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Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the lung lining that is predominantly associated with occupational exposure to asbestos. MPM is responsible for thousands of deaths worldwide every year, with the median survival of MPM of 8–14 months. There are limited biomarkers available in the clinic to effectively diagnose MPM, an invasive biopsy procedure is usually required to provide a definitive diagnosis. Due to the long latency period associated with MPM disease presentation, the cancer is usually at an advanced stage at the time of diagnosis where treatment options are largely ineffective at controlling disease progression. Previous MPM-based pre-clinical studies have made significant strides in determining the exact molecular mechanisms associated with asbestos carcinogenesis. Exploring less invasive blood-based biomarkers and treatment strategies involving targeted therapy, immunotherapy, and virotherapy is particularly important. Research in these areas is of crucial importance in relation to improving the rate of novel diagnostic biomarkers and treatment strategies progressing through to clinical trials and ultimately into the clinical setting. This review comprehensively summarises both previous and current pre-clinical research developments that have specifically contributed to an improved understanding of MPM disease biology, and the development of novel diagnostic biomarkers and treatment strategies.

Objective There are no data on the effect of X-Ray irradiation to the vulnerable pelvic organs of babies during DDH follow-up. This study aims to calculate, for the first time, the radiation exposure to infants during follow-up for DDH harness treatment, and thus quantify the lifetime risk of malignancy. Methods Patients who had completed 5 years’ follow-up following successful Pavlik harness treatment were identified from the hospital DDH database. The radiation dose was extracted from the Computerised Radiology Information System database for every radiograph of every patient. The effective dose (ED) was calculated using conversion coefficients for age, sex and body region irradiated. Cumulative ED was compared to Health Protection Agency standards to calculate lifetime risk of malignancy from the radiographs. Results All radiographs of 40 infants, successfully treated in Pavlik harness for DDH, were assessed. The mean number of AP pelvis radiographs was 7.00 (range: 6–9, mode: 7). The mean cumulative ED was 0.25 mSv (Range: 0.11–0.46, SD: 0.07). This is far lower than the annual ‘safe’ limit for healthcare workers of 20 mSv and is categorised as “Very Low Risk”. Conclusion Clinicians involved in the treatment DDH can be re-assured that the cumulative radiation exposure from pelvic radiographs following Pavlik harness treatment is “Very Low Risk”. Whilst being mindful of any radiation exposure in children, this study provides a scientific answer that help addresses parental concerns.

Does the Supreme Court care what the public thinks? For decades, published articles have consistently reported a significant, positive relationship between public opinion and Supreme Court output. However, these studies posit mutually contradictory theories and report irreconcilable results. We advance this literature in two ways. First, we show that the empirical “fact” driving the search for a workable theory is actually illusory. Second, we defend a theory of judicial independence. To be clear, we do not attempt to prove the Court does not respond to the public’s opinions on policy. We argue that there is little reason the Court should respond and demonstrate that, contrary to twenty-five years of scholarship, there is no good empirical evidence suggesting it does.

Background: Some families living near wind energy facilities report permanently vacating their homes while others contemplate doing so. While these events are reported on the Internet and social media, research is lacking. This study explored why some people living in proximity to wind turbines contemplate such housing decisions. Methods: This ethics-reviewed study used the Grounded Theory methodology and audio recorded interviews with those who had previously lived, or were currently living near wind turbines. Audio files were transcribed to text, and the data analysed using NVivo12 Pro software. Objectives: To explore the events that influenced families living within 10 km from wind energy facilities to contemplate vacating their homes. To generate a substantive theory regarding these housing decisions. Results: All 67 participants associated occurrences of adverse health effects, or the potential for such effects when living within 10 km of a wind energy facility. Some temporarily left during the day and/or night to alleviate effects. Discussion: This article presents an overview of results with additional details pending in future peer-reviewed articles. Using a systematic methodology, data analysis lends support for the theory that housing decisions were motivated by the proximity of wind energy facilities within 10 km of homes and the interviewees’ observations of the occurrence or potential risk of adverse health effects. Members of the public, researchers, health care practitioners, engineers and acousticians, social scientists, and policy makers with an interest in health and social policy are presented with the potential outcomes of placing wind turbines near family homes.

Summary This study assessed the cost-effectiveness of continued denosumab treatment, compared with discontinuation of denosumab after one dose, for the treatment of postmenopausal osteoporosis in Taiwan, using real-world fracture reduction effectiveness and cost data. Outcomes indicate that continued denosumab treatment produces an incremental cost-effectiveness ratio of USD $16,743 per QALY. Purpose To evaluate the cost-effectiveness of continued denosumab use versus discontinuation after one dose, for the treatment of postmenopausal osteoporosis in Taiwan, using real-world fracture reduction effectiveness and cost data. Methods A Markov cohort model was used to evaluate the lifetime costs and QALYs associated with continued denosumab treatment versus discontinuation of treatment after one dose. The evaluation was conducted from the perspective of Taiwan’s healthcare system and used a discount rate of 3% per annum. The patient population consisted of postmenopausal women with osteoporosis with a mean age of 77 years who initiated denosumab treatment. Fracture reduction effectiveness data, baseline fracture rates, mortality data, and costs of fracture were informed by Taiwan’s National Health Insurance Research Database. Results Model outcomes showed that continued treatment with denosumab produced an expected gain of 0.042 QALYs and an incremental cost of USD $704, compared with discontinuation of denosumab after one dose. This corresponds to an incremental cost-effectiveness ratio of USD $16,743 per QALY gained. Probabilistic and scenario analysis showed that results are stable to variations in model assumptions and parameters. Conclusion In a real-world setting, at a cost per QALY threshold equivalent to gross domestic product per capita in 2020 in Taiwan (USD $30,038), continued treatment with denosumab in postmenopausal women with osteoporosis is cost-effective compared with treatment discontinuation.

