nitrides. Initiation sites coincide with nanoscale surface voids created at chromium nitride inclusions under a threshold contact stress. Below the initiation stress, no pitting or corrosive wear was observed on sensitized phases. Material loss ceased to propagate when sliding stresses were removed but accelerated when sliding contact stresses were increased. Wear rates and current in the cell were both linearly correlated with material loss. Electrochemical current data were used to monitor oxide penetration spatially but could not be used to quantify material loss. In situ tribocorrosion using a scan probe tip is a viable platform to resolve mechanisms of failure that originate at the nanoscale on actively passivated metal surfaces.

Solitary fibrous tumors (SFTs) are rare soft tissue neoplasms that can impact the central nervous system (CNS). SFTs comprise

Barnacles interest the scientific community for multiple reasons: their unique evolutionary trajectory, vast diversity and economic impact—as a harvested food source and also as one of the most prolific macroscopic hard biofouling organisms. A common, yet novel, trait among barnacles is adhesion, which has enabled a sessile adult existence and global colonization of the oceans. Barnacle adhesive is primarily composed of proteins, but knowledge of how the adhesive proteome varies across the tree of life is unknown due to a lack of genomic information. Here, we supplement previous mass spectrometry analyses of barnacle adhesive with recently sequenced genomes to compare the adhesive proteomes of Pollicipes pollicipes (Pedunculata) and Amphibalanus amphitrite (Sessilia). Although both species contain the same broad protein categories, we detail differences that exist between these species. The barnacle-unique cement proteins show the greatest difference between species, although these differences are diminished when amino acid composition and glycosylation potential are considered. By performing an in-depth comparison of the adhesive proteomes of these distantly related barnacle species, we show their similarities and provide a roadmap for future studies examining sequence-specific differences to identify the proteins responsible for functional differences across the barnacle tree of life.

CONTEXT During the past two decades, bedside ultrasound has revolutionized the practice of emergency medicine. Physicians are now expected to be competent in utilizing ultrasound skills, for patients presenting with conditions ranging from trauma to skin evaluations. The overall purpose of this quality improvement/patient safety (QIPS) project was to evaluate the effectiveness of a pair of five-hour, hands-on didactic/training sessions, aimed at preparing a sample of emergency medicine physicians, residents and medical students to perform peripheral ultrasound-guided nerve blocks. METHODS The study location was set in a community-based emergency medicine program in Pontiac, Michigan. Data was collected from N = 54 emergency medicine residents, physicians and medical students. Data was collected from two training sessions in November 2017 and January 2018. The training consisted of a 12-question pre-test, followed by five hours of hands on & didactic training, with a subsequent post-test containing the same questions. RESULTS The authors compiled the data from both training sessions and found that the participants had an average correct percentage of 5.52 of 12 (46%) on the pre-test. After attending the training session, participants had an overall correct percentage of 9.24 of 12 (77%) on the post-test. This pre-to post-training increase of the mean scores was statistically significant, t (53) = -10.76 (p < 0.01), with an effect size (Cohen’s d) of 1.82. Post hoc power calculations utilizing the d = 1.82 effect size revealed statistical power (1- β) of 100%. CONCLUSIONS The results of this QIPS evaluation project suggest that emergency physicians, residents and medical students may achieve an improved understanding of key ultrasound-guided nerve block material after a single five-hour session of hands-on training and didactics. Going forward, additional studies employing larger sample sizes that allow for outcome stratification by group (emergency physicians, residents, or medical students) along with relevant demographic variables (age, years in practice, etc.) in similar settings are needed to further verify these findings.

Background:Osteochondral allograft (OCA) transplantation has evolved into a first-line treatment for large chondral and osteochondral defects, aided by advancements in storage protocols and a growing body of clinical evidence supporting successful clinical outcomes and long-term survivorship. Despite the body of literature supporting OCAs, there still remains controversy and debate in the surgical application of OCA, especially where high-level evidence is lacking.Purpose:To develop consensus among an expert group with extensive clinical and scientific experience in OCA, addressing controversies in the treatment of chondral and osteochondral defects with OCA transplantation.Study Design:Consensus statement.Methods:A focus group of clinical experts on OCA cartilage restoration participated in a 3-round modified Delphi process to generate a list of statements and establish consensus. Questions and statements were initially developed on specific topics that lack scientific evidence and lead to debate and controversy in the clinical community. In-person discussion occurred where statements were not agreed on after 2 rounds of voting. After final voting, the percentage of agreement and level of consensus were characterized. A systematic literature review was performed, and the level of evidence and grade were established for each statement.Results:Seventeen statements spanning surgical technique, graft matching, indications, and rehabilitation reached consensus after the final round of voting. Of the 17 statements that reached consensus, 11 received unanimous (100%) agreement, and 6 received strong (80%-99%) agreement.Conclusion:The outcomes of this study led to the establishment of consensus statements that provide guidance on surgical and perioperative management of OCAs. The findings also provided insights on topics requiring more research or high-quality studies to further establish consensus and provide stronger evidence.

