Search

Purpose Evaluation of the medical profession at all levels has exposed episodes of gender-based role misidentification whereby women physicians are disproportionately misidentified as nonphysicians. The authors of this study investigate this phenomenon and its repercussions, quantifying the frequency with which resident physicians experience role misidentification and the effect this has on their experience and behavior. Method In 2018, the authors conducted a cross-sectional survey study of internal medicine, surgical, and emergency medicine residents at a single, large, urban, tertiary academic medical center. The survey tool captured both the self-reported frequency and effect of professional misidentification. The authors used a t test and linear multivariate regression to analyze the results. Results Of the 260 residents who received the survey, 186 (72%) responded, and the authors analyzed the responses of 182. All 85 of the women respondents (100%) reported being misidentified as nonphysicians at least once in their professional experience by patients or staff members, compared with 49% of the 97 men respondents. Of those 182 residents, 35% of women were misidentified more than 8 times per month by patients compared with 1% of men. Of the 85 women physicians responding to the survey, 38% felt angry and 36% felt less satisfied with their jobs as a result of misidentification compared with, respectively, 7% and 9% of men. In response to role misidentification, 51% of women changed their manner of attire and 81% changed their manner of introduction, compared with, respectively, 7% and 37% of men. Conclusions These survey results demonstrate that women physicians are more likely than men physicians to be misidentified as nonphysicians and that role misidentification provokes gender-polarized psychological and behavioral responses that have potentially important professional ramifications.

Objective The study sought to characterize the evaluation of patients who present following detection of an abnormal pulse using Apple Watch. Materials and Methods We conducted a retrospective review of patients evaluated for abnormal pulse detected using Apple Watch over a 4-month period. Results Among 264 included patients, clinical documentation for 41 (15.5%) explicitly noted an abnormal pulse alert. Preexisting atrial fibrillation was noted in 58 (22.0%). Most commonly performed testing included 12-lead echocardiography (n = 158; 59.8%), Holter monitor (n = 77; 29.2%), and chest x-ray (n = 64; 24.2%). A clinically actionable cardiovascular diagnosis of interest was established in only 30 (11.4%) patients, including 6 of 41 (15%) patients who received an explicit alert. Discussion False positive screening results may lead to overutilization of healthcare resources. Conclusions The Food and Drug Administration and Apple should consider the unintended consequences of widespread screening for asymptomatic (“silent”) atrial fibrillation and use of the Apple Watch abnormal pulse detection functionality by populations in whom the device has not been adequately studied.

The Gravity Recovery and Climate Experiment Follow-On (GRACE-FO), launched May 22, 2018 and collecting science data since June 2018, is extending the 15-year data record of Earth mass change established by its predecessor GRACE mission (2002-2017). The GRACE-FO satellites carry onboard a novel technology demonstration instrument for intersatellite ranging, the Laser Ranging Interferometer (LRI), in addition to the microwave interferometer (MWI) carried on GRACE. The LRI has out-performed its in-orbit performance requirements both in terms of accuracy as well as the duration of tracking. Here, we compare and validate LRI-based gravity solutions for January 2019 to September 2020 against the MWI solutions. The comparison between the two sets of gravity solutions shows great similarities in general and nearly perfect consistency at a large hydrologic basin spatial scale (100,000 km

Lever Brothers , the South African tax case that formed the basis of this research, was concerned with determining the source of interest income. In its time, this was one of the landmark cases and established tax principles that were valid for 54 years, until superseded by changes to legislation. The research presented a critical analysis of the three judgments in the case, exposing weaknesses in each. It also provided a condensed account of the history of the company, the historical era in which the transactions giving rise to the case took place, a glimpse into the lives of the judges, as well as a discussion of the development in South Africa of the rules for determining source. The most important focus of the research was the discussion of the use and validity of the practical man principle, and it was concluded that this principle should be applied, not in lieu of legal theory, but to restrain its unbridled use when unjust results would ensue. Keywords: Lever Brothers and Unilever, South African Income Tax, Source of Income, Interest, The “Practical Man”, The “Reasonable Man”, Chief Justice E.F. Watermeyer, Judge of Appeal O.D. Schreiner, Acting Judge of Appeal, R.P.B Davis

Aims Down syndrome (DS) is the most common genetic cause of cognitive disability, with a worldwide incidence between 1 in 1000 and 1 in 1100 live births. Children with DS have characteristic physical features, with an increased incidence of congenital or acquired medical conditions. The Down Syndrome Medical Interest Group (DSMIG) have produced guidance for essential basic medical surveillance in children with DS. Children with DS have also been shown to respond differently to critical illness, requiring a higher proportion of organ support than expected by initial disease severity. This project aimed to produce a hospital guideline for medical care of children with DS, whilst also taking into account specific considerations for care of a child with DS in PICU, to standardise and improve the quality of care. Methods Involvement in medical care of children with DS admitted to PICU revealed that despite the availability of clear DSMIG guidance, there was no hospital guideline for children with DS. Furthermore, in terms of PICU care, key considerations were anecdotally noted, yet these differed between consultants and there was no PICU-specific guideline to outline a gold standard of care. DSMIG guidance was reviewed and PICU consultants approached for key specific considerations for care of a child with DS on PICU. A guideline was produced, edited and reviewed at a hospital guideline meeting, and agreed on by all PICU consultants. Results Using DSMIG guidance, a hospital guideline could be produced for medical care of children with Down Syndrome, with additional specific requirements for PICU. Key PICU-specific considerations were noted and agreed on by a consultant team in terms of: airway; respiratory; cardiovascular; neurological; and infection. Conclusion An admission to PICU can be a window of opportunity to ensure a child with DS is receiving the correct support from a multidisciplinary team, whilst there are also key PICU-specific considerations for their care. An SHO working under different leaders has an opportunity to develop a guideline to define and standardise a gold standard of care.

