Search

Online learning is an important aspect of higher education today. One-third of college students take at least one course online, and almost 70% of chief academic leaders say that online learning is critical to their long-term strategy [1]. Despite the success and growth of online education, the number of courses that currently offer a hands-on laboratory component is extremely limited, resulting in the lack of an entire category of engineering courses.

The recent emergence of the omicron variant of the SARS-CoV-2 virus with large numbers of mutations has raised concern about a potential new surge in infections. Here we use molecular dynamics to study the biophysics of the interface of the omicron spike protein binding to (i) the ACE2 receptor protein, (ii) antibodies from all known binding regions, and (iii) the furin binding domain. Our simulations suggest that while there is significant reduction of antibody binding strength corresponding to escape, the omicron spike pays a cost in terms of weaker receptor binding. The furin cleavage domain is the same or weaker binding than the alpha variant, suggesting less viral load and disease intensity than the extant delta variant.

Northrop Grumman (NG) is developing a photonic waveguide-based imaging spectrometer that promises to dramatically reduce instrument size, weight and power and enable image acquisition in modes not possible with current hyperspectral imagers (HSIs). The objective of our current effort is to develop this novel hyperspectral technology for eventual application to the NASA Sustainable Land Imaging (SLI) mission. For more than 40 years the Landsat program has provided the Earth science community with highly accurate global multispectral imagery (MSI) to monitor our planet and ecosystems. Through extensive modeling and simulation NG has demonstrated that a versatile HSI sensor can meet the goals for a sustainable land imager. Our photonic spectrometer represents a step forward for hyperspectral imaging, providing a path to an extremely compact instrument that will provide fully co-registered spectral and spatial data across the instrument’s field of view.

Under the NASA Earth Science Technology Office Sustainable Land Imaging — Technology (SLI-T) program, Northrop Grumman is building and demonstrating a fully integrated photonic hyperspectral imaging spectrometer. In this approach, lithographically patterned waveguides and planar lightwave circuits replace discrete free-space optical components and enable a miniaturized sensor package that acquires data in modes not possible with current imaging instruments. This summary presents our approach to the instrument design and optimization of the planar lightwave circuits for optical performance, packing density and manufacturability.

OBJECT The impact of central pathology review on outcome has been described in pediatric patients with high-grade glioma (HGG). The objective of this report was to analyze the impact of the central pathology review on outcome in the subgroup of patients with institutional diagnosis of HGG of the spinal cord enrolled in the Children's Cancer Group 945 cooperative study. METHODS Five neuropathologists centrally reviewed the pathology of the 18 patients with HGG of the spinal cord who were enrolled in the study. These reviews were independent, and reviewers were blinded to clinical history and outcomes. A consensus diagnosis was established for each patient, based on the outcome of the review. RESULTS Of 18 patients, only 10 were confirmed to have HGG on central review. At a median follow-up of 12 years, event-free and overall survival for all 18 patients was 43.2% ± 13.3% and 50% ± 13.4%, respectively. After central review, 10-year event-free and overall survival for confirmed HGGs and discordant diagnoses was 30% ± 12.5% versus 58.3% ± 18.8% (p = 0.108) and 30% ± 12.5% versus 75% ± 14.2% (p = 0.0757), respectively. CONCLUSIONS The level of discordant diagnoses in children and adolescents with institutional diagnosis of HGG of the spinal cord was 44% in this experience. However, there was no significant difference in outcome between patients with confirmed and discordant diagnosis. This group of tumor deserves a specific attention in future trials.

Background Multimodal pain management has had a significant effect on improving total joint arthroplasty recovery and patient satisfaction. There is literature supporting that intravenous (IV) acetaminophen reduces postoperative pain and narcotic use in the total joint population. However, there are no studies comparing the effectiveness of IV vs oral (PO) acetaminophen as part of a standard multimodal perioperative pain regimen. Methods One hundred twenty patients undergoing hip and knee arthroplasty surgeries performed by one joint arthroplasty surgeon were prospectively randomized into 2 groups. Group 1 (63 patients) received IV and group 2 (57 patients) received PO acetaminophen in addition to a standard multimodal perioperative pain regimen. Each group received 1 gram of acetaminophen preoperatively and then every 6 hours for 24 hours. Total narcotic use and visual analog scale (VAS) scores were collected every 4 hours postoperatively. Results The 24-hour average hydromorphone equivalents given were not different between groups (3.71 vs 3.48) at 24 hours ( P = .76), or at any of the individual 4-hour intervals. The 24-hour average visual analog scale scores in group 1 (IV) was 3.00 and in group 2 (PO) was 3.40 ( P = .06). None of the 4-hour intervals were significantly different except the first interval (0-4 hour postoperatively), which favored the IV group ( P = .03). Conclusion The use of IV acetaminophen may have a role when given intraoperatively to reduce the immediate pain after surgery. Following that, it does not provide a significant benefit in reducing pain or narcotic use when compared with the much less expensive PO form.

