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Faculty development programs play a crucial role in enhancing learning by equipping educators with the necessary skills, knowledge, and pedagogical strategies to teach more effectively. One such program is the Promoting Active Learning in Analytical Chemistry (PALAC) workshop, which aimed to educate faculty on methods to create and use active learning course materials to support students during the process of learning. This research aimed to assess the design of classroom instructional materials generated by faculty that attended the PALAC workshops. The theories of Vygotsky’s zone of proximal development and scaffolding were used as lenses to characterize the materials because they describe the benefits of providing support through the process of developing knowledge. The active learning materials were analyzed by assigning the cognitive levels of processing, as described by Marzano’s taxonomy, to all questions asked across 134 in-class activities. The use of the cognitive levels of processing allowed the researchers to gauge the presence of scaffolding by tracking how the cognitive levels of processing changed from question to question across each in-class activity. The results from this study indicate that the majority of materials provide opportunities for students to engage with higher-order questions, but there is less evidence for the effective and consistent structuring of the materials. These results have implications for future faculty development programs, suggesting the need to allot more time for faculty to practice developing effective classroom materials. In conjunction, this work demonstrates the effective use of Marzano’s taxonomy in assessing the cognitive structure of in-class activities.

The ocean annually absorbs about a quarter of all anthropogenic carbon dioxide (CO2) emissions. Global estimates of air–sea CO2fluxes are typically based on bulk measurements of CO2in air and seawater and neglect the effects of vertical temperature gradients near the ocean surface. Theoretical and laboratory observations indicate that these gradients alter air–sea CO2fluxes, because the air–sea CO2concentration difference is highly temperature sensitive. However, in situ field evidence supporting their effect is so far lacking. Here we present independent direct air–sea CO2fluxes alongside indirect bulk fluxes collected along repeat transects in the Atlantic Ocean (50° N to 50° S) in 2018 and 2019. We find that accounting for vertical temperature gradients reduces the difference between direct and indirect fluxes from 0.19 mmol m−2d−1to 0.08 mmol m−2d−1(N= 148). This implies an increase in the Atlantic CO2sink of ~0.03 PgC yr−1(~7% of the Atlantic Ocean sink). These field results validate theoretical, modelling and observational-based efforts, all of which predicted that accounting for near-surface temperature gradients would increase estimates of global ocean CO2uptake. Accounting for this increased ocean uptake will probably require some revision to how global carbon budgets are quantified.

The colon is the most common site for endometriosis outside the genital tract. It has a varied presentation and can mimic numerous other conditions, both clinically and pathologically. We investigated the clinicopathological features of a series of colorectal endometriosis with a particular emphasis on the features seen in cases with colonic mucosal involvement. A total of 114 consecutive cases of colorectal endometriosis were reviewed. Forty-eight percent did not have a prior diagnosis of endometriosis and in 34 patients (30%) the endometriosis was determined as the cause for the presentation. Mucosal involvement was present in 31 specimens. Features of chronic colitis were seen in the adjacent mucosa in 90% of cases whilst there were glandular changes mimicking adenocarcinoma in two cases (1.8%). Fifty percent of cases with mucosal involvement also showed glands with a hybrid intestinal-endometrial phenotype by morphology and/or by immunohistochemistry. Endometriosis is an important mimic of other conditions.

This article discusses the design and optimization of a unique high-temperature superconducting (HTS) air-core pulse transformer for the new class of dc series-type hybrid circuit breakers (S-HCBs) operating in the liquid nitrogen under cryogenic environment. The HTS secondary windings of the new pulse transformer carry a dc load current offering ultralow power loss during the normal operation unlike the conventional solid state circuit breakers. Unlike the prior-art HTS power transformers and the superconducting fault current limiters, the new pulse HTS transformer is uniquely designed to prevent the HTS tapes from quenching despite the set of constraints imposed by the S-HCB operation including a large pulse current up to 6 kA and high mechanical stress. A new transformer optimization methodology is proposed using the genetic algorithm in MATLAB coupled with Simulink and a finite element model in COMSOL to find the optimal transformer design meeting the overall 10 kV/150 A S-HCB design requirements within the electromagnetic constraints of the HTS. A 10 kV/150 A HTS transformer prototype is built and the electrical parameters are measured and found consistent with the simulated parameters. The S-HCB with the HTS transformer is tested at 600 V/30 A and 5 kV/150 A to validate the design. The experimental and COMSOL simulation results showed the successful operation of the HTS transformer and the fault currents of 30 and 150 A were forced down to zero within ${\text{10}}\,\mu \text{s}$ and remain as a small ripple current for ${\text{200}}\,\mu \text{s}$ before a series mechanical switch opens arclessly and with no damage caused to the HTS windings.