One of the challenges when building Machine Learning (ML) models using satellite imagery is building sufficiently labeled data sets for training. In the past, this problem has been addressed by adapting computer vision approaches to GIS data with significant recent contributions to the field. But when trying to adapt these models to Sentinel-2 multi-spectral satellite imagery these approaches fall short. Previously, researchers used transfer learning methods trained on ImageNet and constrained the 13 channels to 3 RGB ones using existing training sets, but this severely limits the available data that can be used for complex image classification, object detection, and image segmentation tasks. To address this deficit, we present Distil, and demonstrate a specific method using our system for training models with all available Sentinel-2 channels. There currently is no publicly available rich labeled training data resource such as ImageNet for Sentinel-2 satellite imagery that covers the entire globe. Our approach using the Distil system was: a) pre-training models using unlabeled data sets and b) adapting to specific downstream tasks using a small number of annotations solicited from a user. We discuss the Distil system, an application of the system in the remote sensing domain, and a case study identifying likely locust breeding grounds in Africa from unlabeled 13-channel satellite imagery.

Development of a cardiac lead fracture model has the potential to differentiate well-performing lead designs from poor performing ones and could aid in future lead development.The purpose of this study was to demonstrate a predictive model for lead fracture and validate the results generated by the model by comparing them to observed 10-year implantable cardioverter-defibrillator lead fracture-free survival.The model presented here uses a combination of in vivo patient data, in vitro conductor fatigue test data, and statistical simulation to predict the fracture-free survival of cardiac leads. The model was validated by comparing the results to human clinical performance data from the Medtronic Sprint Fidelis (Minneapolis, MN) models 6931 (single coil, active fixation) and 6949 (dual coil, active fixation), as well as the Quattro model 6947 (dual coil, active fixation).Median patient age in the single coil Fidelis 6931 population (64 years) was less than in the dual coil Fidelis 6949 and Quattro populations (68 years). Modeled and observed fracture-free survival for Quattro (97%) was superior to that for Fidelis (94%). The modeled survival agreed with the observed fracture-free survival data. The average model error was 0.3% (SD 1.2%).This model for cardiac lead fracture-free survival using in vivo lead bending measurements and in vitro bench testing can be used to predict lead performance as observed by alignment with field survival data.

BACKGROUND Radioactive iodine (RAI) is considered the gold standard treatment for feline hyperthyroidism. Currently exposure limits to radiation are regulated by national legislation, therefore the length of the isolation period in hospital for cats receiving radioactive treatment varies according to the place where the radioactive facility is located. The aim of this study was to establish when retained radioactivity decreases in cats receiving subcutaneous I-131 to a level that would allow discharge of cats from the hospital while being compliant with current United Kingdom legislation. METHODS Clinical records of cats treated with subcutaneous I-131 were retrospectively reviewed. Radioactive emission rates were measured using an external probe. Retained radioactivity below 11 MBq at the point of discharge was required by the initial risk assessment to ensure that a 0.3 mSv dose constraint was maintained for owners following standard cat-owner contact restrictions. Average retained activity for each treatment regimen at the time of discharge was calculated. The biological half-life for iodine retention was also calculated. RESULTS Overall, an end activity below 11 MBq was reached at day 11 in 49% of cats, and at day 13 in 91% of cats. These cats were allowed to be discharged according to UK legislation, as long as contact restrictions were applied at home for 2 weeks. CONCLUSION Based on our study, an isolation period of 13 days before allowing discharge of cats treated with subcutaneous RAI (I-131) is compliant with current UK legislation.

Malignant pleural mesothelioma (MPM) is an aggressive asbestos related disease that is generally considered to be difficult to diagnose, stage and treat. The diagnostic process is continuing to evolve and requires highly skilled pathology input, and generally an extensive list of biomarkers for definitive diagnosis. Diagnosis of MPM requires histological evidence of invasion by malignant mesothelial cells often confirmed by various immunohistochemical biomarkers in order to separate it from pleural metastatic carcinoma. Often when invasion of neoplastic mesothelial cells into adjacent tissue is not apparent, further immunohistochemical testing - namely BAP1 and MTAP, as well as FISH testing for loss of p16 (CDKN2A) are used to separate reactive mesothelial proliferation due to benign processes, from MPM. Various combinations of these markers, such as BAP1 and/or MTAP immunohistochemistry alongside FISH testing for loss of p16, have shown excellent sensitivity and specificity in the diagnosis of MPM. Additionally, over the recent years, research into epigenetic marker use in the diagnosis of MPM has gained momentum. Although still in their research stages, various markers in DNA methylation, long non-coding RNA, micro RNA, circular RNA, and histone modifications have all been found to support diagnosis of MPM with generally good sensitivity and specificity. Many of these studies are however, limited by small sample sizes or other study limitations and further research into the area would be beneficial. Epigenetic markers show promise for use in the future to facilitate the diagnosis of MPM.

Introduction: We sought to prospectively evaluate the effectiveness of the multidisciplinary tumour board (MTB) on altering treatment plans for genitourinary (GU) cancer patients.Methods: All GU cancer patients seen at our tertiary care hospital are discussed at MTB. We prospectively collected data on adult patients discussed over a continuous, 20-month period. Physicians completed a survey prior to MTB to document their opinion on the likelihood of change in their patient’s treatment plan. Logistic regression was used to asses for factors associated with a change by the MTB, including patient age or sex, malignancy type, the predicted treatment plan, and the provider’s years of experience or fellowship training.Results: A total of 321 cancer patients were included. Patients were primarily male (84.4%) with a median age of 67 years old (range 20–92). Prostate (38.9%), bladder (31.8%), and kidney cancer (19.6%) were the most common malignancies discussed. A change in management plan following MTB was observed in 57 (17.8%) patients. The physician predicted a likely change in six (10.5%) of these patients. Multivariate logistic regression did not determine physician prediction to be associated with treatment plan change, and the only significant variable identified was a plan to discuss multiple treatment options with a patient (odds ratio 2.46; 95% confidence interval 1.09–9.54). Conclusions: Routine discussion of all urologic oncology cases at MTB led to a change in treatment plan in 17.8% of patients. Physicians cannot reliably predict which patients have their treatment plan altered. Selectively choosing patients to be presented likely undervalues the impact of a multidisciplinary approach to care.