More than 600,000 total knee arthroplasties are performed in the United States every year1. Superficial wound complications occur infrequently, and the overall appearance of the incision is important to judge appropriate healing. Ecchymosis about the knee is common postoperatively and typically resolves within the first few weeks. Persistent skin changes around the incision and knee are rare, and they prompt additional investigation regarding the etiology. We report on a seventy-four-year-old woman who had undergone an uncomplicated right total knee arthroplasty and, almost three and one-half years later, developed an atraumatic ecchymotic-appearing lesion involving the superior aspect of the incision. She was diagnosed with biopsy-proven pigmented purpuric dermatosis (PPD). To our knowledge, this is the first such case reported in the orthopaedic literature. The patient was informed that data concerning the case would be submitted for publication, and she provided consent. A seventy-four-year-old woman with a past medical history of hypertension, hypothyroidism, and a prior left total knee arthroplasty presented for a right total knee arthroplasty. She underwent femoral and sciatic nerve blocks followed by general anesthesia. A posterior cruciate ligament-retaining total knee prosthesis (Vanguard; Biomet, Warsaw, Indiana) was implanted uneventfully. The patella was resurfaced, and a lateral release was performed. She did well in the postoperative period with regard to …

Postoperative vision loss is a rare but devastating surgical complication. Ischemic optic neuropathy (ION) is one such form of vision loss, most commonly recognized with prone positioning in spinal surgery. It is also documented as a complication of multiple surgical specialties, including general orthopaedics1, otolaryngology2, obstetrics and gynecology3, cardiothoracic surgery4,5, and general trauma surgery6. ION is an acute ischemic disorder that causes blindness, with reported postoperative incidence ranging from 0.013% to 1.3%5,7-9. Blood flow to the optic nerve is autoregulated and is dependent on ocular perfusion pressure (OPP). OPP can decrease to a level beyond which autoregulation mechanisms can compensate10, leading to ischemic injury. The most common associated risk factors for this complication are often encountered in orthopaedic trauma, namely length of surgery11 and intraoperative arterial hypotension6,8. To our knowledge, ION has not previously been reported in the orthopaedic trauma literature. We present the case of a fifty-year-old man who developed ION after internal fixation of ipsilateral fractures of the proximal part of the humerus and olecranon. The patient was informed that data concerning the case would be submitted for publication, and he provided consent. A fifty-year-old healthy man sustained an eight-foot fall from a ladder, landing directly on the right elbow. He was hemodynamically stable with isolated closed injuries to the right upper extremity; there were no neurovascular deficits. The general surgery trauma team evaluated the patient, and no additional injuries were found. Radiographs and computed tomography (CT) of the right shoulder showed a comminuted fracture of the proximal part of the humerus, described as an Orthopaedic Trauma Association (OTA) classification type 11-B1.212, as well as a Neer two-part fracture involving the …

Haptic force feedback systems are unique in their ability to dynamically render physical representations. Although haptic devices have shown promise for supporting learning, prior work mainly describes results of haptic-supported learning without identifying underlying learning mechanisms. To this end, we designed a haptic-supported learning environment and analyzed four students who used it to make connections between two different mathematical representations of sine and cosine: the unit circle, and their graph on the Cartesian plane. We highlight moments where students made connections between the representations, and identify how the haptic feedback supported these moments of insight. We use this evidence in support of a proposed theoretical and design framework for educational haptics. This framework captures four types of haptic representations, and focuses on one -- the haptic bridge -- that effectively scaffolds sense-making with multiple representations.

