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Studies of how individuals psychologically experience Holocaust-related exhibits or installations are relatively rare, in part because such investigations lie at the crossroads of Holocaust education and visitor or museum studies. The current study arose out of a unique opportunity during which the authors’ university hosted a traveling exhibit of the United States Holocaust Memorial Museum, Deadly Medicine: Creating the Master Race. One hundred and ninety-four participants responded to a qualitative question regarding the impact of the exhibit. A descriptive form of thematic analysis was used to identify patterns in the data, resulting in three superordinate themes (closed, open, and ambivalent engagement). These themes describe how participants oriented themselves toward the exhibit, negotiating a complex interplay that included a passive to active continuum. Our critical analysis suggests that it may be helpful to view participants as ambivalent or even contradictory human agents, struggling wi...

Elective operation scheduling significantly affects the financial health of a hospital and additional metrics important to stakeholders in an operating theater (OT) environment. In this research, we develop a novel scheduling formulation that explicitly considers the uncertainty in elective operation durations and also plans for potential randomly arriving urgent demands. Using a scenario-based modeling approach, the objective of this formulation is to maximize the expected profit associated with the OT schedule. Since the complexity of the problem is NP-hard, we develop a two-step, heuristic solution approach that allows us to solve practical-sized instances in reasonable time. Experimentation shows that incorporating uncertainty via scenarios increases profit and OT utilization when compared to deterministic scheduling methods. Moreover, explicitly considering urgent arrivals results in a significant reduction in the time that patients of this type wait to receive service, with little impact on other key metrics.

When the United States Congress mandated implementation of unmanned aerial vehicles (UAVs) into the domestic airspace in 2012, there was substantial opposition to the policy change. Critics expressed fears regarding their threat to privacy and safety, and legislatures considered numerous bills that would significantly limit or even ban domestic unmanned flight. UAV advocates used various methods to counter UAV's negative image. This study examines media stories regarding UAVs over a four-year period (2011–2014) and demonstrates that despite the backlash against expansion, media frames emphasizing benefit rather than risk dominated in the U.S. media. The economic opportunities presented by UAVs appeared in most media reports and over time reports increased of relatively noncontroversial applications, such as agriculture. Citizen advocacy or frames that emphasized the personal freedom to fly a UAV also increased. Industry and university officials, who usually support expansion, were the most frequent sponsors of media statements. The framing of media reports can influence public debate. Potential risks of a new technology can be amplified or minimized depending on how the media present the issue to the public.

New technologies often pass through a period of their promoters׳ exaggerations. Unrealistic expectations, or hype, produce consumer excitement and then disenchantment with the technology before its acceptance. Using the Garter Hype Cycle as a framework, this study examines expectations regarding domestic applications of the unmanned aerial vehicle (UAV) in agriculture. A content analysis of 5418 U.S. media reports from 2010 through 2014 shows hype was used in describing potential UAV applications in farming. Media reports were highly speculative and overly optimistic, and in the near term largely unrealistic. The agricultural UAV hype appears to be a response to hostility toward government domestic surveillance use of UAVs. As public hostility toward police use of UAVs increased, media reports shifted away from government deployment to the economic development created by relatively noncontroversial commercial applications. Hype has both potential benefits and costs for those seeking expansion of a technology. The hype was arguably necessary to allay negative public opinion and a hostile political environment toward domestic expansion of the UAV. The negative ramification of hype is that a period of disillusionment follows the inevitable realization that expectations for the technology were unrealistic. Market expansion is stalled or even derailed. According to the Garter Hype Cycle, there will be a period of disillusionment regarding the contributions of UAVs to agriculture once there is the legalization of commercial applications in the U.S. However, UAV deployment on farms should increase after realistic expectations regarding near-term contributions are developed and disseminated.

BACKGROUND Two doses of measles, mumps, and rubella (MMR) vaccine are 97% effective against measles, but waning antibody immunity to measles and failure of the 2-dose vaccine occur. We administered a third MMR dose (MMR3) to young adults and assessed immunogenicity over 1 year. METHODS Measles virus (MeV) neutralizing antibody concentrations, cell-mediated immunity (CMI), and immunoglobulin G (IgG) antibody avidity were assessed at baseline and 1 month and 1 year after MMR3 receipt. RESULTS Of 662 subjects at baseline, 1 (0.2%) was seronegative for MeV-neutralizing antibodies (level

A prospective, multidisciplinary care conference (MDC) has been shown to result in measurable benefits for patients with non-small cell lung cancer (NSCLC). However whether a MDC also results in a difference in resource utilization and cost as well as whether these benefits persist across a multiinstitutional system has not been reported. This investigation compared propensity-matched patients with NSCLC whose care was coordinated through a MDC to patients without access to an MDC across a geographically diverse system of hospitals.The Premiere database (Premier Inc, Charlotte, NC) for a health system's 70 hospitals was used to identify patients undergoing treatment for NSCLC during a 5-year period. Propensity matching was used to populate an MDC and non-MDC cohort. The two cohorts were compared for the costs of staging and diagnosis as well as the timeliness and quality of care metrics.Between 2008 and 2013, 13,254 patients were propensity matched. Patient demographics and Charlson comorbidity scores were comparable after matching. Significant differences were identified in adherence to national guidelines (p0.0001) for staging and treatment (p0.0001), timeliness of care (p0.0001), and costs (p0.0001) between the two groups.This investigation found that patients with NSCLC realize improved quality and timeliness of care when that care is coordinated through an MDC. The use of an MDC was also associated with a significant reduction in cost. These differences persisted across a geographically diverse set of hospitals, providers, and patients. Prospective MDCs should be considered integral and compulsory for patients with NSCLC.