Pluvial floods in urban areas are caused by local, fast storm events with very high rainfall rates, which lead to inundation of streets and buildings before the storm water reaches a watercourse. An increase in frequency and intensity of heavy rainfall events and an ongoing urbanization may further increase the risk of pluvial flooding in many urban areas. Currently, warnings for pluvial floods are mostly limited to information on rainfall intensities and durations over larger areas, which is often not detailed enough to effectively protect people and goods. We present a proof‐of‐concept for an impact‐based forecasting system for pluvial floods. Using a model chain consisting of a rainfall forecast, an inundation, a contaminant transport and a damage model, we are able to provide predictions for the expected rainfall, the inundated areas, spreading of potential contamination and the expected damage to residential buildings. We use a neural network‐based inundation model, which significantly reduces the computation time of the model chain. To demonstrate the feasibility, we perform a hindcast of a recent pluvial flood event in an urban area in Germany. The required spatio‐temporal accuracy of rainfall forecasts is still a major challenge, but our results show that reliable impact‐based warnings can be forecasts are available up to 5 min before the peak of an extreme rainfall event. Based on our results, we discuss how the outputs of the impact‐based forecast could be used to disseminate impact‐based early warnings., Plain Language Summary: Pluvial floods are caused by local rain storms with extreme rainfall rates, which leads to immediate flooding of streets and buildings in urban areas. These events are expected to increase in the future due to climate change and growing urban areas. Pluvial floods are directly caused by a rainstorm, which gives citizens and emergency responders usually only a few minutes to act. Existing forecasting systems for pluvial floods are limited to rainfall forecasts that neither provide information about where a flood might occur nor how severe the impacts will be. Here, the main challenge is that current computer models that predict inundation take too long to run to release flood forecasts early enough. We present a new inundation model that can predict inundation for an upcoming flood event in a fraction of the time of existing models. We combine this model with models that predict the spreading of contamination (e.g., from a car accident) and the damage to residential buildings. For a real flood event we can show that this information can be released up to 5 min before the rainfall peak, which gives citizens and emergency responders the opportunities to safe lives and protect important valuables., Key Points: First impact‐based forecasting for pluvial foods. Artificial neural network inundation model significantly cuts calculation time to 0.1% of a physically based model with comparable accuracy. Forecast with estimates for inundated areas, spreading of contaminants and expected damage could be released 5 min before peak rainfall., Bundesministerium für Bildung und Forschung (BMBF), Z Zurich Foundation, Grantham Foundation for the Protection of the Environment, ESRC Centre for Climate Change Economics and Policy: ES/R009708/1

BACKGROUND: Patient satisfaction metrics are increasingly being utilized as tools to evaluate the quality of healthcare and affect reimbursements. The objectives of this study were to (1) identify factors associated with two-year patient satisfaction after elective knee surgery, (2) compare the Surgical Satisfaction Questionnaire-8 (SSQ-8) and a numeric satisfaction scale (NSS), and (3) determine if two-year patient satisfaction can be predicted based on preoperative factors. METHODS: A total of 365 patients undergoing elective knee surgery at a single center were administered questionnaires to assess demographics, medical history, and various patient-reported outcomes preoperatively and at two years postoperatively. Patient satisfaction was measured at two years postoperatively with SSQ-8 and NSS. Bivariate and multivariate statistical analyses were performed to identify significant associations and independent predictors of satisfaction. RESULTS: SSQ-8 and NSS scores were significantly correlated (r(s) = 0.68, P

Proportional electroluminescence (EL) in noble gases is used in two-phase detectors for dark matter searches to record (in the gas phase) the ionization signal induced by particle scattering in the liquid phase. The "standard" EL mechanism is considered to be due to noble gas excimer emission in the vacuum ultraviolet (VUV). In addition, there are two alternative mechanisms, producing light in the visible and near infrared (NIR) ranges. The first is due to bremsstrahlung of electrons scattered on neutral atoms ("neutral bremsstrahlung", NBrS). The second, responsible for electron avalanche scintillation in the NIR at higher electric fields, is due to transitions between excited atomic states. In this work, we have for the first time demonstrated two alternative techniques of the optical readout of two-phase argon detectors, in the visible and NIR range, using a silicon photomultiplier matrix and electroluminescence due to either neutral bremsstrahlung or avalanche scintillation. The amplitude yield and position resolution were measured for these readout techniques, which allowed to assess the detection threshold for electron and nuclear recoils in two-phase argon detectors for dark matter searches. To the best of our knowledge, this is the first practical application of the NBrS effect in detection science., Comment: 26 pages, 22 figures, 3 tables