Children with high-grade glioma (HGG) have a poor prognosis compared to those with low-grade glioma (LGG). Adjuvant chemotherapy may be beneficial, but its optimal use remains undetermined. Histology and extent of resection are important prognostic factors. We tested the hypothesis that patients with midline HGG treated on Children's Cancer Group Study (CCG) CCG-945 have a worse prognosis compared to the entire group. Of 172 children eligible for analysis, 60 had midline tumors primarily localized to the thalamus, hypothalamus and basal ganglia. Time-to-progression and death were determined from the date of initial diagnosis, and survival curves were calculated. Univariate analyses were undertaken for extent of resection, chemotherapy regimen, anatomic location, histology, proliferation index, MGMT status and p53 over-expression. For the entire midline tumor group, 5-year PFS and OS were 18.3 ± 4.8 and 25 ± 5.4 %, respectively. Many patients only had a biopsy (43.3 %). The sub-groups with near/total resection and hypothalamic location appeared to have better PFS and OS. However, the effect of tumor histology on OS was significant for children with discordant diagnoses on central pathology review of LGG compared to HGG. Proliferative index (MIB-1 > 36 %), MGMT and p53 over-expression correlated with poor outcomes. Children treated on CCG-945 with midline HGG have a worse prognosis when compared to the entire group. The midline location may directly influence the extent of resection. Central pathology review and entry of patients on clinical trials continue to be priorities to improve outcomes for children with HGG.

Fifteen years surely seemed an eternity to Cunxu, on the eve of securing the elusive conquest of the Liang. The man derided a decade ago as, “the kid who fancies cockfights,” had turned the corner as underdog and put residual doubters to rest. A sign of his promising political acumen emerges in several appointments at the onset of 923.

Chapter 5 is about the ascension of Li Siyuan, Cunxu’s fictive brother on the throne. The chapter also details the ensuing battles with Cunxu’s sons that cement Siyuan’s rule as successor to the Later Tang Dynasty.

Death has a way of destabilizing empires organized around hereditary succession, yet transitions for the Shatuo Turks proved more volatile than most. Li Keyong died of a brain tumor on the nineteenth day of the first month (908.01.19). Interment ensued months later at Daizhou, halfway between Taiyuan and Datong in northern Shanxi, where he had once served as prefect. The eldest of eight surviving sons, Cunxu succeeded as Prince of Jin, consistent with his father’s dying wishes. Twenty-seven days of rigorous mourning ensued. But even before the deceased could be laid to rest, a plot would unfold that tested the mettle of Cunxu when loyalties to persons collide with deference for traditions.

The Later Tang was the first of several ephemeral states created by the Shatuo Turks in tenth-century China and Li Cunxu, a martial genius, was its founder. In fifteen years, he turned a small satrapy on China’s periphery into a powerhouse capable of unifying the north and much of the southwest. He governed on the principle of racial inclusion and refused to set the ruling minority above the Chinese majority through special privileges. As someone highly literate and artistically gifted, Li Cunxu seemed uniquely capable of bridging rifts within his culturally diverse ruling elite. Unfortunately, he shared the sort of self-absorbed narcissism typical of dynastic founders, which contributed to his denouement merely three years into the reign. The Later Tang dynasty presided over the epic changes that occasioned the Five Dynasties, when China evolved from a moribund medieval state dominated by hereditary elites to one organized around individual merit, an essential element of the nation-state. Critical to the evolution of governance in the tenth century was the rule of military magnates without vested interest in the old order.

Footing in two cultures proved a mixed blessing for Li Cunxu (885–926), the object of much envy in his day. Through paternal ties to the Shatuo-Turks of Inner Asia, he projected the martial panache reminiscent of his father, Li Keyong (856–908). Equally impressive was Cunxu’s comfort with the culture of his Chinese mother, Woman Cao, who drew upon a dedicated group of local mentors to prepare the youth for his destiny with history. Cunxu made frequent boast of his facility in the literary language and classical traditions of China. He also made much of his creativity as poet and musician, having composed by his own hand the marching songs for his armies. Conscious of his role as model for future Shatuo emperors, Cunxu needed to strike the right balance in negotiating his two identities. But sadly, fifteen years of almost ceaseless warfare in search of realizing other people’s dreams left little time for second thoughts about the cost of dynasty to own individuality. Would he force change upon the institution of monarchy or would the institution humble him? Tragically, so much constructive energy in his short yet historic reign were consumed by this epic contest of wills.