Background Personalized normative alcohol feedback (PNF) is associated with decreased alcohol use among young adults. However, limited research has examined the influence of depressive symptoms on PNF efficacy. This study examined symptoms of depression as a moderator of college student response to a computerized PNF intervention for alcohol use. Methods College students (N = 212, 59% female) who reported drinking in a typical week completed baseline and one-month assessments as part of a previously published intervention trial. We randomized participants to alcohol PNF (n = 153) or assessment only (n = 59). We used regression models to examine the interaction between PNF and symptoms of depression on alcohol outcomes at one-month follow-up. Results One in four participants screened positive for clinically significant symptoms of depression. Depressive symptoms did not moderate intervention effects on drinking quantity. However, PNF was only associated with reduced frequency of heavy episodic drinking and lower probability of any alcohol-related consequence in the context of mild to moderate (not minimal) symptoms of depression. Conclusions PNF is more effective than assessment alone in reducing drinking quantity, regardless of symptoms of depression. However, it may only be more effective in decreasing frequency of heavy episodic drinking and the probability of alcohol-related consequences among those experiencing mild to moderate (as opposed to minimal) symptoms of depression. Alcohol intervention trials should assess symptoms of depression and consider them in data analysis.

The three-member RAF kinase family (A-, B- and C-Raf) are direct Ras effectors and key mediators of the proproliferative MAPK pathway. Somatic driver mutations in the B-Raf kinase domain occur frequently in melanoma and cancers of the thyroid and large intestine. These are predominantly the V600E mutation, which allows B-Raf to signal constitutively as a monomer. Germline mutations in B-Raf also occur and are present in ~67% of the childhood developmental RASopathy-cardiofaciocutaneous (CFC) syndrome. Interestingly, many of these CFC mutations cluster around the cysteine-rich domain (CRD) in the B-Raf regulatory region. CRDs are zinc stabilized structures with two flexible loops that are shown to bind phosphatidylserine (PS), DAG and pro-oncogenic phorbol esters in several PKC family members. Although the B-Raf CRD has not been well characterized, prior studies examining the C-Raf CRD show that it binds to PS through its first flexible loop but does not bind DAG or phorbol esters, likely due to its truncated second loop, which is found in all Raf members. In addition to PS binding, C-Raf CRD may also interact directly with Ras, suggesting a second Ras binding site outside of its Ras binding domain (RBD). Interestingly, B-Raf RASopathy mutations occur in both CRD loops and commonly introduce a positively charged residue suited to interacting with negatively charged lipids in the plasma membrane (PM). Of note, Q257R, which is the most common mutation in CFC, maps to the truncated second loop. Our in-cell studies with full-length B-Raf have shown that RASopathy mutations in both loops enhance biologic activity, PM localization and Ras interaction. However, the biologic activity of loop 1 mutations requires an intact RBD, which is not the case for the loop 2 mutant, Q257R. These data suggest that the Q257R mutant either has increased binding to Ras or allows B-Raf to signal independently of Ras. To further investigate these findings, we are examining differences in localization, Ras interaction and lipid binding using the isolated CRDs of C-Raf, B-Raf and the B-Raf RASopathy mutants. As may be predicted, the RASopathy mutations increased membrane localization over WT B-Raf, with Q257R being the most PM localized. Somewhat surprisingly, expression of the wild-type B-Raf CRD in cells showed greatly enhanced PM localization compared to that of wild-type C-Raf, suggesting functional differences between their CRDs, which we are currently investigating. Citation Format: Russell Spencer-Smith, Elizabeth M. Terrell, Constance Agamasu, Daniel A. Ritt, Alyson K. Freeman, Andrew G. Stephen, Deborah K. Morrison. Germline RASopathy mutations provide functional insights into the Raf cysteine-rich domain (CRD) [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr A31.

For decades, clinicians and researchers have recognized that borderline personality disorder (BPD) and substance use disorders (SUDs) are often diagnosed within the same person (e.g., (Gunderson JG. Borderline personality disorder: A clinical guide. Washington, D.C.: American Psychiatric Press, 2001; Leichsenring et al., Lancet 377:74-84, 2011; Paris J. Borderline personality disorder: A multidimensional approach. American Psychiatric Pub, 1994; Trull et al., Clin Psychol Rev 20:235-53, 2000)). Previously, we documented the extent of this co-occurrence and offered a number of methodological and theoretical explanations for the co-occurrence (Trull et al., Clin Psychol Rev 20:235-53, 2000). Here, we provide an updated review of the literature on the co-occurrence between borderline personality disorder (BPD) and substance use disorders (SUDs) from 70 studies published from 2000 to 2017, and we compare the co-occurrence of these disorders to that documented by a previous review of 36 studies over 15 years ago (Trull et al., Clin Psychol Rev 20:235-53, 2000).