The article introduces the #Maneuver Warfare Card Game (MW: TCG) as a solution to the lack of accessible and relevant wargaming options for Marines. The game is a deck construction-style wargame that incorporates Marine warfighting philosophy and explores the complexities of war in various domains. It aims to be accessible, relevant, and fun, and can be easily carried in a cargo pocket. The game's mechanics involve draining the opponent's "Will" to achieve victory, representing their national commitment to the conflict. The article also mentions the author's design philosophy and the use of generative artificial intelligence to create unique images for the game. Additionally, the text briefly advertises the availability of the game for pre-order and highlights the importance of supporting the Marines through the Samuel Nicholas Society. [Extracted from the article]

Traction motors onboard electric vehicles (EVs) are faced with ever-increasing power density requirements and cost reduction challenges. Although permanent magnet (PM) traction motors have been favored for their potential of higher power densities, the price and supply volatility of PM materials are the major drawbacks. Instead of a single load point, the performance of a traction motor needs to be optimized over various combinations of torque and speed to represent real-world vehicular driving scenarios, which tends to be a time-consuming task with direct optimizations. In this article, as a PM-free solution, a wound field synchronous motor (WFSM) is designed and optimized using a metamodel-based approach to maximize its efficiency over a custom set of load points, while utilizing a fully per-unitized geometry template. The workflow has proven to be timesaving and the optimal design is prototyped and tested.

As a metric for measuring the combined space harmonic content of electric machine winding magnetomotive force (MMF), the winding total harmonic distortion (THD) is defined with an infinite series. Without truncation, the exact THD can be evaluated via a “family grouping” facilitated by a “family sum” over the fewest possible winding factors. Uniformly applicable to distributed windings and fractional-slot concentrated windings (FSCWs), this procedure also explains the inherent difference in harmonic content between both winding categories. Furthermore, the minimal THD (mTHD) that can be achieved by optimizing a winding is revealed with a closed-form expression. While intended for windings, the mTHD concept also benefits the design of low harmonic content rotor magnetic fields. Examples of both winding and rotor mTHD designs are provided.

The article is a response to a previous piece on professional military education (PME) in the Marine Corps Gazette. The author criticizes the previous article for misunderstanding the difference between training and education and for not being aware of the discussions on quality PME. The author argues that PME should focus on preparing for the unexpected, rather than just the expected tasks. They highlight programs like the Women, Peace, and Security Scholars Program as examples of PME providing a mental framework for dealing with unexpected situations. The author also addresses the issue of professional reading and emphasizes the importance of staying updated with current events. They conclude by emphasizing the importance of PME in developing leaders who can handle unexpected events on the battlefield. [Extracted from the article]

The treatment of colorectal malignant polyps is dependent upon quality reporting of the histopathological features known to predict the risk of residual disease or lymph node metastasis. The Royal College of Pathologists of Australasia (RCPA) has produced protocols covering mandatory and recommended pathological parameters to be included in the pathology reporting of malignant polyps. This paper aimed to assess the quality of the pathological reporting in a population-wide analysis from 2011–2019 in Queensland, Australia.

Electrical faults cause fire or shock hazards in homes and offices. Flexible power cords are particularly susceptible to metal or insulation degradation that may lead to a variety of electrical faults. This article introduces a new Smart Plug 2.0 device which offers all-in-one protection against short-circuit, overload, arc, and ground faults in addition to the wireless power control and monitor function of conventional smart plug devices. It offers microsecond-scale time resolution to detect and respond to a fault condition, and significantly reduces the electrothermal stress on household electrical wires and loads. A new arc fault detection method is developed using machine learning models based on load current di/dt events. Comparing to other solid-state circuit breaker designs which typically respond to overcurrent conditions only, Smart Plug 2.0 integrates additional protective functions into the same hardware structure with minimal cost penalty. A 120 V/10 A solid-state Smart Plug 2.0 prototype using power mosefts is designed and tested. It has experimentally demonstrated the comprehensive protection features against all types of electrical faults.