The base plate of the acorn barnacle

Purpose Approximately 25 % of DCIS diagnosed on breast core needle biopsy (CNB) is upgraded to invasive carcinoma on surgical excision. Risk factors to predict the upgrade on excision are not well established, leading many patients to be over or under-treated. EZH2 was shown to be associated with aggressive behavior of cancer from many sites, including breast cancer. We aimed to analyze EZH2 expression and tumor infiltrating lymphocytes (TILs) in DCIS as predictive factors for an upgrade on excision. Methods We assessed EZH2 expression in 34 DCIS cases diagnosed on CNB and upgraded to invasive carcinoma on excision. Then, we compared these cases with 60 control cases that were not upgraded on excision. A staining score for DCIS (0–12) was obtained by multiplying the staining intensity (0–3) and the percentage of positive cells (1–4). The nuclear staining score ≥6 was considered as ‘high’ expression. Results 46 of 94 (49 %) DCIS on CNB showed high EZH2 expression. EZH2 expression was directly correlated with TILs density, nuclear grade, HER2 expression, Ki-67 index and negative ER status. On univariate analysis, upgrade on excision was associated with high EZH2 expression, high TILs density, negative ER status and high Ki-67 index. Multivariate analysis revealed the high EZH2 expression as the only independent predictive factor for upgrade on excision. Conclusions Our study revealed the high EZH2 expression as the only independent predictive factor for an upgrade on excision. Future studies should focus on the evaluation of EZH2 expression in tumor-microenvironment interaction in terms of diagnostic, treatment and prognostic purposes.

Acorn barnacles are major marine fouling organisms. Their success is largely due to an ability to adhere to diverse substrates via a sub-micron thick proteinaceous adhesive layer that develops as the organism molts and expands its base. Recent work has expanded the set of proteins identified within the adhesive interface, but one outstanding question concerns their spatial distribution throughout the organism. Here, we employ immunological analysis of Amphibalanus amphitrite tissue sections and identify the presence of two cement proteins, AaCP19-1 and AaCP43-1, in areas far removed from the adhesive interface. Confocal imaging reveals specific staining along different tissue linings of the organism as well as other non-cementing regions. Additionally, we employ a modified, pressure cycling technology approach to recover protein from histological tissue sections to perform proteomics analysis. Mass spectrometry analysis of proteins recovered from transverse histological sections of the upper portion of barnacles indicates the presence of these same proteins, complementing the immunostaining observations. The proteomics analysis also revealed the presence of other proteins first identified in the adhesive layer. While some proteins are clearly enriched at the surface interface, our findings challenge the concept that cement proteins are exclusive to the substrate interface and suggest they may have an expanded physiological role beyond substrate adhesion-related processes of A. amphitrite.

There have been conflicting data on the relative frequency of common forms of primary nephrotic syndrome (PNS). We undertook this study to look at the causes of PNS in the latest decade from our biopsy population, with a special attention to breakdown by race.Retrospective chart review of all cases of adult PNS extracted from a database of 1388 cases for the last 10 years. We were careful to exclude patients with secondary disease and without the full nephrotic syndrome.There were 115 cases of PNS. Overall, MN was the most common lesion (40.0%), followed by minimal change disease (MCD) (34.0%), focal segmental glomerulosclerosis (FSGS) (13.0%), and IgA nephropathy (IgAN) (11.3%). Among whites, MN was the most common cause of NS (41.7%), followed by MCD (33.3%), IgAN (16.7%), and FSGS (6.3%). Among blacks, FSGS was the most common lesion (33.3%) followed closely by MN (29.6%), and MCD (26.0%). IgAN was present in 7.4%. Among multiracial patients (MR), MGN was the most common (50%) followed by MCD (45.5%) and FSGS (4.5%). In Asians, MCD (50.1%) and MGN (33.3%) were the most common, followed by FSGS and IgAN with 8.3% each.MN and MCD were the most common causes of PNS in our population, with FSGS much less common overall. This is especially the case among whites and MR. Among blacks, MN and FSGS were almost codominant causes. The apparent decreased prevalence of FSGS may be related to more effective exclusion of secondary and maladaptive causes.