BACKGROUND: Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo-oxygenases (COX). COX-1 is expressed constitutively and promotes gut barrier function, whereas COX-2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX-2 selective NSAIDs as compared with horses treated with flunixin meglumine. OBJECTIVES: We hypothesised that treatment of post-surgical SISO horses with firocoxib (COX-2 selective) would reduce the signs of endotoxaemia to a greater extent than flunixin meglumine (nonselective COX inhibitor) while continuing to provide similar levels of pain control. STUDY DESIGN: Blinded randomised clinical trial. METHODS: In addition to clinical monitoring, preoperative and 12-, 24- and 48-h post-operative plasma samples were assessed for prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), TNFα and soluble CD14 (sCD14). RESULTS: In 56 recruited SISO horses, either flunixin meglumine (1.1 mg/kg, i.v., q12h) or firocoxib (0.3 mg/kg, i.v. loading dose; 0.1 mg/kg, i.v., q24h) was given in the post-operative period in three university hospitals from 2015 to 2017. COX-2 selectivity was confirmed by a relative lack of inhibition of the COX-1 prostanoid TXB(2) by firocoxib and significant inhibition by flunixin meglumine (P = 0.014). Both drugs inhibited the COX-2 prostanoid PGE(2). There were no significant differences in pain scores between groups (P = 0.2). However, there was a 3.23-fold increased risk (P = 0.04) of increased plasma sCD14 in horses treated with flunixin meglumine, a validated biomarker of equine endotoxaemia. MAIN LIMITATIONS: Horses were all treated with flunixin meglumine prior to referral. In addition, many horses were treated with lidocaine, which has been shown to mitigate the deleterious effects of flunixin meglumine. CONCLUSIONS: In SISO cases, firocoxib reduced a biomarker of endotoxaemia as compared with flunixin meglumine while continuing to provide similar levels of pain control.

Oscillations of the brain's local field potential (LFP) may coordinate neural ensembles and brain networks. It has been difficult to causally test this model or to translate its implications into treatments, because there are few reliable ways to alter LFP oscillations. We developed a closed-loop analog circuit to enhance brain oscillations by feeding them back into cortex through phase-locked transcranial electrical stimulation. We tested the system in a rhesus macaque with chronically implanted electrode arrays, targeting 8-15 Hz (alpha) oscillations. Ten seconds of stimulation increased alpha oscillatory power for up to 1 second after stimulation offset. In contrast, open-loop stimulation decreased alpha power. There was no effect in the neighboring 15-30 Hz (beta) LFP rhythm or on a neighboring array that did not participate in closed-loop feedback. Analog closed-loop neurostimulation might thus be a useful strategy for altering brain oscillations, both for basic research and the treatment of neuro-psychiatric disease.

The most frequent genetic alterations in melanoma are gain-of-function (GOF) mutations in BRAF, which result in RAF–MEK–ERK signaling pathway addiction. Despite therapeutic success of RAF and MEK inhibitors in treating BRAFV600-mutant tumors, a major challenge is the inevitable emergence of drug resistance, which often involves reactivation of the MAPK pathway. Interestingly, resistant tumors are often sensitive to drug withdrawal, suggesting that hyperactivation of the MAPK pathway is not tolerated. To further characterize this phenomenon, isogenic models of inducible MAPK hyperactivation in BRAFV600E melanoma cells were generated by overexpression of ERK2. Using this model system, supraphysiologic levels of MAPK signaling led to cell death, which was reversed by MAPK inhibition. Furthermore, complete tumor regression was observed in an ERK2-overexpressing xenograft model. To identify mediators of MAPK hyperactivation–induced cell death, a large-scale pooled shRNA screen was conducted, which revealed that only shRNAs against BRAF and MAP2K1 rescued loss of cell viability. This suggested that no single downstream ERK2 effector was required, consistent with pleiotropic effects on multiple cellular stress pathways. Intriguingly, the detrimental effect of MAPK hyperactivation could be partially attributed to secreted factors, and more than 100 differentially secreted proteins were identified. The effect of ERK2 overexpression was highly context dependent, as RAS/RAF mutant but not RAS/RAF wild-type melanoma were sensitive to this perturbation. Implications: This vulnerability to MAPK hyperactivation raises the possibility of novel therapeutic approaches for RAS/RAF-mutant cancers.