Background Studies of prescribing of opioid medication for chronic pain in the UK population show that it has increased sharply over the past 25 years. Although overall rates may have begun to decline recently, longer-term use and prescribing of ‘strong’ opioids continue to rise. Whilst analysis of data at a population level can tell us much about the use of these medications, an analysis at an individual level is needed to understand which patients, and how many, are at greatest risk from these potentially harmful drugs. Harms associated with these drugs are related to dose and length of use. The aim of this study was to develop a method to identify patients prescribed long-term, high doses of these drugs in the community and to assess the prevalence of such use. Methods Details of all opioid prescriptions issued over a four-month period were collected from two demographically dissimilar GP practices. A total of 22,841 patients were registered at the practices, 1488 (6.5%) of whom were prescribed opioids in the study period. Exhaustive examination of prescription data identified all patients who were prescribed oral morphine equivalent (ME) doses of 120 mg/day or more in the census period. An examination of the prescription histories of these patients indicated those who had been prescribed opioids at this level for a year or more. Results Every patient who met our criterion of ≥120 mg/day ME for a year or more was being prescribed that level as a single drug of morphine, oxycodone or fentanyl, irrespective of opioid polypharmacy. Across the two practices, 1.71/1000 patients were identified as long-term, high-dose users of opioid medication for chronic non-cancer pain. Prevalence was similar in the two practices. Unadjusted extrapolation suggests that there are over 100,000 similar patients in the UK. Conclusion This study provides a simple, reliable and practical means of identifying patients prescribed long-term high-dose opioid medication for chronic pain. These regimens are unlikely to provide additional pain relief but increase the risk of harm to patients. They have marked negative effects on day-to-day functioning and quality of life. Patients of interest can be identified simply through their use of three drugs as threshold doses and above. This can help in the further investigation of dysfunctional medication use; in establishing national and local prevalence; in monitoring service provision; and in identifying associated factors, such as social deprivation and regional variation.

The gravity recovery and climate experiment follow-on (GRACE-FO) satellites, launched in May of 2018, are equipped with geodetic quality GPS receivers for precise orbit determination (POD) and gravity recovery. The primary objective of the GRACE-FO mission is to map the time-variable and mean gravity field of the Earth. To achieve this goal, both GRACE-FO satellites are additionally equipped with a K-band ranging (KBR) system, accelerometers and star trackers. Data processing strategies, data weighting approaches and impacts of observation types and rates are investigated in order to determine the most efficient approach for processing GRACE-FO multi-type data for precise orbit determination and gravity recovery. Two GPS observation types, un-differenced (UD) and double-differenced (DD) observations in general can be used for GPS-based POD and gravity recovery. The GRACE-FO KBR observations are mainly used for gravity recovery, but they can be also used for POD to improve the relative orbit accuracy. The main purpose of this paper is to study the impacts of the DD, UD and KBR observations on GRACE-FO POD and gravity recovery. The precise orbit accuracy is assessed using several tests, which include analysis of orbital fits, satellite laser ranging residuals, KBR range residuals and orbit comparisons. The gravity recovery is validated by comparing different gravity solutions through coefficient-wise comparison, degree difference variances and water height variations over the whole Earth and selected area and river basins.

Objectives: To identify the prevalence of and evaluate factors associated with down-titration of sedation in patients receiving neuromuscular blockade. Design: Retrospective cohort study. Setting: Tertiary care teaching hospital in Boston, MA. Patients: All patients over 18 years old admitted to the medical, surgical, or cardiac ICUs from 2013 to 2016, and who received cisatracurium for at least 24 hours. Interventions: We examined patients for whom sedation was decreased despite accompanying ongoing neuromuscular blockade administration. Measurements and Main Results: Of the 300 patients who met inclusion criteria (39% female, mean age of 57 yr old), 168 (56%) had sedation down-titrated while receiving neuromuscular blockade with a mean decrease in sedation dose of 18.7%. Factors associated with down-titration of sedation were bispectral index usage (90/168 [53.6%] vs 50/168 [29.8%] patients; p < 0.01; odds ratio, 1.82; 1.12–2.94), and bolus dose of neuromuscular blockade prior to continuous infusion (138/168 [82.1%] vs 79/168 [47.0%] patients; p < 0.0001). Conclusions: Down-titration of sedation among mechanically ventilated patients receiving neuromuscular blockade was common and was correlated with bispectral index monitor usage. Clinicians should be aware of the limitations of quantitative electroencephalography monitoring devices and recognize their potential to cause inappropriate down-titration of sedation. Substantial opportunity exists to improve the quality of care of patients receiving neuromuscular blockade through development of guidelines and standardized care pathways.

Solar heat could displace fossil fuel to reduce energy cost for brooding livestock and poultry. A transpired solar collector (TSC), consisting of a perforated dark-colored metal surface, can provide considerable heating but metal TSCs (mTSCs) are expensive. Since a perforated black plastic sheet will be less-expensive, a plastic TSC (pTSC) was evaluated. The 1.49 m2 pTSC (porosity of 1.2%) supplemented a propane heater in a room housing 240 turkey poults; an adjacent room without a pTSC, with 240 poults was the control. Monitoring was performed over two flocks of poults. A custom-built controller bypassed the pTSC during nighttime or when the room did not require heating to bring in fresh air. The pTSC gave a maximum temperature rise of 25.4 °C at a solar irradiance (I) of 882 W/m2 and suction velocity (Vs) of 0.033 m/s over 15 min. Over 178 h of operation, with an average I of 668 ± 295 W/m2 and average Vs of 0.036 m/s, the pTSC increased air temperature by an average of 8.1 ± 4.2 °C. Probably due to higher ventilation rate and an oversized propane heater, propane use was not reduced in the Test room with the pTSC vs. the Control room. The Test room had lower CO2 and CO concentrations due to higher ventilation, which may have improved turkey performance. The metal TSC gave a slightly higher temperature rise at a lower Vs but the less-expensive pTSC could be a more cost-effective solar air heater that could readily be scaled up for agricultural and other applications in many parts of the world. Scale-up considerations seem feasible and are presented for a 10,000-poult brooder barn.

The transpired solar collector (TSC) is a low-cost technology for heating ventilation air for mainly for use in industrial and agricultural applications. Storing the excess energy generated during daytime in phase change material (PCM) could improve the economics of using TSCs. Since energy generated for storage could be increased by using a two-stage TSC (with a glazing) vs. a one-stage TSC, first, the thermal performance of the two configurations were compared. Then, performance of the PCM-based thermal energy storage (TES) unit coupled to a TSC was evaluated. At a suction velocity of 0.023 m/s, the one-stage TSC produced a 2 °C higher temperature rise and 8% higher efficiency than the two-stage TSC. The one-stage TSC was coupled to a TES unit packed with 80 kg of salt-hydrate type PCM (specific energy of ∼185 kJ/kg). When evaluated at four airflow rates, the TES unit stored between 76 and 107% of its theoretical heat storage capacity and provided tempered air 4 °C warmer than ambient air during nighttime. While residual energy (for daytime heating) increased with airflow rate, energy charged or discharged was unaffected. Over a week, the TSC-TEC stored 34% of the total useful energy produced for nighttime use, with a potential to displace 1.35 kg of liquefied natural gas. Replacing the expensive metal TSC with a perforated plastic TSC and a simpler TES design would improve the economics of storing solar energy for use after sundown.