Extreme energy-dissipating materials are essential for a range of applications. The military and police force require ballistic armour to ensure the safety of their personnel, while the aerospace industry requires materials that enable the capture, preservation and study of hypervelocity projectiles. However, current industry standards display at least one inherent limitation, such as weight, breathability, stiffness, durability and failure to preserve captured projectiles. To resolve these limitations, we have turned to nature, using proteins that have evolved over millennia to enable effective energy dissipation. Specifically, a recombinant form of the mechanosensitive protein talin was incorporated into a monomeric unit and crosslinked, resulting in a talin shock-absorbing material (TSAM). When subjected to 1.5 km s−1supersonic shots, TSAMs were shown to absorb the impact and capture and preserve the projectile.

This article compares the ways Shakespeare and Burns have been placed on pedestals, shaping our memory of them as national poets. It reviews how each came to represent in different ways ‘national bardship’, identifying a range of public events and statues raised which set the poets’ specific memorialised contexts. It contrasts the localism of Shakespeare memorial activities in Stratford with Burns Suppers as worldwide phenomena as marking a difference between the significance of each as poets ‘of the people’. It explicates ways in which Shakespeare came to embody ‘Britain-as-England’ while Burns embodied ‘Scottishness’ both within ‘Britishness’ and internationally.

Wilson disease (WD) is a rare autosomal recessive condition with protean clinical manifestations that result from biallelic ATP7Bmutations. However, nondestructive tissue tests to be applied clinically to tissue specimens are not widely available to effectively assess patients for possible WD. Previously, we showed that metallothionein (MTH) immunohistochemistry (IHC) has a high sensitivity and specificity for WD diagnosis and, thus, represents a potentially powerful diagnostic tool that can be used in routine histologic sections. This study aimed to validate this finding in a large cohort of bona fide patients with WD and to correlate metallothionein expression with other histologic features. We identified 91 cases of WD, which included 28 needle biopsies and 64 explants from 14 centers worldwide. Histologic features were evaluated, and a histopathological pattern was assigned to each case. All cases were evaluated with Masson trichrome and MTH IHC (clone UC1MT, Abcam) using a previously published technique. Liver tissues from chronic cholestatic diseases (n = 42) were used as controls. The median age of the cohort was 28.5 years. Of the 91 total cases, 83 were positive for MTH immunostain. In the controls, all 42 cases were negative for MTH immunostain. The sensitivity and specificity of MTH immunostain for WD were 91.20% and 100%, respectively. MTH IHC is a highly sensitive and specific cost-effective screening tool for WD. It can be used for patients across age groups, varied histologic patterns, and fibrosis stages. This marker could prove to be a valuable tool in the evaluation of patients with possible WD.

Lakes provide societies and natural ecosystems with valuable services such as freshwater supply and flood control. Water level changes in lakes reflect their natural responses to climatic and anthropogenic stressors; however, their monitoring is costly due to installation and maintenance requirements. With its advanced hardware and computational capabilities, altimetry has become a popular alternative to conventional in-situ gauging, although subject to the temporal availability of altimetric observations. To further improve the temporal resolution of altimetric measurements, we here combine radar altimetry data with Differential Interferometric Synthetic Aperture Radar (D-InSAR), using ten lakes in Sweden as a testing platform. First, we use Sentinel-1A and Sentinel-1B SAR images to generate consecutive six-day baseline interferograms across 2019. Then, we accumulate the phase change of coherent pixels to construct the time series of InSAR-derived water level anomalies. Finally, we retrieve altimetric observations from Sentinel-3, estimate their mean and standard deviation, and apply them to the D-InSAR standardized anomalies. In this way, we build a water-level time series with more temporal observations. In general, we find a strong agreement between water level estimates from the combination of D-InSAR and Satellite Altimetry (DInSAlt) and in-situ observations in eight lakes (Concordance Correlation Coefficient - CCC >0.8) and moderate agreement in two lakes (CCC >0.57). The applicability of DInSAlt is limited to lakes with suitable conditions for double-bounce scattering, such as the presence of trees or marshes. The accuracy of the water level estimates depends on the quality of the altimetry observations and the lake's width. These findings are important considering the recently launched Surface Water and Ocean Topography (SWOT) satellite, whose capabilities could expand our methodology's geographical applicability and reduce its reliance on ground measurements.