Shifting definitions and differences in the conceptualization of bipolar disorders have contributed to long diagnostic delays, poor reliability, and inconsistent findings. Rating scales are independent of clinical judgment and offer a reliable way to assess manic symptoms, making them good tools to improve both clinical and research diagnoses of bipolar disorder. However, there are dozens of candidates, with few obvious distinguishing characteristics, making it difficult to select one. Our goal was to metaanalyze the diagnostic accuracy of rating scales designed to identify [hypo]manic symptoms. Additionally, we explored potential moderator variables including global region, translation into a different language, and sample composition. Nearly 4000 articles were identified with searches in PubMed and PsycINFO, yielding 127 effect sizes from 103 studies that met the following inclusion criteria: (a) statistics reported by which a standardized effect size could be calculated, (b) participants age 18 + years, (c) reference diagnoses made by semistructured/structured diagnostic interview, (d) results published in English. Multivariate mixed regression models accounted for multiple effect sizes nested within sample. One hundred twenty-seven effect sizes across 14 rating scales were evaluated. There was significant heterogeneity across effect sizes; Cochran's Q(126 df) = 1622.08, p < .00005, and substantial variance components both within (σ2 = .057) and between samples (σ2 = .253). Four measures performed similarly well and significantly better than some competitors after controlling for design and reporting features. The best rating scales offer an inexpensive, efficient way to improve research and clinical diagnostic processes across diverse populations, and could also complement formal diagnoses for examining secular and cultural trends. (PsycINFO Database Record

Wireless neural stimulators are being developed to address problems associated with traditional lead-based implants. However, designing wireless stimulators on the sub-millimeter scale (

PURPOSE OF REVIEW Pleural effusions are a common finding in the nearly six million Americans diagnosed with heart failure. This review focuses on the historical, present and potential future trends in the management of such benign pleural effusions. RECENT FINDINGS The management of symptomatic pleural effusions, in general, and in heart failure, specifically, has evolved in the last two decades. With more options, the treatment is often individualized for patients. Newer forms of therapy are also less invasive, resulting in less procedural morbidity, recuperation and cost. SUMMARY The majority of patients with a pleural effusion resulting from heart failure will resolve their symptoms with medical therapy. Patients who experience symptoms from reaccumulation of their effusion have a selection of treatment options that can be individualized based on the patient's prognosis, functional status, need for future intervention and desires.

Esophageal stent placement has been shown to be a safe and effective treatment for acute esophageal perforation in selected patients. However, a comparison between surgical repair and stent placement has not been reported. This investigation compares the outcomes and costs of the 2 treatment modalities.The Premiere database for a single health system's hospitals was used to identify patients undergoing treatment for an acute intrathoracic esophageal perforation over a 4-year period. Patient cohorts for stent placement or surgical repair were formed using propensity matching. The 2 cohorts were compared for length of stay, morbidity, mortality, and costs.Between 2009 and 2012, 60 patients undergoing esophageal stent placement or surgical repair were propensity matched. Mean patient age and Charlson comorbidity scores did not differ significantly (P = .4 and P = .4, respectively). Significant differences in morbidity (4% vs 43%; P = .02), mean length of stay (6 vs 11 days; P = .0007), time to oral intake (3 vs 8 days; P = .0004), and cost ($91,000 vs $142,000; P.0001) were identified in the esophageal stent cohort when compared with patients receiving surgical repair. Operative mortality did not differ significantly.Esophageal stent placement for the treatment of an acute esophageal perforation seems to be as effective as surgical repair when compared between propensity-matched patients. However, stent placement resulted in a shorter length of stay, lower rates of morbidity, and lower costs when compared with traditional surgical repair.

Spindle cell variant of lymphoma is a very rare but known disease entity that can mimic a sarcoma. Diagnosis can be even more challenging if the only site of the disease is in the bone. We report a case of primary lymphoma of bone with spindle cell morphology which was successfully treated with a combination of surgery, chemotherapy, and radiotherapy.

Metastatic tumours of the bone are tumours that spread to bone from another primary site in the body. Histologically they often resemble the cells of the tumour they originated from. Traditionally the presence of a metastatic bone deposit has been seen as a terminal event; however, with the increased survival of patients with carcinoma and improved treatment, long-term survival is possible with metastatic bone disease and treatment can prolong life, or even be curative. Implants used in reconstruction need to be sufficiently robust to survive the patient, and the expertise of reconstruction available within tertiary bone tumour units is increasingly required. Autopsy studies have shown that 70% of patients with breast and prostate carcinoma develop skeletal metastases. The most commonly involved bone sites are those with persistent red marrow, such as the vertebrae, proximal femur, ribs, sternum, pelvis and skull. The precise mechanism of metastases to bone is unclear. However, the understanding of the molecular biology of metastases is becoming increasingly important in providing new therapeutic targets in their treatment. The types of treatment of metastases include medical treatments, radiotherapy and surgery. Bone metastases can cause many complications and have significant morbidity.

Violence is a major determinant of many adverse health outcomes in Canada and worldwide, and it is unacceptable in all forms. The evidence base on effective interventions to prevent violence is now robust.[1][1] Experience of and exposure to violence in childhood is a prominent adverse childhood

Antennas that operate in the low-frequency (LF) band and below are useful for a number of applications. However, the long wavelengths result in very low efficiency for antennas that could be made portable. This has motivated the need for novel approaches for electrically short antenna design. Here, we present the concept of an electromagnetic transmitter that operates by mechanically moving bound static charge. The resulting motion induces electromagnetic fields that are similar to a short dipole antenna. However, the voltage, current, and resistance of a conventional antenna are replaced by force, velocity, and damping in a mechanical system. The mechanical system offers very high efficiency at low frequencies where impedance matching naturally occurs and mechanical structures have very low losses. We present a basic proof-of-concept demonstration by rotating a charged electret material up to 167Hz and measuring the resulting time-varying magnetic field. This work is intended to lay the foundation for future tests involving the implementation of efficient, small form-factor, mechanically-actuated antennas.