School nurses coordinate student health care for prevention and treatment to remove health barriers to learning and to school attendance. They use a team approach to manage students with chronic conditions as they transition among home, school and healthcare settings, working to develop competent self-care aligned with developmental ages of students. Care coordination ensures the continuum of care is unbroken. Meeting the health needs of low-income students can be challenging, because those students are likely to be uninsured or underinsured and often lack necessary resources, such as transportation, to access primary health care. Care coordination is a tenet of school nursing and to optimally serve low-income students, school nurses form partnerships in the community. One innovative and successful partnership is Healthy Learners, an organization that works with community healthcare providers and school district nurses to connect eligible students to needed healthcare services. Always, the goal is to keep students in school, healthy, and ready to learn.

A class of flux compression generators (FCGs) is based on the compression of the cross-sectional area of a coaxial geometry where the current flows along the outer conductor and returns through the inner conductor. This compression causes an increase in current since magnetic flux must be conserved. Kiuttu’s inductive electric-field formulation is a powerful tool for the conceptual design of coaxial FCGs. The usefulness of this formulation is demonstrated in this paper for a simplified geometry using a finite-element partial differential equation solver (FlexPDE) for calculation of the inductive electric field. A time-varying applied current or a moving surface creates the nonconservative electric field. Losses due to diffusion of magnetic flux into conducting surfaces can also be accounted for and modeled in this setting. This analytical–computational approach serves as an important step in validating the magnetohydrodynamic (MHD) portion of the complex multiphysics parallel Lawrence Livermore code, Arbitrary Lagrangian-Eulerian (ALE3D). The nonintuitive boundary conditions involved in solving the otherwise straightforward partial differential equations are described in detail and illustrated in a simple model. The physical parameters used in the simulations are not based on a specific design.

Procedural checklists may be useful for increasing the reliability of safety-critical processes because of their potential capacity to improve teamwork, situation awareness, and error catching. To test the hypothesized utility and adaptability of checklists to surgical teams, we performed a randomized controlled trial of procedural checklists to determine their capacity to increase the frequency of safety-critical behaviors during 47 laparoscopic cholecystectomies. Ten attending surgeons at an academic tertiary care center were randomized into two equal groups - half of these surgeons received basic team training and used a preprocedural checklist whereas the other half performed standard laparoscopic cholecystectomies. All procedures were videotaped and scored by trained reviewers for the presence of safety-critical behaviors. There were no differences detected in patient outcomes, case times, or technical proficiency between groups. Cases performed by surgeons in the intervention (checklist) group were significantly more likely to involve positive safety-related team behaviors such as case presentations, explicit discussions of roles and responsibilities, contingency planning, equipment checks, and postcase debriefings. Overall, situational awareness did not significantly differ between the intervention and control groups. Participants in the intervention (checklist) group consistently rated their cases as involving less satisfactory subjective levels of comfort, team efficiency, and communication compared with those performed by surgeons in the control group. Surgical procedural safety checklists have the capacity to increase the frequency of positive team behaviors in the operating room during laparoscopic surgery. Adapting to the use of a procedural checklist may be initially uncomfortable for participants.

A commercial closed circuit television digital video recorder was investigated to determine if it was possible to extract useful video data from its storage media without access to the manufacturer's application software. After an initial test period the storage disk was removed, imaged and analysed. The file structure of the storage disk was deduced and the features necessary to locate a sequence of video evidence identified. The format of video data from the device was considered and shown to be based upon standard compression technologies. The observed format was fully documented to enable further development. With a little extra effort in processing the raw video data it was shown how video sequences could be extracted for use as evidence even in cases where the recording device is no longer functional, the turnkey software not available, or data partly corrupted. With careful application standard media players can be employed to view the resulting video sequences. Conclusions are that, while based on proprietary file systems and video formats, data from digital video recorder systems is amenable to analysis using commonly available computer tools. In return for investigative work there is a reasonable probability of being able to recover usable video from systems. There is also scope for the development of more specialised software tools to facilitate this process.

Verses 1067–1225 of the Archpriest of Hita’s Libro de buen amor ( LBA ) have long perplexed scholars with respect to content as well as structure. In this episode, the Archpriest and his friends enjoy a gluttonous banquet just before the forces of Sir Flesh face those of Lady Lent in a carnivalesque battle that leads to Flesh’s imprisonment and subsequent penitence. Though the LBA is narrated from a first-person point of view, much of the narration of these verses is told from the third-person, giving rise to the question of who the narrator of this episode really is. Using clues from the text, as well as historical discussion of food in fourteenth-century Castile, this articles concludes that this episode presents a dream of the Archpriest that takes place after he has partaken of too much meat and wine and that reflects the narrator’s lack of religious desire to participate in Lenten customs.

Primary Audience: Feed Mill Managers, Feed Mill Quality Control Managers, Nutritionists SUMMARY An experiment was conducted evaluating several markers to determine mix uniformity. Treatment diet was a corn-soybean meal-based diet formulated for broiler chicks fed from 0 to 17 d posthatch. Dietary nutrients or tracers evaluated included the following: 1) DL-Met (99%), 2) L-Lys-HCl (78%), 3) CP, 4) mixing salt (chloride ion), 5) P, 6) Mn, 7) Fe particles (#40 Red, count), 8) Fe particles (#40 Red, absorbance), 9) Fe particles (RF-Blue Lake), 10) roxarsone, and 11) semduramicin. All minor and microingredients were individually hand-weighed and added to the mixer to insure accuracy and were added at the same location for all treatments. Diets were mixed using a double ribbon mixer for 3 different mix times (0.5, 2.5, and 5.0 min). Overall, from 0.5 to 5.0 min, all markers evaluated showed a numerical reduction in percentage of CV. Crude protein and P should not be considered as markers, because many different components in the batch of feed contribute some level of CP or P, and results can be confounding. DL-Methionine (99%) and L-Lys-HCl (78%) were the only markers that statistically reduced over time and had aC V< 10% (23.86 to 9.47% and 19.75 to 8.70%, respectively). These data suggest that mixer uniformity results can be influenced by the particular marker that is chosen for mixer uniformity analysis.