Incomplete gastric intestinal metaplasia (GIM) is associated with an increased risk of gastric cancer. We aimed to examine the interobserver variability of GIM subtyping (incomplete vs complete) in histological diagnosis of patients with chronic atrophic gastritis and to identify factors with potential impact on agreement. Nine international gastrointestinal expert pathologists assessed 46 cases with complete, incomplete or mixed-type GIM on scanned haematoxylin and eosin (H&E)-stained slides. Results were compared with the consensus diagnosis driven by two experts. Interobserver variability was evaluated by kappa statistics. Focusing on the predominant pattern, the agreement between each observer and the consensus diagnosis ranged from 78% to 98%. The level of agreement was moderate to almost perfect (weighted kappa=0.464–0.984). The participating pathologists reached substantial overall agreement (Fleiss' kappa=0.716, 95% confidence interval 0.677–0.755). Misclassification with potential impact on clinical decision making occurred in 5.7% of case ratings. The pattern of GIM (pure GIM versus mixed-type GIM) differed significantly between cases with high and low agreement (p=0.010), while the number of biopsy pieces per sample and the portion of mucosal surface involved by GIM did not. Pathologists who apply subtyping in daily routine performed better than those who do not (p=0.040). In conclusion,subtyping GIM on H&E-stained slides can be achieved satisfactorily with high interobserver agreement. The implementation of GIM subtyping as a risk stratifying tool in current practice guidelines by the European Society of Gastrointestinal Endoscopy (ESGE) and the American Gastroenterological Association (AGA) carries a low rate of misclassification, at least among gastrointestinal expert pathologists.

Previous studies have described reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal/oropharyngeal swab and saliva samples. This multisite clinical evaluation describes the validation of an improved sample preparation method for extraction-free RT-LAMP and reports clinical performance of four RT-LAMP assay formats for SARS-CoV-2 detection. Direct RT-LAMP was performed on 559 swabs and 86,760 saliva samples and RNA RT-LAMP on extracted RNA from 12,619 swabs and 12,521 saliva samples from asymptomatic and symptomatic individuals across health care and community settings. For direct RT-LAMP, overall diagnostic sensitivity (DSe) was 70.35% (95% CI, 63.48%–76.60%) on swabs and 84.62% (95% CI, 79.50%–88.88%) on saliva, with diagnostic specificity of 100% (95% CI, 98.98%–100.00%) on swabs and 100% (95% CI, 99.72%–100.00%) on saliva, compared with quantitative RT-PCR (RT-qPCR); analyzing samples with RT-qPCR ORF1abCTvalues of ≤25 and ≤33, DSe values were 100% (95% CI, 96.34%–100%) and 77.78% (95% CI, 70.99%–83.62%) for swabs, and 99.01% (95% CI, 94.61%–99.97%) and 87.61% (95% CI, 82.69%–91.54%) for saliva, respectively. For RNA RT-LAMP, overall DSe and diagnostic specificity were 96.06% (95% CI, 92.88%–98.12%) and 99.99% (95% CI, 99.95%–100%) for swabs, and 80.65% (95% CI, 73.54%–86.54%) and 99.99% (95% CI, 99.95%–100%) for saliva, respectively. These findings demonstrate that RT-LAMP is applicable to a variety of use cases, including frequent, interval-based direct RT-LAMP of saliva from asymptomatic individuals who may otherwise be missed using symptomatic testing alone.

Wound field synchronous machines (WFSMs) are an attractive alternative to permanent magnet synchronous machines (PMSMs) given their competitive power/torque density and direct field excitation control for easy weakening. Here, a design process is presented for a low-cost and contactless capacitive power coupler (CPC) for WFSM rotor winding excitation using only simple printed circuit boards (PCBs). These PCBs are an extension of the machine’s rotating rectifier. Experimental verification of the design shows 675-W power transfer at 90.3% efficiency to the rotor field of a 30/55 kW (continuous/peak) WFSM operating as a generator. A GaN inverter switching at 2 MHz reduces passive component sizes and keeps CPC voltages within safe limits. Parasitic loss minimization design rules for trace layout in the CPC PCB structure are established for high-frequency operation along with a partial capacitance approach for the coupling matrix. Tank inductor loss was reduced by using a cored design, while a buck converter integrated into the rotating rectifier matches the load impedance of the rotor to the CPC system, reducing the complexity of the tank compensation circuit. Finally, the CPC as a platform for position self-sensing is introduced conceptually using two methods. First, a phase-locked loop (PLL) tracks the resonant tank frequency of the CPC, whose saliency is spatially tied to the rotation of the machine. Second, the rotating buck converter effectively injects high-frequency content into the field that can be tracked by the stator drive controls.