Traditionally, gold standard treatment for an acute esophageal perforation has been operative repair. Over the past two decades, there has been a paradigm shift towards the use of esophageal stents. Recent advances in biomaterial allowed a new generation of stents to be manufactured that combined (I) a non-permeable covering; (II) radial force sufficient to occlude a transmural esophageal injury and (III) improved ease of removability. The amalgamation of these developments set the stage for utilizing esophageal stents as part of the management algorithm of an acute esophageal perforation. This provides a safe and less invasive treatment route in lieu of direct primary repair and its well-documented significant failure rate. Esophageal stent placement for failed operative repair or esophageal leaks also had the potential to minimize the need for esophageal resection and diversion. When included in a multimodality hybrid treatment protocol, esophageal stents can optimize healing success rates and minimize the risks of adverse complications. This review summarizes the modern history of esophageal stent use in the treatment of esophageal perforation as well as the evidenced based recommendations for the use of esophageal stent placement in the treatment of acute esophageal perforation.

We present an integrated model for simultaneous optimization of the loading and routing decisions associated with an automotive supplier’s outbound supply chain. The supplier, Webb Wheel (WW), is a manufacturer of brake drums, rotors, hubs, and spoke wheels. WW accepts new orders from customers each day. Given sufficient inventory, it combines these orders into loads, releases them based on various dispatch criteria (e.g., truck-utilization, route-utilization, or penalty-based dispatch policies) and due-date considerations, and ships them in truckloads, less-than-truckloads, and containers. Dynamically changing demand information, inventory rationing, inventory interactions among orders, and lead-time considerations are some of the challenging aspects of the problem. Our optimization model is based on the decomposition of the problem into assignment and routing subproblems. The assignment subproblem determines the transportation mode and carrier choices, while considering total transportation costs. These costs depend on a variety of factors, including destination, number of drop locations on the route, and needs of customers on the route. Given the customer clusters and transportation modes from the assignment subproblem, the routing subproblem determines the sequence of drops and the true cost of the shipment using a modified traveling salesman problem. A scalable database with a graphical user interface supports the optimization model. We test our algorithm using four months of WW data and compare these data to the company’s practice. Our results demonstrate the impact of transportation mode-specific capacities, customer locations, inventory availabilities, and due-date restrictions on outbound logistics costs. Since implementing our load-planning algorithm, WW has achieved cost savings of 4.4 percent over its previous load-planning process.

Background Surgical repair of esophageal perforation has been the mainstay of therapy for patients without associated esophageal malignancy or diffuse mediastinal necrosis. However, the leak rate after primary surgical repair is reported to range between 15% and 20% and increases to 45% and 70% in patients whose repair is delayed beyond 24 hours. This analysis reviews patients who experienced a leak after the operative repair of an esophageal perforation treated with esophageal stent placement. Methods Patients undergoing esophageal stent placement for the treatment of a leak after the operative repair of an intrathoracic esophageal perforation were identified from a single institution's database, which included patients initially treated at other facilities. Patient outcomes were recorded and analyzed. Results During a 7-year period, 32 esophageal stents were placed in 29 patients who experienced an esophageal leak after operative repair. Associated surgical procedures were simultaneously performed in 7 (24%) patients. Leak occlusion occurred in 27 patients (93%). Two patients required a reoperative repair. Twenty-five patients (86%) were able to initiate oral nutrition within 72 hours of stent placement. Stent migration in 5 patients (19%) required repositioning (n = 2) or replacement (n = 3). Stents were removed at a mean of 22 ± 16 days after placement. Mean hospital length of stay was 8 ± 11 days. Conclusions Endoluminal esophageal stent placement is a safe and effective treatment for the majority of leaks after the operative repair of an intrathoracic esophageal perforation. Stent placement resulted in rapid leak occlusion and provided the opportunity for early oral nutrition while eliminating the need for reoperative repair or esophageal exclusion in the majority of patients.

This article considers scheduling products in a parallel, non-identical machine environment subject to sequence-dependent setup costs and sequence-dependent setup times, where production waste and processing time of a product depend on feasible machine assignments. A Mixed-Integer Programming (MIP) formulation is developed that captures trade-offs between overtime labor costs and waste costs. Two solution procedures are developed to address large problem instances. One procedure is an algorithm that determines a vector of product-to-machine assignments that assists an MIP solver to find an initial feasible solution. The second procedure is a decomposition heuristic that iteratively solves a relaxed subproblem and uses the subproblem solution to fix assignment variables in the main MIP formulation. In addition, bounds on the quality of solutions found using the decomposition heuristic are presented. Experiments are conducted that show the developed formulation outperforms more traditional scheduling object...

