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In preparation for exhibition, an ancient Greek terracotta krater received treatment which included selective in-painting with cadmium orange (CdSSe). After one year on display the object displayed disfiguring alteration in select areas of restoration. Cross-section analysis of samples taken from the object revealed that alteration only occurred in areas where the paint was in direct contact with darkened and abraded areas of the terracotta surface, in which analysis found the presence of chlorine. The alteration was recreated in mock-ups for more in-depth analysis. Using Raman spectroscopy and scanning electron microscopy with energy-dispersive X-rays (SEM-EDS) it was discovered that selenium-rich structures were forming throughout the paint films. The observed alteration is the result of degradation of the CdSSe pigment which occurs in the presence of chlorine and light. This research highlights the need for careful selection of restoration materials when dealing with objects suspected to contain residual chloride ions if desalination cannot be undertaken.

This paper describes a multi-center collaborative project involving curators, conservators, scientists and artists to investigate the Chinese ceramics known as numbered Jun Ware. This rare group of...

BackgroundThe following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services.ObjectivesThis material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures.ConclusionAs evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.

© 2021, The Author(s). Background: Biomarkers that can objectively guide the diagnosis of sports-related concussion, and consequent return-to-play decisions, are urgently needed. In this study, we aimed to determine the temporal profile and diagnostic ability of serum levels of neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP), and tau in concussed male and female Australian footballers. Methods: Blood was collected from 28 Australian rules footballers (20 males, 8 females) at 2-, 6-, and 13-days after a diagnosed concussion for comparison to their levels at baseline (i.e. pre-season), and with 27 control players (19 males, 8 females) without a diagnosis of concussion. Serum concentrations of protein markers associated with damage to neurons (UCHL1), axons (NfL, tau), and astrocytes (GFAP) were quantified using a Simoa HD-X Analyzer. Biomarker levels for concussed players were compared over time and between sex using generalised linear mixed effect models, and diagnostic performance was assessed using area under the receiver operating characteristic curve (AUROC) analysis. Results: Serum NfL was increased from baseline in male footballers at 6- and 13-days post-concussion. GFAP and tau were increased in male footballers with concussion at 2- and 13-days respectively. NfL concentrations discriminated between concussed and non-concussed male footballers at all time-points (AUROC: 2d = 0.73, 6d = 0.85, 13d = 0.79), with tau also demonstrating utility at 13d (AUROC = 0.72). No biomarker differences were observed in female footballers after concussion. Conclusions: Serum NfL may be a useful biomarker for the acute and sub-acute diagnosis of concussion in males, and could inform neurobiological recovery and return-to-play decisions. Future adequately powered studies are still needed to investigate biomarker changes in concussed females.

© Copyright © 2020 Major, McDonald, O'Brien, Symons, Clough, Costello, Sun, Brady, Mccullough, Aniceto, Lin, Law, Mychasiuk, O'Brien, Agoston and Shultz. Studies have indicated that concussive and sub-concussive brain injuries that are frequent during collision sports may lead to long-term neurological abnormalities, however there is a knowledge gap on how biological sex modifies outcomes. Blood-based biomarkers can help to identify the molecular pathology induced by brain injuries and to better understand how biological sex affects the molecular changes. We therefore analyzed serum protein biomarkers in male (n = 50) and female (n = 33) amateur Australian rules footballers (i.e., Australia's most participated collision sport), both with a history of concussion (HoC) and without a history of concussion (NoHoC). These profiles were compared to those of age-matched control male (n = 24) and female (n = 20) athletes with no history of neurotrauma or participation in collision sports. Serum levels of protein markers indicative of neuronal, axonal and glial injury (UCH-L1, NfL, tau, p-tau, GFAP, BLBP, PEA15), metabolic (4-HNE) and vascular changes (VEGF-A, vWF, CLDN5), and inflammation (HMGB1) were assessed using reverse phase protein microarrays. Male, but not female, footballers had increased serum levels of VEGF-A compared to controls regardless of concussion history. In addition, only male footballers who had HoC had increased serum levels of 4-HNE. These findings being restricted to males may be related to shorter collision sport career lengths for females compared to males. In summary, these findings show that male Australian rules footballers have elevated levels of serum biomarkers indicative of vascular abnormalities (VEGF-A) and oxidative stress (4-HNE) in comparison to non-collision control athletes. While future studies are required to determine how these findings relate to neurological function, serum levels of VEGF-A and 4-HNE may be useful to monitor subclinical neurological injury in males participating in collision sports.