Pathologists have an important and expanding role in the diagnosis and management of inflammatory bowel disease. This role includes the initial diagnosis of the disease, assessment of the response to treatment and the identification of short-term complications such as cytomegalovirus infection and long-term complications such as dysplasia. Furthermore, the assessment of resection specimens for complication of disease is important to determining the risk of subsequent disease or inflammation within an ileal pouch. Adequate sampling of the disease at endoscopy and from the surgical resection specimen is vital to determining the ultimate information that can be provided by the pathologist. This sampling is determined by the clinical scenario. Similarly, a standardized approach to reporting and synthesizing the histologic findings will improve patient management. This is best exemplified by the increasing interest in histologic activity indices, such as the Nancy index in ulcerative colitis, and in the standardized reporting for inflammatory bowel disease dysplasia recommended by the SCENIC international consensus.

This focus article has been prepared by Marco Falchieri, Scott M. Reid, Craig S. Ross, Joe James, Alexander M. P. Byrne, Madalina Zamfir, Ian H. Brownand Ashley C. Banyardof the APHA; Glen Tylerand Emma Philipof NatureScot; and Will Milesof Scottish Oceans Institute, School of Biology, University of St Andrews.

Purpose: As the police service across England and Wales moves towards degree-level study for new recruits as a component of recognising the profession of policing, this paper describes and discusses the introduction of the Police Constable Degree Apprenticeship (PCDA) and the core skills of evidence-based policing (EBP) as an educational theme for solving work-based problems. Design/methodology/approach: Authored by both policing practitioners and researchers, this paper refers to key literature whilst exploring the implementation of the PCDA as a component of a Policing Education Qualifications Framework (PEQF). It highlights some of the challenges faced with its implementation along with the benefits of the adopting this degree-level education and work-based programme where EBP is embedded in to both study and professional practice. Findings: There are significant benefits to the police service of adopting the PCDA as one of the entry routes for new police constables and embracing the educational development and professional application of EBP. However, this does not come without a number of challenges for the service and the professional body for policing. Originality/value: This paper, co-authored by both policing practitioners and researchers, provides a contemporary view on the introduction of the PCDA as an initial entry route for new police constables and the embedding of EBP within both their learning and professional practice. As the first graduates complete their studies, the paper discusses the opportunities the adoption presents and the challenges it faces both locally and nationally.

This study investigates the consolidation of pre-alloyed Ti–6Al–4V powder through thermomechanical processing that involves cold isostatic pressing, sintering, hot pressing and extrusion. The microstructural evolution, oxygen pick-up and tensile properties attained after each major consolidation step reveal that there was a significant oxygen pick-up during de-binding/sintering, hot pressing had improved strength/ductility by eliminating porosity and extrusion resulted in a relatively fine lamellar structure. Overall, as-extruded material had an oxygen content of 0.22?wt-%, impact toughness of 21?J, yield strength of 971?MPa, ultimate strength of 1124?MPa and ductility of 9–11% which is comparable to corresponding values reported in the literature. An investigation of fracture surfaces along with crack propagation behaviour highlights that ductile fracture was the predominant mode of failure.

This study investigates the consolidation of pre-alloyed Ti–6Al–4V powder through thermomechanical processing that involves cold isostatic pressing, sintering, hot pressing and extrusion. The microstructural evolution, oxygen pick-up and tensile properties attained after each major consolidation step reveal that there was a significant oxygen pick-up during de-binding/sintering, hot pressing had improved strength/ductility by eliminating porosity and extrusion resulted in a relatively fine lamellar structure. Overall, as-extruded material had an oxygen content of 0.22 wt-%, impact toughness of 21 J, yield strength of 971 MPa, ultimate strength of 1124 MPa and ductility of 9–11% which is comparable to corresponding values reported in the literature. An investigation of fracture surfaces along with crack propagation behaviour highlights that ductile fracture was the predominant mode of failure.

There is now evidence that gene fusions activating the MAPK pathway are relatively common in pancreatic acinar cell carcinoma with potentially actionable BRAFor RETfusions being found in ~30%. We sought to investigate the incidence of RAF1fusions in pancreatic malignancies with acinar cell differentiation. FISH testing for RAF1was undertaken on 30 tumors comprising 25 ‘pure’ acinar cell carcinomas, 2 mixed pancreatic acinar-neuroendocrine carcinomas, 1 mixed acinar cell-low grade neuroendocrine tumor and 2 pancreatoblastomas. RAF1rearrangements were identified in 5 cases and confirmed by DNA and RNA sequencing to represent oncogenic fusions (GATM-RAF1, GOLGA4-RAF1, PDZRN3-RAF1, HERPUD1-RAF1and TRIM33-RAF1) and to be mutually exclusive with BRAFand RETfusions, as well as KRASmutations. Large genome-wide copy number changes were common and included 1q gain and/or 1p loss in all five RAF1FISH-positive acinar cell carcinomas. RAF1 expression by immunohistochemistry was found in 3 of 5 (60%) of fusion-positive cases and no FISH-negative cases. Phospho-ERK1/2 expression was found in 4 of 5 RAF1-fusion-positive cases. Expression of both RAF1 and phospho-ERK1/2 was heterogeneous and often only detected at the tumor-stroma interface, thus limiting their clinical utility. We conclude that RAF1gene rearrangements are relatively common in pancreatic acinar cell carcinomas (14.3% to 18.5% of cases) and can be effectively identified by FISH with follow up molecular testing. The combined results of several studies now indicate that BRAF, RETor RAF1fusions occur in between one third and one-half of these tumors but are extremely rare in other pancreatic malignancies. As these fusions are potentially actionable with currently available therapies, a strong argument can be made to perform FISH or molecular testing on all pancreatic acinar cell carcinomas.