Objective We evaluated the impact of loan repayment programmes, revising Medicaid fee-for-service rates, and changing dental hygienist supervision requirements on access to preventive dental care for children in Georgia. Methods We estimated cost savings from the three interventions of preventive care for young children after netting out the intervention cost. We used a regression model to evaluate the impact of changing the Medicaid reimbursement rates. The impact of supervision was evaluated by comparing general and direct supervision in school-based dental sealant programmes. Results Federal loan repayments to dentists and school-based sealant programmes (SBSPs) had lower intervention costs (with higher potential cost savings) than raising the Medicaid reimbursement rate. General supervision had costs 56% lower than direct supervision of dental hygienists for implementing a SBSP. Raising the Medicaid reimbursement rate by 10 percentage points would improve utilization by

Objectives: Demand for dental care is expected to outpace supply through 2025. The objectives of this study were to determine the extent of pediatric dental care shortages in Georgia and to develop a general method for estimation that can be applied to other states. Methods: We estimated supply and demand for pediatric preventive dental care for the 159 counties in Georgia in 2015. We compared pediatric preventive dental care shortage areas (where demand exceeded twice the supply) designated by our methods with dental health professional shortage areas designated by the Health Resources & Services Administration. We estimated caries risk from a multivariate analysis of National Health and Nutrition Examination Survey data and national census data. We estimated county-level demand based on the time needed to perform preventive dental care services and the proportion of time that dentists spend on pediatric preventive dental care services from the Medical Expenditure Panel Survey. Results: Pediatric preventive dental care supply exceeded demand in Georgia in 75 counties: the average annual county-level pediatric preventive dental care demand was 16 866 hours, and the supply was 32 969 hours. We identified 41 counties as pediatric dental care shortage areas, 14 of which had not been designated by the Health Resources & Services Administration. Conclusions: Age- and service-specific information on dental care shortage areas could result in more efficient provider staffing and geographic targeting.

Background There is substantial evidence for a cumulative dose-related response to ionizing radiation in the form of cancer development years after initial exposure. Therefore, this study focused on effective dose, a quantity with direct correlations to biologic risk from dental x-ray exposures. Objective The purpose of this study was to measure doses and to calculate the effective doses (E) resulting from exposure parameters that are used for stationary intraoral tomosynthesis (s-IOT) and conventional imaging for adult posterior bitewing examinations of the dentition. Additionally, this study sought to evaluate the effect of sensor attenuation on patient dose. Materials and Methods To meet these aims, a human tissue equivalent adult phantom and optically stimulated luminescent (Landauer, Inc., Glenwood, IL) dosimeters were used to measure dose produced during simulated posterior bitewing examinations (n = 4). Optically stimulated luminescent dosimeters were used to measure x-ray dose at 24 head and neck tissue/organ sites of interest. Dosimetry was acquired by using a tissue equivalent phantom simulating the anatomy of an average adult male (AtomMax Model 711 HN,CIRS Inc., Norfolk, VA). Exposure parameters used were 70 kV/7 mA (0.7 mAs) and 0.12 mAs for s-IOT and conventional (KaVo FOCUS, Charlotte, NC), respectively. Analysis of variance (ANOVA) and Tukey’s HSD (“honest significant difference”) statistics on dose were utilized to demonstrate significant data relationships. Results Effective dose by modality (μSv) Modality Dose (μSv) Rectangular Conventional with Sensor 1.1 Rectangular Conventional without sensor 4.6 s-IOT with sensor 5.9 s-IOT without sensor 11.9 Circular Conventional with sensor 8.2 Circular Conventional without sensor 15.7 Sensor-present doses were significantly lower than sensor-absent for all modalities (P = .0001). Significant differences in E were found for all modality combinations with the exception of s-IOT sensor-present modalities vs conventional rectangular sensor-absent modalities (P = .0482). Discussion Unadjusted s-IOT dose was 26% less than conventional-circular exposures and 61% greater than conventional-rectangular for sensor-absent exposures. Unadjusted sensor-present s-IOT dose was 28% less than conventional-circular exposures and 81% greater than conventional-rectangular exposures. Despite a 4-fold increase in mAs for s-IOT imaging compared with conventional imaging, E from s-IOT imaging was at least 26% less than the current most commonly implemented bitewing technique, conventional-circular, while providing substantially greater diagnostic yield in the form of 3-dimensional (3-D) information.

This article is a case study for an energy savings performance contract (ESPC) at the wastewater treatment plant for the City of Riverbank in California. The existing plant has an average of 1.67 million gallons per day (MGD) flow and consists of the headworks, four treatment ponds, and seven percolation ponds. Prior to the project, the treatment ponds used surface aerators to provide oxygen for the biologic process. The plant was primarily operated manually with limited dissolved oxygen control. The utility bills showed excessive energy use—annual usage was 5,673 kWh/MG/yr. Schneider Electric and the City of River-bank entered into a construction contract to retrofit the treatment ponds with blowers and fine-bubble diffusers for more efficient oxygen transfer. Additionally, a control system was installed to maintain a dissolved oxygen set point. This scope of work is estimated to save 75% of the electricity consumption at the wastewater treatment plant and will save the city 65% of their electric...

The report examines the differences in costs between strategic-beta (smart beta) exchange-traded funds (ETFs) and their more ordinary passive peers. Cost is an important consideration that isn’t always at the forefront of investors’ minds when selecting strategic-beta funds. The study assesses differences in fees, replication costs, and trading costs for a selection of European-domiciled, strategic-beta ETFs and market-cap-weighted ETFs linked to some of the most widely used broad equity benchmarks, including the S&P 500, MSCI World, and MSCI Emerging Markets indexes. The authors find a wide disparity in the fees charged by strategic-beta funds and that their total cost of ownership is, on average, significantly higher.

We present a CMOS image sensor for efficient capture of polar symmetric imaging targets. The array uses circular photodiodes, arranged in concentric rings to capture, for example, diffraction patterns generated by optically probing a revolving MEMS device. The chip is designed with a vacant, central spot to facilitate the easy single-axis alignment of the probing illumination, target device, and detector. Imaging of high-speed rotation (>1 kfps) is made possible by dividing the array into multiple concentric bands with sectorwise addressing control. We introduce a global shutter pixel reset scheme that reduces fixed pattern noise by being insensitive to parasitic capacitance from variable routing. We demonstrate the sensor’s capability to measure the rotation angle with a precision of 32 $\mu$ rad and the rotation rates up to 300 rpm. Finally, we demonstrate the concept of a compact optical metrology system for continuous inertial sensor calibration by imaging the diffraction pattern created by a commercial MEMS accelerometer probed by a red laser shone through the axis of symmetry of the image sensor.