SummaryObjective: An increased risk of mast cell tumours (MCT) in certain breeds has been described repeatedly in the literature. The incidence of MCTs for registered breeds in Austria, an estimate of the risk by means of the odds ratios based on breed as well as the anatomic localisation of MCTs were examined. Material and methods: In the first part of the study, the ranking of breeds in Austria based on 147,802 dogs with known breed (including mixed breed) was determined, based on those dogs included in the laboratory data base from 2000 to 2010. In the second part of the study, 476 dogs were identified with MCTs and analysed by age, sex, Patnaik grade of MCT and breed distribution. The odds ratios with confidence intervals were calculated for all breeds with skin tumours. Results: The age distribution showed a peak in the age group from 6.1 to 8.0 years; 70% of MCTs were localised to the head and trunk. No significant difference was found based on gender. The evaluation of the odds ratios showed that only four of the 20 of the most popular in Austria breeds (Boxer, Bernese Mountain Dog, Golden Retriever, Spaniel) had an increased risk; on the other hand, some breeds which have not been previously identified in the literature were indicated to have a significantly increased risk for MCT (e.g., Dogo Argentino, Tibetan Spaniel, Pyrenean Mountain Dog, Beauceron, and Austrian Smooth-haired Hound). Conclusion and clinical relevance: Because disease risk may influence the popularity of some currently rare breeds, consultation with breeders and owners regarding the identification of the breeds newly identified in this study as an increased risk for development of mast cell tumours is indicated.

Process improvement, in its broadest sense, is the analysis of a given set of actions with the aim of elevating quality and reducing costs. The tenets of process improvement have been applied to medicine in increasing frequency for at least the last quarter century including thoracic surgery. This review outlines the theory underlying process improvement, the currently available data sources for process improvement and possible future directions of research.

Background Cutaneous plasmacytosis (CP) is a syndrome of multiple cutaneous plasma cell tumors, in the absence of multiple myeloma. Although rare in both humans and dogs, treatment recommendations are usually extrapolated from multiple myeloma protocols. To date, no case series of CP have been described in the veterinary literature. Hypothesis/Objectives To describe clinical presentation, determine treatment response rates and duration, and report overall survival of dogs with CP. Animals Twenty-one client-owned dogs with CP. Methods Medical records of 21 dogs with CP were reviewed. Diagnosis was based on histopathologic evaluation of at least 1 representative cutaneous or subcutaneous lesion in dogs with ≥3 lesions. Dogs with suspicion of multiple myeloma were excluded. Results The most commonly affected breeds were the golden (5/21) and Labrador retriever (3/21). Fourteen of 21 dogs had >10 lesions, with some having >100. Lesions commonly were described as round, raised, pink-to-red, and variably alopecic or ulcerated. The most commonly used drug protocol was combined melphalan and prednisone, with an overall response rate (ORR) of 73.7% (14/19 dogs). Single-agent lomustine was associated with a similar ORR of 71.4% (5/7 dogs). For all treatments combined, the median progression-free interval after the first treatment was 153 days. The median survival time from the first treatment was 542 days. Conclusions and Clinical Importance Alkylating agents were effective in inducing remission of CP; corticosteroids, melphalan, and lomustine were the most commonly used drugs. Survival times were similar to those reported in dogs with multiple myeloma treated with alkylating agents.

SETTING: Alberta is a prairie province located in western Canada, with a population of approximately 4.3 million. In 2016, 363 Albertans died from apparent drug overdoses related to fentanyl, an opioid 50–100 times more toxic than morphine. This surpassed the number of deaths from motor vehicle collisions and homicides combined. INTERVENTION: Naloxone is a safe, effective, opioid antagonist that may quickly reverse an opioid overdose. In July 2015, a committee of community-based harm reduction programs in Alberta implemented a geographically restricted take-home naloxone (THN) program. The successes and limitations of this program demonstrated the need for an expanded, multi-sectoral, multi-jurisdictional response. The provincial health authority, Alberta Health Services (AHS), used previously established incident command system processes to coordinate implementation of a provincial THN program. OUTCOMES: Alberta’s provincial THN program was implemented on December 23, 2015. This collaborative program resulted in a coordinated response across jurisdictional levels with wide geographical reach. Between December 2015 and December 2016, 953 locations, including many community pharmacies, registered to dispense THN kits, 9572 kits were distributed, and 472 reversals were reported. The provincial supply of THN kits more than tripled from 3000 to 10 000. IMPLICATIONS: Alberta was uniquely poised to deliver a large, province-wide, multi-sectoral and multi-jurisdictional THN program as part of a comprehensive response to increasing opioid-related morbidity and mortality. The speed at which AHS was able to roll out the program was made possible by work done previously and the willingness of multiple jurisdictions to work together to build on and expand the program.