There is now evidence that gene fusions activating the MAPK pathway are relatively common in pancreatic acinar cell carcinoma with potentially actionable BRAFor RETfusions being found in ~30%. We sought to investigate the incidence of RAF1fusions in pancreatic malignancies with acinar cell differentiation. FISH testing for RAF1was undertaken on 30 tumors comprising 25 ‘pure’ acinar cell carcinomas, 2 mixed pancreatic acinar-neuroendocrine carcinomas, 1 mixed acinar cell-low grade neuroendocrine tumor and 2 pancreatoblastomas. RAF1rearrangements were identified in 5 cases and confirmed by DNA and RNA sequencing to represent oncogenic fusions (GATM-RAF1, GOLGA4-RAF1, PDZRN3-RAF1, HERPUD1-RAF1and TRIM33-RAF1) and to be mutually exclusive with BRAFand RETfusions, as well as KRASmutations. Large genome-wide copy number changes were common and included 1q gain and/or 1p loss in all five RAF1FISH-positive acinar cell carcinomas. RAF1 expression by immunohistochemistry was found in 3 of 5 (60%) of fusion-positive cases and no FISH-negative cases. Phospho-ERK1/2 expression was found in 4 of 5 RAF1-fusion-positive cases. Expression of both RAF1 and phospho-ERK1/2 was heterogeneous and often only detected at the tumor-stroma interface, thus limiting their clinical utility. We conclude that RAF1gene rearrangements are relatively common in pancreatic acinar cell carcinomas (14.3% to 18.5% of cases) and can be effectively identified by FISH with follow up molecular testing. The combined results of several studies now indicate that BRAF, RETor RAF1fusions occur in between one third and one-half of these tumors but are extremely rare in other pancreatic malignancies. As these fusions are potentially actionable with currently available therapies, a strong argument can be made to perform FISH or molecular testing on all pancreatic acinar cell carcinomas.

Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are non-competing but complementary therapeutic options. In addition, histological examination of ER specimens can either confirm or refine the pre-procedure diagnosis. ER is used for the treatment of Barrett's related early carcinomas and dysplasias, early-esophageal squamous cell carcinomas and dysplasias, early gastric carcinomas and dysplasia, as well as low-risk submucosal invasive carcinomas (LR-SMIC) and, large laterally spreading adenomas of the colon. For invasive lesions, histological risk factors predict risk of lymph node metastasis and residual disease at the ER site. Important pathological risk factors predictive of lymph node metastasis are depth of tumor invasion, poor differentiation, and lymphovascular invasion. Complete resection with negative margins is critical to avoid local recurrences. For non-invasive lesions, complete resection is curative. Therefore, a systematic approach for handling and assessing ER specimens is recommended to evaluate all above key prognostic features appropriately. Correct handling starts with pinning the specimen before fixation, meticulous macroscopic assessment with orientation of appropriate margins, systematic sectioning, and microscopic assessment of the entire specimen. Microscopic examination should be thorough for accurate assessment of all pathological risk factors and margin assessment. Site-specific issues such as duplication of muscularis mucosa of the esophagus, challenges of assessing ampullectomy specimens and site-specific differences of staging of early carcinomas throughout the gastrointestinal tract (GI) tract should be given special consideration. Finally, a standard, comprehensive pathology report that allows optimal staging with potential cure of early-stage malignancies or better stratification and guidance for additional treatment should be provided.

Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are non-competing but complementary therapeutic options. In addition, histological examination of ER specimens can either confirm or refine the pre-procedure diagnosis. ER is used for the treatment of Barrett's related early carcinomas and dysplasias, early-esophageal squamous cell carcinomas and dysplasias, early gastric carcinomas and dysplasia, as well as low-risk submucosal invasive carcinomas (LR-SMIC) and, large laterally spreading adenomas of the colon. For invasive lesions, histological risk factors predict risk of lymph node metastasis and residual disease at the ER site. Important pathological risk factors predictive of lymph node metastasis are depth of tumor invasion, poor differentiation, and lymphovascular invasion. Complete resection with negative margins is critical to avoid local recurrences. For non-invasive lesions, complete resection is curative. Therefore, a systematic approach for handling and assessing ER specimens is recommended to evaluate all above key prognostic features appropriately. Correct handling starts with pinning the specimen before fixation, meticulous macroscopic assessment with orientation of appropriate margins, systematic sectioning, and microscopic assessment of the entire specimen. Microscopic examination should be thorough for accurate assessment of all pathological risk factors and margin assessment. Site-specific issues such as duplication of muscularis mucosa of the esophagus, challenges of assessing ampullectomy specimens and site-specific differences of staging of early carcinomas throughout the gastrointestinal tract (GI) tract should be given special consideration. Finally, a standard, comprehensive pathology report that allows optimal staging with potential cure of early-stage malignancies or better stratification and guidance for additional treatment should be provided.

Pancreatic acinar cell carcinoma is relatively rare (1 to 2% of pancreatic malignancies) but may be under-recognized. In contrast to pancreatic ductal adenocarcinoma, most acinar cell carcinomas lack mutations in KRAS, DPC, CDKN2Aor TP53, but appear to have a high incidence of gene rearrangements, with up to 20% reported to be driven by BRAFfusions. With the development of a new class of RET-specific tyrosine kinase inhibitors, which appear to have particularly strong activity against RETgene rearranged tumours, there is now considerable interest in identifying RETgene rearrangements across a wide range of cancers. RETrearrangements have been reported to occur at a very low incidence (<1%) in all pancreatic carcinomas. We postulated that given its unique molecular profile, RETgene rearrangements may be common in acinar cell carcinomas. We performed fluorescent in-situ hybridization (FISH) studies on a cohort of 40 acinar cell spectrum tumours comprising 36 pure acinar cell carcinomas, three pancreatoblastomas and one mixed acinar-pancreatic neuroendocrine tumour. RETgene rearrangements were identified in 3 (7.5%) cases and BRAFgene rearrangements in 5 (12.5%). All gene rearranged tumours were pure acinar cell carcinomas. Our findings indicate that amongst all pancreatic carcinomas, acinar carcinomas are highly enriched for potentially actionable gene rearrangements in RETor BRAF. FISH testing is inexpensive and readily available in the routine clinical setting and may have a role in the assessment of all acinar cell carcinomas—at this stage to recruit patients for clinical trials of new targeted therapies, but perhaps in the near future as part of routine care.

Pancreatic acinar cell carcinoma is relatively rare (1 to 2% of pancreatic malignancies) but may be under-recognized. In contrast to pancreatic ductal adenocarcinoma, most acinar cell carcinomas lack mutations in KRAS, DPC, CDKN2Aor TP53, but appear to have a high incidence of gene rearrangements, with up to 20% reported to be driven by BRAFfusions. With the development of a new class of RET-specific tyrosine kinase inhibitors, which appear to have particularly strong activity against RETgene rearranged tumours, there is now considerable interest in identifying RETgene rearrangements across a wide range of cancers. RETrearrangements have been reported to occur at a very low incidence (<1%) in all pancreatic carcinomas. We postulated that given its unique molecular profile, RETgene rearrangements may be common in acinar cell carcinomas. We performed fluorescent in-situ hybridization (FISH) studies on a cohort of 40 acinar cell spectrum tumours comprising 36 pure acinar cell carcinomas, three pancreatoblastomas and one mixed acinar-pancreatic neuroendocrine tumour. RETgene rearrangements were identified in 3 (7.5%) cases and BRAFgene rearrangements in 5 (12.5%). All gene rearranged tumours were pure acinar cell carcinomas. Our findings indicate that amongst all pancreatic carcinomas, acinar carcinomas are highly enriched for potentially actionable gene rearrangements in RETor BRAF. FISH testing is inexpensive and readily available in the routine clinical setting and may have a role in the assessment of all acinar cell carcinomas—at this stage to recruit patients for clinical trials of new targeted therapies, but perhaps in the near future as part of routine care.