We report on a technology development to address explosive detector system throughout with increased detection probability. The system we proposed and are studying consists of a pixelized X-ray based pre-screener and a pulsed neutron source quantitative post verifier. Both technologies are derived from our compact accelerator development program for the Department of Energy Radiography Mission that enables gradients >10 MV/m. For the pixelized X-ray source panel technology, we have performed initial integration and testing. For the accelerator, we are presently integrating and testing cell modules. For the verifier, we performed MCNP calculations that show good detectability of military and multi-part liquid threat systems. We detail the progress of our overall effort, including research and modeling to date, recent high voltage test results and concept integration.

Occupational exposure to metal fume promotes a reversible increase in the risk of pneumonia, but by mechanisms which are unclear. To investigate, the current authors measured various markers of host defence function in welders and nonwelders. Induced sputum and venous blood samples were collected from 27 welders with regular long-term exposure to ferrous metal fume and 31 unexposed matched controls. In sputum, the present authors measured cell counts, the soluble and cellular iron concentration, and levels of interleukin-8, tumour necrosis factor-alpha, myeloperoxidase, matrix metalloproteinase-9, immunoglobulin (Ig)A, alpha(2)-macroglobulin and unsaturated iron-binding capacity. Blood samples were assayed for evidence of neutrophil activation and pneumococcal IgG antibodies. Welders had significantly higher iron levels and a substantially lower unsaturated iron-binding capacity in their sputum, but, despite a high iron challenge, there was a noteworthy absence of an inflammatory response. Only blood counts of eosinophils and basophils were significantly related to the extent of welding. Weak nonsignificant trends were observed for several other measures, consistent with low-grade priming of neutrophils. In conclusion, these data suggest that chronic exposure to metal fume blunts responsiveness to inhaled particulate matter. However, the mechanism behind the lack of detectable local inflammatory response requires further investigation.

Summary Objective Injury to the anterior cruciate ligament (ACL) frequently leads to post-traumatic osteoarthritis (OA). In this study we determined whether early degenerative changes characteristic of idiopathic OA are induced in articular cartilage following ACL injury. Methods A small sample of femoral articular cartilage was removed at surgery, as part of ACL reconstruction, from a total of 50 patients with ACL injuries. Of these, 28 underwent surgery less than 1 year post-injury. Control cartilages were obtained from the same site from 21 persons at autopsy. All cartilages were examined for molecular changes. The content of type II collagen, its cleavage by collagenases and its denaturation were determined by immunoassay. The total content of glycosaminoglycan (GAG), which is principally aggrecan, was measured colorimetrically. Data were expressed per unit DNA (GAG and collagen content) or as a percentage of total collagen cleaved or denatured. Other cartilages from the same site (8 controls, 12 less than 1 year and 8 more than 1 year post-injury) were frozen sectioned and examined histologically to determine by Mankin grading cartilage degeneration. Results Histological analyses revealed that control subjects exhibited staining for proteoglycan, which was reduced in some patients following ACL rupture. Degeneration of the articular surface was sometimes observed 1 year after ACL rupture. Although the Mankin grade increased with time after rupture these changes were not significant. Immunoassays, however, revealed an increase in GAG content within 1 year which was maintained after 1 year although no longer significant. No changes in total type II collagen content were observed during the period of study. However, there were significant increases in the denaturation and cleavage of type II collagen less than and more than 1 year post-ACL rupture. Total type II collagen content was directly correlated with GAG content in all three groups, with the significance being weakest at more than 1 year. After 1 year an inverse correlation was observed between total type II collagen content and collagen cleavage as well as denaturation. Conclusions These observations reveal that joint instability resulting from ACL injury rapidly results in degenerative changes characteristic of those seen in idiopathic OA at arthroplasty and in experimental OA following ACL surgery. These changes may contribute to the development of post-traumatic OA that is commonly observed following ACL injury. The observations support and extend conclusions from other studies on human and animal articular cartilage and synovial fluids post-ACL injury that have revealed a rapid onset of damage to type II collagen and an initial increase in proteoglycan content characteristic of experimental OA post-ACL injury. This study provides direct evidence for the rapid development of degenerative changes characteristic of OA following ACL injury.

The backscattering of light by quasi-horizontally oriented hexagonal ice plates is investigated because of its pertinence to lidar measurements of cirrus clouds. For oriented ice crystals, the commonly used geometric optics ray-tracing method is not applicable to the computation of the scattered field in certain scattering directions, in particular, the backscattering direction, because of the singularity problem inherent to the ray-tracing technique. In this study, we solve for the electric field due to scattering by quasi-horizontally oriented ice plates using an approach based on the electromagnetic wave theory. We simplify the analysis by ignoring the effect of the plate's side faces on the internal field inside the particle. This is a reasonable approximation when the ratio of the particle diameter to its thickness is large. This approximation is also valid if the tilt of the particle's symmetric axis from zenith is small and the size parameter is large. The present numerical results indicate that very strong oscillations in the backscattering cross section occur with the variation of size parameter. Furthermore, the bulk backscattering intensity has been calculated by including the effect of a particle size distribution and the random tilt of particle symmetric axis within a small angular region, for example, 2°. A strong dependence is found between the lidar backscattering cross section and the degree of the random tilt of the particles. A combination of the present method with the T-matrix method, which works well for particles having small and moderate size parameters, may provide a more complete picture of the lidar backscattering by quasi-horizontally oriented ice plates.