Colorectal cancer (CRC) is third deadliest cancer in United States, only behind lung and prostate cancer. Myeloid cell involvement in tumor development is dichotomous. There is evidence that they can be immunostimulatory and tumor suppressive as well as immunosuppressive and tumorigenic. These cells seem to play a crucial role in tumor angiogenesis & vasculogenesis. The functional fluidity is driven by factors present in the tumor microenvironment (TME), which alter myeloid cell gene expression and thus phenotype & function. Broadly, the pathologic myeloid cells present within the tumor can be broken down into two classes: immature myeloid-derived suppressor cells (MDSCs) & mature tumor-associated myeloid cells (TAMCs). This project investigates the angiogenic/vasculogenic gene signatures of MDSCs & TAMCs. Seven genes that were either markers of myeloid cells or expressed by pro-angiogenic MDSCs & TAMCs: CD14, CD15, VEGF, TNF-a, TGF-b, cathepsin B, & MMP-14 were analyzed in tumor samples using Syber Green qPCR. The aim of this study is to determine possible associations of gene expression with endpoints such as tumor stage, tumor grade & patient survival, so as to determine their prognostic value in predicting outcome in CRC patients. Under the IRB approved protocol, a total of 750 colon cancer patients at Medical College of Georgia with 5 years follow-up were initially selected. The patients were stratified on the basis of overall survival in two groups, with higher (> 5 years) and lower survival ( Citation Format: Ben Johnson, Nikhil Sahajpal, Pankaj Ahaluwalia, Ashis Mondal, Allan Njau, Meenaskhi Ahaluwalia, Ravindra Kolhe. Pro-angiogenic and myeloid cell gene expression markers in prognostication of advanced stage colorectal cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-213.

Background There is substantial evidence for a cumulative dose-related response to ionizing radiation in the form of cancer development years after initial exposure. Therefore, this study focused on effective dose (E), a quantity with direct correlations to biologic risk from dental x-ray exposures. Objectives The purpose of this study was to measure doses and calculate (E) from adult full-mouth examinations (FMXs) by using handheld and conventional wall-mounted x-ray sources with both circular and rectangular collimation (RC). Materials and Methods A human tissue-equivalent phantom and optically stimulated luminescent dosimeters were used to measure dose from simulated FMXs (n = 18) at 24 head/neck tissue sites. The parameters were 70 kV/7 mA (0.84 mAs and 1.34 mAs) for Conventional Circular and RC handheld device; 60 kV/2.5 mA (2.16 mAs) for NOMAD Circular and RC handheld device; and 60 kV/2.0 mA (1.98 mAs) for Xray2 Go Circular (XTG) handheld device. Analysis of variance (ANOVA) and Tukey’s HSD (“honest significant difference”) statistics demonstrated significant relationships. Results The FMX E (µSv) values were: NOMAD RC (6.9); XTG (16.7); NOMAD Circular (17.4); and Conventional Circular (26.3). For circular techniques, the handheld device E was significantly lower than the conventional unit for both devices (P Discussion Handheld device E was at least 34% less than conventional circular and as much as 74% less with the use of RC. Operator exposure to the groin can increase significantly from overangulating the handheld sources; however, the addition of RC can reduce this exposure by as much as 76%.

Aims\ud To explore the experiences of young adults with regard to self‐management of Type 1 diabetes in the context of a structured education programme.\ud \ud Methods\ud Qualitative interviews and focus groups were conducted with young adults attending a structured education course promoting a flexible and self‐directed format. Participants attending the structured education courses were recruited using purposive sampling to acquire a broad mix of participants based on age and equal numbers of young men and women. Fifteen interviews were conducted 12 weeks after each course, whilst seven focus groups and observations of the course delivery were conducted at two course sites and were led by nurse/dietitian educators representing two different diabetes centres (paediatric and adult). The interview and focus group data were audio recorded and transcribed, coded, and analysed thematically to identify similarities and differences.\ud \ud Results\ud The analysis revealed three themes, ‘we're in it together’, ‘tacit benefits’ and ‘transitions beyond the structured education programme’. The findings show that structured education programmes can facilitate reflective critical thinking and greater engagement with diabetes self‐management if they: a) foster maximal learning from fellow participants to decrease feelings of isolation, b) maximize engagement during the course by delivering the content in a flexible manner, and c) recognize the social and emotional needs of young adults.\ud \ud Conclusion\ud Structured education courses can result in improved critical thinking and engagement with diabetes self‐management by empowering young adults through a flexible and self‐directed learning style that encourages peer group discussion.

Does the Supreme Court care what the public thinks? For decades, articles in leading political science journals have consistently answered in the affirmative. They regularly report a significant, positive relationship between public opinion and Supreme Court output. Given this accepted empirical fact, attention has turned to how or when public opinion affects the Court. Theories that attempt to answer these questions, however, face unresolved challenges: the mechanisms are left unexplained, and the studies are mutually contradictory. We advance this literature by showing that the empirical “fact” driving the search for a workable theory is actually ephemeral. To be clear, we do not attempt to prove the Court does not respond to public opinion. We do demonstrate, however, that contrary to twenty-five years of scholarship, there is no good empirical evidence suggesting it does. Doing so returns the field to the central question of whether opinion matters.

In recent history, wiretapping has provided an effective means for uncovering potential security threats, both domestically and abroad. Wiretapping as a technology developed first in the 1890’s with the development of the telephone recorder, which quickly followed the invention of the telephone in 1876. Through the years, as new communications technology was developed, methods were quickly adopted to capture the information shared through the new method. The biggest challenge initially with capturing the information has been the ethical and legal battles that have ensued. The ethics and legality associated with wiretapping has been accessed and reassessed with a slew of hearings, policies, and court orders. The amount of discussion on the issue makes the controversial nature of the method clear. Later, with the invention of computers and the internet, wiretapping technology was needed to allow the government a method to maintain security, and policies shifted from a focus on the legality of wiretapping to a focus on regulating technology so the government could maintain necessary security measures.