Objectives To compare retrograde versus antegrade femoral bone graft harvesting using the reamer-irrigator-aspirator system to determine whether there was any difference in intraoperative, postoperative, or patient outcome variables. Design Retrospective cohort study. Setting Urban Level I Trauma Center. Patients/participants Ninety-four (62 antegrade and 32 retrograde procedures) consecutive adult patients who underwent femoral autologous bone graft harvesting using the Synthes reamer-irrigator-aspirator system between April 2008 and March 2013. Main outcome measurements Amount of bone graft, perioperative fractures or other complications, and postoperative hip and/or knee pain. Results There was no significant difference between demographic or medical comorbidities between the groups. There was no significant difference in the side of the graft harvest, graft volume, hospital length of stay, or the ability to ambulate on postoperative day 1. There was a significantly increased incidence of iatrogenic fracture or prophylactic nailing with antegrade reaming (4 vs. 0, P = 0.01). Average length of follow-up was 500 (range, 20-1477) days for the antegrade group and 378 (range, 19-706) days for the retrograde group. The antegrade group had a nonsignificant increased incidence of hip pain (8.1% vs. 3.1%, P = 0.66), and the retrograde group had a significantly higher incidence of knee pain (15.6% vs. 1.6%, P = 0.02) at 6-month follow-up. Neither hip nor knee complaints were present at final follow-up. No cases of delayed femur fracture, infection, or abductor and/or antalgic gait involving the donor extremity were seen at final follow-up. Conclusions This study provides support to the safety of femoral bone graft harvesting using both antegrade and retrograde techniques. Both techniques provide reliable, high-volume, nonstructural autologous bone graft with minimal associated morbidity. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

CNS involvement by systemic Hodgkin lymphoma (HL) is quite rare, but the disease limited to the CNS is an exceptionally rare entity. The incidence of CNS-HL has been estimated at 0.2-0.5% of cases, but a more recent study has modified that figure to less than 0.02%. Like the conventional form, the diagnosis of primary CNS-HL rests upon distinct morphological and immunohistochemical characteristics, including diagnostic Reed-Sternberg cells, in addition to staging studies demonstrating a lack of disease elsewhere. The paucity of cases in the literature precludes reliable clinical and demographic data, as well as a consensus on treatment and prognosis. We present two cases of primary cerebellar HL, one with 10-year follow-up, and a relevant review of the literature.

Haptic technology has the potential to expand and transform the ways that students can experience a variety of science, technology, engineering, and math (STEM) topics. Designing kinesthetic haptic devices for educational applications is challenging because of the competing objectives of using low-cost components, making the device robust enough to be handled by students, and the desire to render high fidelity haptic virtual environments. In this paper, we present the evolution of a device called "Hapkit": a low cost, one-degree-of-freedom haptic kit that can be assembled by students. From 2013–2015, different versions of Hapkit were used in courses as a tool to teach haptics, physics, and control. These include a Massive Open Online Course (MOOC), two undergraduate courses, a graduate course, and a middle school class. Based on our experience using Hapkit in these educational environments, we evolved the design in terms of its structural materials, drive mechanism, and mechatronic components. Our latest design, Hapkit 3.0, includes several features that allow students to manufacture and assemble a robust and high-fidelity haptic device. First, it uses 3-D printed plastic structural material, which allows the design to be built and customized using readily available tools. Second, the design takes into account the limitations of 3-D printing, such as warping during printing and poor tolerances. This is achieved at a materials cost of approximately US $50, which makes it feasible for distribution in classroom and online education settings. The open source design is available at http://hapkit.stanford.edu.

The modified Dunn procedure has been shown to be safe and effective in treating unstable slipped capital femoral epiphysis (SCFE). We present a consecutive series of unstable SCFE managed by a single surgeon with a focus on timing of surgical intervention, postoperative complications, and radiographic results. Thirty-one consecutive unstable SCFEs were treated. Demographics, presentation time to time of operation, surgical times, and complications were recorded. Bilateral hip radiographs at latest follow-up were utilized to record slip angle, α angle, greater trochanteric height, and femoral neck length. Thirty-one consecutive hips in 30 patients were reviewed: 15 males (50%) and 15 females (50%), average age 12.37 years (range, 8.75 to 14.8 y), 20 left hips (65%) and 11 right hips (35%). Mean follow-up was 27.9 months (range, 1 to 82 mo). Time from presentation to intervention averaged 13.9 hours (range, 2.17 to 23.4 h). Two patients (6%) developed avascular necrosis at average 19 weeks postoperative. Three patients (10%) developed mild heterotopic ossification requiring no treatment. Two patients (6%) required removal of symptomatic hardware. One patient had hardware failure and in no patients was nonunion, delayed union, or postoperative hip subluxation/dislocation seen. Three patients (10%) presented with bilateral, stable SCFE requiring contralateral in situ pinning. Five patients (16%) had sequential SCFE requiring treatment with 1 patient having an acute, unstable SCFE 10 months after the previous realignment. Mean postoperative slip angle measured 2.5 degrees (range, +19 to −9.4 degrees) (SD, 7.2), α angle 47.43 degrees (range, 34 to 64 degrees) (SD, 7.49), greater trochanteric height averaged 3.5 mm below the center of femoral head (−17.5 to +25 mm), and mean femoral neck length difference measured −7.75 mm (range, −1.8 to −18.6 mm). A single surgeon series of unstable SCFEs treated by a modified Dunn procedure showed a 6% incidence of avascular necrosis and low complication rates at latest follow-up. Radiographs showed restoration of the slip angle, α angle, femoral neck length, and greater trochanteric height. This series reveals the safety and effectiveness of the modified Dunn procedure for unstable SCFE. Level III—retrospective review.