Strategies to value physician work continue to evolve. The Society of Thoracic Surgeons and The Society of Thoracic Surgeons National Database have an increasingly important role in this evolution. An understanding of the Current Procedural Terminology (CPT) system (American Medical Association [AMA], Chicago, IL) and the Relative Value Scale Update Committee (RUC) is necessary to comprehend how physician work is valued. In 1965, with the dawn of increasingly complex medical care, immense innovation, and the rollout of Medicare, the need for a common language describing medical services and procedures was recognized as being of critical importance. In 1966, the AMA, in cooperation with multiple major medical specialty societies, developed the CPT system, which is a coding system for the description of medical procedures and medical services. The RUC was created by the AMA in response to the passage of the Omnibus Budget Reconciliation Act of 1989, legislation of the United States of America Federal government that mandated that the Centers for Medicare & Medicaid Services adopt a relative value methodology for Medicare physician payment. The role of the RUC is to develop relative value recommendations for the Centers for Medicare & Medicaid Services. These recommendations include relative value recommendations for new procedures or services and also updates to relative value recommendations for previously valued procedures or services. These recommendations pertain to all physician work delivered to Medicare beneficiaries and propose relative values for all physician services, including updates to those based on the original resource-based relative value scale developed by Hsaio and colleagues. In so doing, widely differing work and services provided can be reviewed and comparisons of their relative value (to each other) can be established. The resource-based relative value scale assigns value to physician services using relative value units (RVUs), which consist of three components: work RVU, practice expense RVU, and malpractice RVU, also known as professional liability insurance RVU. The Centers for Medicare & Medicaid Services retains the final decision-making authority on the RVUs associated with each procedure or service. The purpose of this article is to discuss the role that the CPT codes and the RUC play in the valuation of physician work and to provide an example of how the methodology for valuation of physician work continues to evolve.

Murray’s letter repeats a common mistake in thinking about screening, that “doing any test is better than doing nothing at all.”[1][1] In fact, sometimes doing nothing is better than doing something: more is not always better.[2][2] There are risks and harms with all medical interventions

OBJECTIVE Recent developments in peripheral nerve electrodes allow the efficient and selective neuromodulation of somatic and autonomic nerves, which has proven beneficial in specific bioelectronic medical applications. However, current most clinical devices are wired and powered by implantable batteries which suffer from several limitations. We recently developed a sub-millimeter inductively powered neural stimulator (electroparticle; EP), and in this study, we report the integration of the EP onto commercial cuff electrodes (EP-C) allowing the wireless activation of peripheral nerves. APPROACH The current output of this device was defined at different magnetic field strenghts, and with respect to external antenna distance and activation angles. In acute in vivo testing, stimulation of the rat sciatic nerve (ScN) with the EP-C was able to evoke motor responses quantified by 3D tracking of the hind limb movement. Motor recruitment curves were obtained in response to variations in magnetic field strength (0-92.91 A m-1), stimulation frequencies (2-7 Hz), and pulse widths (50-200 µs). MAIN RESULTS The results show constant output voltage throughout 50 400 stimulating cycles on a benchtop setting, and successful ScN motor activation with a 4 cm distance between external antenna and receiver. We achieved optimal motor recruitment indicated by maximizing range of hindlimb movement (6.01 ± 2.92 mm) with a magnetic field of 40.02 ± 2.85 A m-1 and 150 µs pulse width. Stimulating pulse width or frequency did not significantly influence motor recruitment. SIGNIFICANCE We confirmed that continuous stimulation for 14 min using monophasic pulses did not deleteriously affect the evoked motor responses when compared to wired charge-balanced biphasic electrical stimulation. We observed, however, a 36%-44% decrease in the evoked limb movement in both groups over time due to muscle fatigue. This study shows that the EP-C device can be used effectively for peripheral nerve neuromodulation.

e20719 Background: Genomic profiling of advanced non-squamous lung cancer is integral for appropriate management. Appropriate testing and timeliness in getting the results often pose a challenge in a community setting. We share our experience in a community setting and the importance of an integrated approach to improve outcomes. Methods: Retrospective review of the charts of patients with stage- III-B/IV was conducted to gather data. Effect of Multi-disciplinary meetings to improving coordination among treating physicians and Incorporation of reflex testing for complete mutational profiling on diagnosis was studied. Results: Between 04/2016 and 10/2018, 127 patients charts were reviewed. 83% were stage-IV and 17% stage-III-B. Males (61%), Females (49%). Median age was 62 yrs. 76% had smoking history.There were 53% core biopsies, 42% FNAs and 5% resections. Mutational profiling panel was based on the NCCN guidelines. Adequate specimen for complete profiling was available in 111/127 (87%) of the patients. Two/16 (12%) of pts with in-adequate sample had a repeat biopsy and 12/16 ( 75%) had liquid biopsies done. Remaining 2 pts didnot have further w/u due to declining PS. Complete mutational profile (EGFR/ALK/ROS-1/MET/RET/BRAF/PDL-1) was available in 100% of pts. after re-biopsy/liquid bx. Incorporation of reflex testing decreased the reporting time from an average of 11.6 days to 6.9 days. The results of mutational profiling were available in 94% of pts. before starting the treatment. Prevalence of mutations were, EGFR:14%, ALk:3%, BRAF:1%, MET:0%, RET:1%, ROS-1:2%. Conclusions: Multi-disciplinary integrated approach and reflex testing upon diagnosis is essential for appropriate and timely genomic profiling of locally advanced/ metastatic non-squamous lung cancer patients to deliver appropriate treatment in a community setting.