Background Selecting heart failure (HF) patients for intensive management to reduce readmissions requires effective targeting. However, available prediction scores are only modestly effective. We sought to develop a prediction score for 30-day all-cause rehospitalization or death in HF with the use of nonclinical and clinical data. Methods and Results This statewide data linkage included all patients who survived their 1st HF admission (with either reduced or preserved ejection fraction) to a Tasmanian public hospital during 2009–2012. Nonclinical data (n = 1,537; 49.5% men, median age 80 y) included administrative, socioeconomic, and geomapping data. Clinical data before discharge were available from 977 patients. Prediction models were developed and internally and externally validated. Within 30 days of discharge, 390 patients (25.4%) died or were rehospitalized. The nonclinical model (length of hospital stay, age, living alone, discharge during winter, remoteness index, comorbidities, and sex) had fair discrimination (C-statistic 0.66 [95% confidence interval (CI) 0.63–0.69]). Clinical data (blood urea nitrogen, New York Heart Association functional class, albumin, heart rate, respiratory rate, diuretic use, angiotensin-converting enzyme inhibitor use, arrhythmia, and troponin) provided better discrimination (C-statistic 0.72 [95% CI 0.68–0.76]). Combining both data sources best predicted 30-day rehospitalization or death (C-statistic 0.76 [95% CI 0.72–0.80]). Conclusions Clinical data are stronger predictors than nonclinical data, but combining both best predicts 30-day rehospitalization or death among HF patients.

BACKGROUND Steroid-eluting (SE) electrodes suppress local inflammation and lower pacing capture thresholds (PCT); however, their effectiveness on quadripolar left ventricular (LV) leads in the cardiac vein is not fully studied. We evaluated the effectiveness of SE on all four LV pacing electrodes in human subjects enrolled in the Medtronic Attain® Performa™ quadripolar LV lead study. METHODS A total of 1,097 subjects were included in this evaluation. At each follow-up visit (1, 3, 6, and 12 months), LV PCT and pacing impedance were measured using either manual or automated testing methods. Summary statistics for PCT and impedance values were obtained for implant and each scheduled follow-up visit for all lead models. RESULTS Average extended bipolar (LV electrode to right ventricular Coil) PCTs for the four LV SE pacing electrodes (LV1, LV2, LV3, and LV4) on the three shapes of the quadripolar LV leads were 1.06 ± 0.97 V, 1.38 ± 1.26 V, 1.51 ± 1.33 V, and 2.25 ± 1.63 V, respectively, at 0.5-ms pulse width. PCTs remained low and stable throughout the 12-month follow-up period. CONCLUSION This clinical trial demonstrated that SE on all LV pacing electrodes is associated with low and stable PCTs for all quadripolar LV lead electrodes, resulting in multiple viable vectors for LV pacing. The large number of available vectors facilitates basal pacing, avoidance of PNS, and potentially prolongs generator longevity due to lower PCTs.

International audience; Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets—consistent with expectations—but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response.

INTRODUCTION This paper considers the impact of geographic distance from cystic fibrosis centers on lung function in children, young adults, and adults with cystic fibrosis. METHODS Clinical patient-level data on 20 351 patients from 1986 to 2011 were evaluated from the Cystic Fibrosis Foundation National Patient Registry. We measure distance using a patient's zip code centroid to the center where they received care. A heteroscedastic mixed effects model was used to capture the association of distance with longitudinal variation in patients' lung function. RESULTS Children, young adults, and adults in lower socioeconomic categories had a %FEV1 between 3 and 10 percentage-points lower than those living in higher income areas and those privately insured. For patients who changed distance categories, high distance was associated with lower lung function in young adults (P-value

For open access (OA) to become a reality, all stakeholders will need to engage positively with each other to rise to the substantial practical challenges it brings. This means moving beyond advocacy and resistance towards a more mature, evidence-based dialogue that seeks to understand all perspectives and find workable solutions. For research funders, scholarly publication delivers crucial public benefits; funders' OA mandates should be seen as tools for maximizing these benefits. The Higher Education Funding Council for England's (HEFCE) policy for open access in the next Research Excellence Framework (REF) has been put together by listening to all sides of the debate, and its success depends on continuing positive, sensitive and engaged discussions between everyone involved.

Purpose – Given the widespread popularity of social media, such as Twitter, Facebook, Google+, and LinkedIn, theorizing and understanding the user attitude and usage behavior of social media site is fundamental in developing future understandings and deployment of these new technologies. One approach to such studies on drivers of social media usage behavior would be to revisit the technology acceptance model (TAM). The purpose of this paper is to discuss these issues. Design/methodology/approach – Decades of extensive research have focussed on validating the TAM, proposed by Davis (1986), for various types of information systems and communication technologies. TAM forecasts individual adoption and voluntary use of technology. This study examines individual adoption behavior of the most popular social networking site Facebook. The influences on the intention of using social networking based on individual's perceived ease of use (EU), the user's critical mass (CM), social networking site capability (CP), perceived playfulness (PP), trustworthiness (TW), and perceived usefulness (PU) is empirically examined with a primary data set of 398 users of Facebook gathered from a web-based questionnaire survey. Findings – The results demonstrate that the revised social media TAM model proposed in this study supports all the hypotheses of social media usage behavior. The results of this study provide evidence for the importance of additional key variables to TAM in considering user engagement on social media sites and other social-media-related business strategies. Originality/value – Based on our review of existing scientific literature on social media, few empirical studies have been conducted to scientifically evaluate and explain the usage behavior of social media using Facebook. A validated instrument of usage behavior of social media can provide usability experts and practitioners with a validated tool to assess social media acceptance and usage behavior. This can help us gain a better understanding of “who is and who is not using these sites, why and for what purposes” (Boyd and Ellison, 2007).

This paper draws on the work of Dror Paley et al and describes the basic principles of clinical and radiographic assessment of coronal plane lower limb deformity. It covers concepts of mechanical axis deviation and of the Centre of Rotation of Angulation (CORA) which influence the choice of corrective osteotomy shape and its location.

This paper presents closed form solutions to the classical beam elasticity differential equation in order to effectively model the displacement of standard aerodynamic geometries used throughout a number of industries. The models assume that the components are constructed from in-plane generally anisotropic (though shown to be quasi-isotropic) composite materials. Exact solutions for the displacement and strains for elliptical and FX66-S-196 and NACA 63-621 aerofoil approximations thin wall composite material shell structures, with and without a stiffening rib (shear-web), are presented for the first time. Each of the models developed is rigorously validated via numerical (Runge-Kutta) solutions of an identical differential equation used to derive the analytical models presented. The resulting calculated displacement and material strain fields are shown to be in excellent agreement with simulations using the ANSYS and CATIA commercial finite element (FE) codes as well as experimental data evident in the literature. One major implication of the theoretical treatment is that these solutions can now be used in design codes to limit the required displacement and strains in similar components used in the aerospace and most notably renewable energy sectors.