While the respective effects of nose radius, feed and cutting edge geometry on surface integrity have each been studied at depth, coupling between these effects is not yet sufficiently understood. Recent studies have clearly established that cutting edge micro-geometries may not only have positive effects on tool-life, but can also be used to tailor surface integrity characteristics, such as surface roughness and near-surface severe plastic deformation. To further a more fundamental understanding of the effects of cutting edge micro-geometries on surface integrity, experimental turning data was generated for a varied range of cutting tool geometries and feeds. Scanning laser interferometry was used in conjunction with a recently developed profile-analysis algorithm to analyze, characterize, and verify the geometry of complex cutting edge micro-geometries. Near surface nanostructure, and surface roughness of the produced surfaces were characterized and correlated to the varied tool geometries. An interaction between two geometry characteristics, predicted kinematic roughness and hone size, was discovered. Scanning laser interferometry analysis of the surfaces revealed that large hones provided either an increase or decrease in roughness, depending on predicted kinematic roughness.

Most patients with Cowden syndrome have lesions in the gastrointestinal tract, characterized by multiple polyps of various histologic types in the large bowel, polyps in the upper gastrointestinal tract, and esophageal glycogenic acanthosis. However, pathologists are often unaware of the distinctive polyposis phenotype of Cowden syndrome. In this multicenter study, we report the spectrum of gastrointestinal manifestations in a series of 43 Cowden syndrome patients who had at least one endoscopy. The median age at the first endoscopy was 46 years and 58% were women. In 24 of 29 (83%) tested patients, a pathogenic germline mutation in PTEN was identified. The histology from 199 endoscopy procedures (67 upper gastrointestinal endoscopy and 132 colonoscopies) was reviewed. Hamartomatous polyps of the large bowel were the most common lesions, present in 85% of patients. Hamartomatous polyps showed varied histology, including lymphoid aggregates in 55% of patients, a lipomatous component in 52%, a ganglioneuromatous component in 52%, and a fibrous-rich component in 14%. Polyps with at least two different stromal components were found in 55% of patients. Inflammatory polyps were present in 21% of patients. Conventional adenomas and serrated polyps were identified in 48% and 62% of patients, respectively. In the upper gastrointestinal tract, the most common lesions were esophageal glycogenic acanthosis (37%), gastric hamartomatous polyps (47%), and duodenal hamartomatous polyps (20%). All patients with glycogenic acanthosis who had a colonoscopy had hamartomatous polyps of the large bowel. In five patients, the diagnosis of Cowden syndrome was established after the pathology report raised suspicion for the diagnosis. Pathologists who are aware of the characteristic admixture of lesions in Cowden syndrome can play an essential role in recommending referral to genetic counseling and gene testing. Early diagnosis of Cowden syndrome is important, as these patients and their relatives are at increased risk for developing multiple cancers.

Most patients with Cowden syndrome have lesions in the gastrointestinal tract, characterized by multiple polyps of various histologic types in the large bowel, polyps in the upper gastrointestinal tract, and esophageal glycogenic acanthosis. However, pathologists are often unaware of the distinctive polyposis phenotype of Cowden syndrome. In this multicenter study, we report the spectrum of gastrointestinal manifestations in a series of 43 Cowden syndrome patients who had at least one endoscopy. The median age at the first endoscopy was 46 years and 58% were women. In 24 of 29 (83%) tested patients, a pathogenic germline mutation in PTEN was identified. The histology from 199 endoscopy procedures (67 upper gastrointestinal endoscopy and 132 colonoscopies) was reviewed. Hamartomatous polyps of the large bowel were the most common lesions, present in 85% of patients. Hamartomatous polyps showed varied histology, including lymphoid aggregates in 55% of patients, a lipomatous component in 52%, a ganglioneuromatous component in 52%, and a fibrous-rich component in 14%. Polyps with at least two different stromal components were found in 55% of patients. Inflammatory polyps were present in 21% of patients. Conventional adenomas and serrated polyps were identified in 48% and 62% of patients, respectively. In the upper gastrointestinal tract, the most common lesions were esophageal glycogenic acanthosis (37%), gastric hamartomatous polyps (47%), and duodenal hamartomatous polyps (20%). All patients with glycogenic acanthosis who had a colonoscopy had hamartomatous polyps of the large bowel. In five patients, the diagnosis of Cowden syndrome was established after the pathology report raised suspicion for the diagnosis. Pathologists who are aware of the characteristic admixture of lesions in Cowden syndrome can play an essential role in recommending referral to genetic counseling and gene testing. Early diagnosis of Cowden syndrome is important, as these patients and their relatives are at increased risk for developing multiple cancers.