The Raf family of protein kinases are key signaling intermediates, acting as a central link between the membrane-bound Ras GTPases and the downstream kinases MEK and ERK. Raf kinase regulation is well-known for its complexity but only recently has it been realized that many of the mechanisms involved in Raf regulation also modulate Raf dimerization, now acknowledged to be a required step for Raf signaling in multiple cellular contexts. Recent studies have shown that Raf dimerization is necessary for normal Ras-dependent Raf kinase activation and contributes to the pathogenic function of disease-associated mutant Raf proteins with all but high intrinsic kinase activity. Raf dimerization has also been found to alter therapeutic responses and disease progression in patients treated with ATP-competitive Raf inhibitors as well as certain other kinase-targeted drugs. This demonstration of clinical significance has stimulated the recent development of biosensor assays that can monitor inhibitor-induced Raf dimerization as well as studies demonstrating the therapeutic potential of blocking Raf dimerization.

Apical hypertrophic cardiomyopathy (HC) has been considered a "benign" form of HC, with limited data on long-term outcome. We compared apical HC patients with a non-HC, age- and gender-matched Minnesota white population to identify outcomes and prognostic factors. Between 1976 and 2006, 193 patients (62% men) with apical HC were seen at our clinic. Their most recent echocardiographic examinations were reviewed. Mean ± SD age at first presentation was 58 ± 17 years. A family history of HC or sudden cardiac death (SCD) was reported by 43 patients (22%); coronary artery disease was known in 22 (11%). An apical pouch was present in 29 patients, including an apical aneurysm in 6 and apical dilatation with hypokinesis in 23. Median follow-up (187 patients [97%]) was 78 months (range, 1-350). Death from all causes occurred in 55 patients (29%; 33 women) at a mean age of 72 years (range, 20-92). During follow-up, more women had heart failure (p = 0.001), atrial fibrillation (p = 0.009), or died (p

Three-phase (G/L/S) horizontal pipe flow data collected from the literature are used to evaluate the performance of a number of correlations designed to predict the pipeline pressure gradient. In the present study, a number of popular two-phase gas–liquid pressure loss correlations were modified for three-phase flow predictions. The primary modification is to assume that the slurry (L/S) mixture behaves as a singlephase. The modified Dukler and the Beggs and Brill correlations did not provide accurate estimates of the three-phase pressure gradients. When the classical Lockhart–Martinelli (L–M) correlation was used, along with a kinematic friction loss model to calculate the slurry (L/S) superficial flow pressure gradient, accurate predictions of the three-phase (G/L/S) pressure gradient were obtained provided the slurry did not exhibit non-Newtonian behaviour and that Coulombic (sliding bed) friction was negligible. Additional experiments should be conducted before the improved version of the L–M correlation is applied to commercial installations with pipe diameters greater than 100 mm.

Objectives This investigation compared patients undergoing lobectomy for non–small cell lung cancer by either a general surgeon or a cardiothoracic surgeon across a geographically diverse system of hospitals to see whether a significant difference in quality or cost was present. Methods The Premiere administrative database and tumor registry data of a single health system's hospitals was used to compare adherence to national treatment guidelines, patient outcomes, and charges for patients undergoing lobectomy for non–small cell lung cancer in a 5-year period. Surgeons performing lobectomy were designated as a general surgeon or cardiothoracic surgeon according to their national provider number and board certification status. Excluded from analysis were centers that performed fewer than 50 lobectomies during the study period. Results During the study period, 2823 lobectomies were performed by 46 general surgeons and 3653 lobectomies were performed by 29 cardiothoracic surgeons in 54 hospitals in a single health care system. Significant differences were found between general and cardiothoracic surgeons with respect to adherence to national guidelines in staging and treatment, mean length of stay, significant morbidity, and operative mortality. Mean charges for lobectomy of the lung were also found to differ significantly between general and cardiothoracic surgeons. Conclusions This review found that currently measurable indicators for quality of care were significantly superior and overall charges were significantly reduced when a lobectomy for non–small cell lung cancer was performed by a cardiothoracic surgeon rather than by a general surgeon.

Objectives Palliative care is a medical specialty focused on improving the quality of life of patients and their families with life threatening illness by preventing or relieving suffering. An assessment of a thoracic surgery service was performed to identify the scope and frequency of care that was considered palliative and any implications the findings might have on the current thoracic surgery residency curriculum. Methods A retrospective review of a prospectively collected database of general thoracic surgery procedures performed over a 5-year period at a single institution was performed. Procedures considered palliative were reviewed for demographics, diagnoses, palliative prognosis score, treatment, morbidity, operative mortality, and survival. Excluded were referrals from thoracic surgery to other specialties for palliative procedures. Results During the study period, 3842 procedures were performed of which 884 (23%) were palliative. Indications included pleural or pericardial effusion or both, dysphagia, hemoptysis, tracheobronchial obstruction, bronchopleural fistula, and tracheoesophageal fistula. The majority was related to a malignancy. Only 127 patients (14%) had a palliative care assessment before thoracic surgery consultation. Mean survival following thoracic surgery intervention was 110 days for patients with malignancy. Conclusions This investigation found that thoracic surgeons commonly care for patients when the intention or indication or both is palliation. Most of these patients have an associated malignancy, a poor performance status and a projected significantly decreased survival compared with the general population. Thoracic surgeons should be familiar with the concepts of palliative care and consideration should be given to expanding exposure to the principles of palliative care in the cardiothoracic residency training curriculum.