The collection of the Worcester Art Museum includes two rare Magna Graecia terracotta funerary statues from Canosa, Italy dating to the third century BCE. Each depicts a female figure in prayer or lament known as an orante. The orantes were purchased by the museum in 1927, but shortly thereafter were separated. One was left in storage for nearly seven decades and the other was sold, and ultimately entered a private collection halfway around the world. The orantes were recently reunited under serendipitous circumstances and, after more than 80 years, will finally be placed on display at the Museum. As part of a comprehensive treatment, a technical study was carried out to identify the materials and methods used in their manufacture and in previous restoration campaigns. Materials were characterized by cross-section analysis, spot tests, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), neutron activation analysis (NAA), thermogravimetric analysis (TGA), thermolumin...

This article presents several examples of settings that led to the unintended operation of distribution protection, including transformer delta-winding residual overcurrent protection, transformer high-voltage phase overcurrent protection, and others. The nature of the unintended operation is explored, and the methods for calculating more secure settings are discussed.

Background Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. Methods In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Findings Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Interpretation Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Funding Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT).

The town of Matata in the Eastern Bay of Plenty (New Zealand) experienced an extreme rainfall event on the 18 May 2005. This event triggered widespread landslips and large debris flows in the Awatarariki and Waitepuru catchments behind Matata. The Light Detection and Ranging technology (LIDAR) data sets flown prior to and following this event have been differenced and used in conjunction with a detailed field study to identify the distribution of debris and major sediment pathways which, from the Awatarariki catchment, transported at least 350,000 ± 50,000 m3 of debris. Debris flows were initially confined to stream valleys and controlled by the density and hydraulic thrust of the currents, before emerging onto the Awatarariki debris fan where a complex system of unconfined sediment pathways developed. Here, large boulders, clasts, logs and entire homes were deposited as the flows decelerated. Downstream from the debris fan, the pre-existing coastal foredune topography played a significant role in deflecting the more dilute currents that in filled lagoonal swale systems in both directions. The differenced LIDAR data have revealed several sectors characterised by significant variation in clast size, thickness and volume of debris as well as areas where post-debris flow cleanup and grading operations have resulted in man-made levees, sediment dumps, scoured channels and substantial graded areas. The application of differenced LIDAR data to a debris flow event demonstrates the techniques potential as a precise and powerful tool for hazard mapping and assessment.

Aim: AFRESA™ [Technosphere® Insulin (TI); MannKind Corporation, Valencia, CA], a dry powder preparation of regular human insulin (RHI), utilizes a novel and versatile drug carrier platform that enables pulmonary administration of medications typically administered by injection. The aim of this study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of three different inhaled doses of TI with those of subcutaneous (s.c.) RHI. Methods: This randomized, open-label, four-way crossover study of 11 healthy, non-smoking volunteers evaluated PK and PD profiles following single inhalations of 25, 50 or 100 U TI and 10 IU RHI administered subcutaneously using a euglycaemic clamp technique. Results: Following inhalation of TI, peak insulin concentrations (Cmax) were achieved approximately 2 h earlier than with RHI (12–17 min for TI vs. 134 min for RHI). Area under the insulin concentration–time curve (AUC) and insulin Cmax values increased with increasing TI dose. Insulin exposure, as measured by AUC, was found to be linear over the dose range studied. Compared with s.c. RHI, TI at doses of 25, 50 and 100 U showed a relative bioavailability of 25, 23 and 21%, respectively. The maximum bioeffect, as measured by the glucose infusion rate, occurred approximately 2 h earlier for all three TI doses (42, 50 and 58 min, respectively) than for s.c. RHI (171 min). No treatment-related adverse events were reported with TI. Conclusion: TI is an inhaled insulin with a more rapid absorption and a more rapid elimination than subcutaneously administered RHI, resulting in a quick onset and short duration of action. Insulin exposure following TI administration was found to be linear over the dose range of 25–100 U.