Cindy Strehl,1,2 Timo Gaber,1–3 Lionel Maurizi,4 Martin Hahne,1,2 Roman Rauch,1,2 Paula Hoff,1–3 Thomas Häupl,1 Margarethe Hofmann-Amtenbrink,5 A Robin Poole,6 Heinrich Hofmann,4 Frank Buttgereit1–3 1Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany; 2German Rheumatism Research Centre (DRFZ), Berlin, Germany; 3Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany; 4Powder Technology Laboratory, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland; 5MatSearch Consulting Hofmann, Pully-Lausanne, Switzerland; 6Department of Surgery, McGill University, Montreal, QC, Canada Abstract: Nanotechnology provides new opportunities in human medicine, mainly for diagnostic and therapeutic purposes. The autoimmune disease rheumatoid arthritis (RA) is often diagnosed after irreversible joint structural damage has occurred. There is an urgent need for a very early diagnosis of RA, which can be achieved by more sensitive imaging methods. Superparamagnetic iron oxide nanoparticles (SPION) are already used in medicine and therefore represent a promising tool for early diagnosis of RA. The focus of our work was to investigate any potentially negative effects resulting from the interactions of newly developed amino-functionalized amino-polyvinyl alcohol coated (a-PVA) SPION (a-PVA-SPION), that are used for imaging, with human immune cells. We analyzed the influence of a-PVA-SPION with regard to cell survival and cell activation in human whole blood in general, and in human monocytes and macrophages representative of professional phagocytes, using flow cytometry, multiplex suspension array, and transmission electron microscopy. We found no effect of a-PVA-SPION on the viability of human immune cells, but cytokine secretion was affected. We further demonstrated that the percentage of viable macrophages increased on exposure to a-PVA-SPION. This effect was even stronger when a-PVA-SPION were added very early in the differentiation process. Additionally, transmission electron microscopy analysis revealed that both monocytes and macrophages are able to endocytose a-PVA-SPION. Our findings demonstrate an interaction between human immune cells and a-PVA-SPION which needs to be taken into account when considering the use of a-PVA-SPION in human medicine. Keywords: nanoparticle, cell viability, cytokine, monocyte, macrophage

Clinical relevance Measurement of markers of cartilage pathology in synovial fluid may provide clinical rheumatologists and osteoarthritis (OA) researchers important information for early diagnosis of OA as well as a method for monitoring disease progression and response to treatment. This study demonstrates the value of this approach in an established model of OA (cranial cruciate ligament rupture) at a point distant enough from the original surgical manipulation so as to have little to no effect on the marker concentrations. Objective The objective of this study was to determine whether measurement of markers of cartilage collagen cleavage and proteoglycan turnover in synovial fluid from a canine model could be used to detect cartilage changes following the onset of joint instability during the development of OA. Design A model of joint instability that develops OA was created in 18 mature dogs using monopolar radiofrequency energy (MRFE). MRFE was arthroscopically applied to one cranial cruciate ligament (CCL) while the contralateral CCL was sham treated. The treated CCLs ruptured approximately 8 weeks (55±1.6 days) after MRFE treatment. Synovial fluid was collected at time zero prior to MRFE treatment, 4 weeks after MRFE treatment, and at 4, 8, and 16 weeks after CCL rupture. Synovial fluid concentrations of the neoepitope COL2-3/4C long (type II collagen cleavage by collagenase) and epitopes 3B3(−) (proteoglycan aggrecan sulfation) and 846 (associated with aggrecan synthesis) were analyzed. Results Compared to sham treated joints, the synovial fluid concentrations of COL2-3/4C long and 3B3(−) were significantly increased 2.2 fold and 2.9 fold, respectively, in joints with MRFE treated CCLs following CCL rupture. Concentrations of the 846 epitope in synovial fluid showed a trend toward an increase, which was not significant, after CCL rupture. Conclusions Concentrations of the collagenase-cleaved type II collagen neoepitope and 3B3(−) epitope in synovial fluid were significantly increased by 4 weeks and remained elevated for at least 16 weeks after CCL rupture. This suggests that in dogs the COL2-3/4C long neoepitope and 3B3(−) epitope are sensitive markers for changes in joint cartilage turnover in joints that are developing OA. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved .

A fast Monte Carlo simulation scheme is developed to assess the impact of multiple scattering on space-based lidar backscattering depolarization measurements. The specific application of our methodology is to determine cloud thermodynamic phase from satellite-based lidar depolarization measurements. Model results indicate that multiple scattering significantly depolarizes backscatter return from water clouds. Multiple scattering depolarization is less significant for non-spherical particles. There are sharp contrasts in the depolarization profile between a layer of spherical particles and a layer of non-spherical particles. Although it is not as obvious as ground-based lidar observations, it is likely that we can identify cloud phase not only for a uniform cloud layer, but also for overlapping cloud layers where one layer contains ice and the other water droplets.

The rapid growth of Atlantic salmon, Salmo salar L., culture in north-western Europe has given rise to concerns regarding the biological consequences of fish farm escapes on wild salmonid populations. Canthaxanthin, a carotenoid pigment additive to farmed salmon feed which is passed from females to their progeny, may be used as an indicator of the numbers of escaped farmed salmon which spawn in the wild. In the present study, thin-layer chromatography and high-performance liquid chromatography (HPLC) were used to screen emergent Atlantic salmon fry sampled from seven river catchments in Ireland for canthaxanthin. The incidence of fry containing canthaxanthin at greater than trace levels (

The substantial growth of the farmed salmon industry in Europe since the 1970s has highlighted concerns regarding the genetic impact of escaped farmed salmon on wild salmonid stocks. High incidences of salmon × trout hybrids have been recorded in rivers situated near intensive salmon farming in Norway and Scotland, which may be indicative of a breakdown in reproductive isolation between salmon, Salmo salar L., and brown trout, Salmo trutta L. In the present study, salmonid fry and 0+ parr were collected from rivers in western Ireland. Allozyme and minisatellite DNA analysis were carried out on fry to determine the frequency of F1 hybrids from 10 rivers located within 38 km of salmon farms and three rivers at least 80 km from salmon farms. A total of 49 hybrids were recorded from 4135 salmonid fry (frequency = 1.2%). Mitochondrial DNA analysis showed that all hybrids arose from Atlantic salmon female × brown trout male crosses. Hybrid parr were recorded from one of the low-risk rivers (1.0%), but were present in seven out of the 10 catchments located within 38 km of salmon farms, with frequencies ranging from 0.7% to 3.1%. The results of the present survey, which represents the first extensive record of the levels of salmon-trout hybridization in Ireland, are discussed in relation to the continued growth of salmon farming in this country.