Embodied, physical interaction can improve learning by making abstractions concrete, while online courses and interactive lesson plans have increased education access and versatility. Haptic technology could integrate these benefits, but requires both low-cost hardware (recently enabled by low-cost DIY devices) and accessible software that enables students to creatively explore haptic environments without writing code. To investigate haptic e-learning without user programming, we developed HandsOn, a conceptual model for exploratory, embodied STEM education software; and implemented it with the SpringSim interface and a task battery for high school students. In two studies, we confirm that low-cost devices can render haptics adequately for this purpose, find qualitative impact of SpringSim on student strategies and curiosity, and identify directions for tool improvement and extension.

WMAP data when combined with ancillary data on free-free, synchrotron and dust allow an improved understanding of the spectrum of emission from each of these components. Here we examine the sky variation at intermediate and high latitudes using a cross-correlation technique. In particular, we compare the observed emission in several large partitions of the sky plus 33 selected sky regions to three "standard" templates. The regions are selected using a criterion based on the morphology of these template maps. The synchrotron emission shows evidence of steepening between GHz frequencies and the \emph{WMAP} bands. There are indications of spectral index variations across the sky but the current data are not precise enough to accurately quantify this from region-to-region. The emission correlated with the $H_{\alpha}$ template shows clear evidence of deviation from a free-free spectrum. The emission can be decomposed into a contribution from both free-free and spinning dust in the warm ionised medium of the Galaxy. The derived free-free emissivity corresponds to a mean electron temperature of $\sim 6000$ K, although the value depends critically on the impact of dust absorption on the $H_{\alpha}$ intensity. The WIM spinning dust emission has a peak emission in intensity in the range 40--50 GHz. The anomalous microwave emission associated with dust is detected at high significance in most of the 33 fields studied. The anomalous emission correlates well with the Finkbeiner et al. (1999) model 8 predictions (FDS8) at 94 GHz, and is well described globally by a power-law emission model with an effective spectral index between 20 and 60 GHz of $\beta \approx -2.7$. It is clear that attempts to explain the emission by spinning dust models require multiple components, which presumably relates to a complex mix of emission regions along a given line-of-sight.

Medical education often presents new material as large data dumps at a single live event (lecture or symposium), in part because it is traditional, and also because this structure can be perceived as the most time efficient for busy clinicians and their teachers. However, modern learning theory and new insights from the neurobiological basis of long-term memory formation show that the format of single-event presentation of materials is not very effective. Rather, seeing the presentation of new materials over time, in bite-sized chunks, and then seeing them again at a later time, particularly as a test, leads to more retention of information than does learning the same amount of material as a large bolus in a single setting. This notion of learning over time, also called “interval learning” or “spaced learning,” is particularly well adapted to the Internet era. Here we describe an application of this concept to the learning of psychopharmacology over time in bite-sized and repeated portions structured as an “online fellowship” called the Master Psychopharmacology Program (www.neiglobal.com/mpptour).

Lanthanum carbonate (LaCO(3)) is an oral phosphate binder widely used in end-stage renal disease (ESRD). Preclinical animal studies reported the highest La concentrations outside the gut to be in mesenteric lymph nodes. We observed previously unreported La deposition visible by light microscopy and confirmed by scanning electron microscopy with energy dispersive x-ray spectroscopy in a mesenteric lymph node at autopsy of a 38-year-old female ESRD patient 3 years following LaCO(3) administration. Although LaCO(3) is generally thought to be minimally absorbed, this demonstration suggests the need for further investigation of the extent and potential effects of such absorption.