This paper presents a CMOS sensor array with a 768 low-noise recording sites for neural recording with 2048 intercalated angle-sensitive pixels for optical read-out. The array is highly scalable because of electrode-level digitization with serial data stream-out. The front-end amplifiers use chopping to reduce flicker noise and achieve an input-referred noise of 4.1 μVrms over a 3.6 kHz bandwidth while occupying an area of only 800 μm2. Digitization is performed using a distributed ramp ADC that samples every sensor site at 10 kHz. The electrodes have a 50 μm pitch and are plated with platinum to increase the interface capacitance and ensure biocompatibility. The sensor array is used to refocus a lenless image and to record neural spiking and local field potentials from a mouse olfactory bulb slice.

We demonstrate a micropower low-noise CMOS amplifier array that reuses bias current to improve the fundamental noise-power tradeoffs of fully-differential amplifier designs. The presented circuit implements current-reuse by stacking the differential input pairs of four amplifiers. The output drain currents of each channel's differential pair are used as the tail currents for the differential pairs of the succeeding channel. Orthogonal current-reuse improves the noise and power tradeoff by sharing bias devices to conserve headroom. With four channels (n = 4), there are 16 unique output currents (2n) from the stack, each of which is a linear combination of the four inputs. Amplified versions of the original input signals are reconstructed by appropriately combining the small-signal output currents in output stages that operate at much lower bias currents. With an input-referred noise of 3.7 μVrms and a bandwidth of 19.9 kHz, a single channel achieves a noise efficiency factor (NEF) of 3.0. Amortizing the bias current across the amplifier's four channels yields an effective NEF of 1.64. The total power consumption is 15.6 μW, or 3.9 μW per path from a 1.5 V supply. Orthogonal biasing suppresses crosstalk between the channels, providing an isolation of 40 dB under 3-σ mismatch. The implemented circuit was fabricated in a standard 130 nm CMOS process and occupies an area of 0.125 mm2. The proposed technique is useful for a variety of applications ranging from low-power neural recording arrays to multiphase radio baseband amplifiers.

Online social media, such as Facebook, YouTube, Twitter, and LinkedIn continue to influence and penetrate people's lives from multiple dimensions: communal, commercial, political, religious, and so forth. Motivated by developing a good understanding of such social media user behavior and user satisfaction, the current study develops a theoretical model of social media user satisfaction that incorporates constructs such as value to the user, content, critical mass, capability, timeliness, perceived privacy, ease of use, and format of a social media. The current researchers hypothesize eight positive relationships between the theoretical constructs and user satisfaction in the model. Using a sample size of 398 from the users of Facebook, all eight hypotheses proposed in the model were supported by the data. Discussion of research findings, limitations of the current studies, and direction for future studies are also provided.

In this work we present an architecture for a low power SDR which draws on techniques from both narrowband low power radios and recent work in SDRs. The receiver consists of a wide tuning-range passive mixer, driven with resonant non-overlapping LO drive combined with a noise-power optimized multi-path baseband amplifier. LO generation circuitry drives the mixer with an 8-phase, 12.5% duty cycle LO, but does so directly from complementary LC-tank VCOs in order to resonate out the gate capacitance of the mixer. A capacitor sharing technique on the baseband side of the mixer doubles the RX frequency range of the 8-phase clock at no added cost in power or performance, while achieving a NF as low as 7 dB. The 1.8 mW low noise baseband amplifier reuses the bias current of its four input channels while rejecting the 3rd/5th harmonics by >34 dB. The receiver consumes 10–12 mW (including VCOs, pulse generation and baseband) over a frequency range of 0.7–3.2 GHz with a 1.3 V supply.

Aims To demonstrate that critical conduction within the cavotricuspid isthmus (CTI) can be directly visualized by voltage gradient mapping and facilitate efficient ablation compared to standard techniques. Methods and results Group 1 (1 operator, n = 11) ablated based upon contact voltage measurements and voltage gradient mapping. Ablation targeted low-voltage bridges (LVBs) within the CTI. Repeat maps were obtained following ablation. Group 2 (operators 2, 3, and 4 n = 35) utilized electroanatomic navigation and ablated by the creation of linear lesions from the tricuspid valve to the inferior vena cava. Demonstration of bidirectional block (BDB) was required in both groups. LVB were associated with CTI conduction in all Group A patients. LVB ablation terminated flutter, or created BDB. Following ablation, CTI voltage connections were absent in all patients. Compared with Group B, Group A had less radiofrequency (RF) lesions to atrial flutter (AFL) termination (P = 0.001), less total RF lesions (P = 0.0001), and less total RF time (P = 0.001). Group 1 had no recurrent AFL whereas Group 2 had three recurrences. (follow-up median of 231 ± 181 days). Conclusion (i) Voltage gradient mapping visualized regions of critical CTI conduction, (ii) ablation of LVB terminated AFL and resulted in BDB, (iii) repeat mapping confirmed the absence of trans-isthmus voltage, and (iv) Compared with standard ablation, voltage gradient mapping decreases total RF lesions, lesions to AFL termination, and total RF time. Use of voltage gradient mapping can facilitate successful AFL ablation.

Trauma is one of the leading prehospital disease profiles in South Africa in general and in KwaZulu-Natal (KZN) in particular. The present study was designed to review the prehospital burden of injury in KZN, identify trauma burden to ambulance ratios, analyze system deficiencies, and propose a prehospital trauma system that is Afrocentric in nature. Approval from the relevant ethics authorities was obtained. Using a convenience data set all Emergency Medical Service (EMS) call data for the months of March and September 2010 were reviewed for the three main EMS providers in KZN. Data were extrapolated to annual data and placed in the context of population, ambulance service, and facility. The data were then mapped for area distribution and prehospital workload relative to the entire province. Questionnaire-based assessments of knowledge and deficiencies of the current system were completed by senior officers of the provincial system as part of the analysis of the current system. The total annual call burden for trauma ranges between 94,840 and 101,420, or around 11.6 trauma calls per thousand of the population per year. Almost 70 % of calls were either for interpersonal intentional violence or vehicular collisions. Only 0.25 % of calls involved aeromedical resources. Some 80 % of patients were considered to be moderately to seriously injured, yet only 41 % of the patients were transported to a suitable level of care immediately, with many going to inappropriate lower level care facilities. Many rural calls are not attended within the time norms accepted nationally. Deficiencies noted by the questionnaire survey are the general lack of a bypass mechanism and the feeling among staff that most EMS bases do not have a bypass option or feel part of a system of care, despite large numbers of staff having been recently trained in triage and major trauma care. The prehospital trauma burden in KZN is significant and consumes vital resources and gridlocks facilities. A prehospital trauma system that is financially sustainable and meets the needs of the trauma burden is proposed to enable Afrocentric emergency care planning for low and middle income regions.