Background:Accidental and non-accidental applications of superglue in the ear, nose and oral cavity have been reported previously. Surgical removal of glue from the nose is the current practice.Case report:This paper reports the case of an 18-year-old female, who presented with complete bilateral nasal occlusion due to deliberate self-application of superglue in both nostrils to avoid nasogastric tube insertion.Results:Removal of glue was accomplished with a combination of local anaesthetic cream and acetone-soaked cotton buds, which caused only minimal discomfort to the patient. All traces of glue disappeared within 10 days, without causing damage to the nasal mucosa, nasal blockage or pain.Conclusion:To the best of our knowledge, this is the first case report of deliberate self-application of superglue in the nose. A successful non-surgical management option for the removal of glue from the nose is introduced.

Dispersed fluorescence spectroscopy has been used to study jet-cooled AgAu and Pt2. Fluorescence resulting from the excitation of five bands of the A←X 1Σ+ system of AgAu was dispersed, and 51 measured ground state vibrational levels were fit to provide ground state vibrational constants of ωe″=198.22±0.11 cm−1 and ωe″xe″=0.512±0.002 cm−1. A Franck–Condon calculation was performed using the experimental values of the ground and excited state vibrational frequencies and anharmonicities, providing an estimate of the change in bond length upon excitation of the A←X system of Δre=0.214±0.005 A. Fluorescence resulting from four different excitations of Pt2 was dispersed, providing vibrational constants for the ground and two low-lying excited states. Ground state vibrational constants of ωe=222.3 cm−1 and ωexe=0.62 cm−1 were obtained, based on the analysis of 16 measured ground state vibrational levels. In addition, a low-lying excited state was located at T0=2877 cm−1, with ωe=197 cm−1. This state perturbed t...

Reverse Engineering is used to determine the inlet port geometry of a diesel engine. The case described illustrates a general problem where the precise nature of manufactured components relies heavily on the skills of pattern makers and foundrymen. Two methods are used, one in which the geometry is determined by used or silicon rubber moulding and one by machining planes off a cylinder head. In the latter case the geometry was measured by a contact probe on a CMM, generated in the CMM software files and transferred to Pro/ENGINEER® data files. The procedure, and the difficulties experienced with applying surface modelling to the generated data are described. General conclusions are drawn on the present state of reverse engineering as a means of adjusting CAD data to ensure conformance to specification.

A novel synthesis of symmetric and nonsymmetric 9,9-disubstituted 4,5-diazafluorenes has been developed. These compounds have activity in both an in vitro acetylcholine release assay and in vivo rodent models of learning and memory. Preparation of these compounds involves a unique aldol condensation between 4,5-diazafluoren-9-one (4) and 4-picoline. Reduction of aldol product 5 (5-(4-pyridinylmethylene)-5H-cyclopenta[2,1-b:3,4-b‘]dipyridine) provides monoalkylated diazafluorene 6 (5-(4-pyridinylmethyl)-5H-cyclopenta[2,1-b:3,4-b‘]dipyridine) which proved to be a key intermediate for synthesis of nonsymmetric analogs.

This paper describes epee, a distributed environment for the integration of software applications. It was developed with the aim of aiding the process of design by providing the necessary support for a design information management system. The software environment is first described in general terms and then our specific application of epee to process engineering design is presented. epee uses an object-oriented approach to data management. Data are represented as objects whose definitions, via templates, reflect the process engineering design environment. The use of focussed methods promotes a consistent look and feel to the tools in the environment. Method reuse reduces software development costs and increases users' confidence in the reliability of the methods. The benefits of the history recording mechanism in epee and its object publishing facilities are described. A history record is a critical component of a high level design management system. This, together with the sharing of data through object publishing, provides the necessary support for collaborative design. The application of epee to process engineering design illustrates the benefits of object-oriented techniques to the process systems and design community. The inherent extensibility of object definitions facilitates the application of the support system to any area of design. The dynamic nature of object definitions in epee encourages exploration and experimentation with new data types and methods.