Unmanned Aerial Vehicle (UAV) operators have identified sudden turbulence as being potentially detrimental to safe and effective UAV control. This is especially true for those UAVs that require direct manual control in order to land. Turbulence is currently indicated solely by an unexpected perturbation of video images being transmitted from a UAV-mounted camera to the operator control station. This study investigated the usefulness of haptic feedback technology to provide the UAV operator with an enhanced indication of the sudden onset of turbulence. Visual feedback was supplemented by haptic feedback applied directly to the operator's control stick, providing a redundant kinesthetic alert. Five rated pilots performed 16 simulated UAV landing trials in a within-subject design with four independent variables: haptic feedback (off, on), turbulence strength (mild, severe), turbulence direction (primarily horizontal or vertical), and proximity to the runway when the turbulence occurred (near, far). Dependent measures included subjective assessments of situation awareness at turbulence onset, assessments of landing difficulty and landing performance, and post-test workload ratings and preferences. Results indicated that awareness of turbulence was significantly improved in the haptic feedback condition. Participant comments indicated that haptic feedback was a useful tool for the task, however, the magnitude of the control stick force deflections was judged to be too severe for actual use. The application of haptic feedback technologies to UAV interfaces is discussed and current research directions are described.

Pulmonary fibrosis is a well-recognized feature of acute respiratory distress syndrome (ARDS). Using immunoassays of bronchoalveolar lavage (BAL), fluid we investigated the synthesis of type I procollagen (PICP) and type I/II collagen degradation products (COL2-3/4C(short) neoepitope) in patients with ARDS, acute lung injury (ALI), subjects with risk factors for ARDS (At Risk), and healthy/ventilated control subjects. PICP was measured by ELISA as a marker of type I procollagen synthesis. COL2-3/4C(short) neoepitope was measured by an inhibition ELISA as a marker of collagenase degradation of type I/II collagen. BAL was performed initially within 48 h of ventilation (Day 1) and then subsequently on Day 4. Dilution of epithelial lining fluid (ELF) was corrected for by plasma urea comparison. Increased PICP levels were observed in the ELF from ARDS and ALI subjects on Day 1 compared with subjects At Risk (median values, 124.9 and 95.0 ng/ml versus 38.0 ng/ml, respectively, p < 0.0005). By contrast, the levels of COL2-3/4C(short) neoepitope were significantly reduced in the subjects with ARDS versus the At Risk subjects (13.22 ng/ml versus 32.33 ng/ml, p < 0.0005). This translated into a greatly increased PICP:COL2-3/4C(short) ratio in the subjects with ARDS (p < 0.0001). There was a significant decline in the PICP level in the subjects with ARDS between Days 1 and 4 (n = 15, p < 0.05). Linear regression analysis showed a significant association between PICP and lung injury score in the subjects with ARDS (p = 0.01). Our data suggests an early shift in balance between type I collagen synthesis and degradation by collagenase. The resultant increase in type I collagen would favor matrix deposition and the development of pulmonary fibrosis in the lungs of subjects with ARDS.

Objective The Arg519–Cys mutation in type II collagen results in severe, precocious familial osteoarthritis (OA) in 100% of carriers within the first 3 decades of life. The carrier population provided a well-defined patient population for the study of serum markers of familial OA with respect to pathogenesis, diagnosis, and prognosis. Methods Serum was obtained from 31 mutation-positive individuals and 16 mutation-negative individuals. OA severity was determined by clinical and radiologic assessments. Levels of serum cartilage oligomeric matrix protein (COMP), keratan sulfate (KS) epitope, the 846 epitope of aggrecan, and the C propeptide of type II collagen (CPII) were measured and were correlated with the radiologic findings. Results COMP and KS levels, both of which have been suggested to be indicative of disturbed cartilage turnover, were significantly elevated in mutation-positive individuals and in the individuals with OA regardless of mutation status. There was no statistically significant difference between mutation-positive, mutation-negative, OA-positive, and OA-negative individuals with respect to serum concentrations of epitope 846 or CPII, both of which are putative markers of cartilage repair. Conclusion Study of the macromolecular constituents of cartilage released into serum in subjects with familial OA revealed altered metabolism in OA, as demonstrated by elevated COMP and KS levels. Other constituents, the 846 epitope and CPII, were not altered, indicating dissociation of cartilage anabolism and breakdown. Future sequential studies will provide an opportunity to define biochemical changes as familial OA develops and to monitor therapeutic responses.

Currently, flexibility and time to market have become the new keys to product development. The need for versatility, low overheads, and direct customer communication has led to the birth of an emerging breed of organizations that employ a virtual product development model (VPDM). This paper explores the role of user-centered design within a VPDM being used in an actual industrial organization, and is based on the experiences of the authors working in that organization. It also discusses possible user-centered evaluation methods, and the factors that influence their use in this model. Finally, it provides recommendations for a more seamless integration of user-centered design within this model.

Results of large-eddy simulations of an aircraft wake are compared with results from ground-based lidar measurements made at NASA Langley Research Center during the Subsonic Assessment Near-Field Interaction Flight Experiment field tests. Brief reviews of the design of the field test for obtaining the evolution of wake dispersion behind a Boeing 737 and of the model developed for simulating such wakes are given. Both the measurements and the simulations concentrate on the period from a few seconds to a few minutes after the wake is generated, during which the essentially two-dimensional vortex pair is broken up into a variety of three-dimensional eddies. The model and experiment show similar distinctive breakup eddies induced by the mutual interactions of the vortices, after perturbation by the atmospheric motions.

This report describes two cases of Di-George syndrome presenting with hypoparathyroidism in adulthood. The first patient presented with profound hypocalcaemia that resulted in a generalised seizure. Routine investigations revealed hypoparathyroidism. The clue to her underlying condition was the postnatal death of her young child. This case shows that Di-George syndrome can present in adulthood with hypocalcaemia in the absence of other classic features of this condition. This has enormous implications for future family planning and may also have important health implications. The second patient, diagnosed on routine blood testing, had previously suffered with a congenital heart condition, but the syndrome was not revealed until she was of postmenopausal age. These two patients show that Di-George syndrome can present in adulthood with hypocalcaemia. This is an important observation because the condition has profound implications for health and family planning.