Background Electrical heterogeneity (EH) during cardiac resynchronization therapy may vary with different left ventricular (LV) pacing sites. Objective The purpose of this study was to evaluate the relationship between such changes and acute hemodynamic response (AHR). Methods Two EH metrics—standard deviation of activation times and mean left thorax activation times—were computed from isochronal maps based on 53-electrode body surface mapping during baseline AAI pacing and biventricular (BiV) pacing from different pacing sites in coronary veins in 40 cardiac resynchronization therapy–indicated patients. AHR at different sites was evaluated by invasive measurement of LV-dp/dt max at baseline and BiV pacing, along with right ventricular (RV)–LV sensing delays and QRS duration. Results The site with the greatest combined reduction in standard deviation of activation times and left thorax activation times from baseline to BiV pacing was hemodynamically optimal (defined by AHR equal to, or within 5% of, the largest dp/dt response) in 35 of 40 patients (88%). Sites with the longest RV–LV and narrowest paced QRS were hemodynamically optimal in 26 of 40 patients (65%) and 28 of 40 patients (70%), respectively. EH metrics from isochronal maps had much better accuracy (sensitivity 90%, specificity 80%) for identifying hemodynamically responsive sites (∆LV dp/dt max ≥10%) compared with RV–LV delay (69%, 85%) or paced QRS reduction (52%, 76%). Multivariate prediction model based on EH metrics showed significant correlation (R 2 = 0.53, P Conclusion Changes in EH from baseline to BiV pacing more accurately identified hemodynamically optimal sites than RV–LV delays or paced QRS shortening. Optimization of LV lead location by minimizing EH during BiV pacing, based on body surface mapping, may improve CRT response.

We present a 72 × 60, angle-sensitive single photon avalanche diode (A-SPAD) array for lens-less 3D fluorescence lifetime imaging. An A-SPAD pixel consists of (1) a SPAD to provide precise photon arrival time where a time-resolved operation is utilized to avoid stimulus-induced saturation, and (2) integrated diffraction gratings on top of the SPAD to extract incident angles of the incoming light. The combination enables mapping of fluorescent sources with different lifetimes in 3D space down to micrometer scale. Futhermore, the chip presented herein integrates pixel-level counters to reduce output data-rate and to enable a precise timing control. The array is implemented in standard 180 nm complementary metal-oxide-semiconductor (CMOS) technology and characterized without any post-processing.

Wetland restoration projects across the United States commonly lack the species and hydrology of the targeted community being restored. A better understanding of natural wetlands would help restoration project designers achieve community composition and hydrologic regimes that more closely resemble natural conditions. We investigated two different methods to identify patterns in hydrologic regime useful to restoration design. The first method was based on success criteria commonly used by North Carolina wetland mitigation projects. The second method was based on The Nature Conservancy's Indicators of Hydrologic Alteration. To test these two methods, we collected hydrologic and compositional data across the natural variation of nonriverine wet hardwood forest stands, a rare wetland community type commonly restored in North Carolina. Our results show that hydrologic parameters from the first method, based on current success criteria used in North Carolina, are not related to community composition. Hydrologic parameters from the second method, e.g. the maximum water table level over a 3-day span, explained much of the variation in nonriverine wet hardwood forest community composition. Our results found that clear relationships do exist between hydrologic regime and community composition. Hydrologic parameters that are related to community composition need to be used as success criteria in future restoration designs. This will ensure that projects establish the appropriate hydrologic regime necessary to foster the desired wetland community type. Copyright © 2011 John Wiley & Sons, Ltd.

Background Magnetic resonance imaging (MRI) of pacemaker patients is contraindicated due to documented potential risks to the patient from hazardous interactions between the MRI and pacemaker system. Objective The purpose of this prospective, randomized, controlled, worldwide clinical trial was to evaluate the safety and effectiveness of a pacemaker system designed for safe use in MRI for any bradycardia indicated patient. Methods Patients (n = 464) were randomized to undergo an MRI scan between 9 and 12 weeks postimplant (MRI group, n=258) or not to undergo MRI (control group, n=206) after successful implantation of the specially designed dual-chamber pacemaker and leads. Patients were monitored for arrhythmias, symptoms, and pacemaker system function during 14 nonclinically indicated relevant brain and lumbar MRI sequences. Sequences were performed at 1.5 T and included scans with high radiofrequency power deposition and/or high gradient dB/dt exposure. Clinical evaluation of the pacemaker system function occurred immediately before and after MRI, 1 week and 1 month post-MRI, and at corresponding times for the control group. Primary endpoints for safety analyzed the MRI procedure complication-free rate and for effectiveness compared capture and sensing performance between MRI and control groups. Results No MRI-related complications occurred during or after MRI, including sustained ventricular arrhythmias, pacemaker inhibition or output failures, electrical resets, or other pacemaker malfunctions. Pacing capture threshold and sensed electrogram amplitude changes were minimal and similar between study groups. Conclusion This trial documented the ability of this pacemaker system to be exposed in a controlled fashion to MRI in a 1.5 T scanner without adverse impact on patient outcomes or pacemaker system function.