Traditional syntheses of benzodiazepines involve a Bischler-Napieralski reaction which is a three step process and gives low overall yields. An attractive alternative is to construct the diazepine ring under Pictet-Spengler conditions. This paper reports the synthesis of a novel pyridoindolo-benzodiazepine as a potent atypical antipsychotic agent. The key step in the synthesis is the ring formation of the diazepine ring in neat trifluoroacetic acid.

In 2009, the University of Texas at Austin established the Texas Synchrophasor Network which monitors voltages in the ERCOT grid in Texas plus several other points outside Texas. The monitoring points are mainly 120V wall outlets. This document summarizes the important lessons learned through analyzing the recorded data. These lessons include observations that wind generation up to 20% of total does not effect grid inertia or damping.

Traditional syntheses of benzodiazepines involve a Bischler-Napieralski reaction which is a three step process and gives low overall yields. An attractive alternative is to construct the diazepine ring under Pictet-Spengler conditions. This paper reports the synthesis of a novel pyridoindolo-benzodiazepine as a potent atypical antipsychotic agent. The key step in the synthesis is the ring formation of the diazepine ring in neat trifluoroacetic acid.

A convergent, large-scale, chiral synthesis of isoxazoline 1 has been achieved in 37% overall yield and >99.6% optical purity, starting from l-asparagine and 4-cyanobenzaldehyde. Hofmann reaction of Nα-n-Boc-l-asparagine with iodosobenzene diacetate provides optically pure Nα-n-Boc-l-α,β-diaminopropionic acid (8) in 75% yield. A process of lipase resolution−base catalyzed epimerization gives the single enantiomer 5. Reaction of acid 5 with amine 9 in the presence of thionyl chloride forms the framework of 1. A Pinner reaction of intermediate 4 in methyl acetate or anisole, followed by an amidination with ammonium acetate, gives optically pure product 1.

In October 2008, a 44-year-old lady was referred for optimization of her asthma therapy prior to commencing in vitro fertilization treatment. She had been diagnosed with asthma in 2006 following a viral infection and was using inhaled beclamethasone (200 μg twice daily) and inhaled salbutamol when required. In the preceding 18 months, she had made two visits to the emergency room with breathlessness, and improved with nebulized salbutamol and a course of oral corticosteroids. She had felt increasingly breathless over the previous 3 months. There was no other past medical history. Written consent was obtained from the patient. Clinical examination did not reveal any evidence of expiratory wheeze or inspiratory stridor, and chest radiograph was normal. Spirometry revealed a forced …

Objectives:To demonstrate the importance of thorough investigation of patients with Horner syndrome, and to explain the relevant anatomy.Case report:A 46-year-old man presented with right-sided Horner syndrome. No other abnormality was found. Magnetic resonance imaging showed calcification of the stylohyoid ligament, with a pseudoarthrosis in the mid-portion of the ligament. This pseudoarthrosis was displacing and compressing the internal carotid artery and the adjacent sympathetic chain, causing Horner syndrome.Conclusion:In this case, magnetic resonance imaging was invaluable in elucidating the cause of the Horner syndrome. This is the first described case of pseudoarthrosis of a calcified stylohyoid ligament causing Horner syndrome.