OBJECTIVE: To determine how acute but transient inflammation affects the cartilage proteoglycan aggrecan and the value of analyses of synovial fluid to study this. METHODS: For 96 hours after a single intra-articular injection of rabbit knees with human interleukin-1 alpha (IL-1 alpha) or vehicle, articular cartilage and synovial fluid were examined using a putative indicator of aggrecan synthesis (aggrecan chondroitin sulphate epitope 846), immunoreactive keratan sulphate, and total glycosaminoglycan (GAG) content. Aggrecan extractability (with 0.5 M NaCl) followed by 4 M guanidine hydrochloride extraction permitted analyses of cartilage damage, total content and aggrecan heterogeneity. Aggrecan epitopes as well as GAG were assayed in synovial fluid. Changes were related to total joint leucocyte content in synovial fluid. RESULTS: At 10 ng, IL-1 alpha produced a transient increase in synovial fluid leucocytes at six hours and 24 hours. This accompanied a reduction in content and increased extractability of GAG, which was greatest in the tibial medial compartment of the knee. Further studies of this compartment showed no change in keratan sulphate epitope content, but a transient increase in extractability in 0.5 M NaCl. Epitope 846 content and extractability were unchanged. Total contents and extractability for GAG were inversely correlated in both controls and joints injected with IL-1 alpha. These changes were accompanied by transient increases in GAG, keratan sulphate epitope, and 846 content in synovial fluid. CONCLUSION: According to the aggrecan component measured, damage to the matrix of articular cartilage was sometimes reflected by a transient increased extractability and a net loss of aggrecan. There was always an increased release of GAG, and keratan sulphate, and 846 epitopes into synovial fluid. These studies show that changes in aggrecan epitopes and GAG in synovial fluid reflect changes in cartilage metabolism induced by acute transient inflammation.

Therapy for X-linked hypophosphatemia (XLH) only partially corrects skeletal lesions and is often complicated by hyperparathyroidism. 24,25(OH)2 D3 improves skeletal lesions in a murine model of XLH and suppresses PTH secretion in animals. Therefore, we undertook a placebo-controlled trial of 24,25(OH)2 D3 supplementation to standard treatment in patients with XLH to improve bone disease and reduce hyperparathyroid complications. Fifteen subjects with XLH receiving standard treatment [1,25(OH)2 D3 or dihydrotachysterol plus phosphate] were evaluated, supplemented with placebo, and reevaluated one yr later. 24,25(OH)2 D3 supplementation was then begun and studies repeated after another year. Each patient underwent a detailed evaluation of calcium homeostasis over a 24-h period. Rachitic abnormalities were assessed radiographically in children. Adults underwent bone biopsies. 24,25(OH)2 D3 normalized PTH values in nine subjects (peak PTH was 46.5 +/- 6.6 pmol/L at entry, 42.3 +/- 5.9 pmol/L after placebo, and 23.3 +/- 5.4 pmol/L after 24,25(OH)2 D3). Nephrogenous cAMP decreased at night, coincident with the decrease in PTH, and serum phosphorus was slightly greater with 24,25(OH)2 D3. Radiographic features of rickets improved during 24,25(OH)2 D3 supplementation in children, and osteoid surface decreased in adults. 24,25(OH)2 D3 is a useful adjunct to standard therapy in XLH by effecting correction of hyperparathyroidism and improvement of rickets and osteomalacia.

A Monte-Carlo model is described which has been developed for calculation of multiply scattered LIDAR returns. Results are shown for the common problem selected by the MUSCLE (MUltiple SCattering LIDAR Experiments) group for intercomparison, which represents a typical ground-based cloud-sensing scenario. This is contrasted with returns from the same cloud sensed by a space-based LIDAR, where multiple-scattering effects are much greater. The magnitude of multiple-scattering effects is seen to be largely determined by the optical depth across the receiver field of view at the cloud.

Content and structure in cartilage Type II collagen is one of the primary structural components of hyaline cartilage, constituting approximately half the dry weight of extracellular matrix. It is composed of a triple helix of three identical a chains organized in fibrils within the extracellular matrix. Whereas these fibrils are ordinarily clearly visible throughout the matrix, close to the cell in the pericellular domain, their identity is often difficult to discern. It is here that there is likely more active turnover of collagen, such as in rheumatoid arthritis (Mansson et al. 1995).

Periosteal grafts have chondrogenic potential and have been used to repair defects in articular cartilage. We studied the effects of the culture conditions and of transforming growth factor-beta 1 on chondrogenesis in rabbit periosteal explants that were cultured in vitro. A total of 390 periosteal explants were obtained from the anteromedial sides of the proximal parts of the tibiae of eleven rabbits that were two weeks, two months, or six months old. The culture medium (alpha minimum essential medium or Dulbecco minimum essential medium) contained fetal calf serum, with or without transforming growth factor-beta 1, at a concentration of one or ten nanograms per milliliter for the first two weeks of culture. Three hundred and twenty-one explants were submerged in liquid medium and sixty-nine were suspended in an agarose gel; they were then evaluated histochemically, histomorphometrically, and by collagen-typing. In the media without agarose, in the presence of ten nanograms of transforming growth factor-beta 1 per milliliter, chondrogenesis was commonly seen after two to four weeks with use of safranin-O staining and histomorphometry. In the agarose gels, chondrogenesis from the periosteum was observed at four and six weeks and was enhanced by the presence of one or ten nanograms of transforming growth factor-beta 1 per milliliter. The combination of agarose with transforming growth factor-beta 1 most favored the formation of cartilage, which was maximum at six weeks in the presence of ten nanograms of transforming growth factor-beta 1 per milliliter. Under these conditions, chondrogenesis occurred in almost every explant, with 50 +/- 30 per cent of the tissue being composed of cartilage. Type-II collagen was present in the explants that had undergone chondrogenesis.

The Dielectric Wall Accelerator (DWA) offers the potential to produce a high gradient linear accelerator for proton therapy and other applications. The current status of the DWA for proton therapy will be reviewed. Recent progress in SiC photoconductive switch development will be presented. There are serious beam transport challenges in the DWA arising from short pulse excitation of the wall. Solutions to these transport difficulties will be discussed.