Medical presentations can be designed as a data dump or as a story. One effective communication strategy is to organize a lecture as a three act play, starting with previews as the first act and ending with reviews as the third act. Previews facilitate learner achievement and may help learners view a medical instructor more positively. Reviews also help consolidate audience learning and ensure that messages have been clearly delivered and received. The main act is in the middle and is the content itself. Delivering this content in small multiples gives learners manageable packets of information and can help them to see the differences and similarities between conditions, deepening their understanding of what was presented.Applying principles of adult learning can enhance the effectiveness of a medical presentation. A previous “Trends in Psychopharmacology” presented an overview of these principles and discussed targeting the learner rather than the content or the lecturer as the focus for a medical presentation. Here we cover the concept of presenting content to a learner as a story and show how to organize or “storyboard” it as a three act play.Lectures can be arranged as a dull recitation of facts or as a story that makes the facts come alive. Generally speaking, a participant is less interested in hearing the facts that a lecturer has to present than in listening to a story the lecturer has to tell. Organizing content into a “three act play” can make a lecture memorable and its lessons practical. Classically, teachers have explained the three parts as: “Say what you are gonna say; say it; then say what you said.” More specifically, the previews are the first part, the presentation itself is the second part, and the reviews are the third part of this structure.

This paper introduces a new environment for programming robots and physical computing devices---the Spatial Computing Platform (SCP)---and compares it to a text-based programming environment (the Cricket Logo). The SCP simplifies the process of constructing conditional statements that link the robot's inputs and outputs together. It does this by providing the user with a virtual canvas that they can draw rectangles on using the mouse. Each rectangle represents a range of sensor values, and specific outputs can be assigned to each rectangle. When the sensor values enter into the specified range, the outputs will turn on. We designed a study with 60 youth to compare this environment to Cricket Logo, a well-known variant of Logo designed to control robotic devices. We found that participants using the spatial computing platform were able to build programs of higher complexity and make more changes to their programs over the course of an hour-long workshop.

Poor range of motion may decrease a patient's ability to participate in activities of daily living after total knee arthroplasty. Manipulation under anesthesia has been shown to improve range of motion; however, some patients have persistent stiffness even after manipulation. The goal of this study was to evaluate the outcomes and complications of patients who underwent a second manipulation under anesthesia for persistent stiffness after total knee arthroplasty. The review of surgical records of two joint arthroplasty surgeons identified 226 knees in 210 patients who underwent a manipulation under anesthesia for poor range of motion after total knee arthroplasty. Of these patients, 16 patients underwent a second manipulation under anesthesia. For patients undergoing two manipulations under anesthesia procedures, at latest follow up (mean 539 days), mean extension improved from 10.50° to 2.50° (p=0.001) and mean flexion improved from 87.50° to 112.69° (p=0.001) respectively. SF-12 scores were available for 12 of 16 knees with a mean score of 34.42. Two of 16 patients (12.5%) experienced a complication. Three of 16 (18.8%) patients who underwent a second manipulation required a revision arthroplasty procedure. In conclusion, a second manipulation under anesthesia can achieve functional range of motion that is sustained after total knee arthroplasty.

Because continuing medical education (CME) activities in psychopharmacology have traditionally documented only that participants have been exposed to a great deal of new information, it has been difficult to gauge to what extent CME leads to the acquisition of new knowledge or to the translation of this knowledge into clinical practice. The goal of modern CME is not only to facilitate learning and knowledge translation, but to evaluate whether these outcomes have occurred. Although further research will be required to develop practical, affordable, and proven methods that are capable of measuring the extent to which a CME activity facilitates sustained knowledge translation into clinical practice, it is already possible to incorporate participant-focused educational designs, measurements of learning with pre-and posttesting, and case-based exercises to assess whether the translation of knowledge into proxies of clinical practice is now beginning to occur.

Alzheimer disease is characterized by extracellular plaques composed of Abeta peptides. We show here that these plaques also contain the serine protease inhibitor neuroserpin and that neuroserpin forms a 1:1 binary complex with the N-terminal or middle parts of the Abeta(1-42) peptide. This complex inactivates neuroserpin as an inhibitor of tissue plasminogen activator and blocks the loop-sheet polymerization process that is characteristic of members of the serpin superfamily. In contrast neuroserpin accelerates the aggregation of Abeta(1-42) with the resulting species having an appearance that is distinct from the mature amyloid fibril. Neuroserpin reduces the cytotoxicity of Abeta(1-42) when assessed using standard cell assays, and the interaction has been confirmed in vivo in novel Drosophila models of disease. Taken together, these data show that neuroserpin interacts with Abeta(1-42) to form off-pathway non-toxic oligomers and so protects neurons in Alzheimer disease.