In reaction to the March 1989 oil spill in Prince William Sound, Alaska, the oil industry formed a high-level task force to study the problems associated with maritime transportation of petroleum. The task force recommended the creation of a Petroleum Industry Response Organization (PIRO), financed entirely by industry. This company would have three missions: response, readiness, and research and development. PIRO was conceived to fill the void in the nation's capability to manage catastrophic offshore spills of persistent oils. Bringing the PIRO concept to reality required resolving many organizational, legal, and operational issues. PIRO was originally conceived as an industry initiative. However, passage of federal legislation made the creation of an organization—broadened in scope and renamed the Marine Spill Response Corporation (MSRC)—a necessity for those that ship and handle bulk oil in the maritime environment of the United States. The federal law also provided the states with important powers, especially in determining the liability limits that affect shippers, handlers, and responders. Original assumptions about PIRO's resources requirements for response and cleanup were adjusted as more detailed analyses were completed. MSRC has considerably more capability than was originally contemplated for PIRO. PIRO was estimated to require $250 million in its first five years to cover its operating, capital, and research and development costs. The corresponding estimate for MSRC is $800 million.

Ensuring correct setting and installation of a transformer differential relay is critical. A transformer differential relay must detect internal faults, damaging overloads, and through-fault currents while remaining secure against misoperation. The ability to use wye-connected CTs with microprocessor-based relays has simplified installations, and these relays provide better commissioning tools than those available with traditional relays. However, installations and commissioning remain complicated. Installation and settings errors continue to be widespread, implying a need for more rigorous commissioning tests. Even with greater commissioning effort, occasional wiring problems develop over time, and these can best be resolved through analysis of relay event report data. In the interest of reducing transformer differential misoperations, we share in this technical paper practical lessons we have learned through experience with commissioning and relay event report analysis. In the interest of reducing transformer differential misoperations, we share in Part 1 of this technical paper a review of transformer differential basics, settings examples and concerns, and recommended commissioning practices. In Part 2 of this technical paper, we continue with practical lessons we have learned through experience with commissioning and relay event report analysis.

Since the end of the Cold War the United States has experienced a dramatic shift in strategic and military threats. The terror attacks of September 11 2001 have identified that emerging threats of the new millennium threats led by rogue nations and terror organizations are capable of inflicting substantial economic and physical damage to the United States. The organization and employment of space systems which are crucial in the strategic operational and tactical levels of military operations need to transform in order to meet the increasing command control and information dissemination requirements. This paper will determine if the merger between U.S. Space Command and U.S. Strategic Command enables the Department of Defense to transform its military space operations in order to engage and defend against the emerging asymmetric threats of the 21st century. This study will review the military objectives for transformation previous examples of transformations in the military space program and the external factors which drove the current need for transformation. This paper concludes that the U.S. Space Command and U.S. Strategic Command merger is an evolutionary transformation that not only meets the requirements for today but will also enable future transformations in space operations as emerging capabilities and threats develop.

The XC8100 FPGA family is based on a new metal-to-metal antifuse technology and a "sea-of-gates" type architecture. Programmable interconnect elements are stacked vertically between metal layers and above the fine-grained logic cells, resulting in small die sizes and low cost. The basic cell is designed specifically for technology-independent design. Each cell can be configured to implement combinatorial, sequential, or three-state buffering functions. Other architectural features include a flexible set of high-drive buffers, output slew rate controls, and PCI-compatible I/O structures. A patented programming and test structure addresses the problem of providing for 100% post-program verification without test vectors.

St. Paul's Hospital, Vancouver, is BC's quaternary centre for cardiac care. As such, nurses from all over the world seek employment in the Cardiac Surgery Intensive Care Unit. For this and a variety of reasons, many internationally educated nurses (IENs) are hired to join our team. The purpose of this project is to create an orientation program for newly hired IENs, which extends beyond the conventional unit orientation to help them better adapt to both the culture of the unit and the multicultural Vancouver lifestyle. This paper will describe the varied aspects of the project. Our IEN mentorship program begins by matching learning/teaching styles between the mentor and mentee, using our research-based questionnaire. Mentors are supported by education around cultural issues specific to the IEN. The mentor may be one of several nurses who orientate at the bedside with the IEN. Mentors are the "check-in" persons who meet with the IEN mentee at scheduled intervals and are available via phone or email. We began the implementation phase of this program in January, 2011. Thus far, the responses have been positive. We plan to evaluate this project by surveying IENs and mentors, assessing turnover rates, job satisfaction, and other outcomes. We aim to promote awareness of cultural sensitivity among mentors, educators and managers on units who employ IENs. The success of this program will demonstrate that an enhanced orientation program can provide improved job retention and satisfaction for IENs.