A relativistic backward-wave oscillator (BWO) operating at a frequency near 8 GHz has been built. The parameters of the 60-ns electron beam driving this microwave source are varied over the ranges 0.8-1.5 MV and 2-10 kA. Several different annular cathodes for launching the electron beam are tried, varying the outer radius and shape. The axial magnetic field guiding the beam through the BWO is varied between 0.6 and 3 T. The power transfer downstream to an output waveguide is investigated as a function of the shape of the transition from the BWO to the waveguide. The scaling of the output power and frequency with these variations is discussed. Time-resolved measurements of 2-ns-long segments of the microwave output are shown. In observations of the microwave signal, it is found that the frequency shifts as the output power envelope passes through a sharp dip. It is proposed that this shift corresponds to a change in the longitudinal operating mode of the BWO. >

The technique for normalizing airborne lidar measurements of chlorophyll fluoresence by the water Raman scattering signal is investigated for laser-excitation wavelengths of 480 and 532 nm using a semianalytic Monte Carlo methodology (SALMON). The signal-integration depth for chlorophyll fluorescence Z(90,F), is found to be insensitive to excitation wavelength and ranges from a maximum of 4.5 m in clearest waters to less than 1 m at a chlorophyll concentration of 20 microgram/liter. For excitation at 532 nm, the signal-integration depth for Raman scattering, Z(90,R), is comparable to Z(90,F). For excitation at 480 nm, Z(90,R) is four times as large as Z(90,F) in clearest waters but nearly equivalent at chlorophyll concentrations greater than 2-3 microgram/liter. Absolute signal levels are stronger with excitation at 480 nm than with excitation at 532 nm, but this advantage must be weighed against potential ambiguities resulting from different integration depths for the fluorescence and Raman scattering signals in clearer waters. To the precision of the simulations, Raman normalization produces effectively linear response to chlorophyll concentration for both excitation wavelengths.

All citizens have the right to access information from their government. At both the federal and state levels in the United States, citizens with impairments expect the same access to government information as anyone else. When government information is available on a web site, that information must be accessible for people with impairments. People with perceptual, motor, and/or cognitive impairments may access web sites using different assistive technologies, such as screen readers or alternative keyboards, or may need content in alternative formats (e.g. a transcript needs to exist for any audio). In cooperation with the Maryland Technology Assistance Program, a research group from Towson University evaluated Maryland state government web sites for accessibility. The goal of this paper is to report on how well Maryland state government web sites are currently meeting the needs of these diverse user populations. This is a major issue: recent population estimates indicate that approximately 112 000 individuals in Maryland between the ages of 16 and 74 have a sensory impairment, and 281 000 individuals in Maryland between the ages of 16 and 74 have a physical impairment (see www.ilr.cornell.edu/edi/DisabilityStatistics/acs.cfm for more population statistics).

To compare six assays of hyaluronan (hyaluronic acid; HYA) in serum, developed in different laboratories, we analyzed 10 samples from each of three groups: healthy persons, patients with primary biliary cirrhosis, and patients with rheumatoid arthritis. All the assays are based on the use of affinity proteins specific for HYA, prepared from cartilage or brain tissue, and are analogous to RIA or enzyme immunoassay techniques. The assay results were of the same magnitude. Although statistical analysis indicated that the methods in some cases deviated significantly from one another, this variation was less than the physiological variation in the healthy population. Therefore, the results of clinical investigations in which the various methods have been used are comparable. The analyses have high specificity and sensitivity for primary biliary cirrhosis but are somewhat less suitable for detecting rheumatoid arthritis. A seventh laboratory, which obtained antibodies to HYA, used these in an RIA to analyze a separate series of serum specimens. Results were in agreement with those obtained by one of the other assays.

Prediction, assessment, and mitigation of surface-affecting natural hazard processes such as landslides, avalanches, earthquakes, and floods call upon geoscientists to rapidly deploy instruments and accurately characterize these earth processes, often with little lead time and under dangerous working conditions. Affected areas may have heavy tree canopies, or high atmospheric dust loads (volcanic eruptions), precluding the use of traditional location techniques like Global Positioning System (GPS). The proliferation of inexpensive radio systems provides a technology that has the potential to redefine the approach to rapid characterization of hazardous earth processes. The research effort described in this paper developed and demonstrated an inexpensive, cooperative radar-like technology for precise distance measurement between intelligent radio nodes.

An analytic and numerical examination of the slow wave Cerenkov free electron maser is presented. We consider the steady state amplifier configuration as well as operation in the selfamplified spontaneous emission (SASE) regime. The linear theory is extended to include electron beams that have a parabolic radial density inhomogeneity. Closed form solutions for the dispersion relation and modal structure of the electromagnetic field are determined in this inhomogeneous case. To determine the steady state response, a macro-particle approach is used to develop a set of coupled nonlinear ordinary differential equations for the amplitude and phase of the electromagnetic wave, which are solved in conjunction with the particle dynamical equations to determine the response when the system is driven as an amplifier with a time harmonic source. We then consider the case in which a fast rise time electron beam is injected into a dielectric loaded waveguide. In this case, radiation is generated by SASE, with the instability seeded by the leading edge of the electron beam. A pulse of radiation is produced, slipping behind the leading edge of the beam due to the disparity between the group velocity of the radiation and the beam velocity. Short pulses of microwave radiationmore » are generated in the SASE regime and are investigated using particle-in-cell (PIC) simulations. The nonlinear dynamics are significantly more complicated in the transient SASE regime when compared with the steady state amplifier model due to the slippage of the radiation with respect to the beam. As strong self-bunching of the electron beam develops due to SASE, short pulses of superradiant emission develop with peak powers significantly larger than the predicted saturated power based on the steady state amplifier model. As these superradiant pulses grow, their pulse length decreases and forms a series of soliton-like pulses. Comparisons between the linear theory, macro-particle model, and PIC simulations are made in the appropriate regimes.« less

Intended for first-time physical education teachers, this article provides graduate assistants with information about teaching activity classes in the basic program.

The introduction of a new microanalytical approach has made it possible to investigate the molecular structure and content of proteoglycans within the extracellular matrix of the physis when the volumes of the matrix and the cells change before mineralization of the extracellular matrix. By using extracts of serial frozen sections with a combination of gel chromatography and chemical, radioimmunoassay, and morphometric analyses, we demonstrated that, in the bovine fetal physis, the content of large aggregating proteoglycans reaches a maximum in the extracellular matrix of the hypertrophic zone, in the region where calcification begins, at the time when calcification starts. Morphometric analyses revealed that, at this time, the volume of matrix is reduced to a minimum. There was no evidence that the remaining proteoglycans were reduced in size, nor was aggregation changed at the time when calcification was initiated. Thus, contrary to earlier reports, there is no indication that these molecules need to be degraded and removed for calcification to begin, although a progressive loss of proteoglycans clearly occurs as the volume of the matrix is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)