Background Alcohol is a major contributing cause of violence in Australia. Injury and damage from excessive alcohol consumption on single occurrences have been shown to generally cause more problems than long term alcohol dependence. In particular, licensed premises have been identified as locations that are especially high risk for alcohol-related intoxication and problem behaviours such as aggression and violence. Research carried out by Injury Control Council of Western Australia on community violence among young people indicated that perpetrators of violence regard the practice of serving to intoxication at licensed premises as a major contributing factor to violence. Aims The drink or drunk project has been funded through the National Drug Law Enforcement Research Fund. The project examines why staff at licensed premises continue to serve to intoxication despite current laws and interventions. The objectives of the study are to better understand why staff continue to serve to intoxication, examine factors that increase the probability of staff serving to intoxication and to identify new strategies to reduce the likelihood of this occurring. Methods This project collected data from those with experience in working in licensed premises across both metropolitan and rural locations. Data was mostly collected through written, telephone and online surveys. The data has been analysed and the final report has recently been submitted to the funding agency. Discussion It is envisaged that the findings and recommendations will play a key role in informing both enforcement and management practices around licensed venues, in order to make them safer places for staff and patrons.

The Federal Energy Management Program (FEMP) must help Federal agencies reduce energy costs by delivering effective outreach programs. It is crucial that all professionals involved with the management of Federal facilities receive a clear message that FEMP offers effective information, education, tools, training, and resources. To achieve this objective, American Ideas and Designs, Inc., d/b/a Greening America, assisted FEMP in continuing a comprehensive energy efficiency outreach program titled ''You Have the Power.'' The ''You Have the Power'' campaign emphasized the ability of individual Federal employees, Federal agencies, and stakeholder organizations to easily access FEMP's energy efficiency tools and resources through a set of integrated interagency delivery programs.

The advent of lymphatic mapping and sentinel lymph node biopsy provides an effective and less morbid procedure for staging patients with malignant melanoma. There is considerable variation on this technique. This article describes the technique that was developed and is currently in application at the H. Lee Moffitt Cancer Center and Research Institute. Understanding all the steps and paying close attention to all details are important to ensure successful mapping.

Market-based healthcare reform has placed great financial pressures on academic departments of internal medicine. The current emphasis and increased recruiting for primary care have not been accompanied by a financially supportive institutional culture or favorable third-party reimbursement system for the generalist practitioners. In one department's analysis, there was a large difference in revenue (-$130,000) compared to a Medical Group Management Association (MGMA) standard, yet a reduced level of compensation for primary-care physicians, $61,000 less per full-time equivalent (FTE). Total overhead per FTE in our department was $80,000 greater than comparable practices of the MGMA standard. We have estimated the institutional strategic costs of having primary-care clinics in three separate locations in the city of Richmond ($74,000/FTE). No viable cost-cutting options placed the primary-care program in positive balance, but the analysis contributed to a creative institutional approach for a solution.

A convergent, large-scale, chiral synthesis of isoxazoline 1 has been achieved in 37% overall yield and99.6% optical purity, starting from L-asparagine and 4-cyanobenzaldehyde. Hofmann reaction of N(alpha)-n-Boc-L-asparagine with iodosobenzene diacetate provides optically pure N(alpha)-n-Boc-L-alpha,beta-diaminopropionic acid (8) in 75% yield. A process of lipase resolution-base catalyzed epimerization gives the single enantiomer 5. Reaction of acid 5 with amine 9 in the presence of thionyl chloride forms the framework of 1. A Pinner reaction of intermediate 4 in methyl acetate or anisole, followed by an amidination with ammonium acetate, gives optically pure product 1.