Background: Cardiac resynchronization therapy (CRT) has proven to be a valuable therapy addition for patients with drug-refractory heart failure and a ventricular conduction delay. Delivery of CRT is dependent upon the successful implantation and chronic performance of a left ventricular (LV) pacing lead. This study assessed the long-term electrical performance and safety of a steroid-eluting, transvenous, over-the-wire, cardiac vein pacing lead. Methods: The Attain Model 4193 LV lead (Medtronic, Inc, Minneapolis MN, USA) was successfully implanted in 1,070 patients with 286 patients completing 3 years of follow-up. Clinical data were collected at pre-implant, implant, and at 6-month intervals for 3 years. Results: Over 3 years, the mean chronic pacing threshold ranged from 1.9 V to 2.1 V, the mean R-wave sensing amplitudes ranged between 13.6 mV and 15.0 mV, and the mean pacing impedance ranged between 562 ohms and 590 ohms. Additionally, the observed freedom from first post-implant LV-lead-related complications was 90.4%. Of 1,070 total patients, 82 experienced 89 LV-lead-related adverse events requiring invasive interventions or resulting in the termination of the CRT therapy. The LV lead was repositioned in 31 patients, replaced in 21 patients, and explanted/capped in four patients. There were no deaths related to the LV lead during implantation or during the follow-up period. Conclusions: The data suggest that the 4193 LV lead is safe and effective over time. The LV lead electrical measurements remained stable through follow-up, demonstrating reliable long-term performance within the recommended value range at 36 months and had an acceptable complication rate.

PurposeThe purpose of this paper is to report an investigation into the social and citation networks of three information scientists: David Nicholas, Peter Williams and Paul Huntington.Design/methodology/approachSimilarities between citation patterns and social closeness were identified and discussed. A total of 16 individuals in the citation network were identified and investigated using citation analysis, and a matrix formed of citations made between those in the network. Social connections between the 16 in the citation network were then investigated by means of a questionnaire, the results of which were merged into a separate matrix. These matrices were converted into visual social networks, using multidimensional scaling. A new deviance measure was devised for drawing comparisons between social and citation closeness in individual cases.FindingsNicholas, Williams and Huntington were found to have cited 527 authors in the period 2000‐2003, the 16 most cited becoming the subjects of further citation and social investigation. This comparison, along with the examination of visual representations indicates a positive correlation between social closeness and citation counts. Possible explanations for this correlation are discussed, and implications considered. Despite this correlation, the information scientists were found to cite widely outside their immediate social connections.Originality/valueSocial network analysis has not been often used in combination with citation analysis to explore inter‐relationships in research teams.

Objective Single-nucleotide polymorphisms (SNPs) in the SLC22A4 gene encoding the organic cation transporter OCTN1 have been associated with rheumatoid arthritis (RA) in the Japanese population and with Crohn's disease in a Canadian cohort. The RA-associated and Crohn's disease–associated SNPs include, respectively, an intronic variant (slc2F2) and an exonic variant (1672T). We used a case–control approach to investigate the prevalence of these variants in a Canadian RA cohort and to determine whether RA and Crohn's disease share SLC22A4 susceptibility alleles. Methods Nine hundred eighteen unrelated patients with RA, 507 patients with Crohn's disease, and 623 healthy controls were genotyped for the putatively RA-associated slc2F1 and slc2F2 variants and the Crohn's disease–associated SLC22A4 1672T variant. Results Neither slc2F1 nor slc2F2 showed evidence for association with RA, the allele frequencies of these variants being significantly different in the Canadian population compared with those reported in the Japanese population, but not significantly different between patients with RA and controls. In addition, associations between the 1672T Crohn's disease risk allele and RA or between the slc2F1-A and slc2F2-T risk alleles and Crohn's disease were not detected in this study cohort, and the latter 2 alleles were not in linkage disequilibrium with the 1672T variant. Conclusion These observations do not support roles for any of the previously identified SLC22A4 disease risk alleles in RA susceptibility in the Canadian population. The slc2F1/slc2F2 risk alleles were not associated with Crohn's disease nor in linkage disequilibrium with the Crohn's disease–associated 1672T variant, and accordingly, also appear to be irrelevant to Crohn's disease susceptibility in the population under study.

Quite correctly, the majority of road safety speeding initiatives focus on drivers travelling at excessive speeds. This study, however, focused on the potential problem of driving too slowly. Six thousand, four hundred and eighty vehicles from around the Perth metropolitan area in Western Australia had their speeds recorded; observations were also made of these vehicles to identify characteristics of the driver and vehicle. In addition, a community survey with 240 members of the public was conducted to examine their attitudes towards slow drivers. As expected, results showed that older drivers drove more slowly than the other age brackets, women drove more slowly than men, and that heavily laden vehicles drove more slowly than other types of vehicles. Additionally, the slowest days were weekdays and the quickest were Saturdays. Community attitudes, generally mirrored the observational findings, and indicated that the public believed that slow driving was sometimes a safety problem causing some accidents. These data are discussed, and some possible countermeasures are briefly introduced to address the problem.

Objective To introduce a model treatment algorithm for use in the managed care setting as a strategy to provide ongoing disease management and long-term care for patients with multiple sclerosis (MS), with the goal of delaying disease progression and the associated disability and cognitive dysfunction. Summary MS is a chronic inflammatory disorder of the central nervous system that is associated with progressive disability and cognitive dysfunction. Currently, management of MS involves planning an effective long-term treatment strategy that can delay the progression of the disease. This article reviews a typical stepped-care approach to treating MS that is based on the concept of a platform drug, which is an agent that provides baseline immunomodulatory action throughout the course of the disease. Considerations for selecting a platform therapy include the effect on the full spectrum of MS (disability, relapses, lesion load, and atrophy as well as patient compliance and the potential impact of neutralizing antibodies [NAbs]). Currently, 4 first-line therapies are approved for relapsing MS: the 3 interferon beta (IFNbeta) products and glatiramer acetate. Of these, the IFNbetas are generally recommended as platform therapy because all have shown significant effects on relapses, magnetic resonance imaging parameters of the disease, and because intramuscular (i.m.) IFNbeta-1a (Avonex) and subcutaneous (s.c.) IFNbeta-1a (Rebif) have been shown to slow the progression of sustained disability. Patients being treated with IFNbetas can develop NAbs to the drug, which can lead to a loss of efficacy and subsequent occurrence of breakthrough disease. The 3 different formulations of IFNbeta are associated with a varying incidence of NAbs (i.m. IFNbeta-1a, 5%; s.c. IFNbeta-1a, 24%; IFNbeta-1b [Betaseron], 45%). Antibodies also form against glatiramer acetate, although their clinical significance needs to be elucidated. As the disease progresses or has periods of aggressive activity, the stepped-care approach is to add other agents onto the platform therapy to improve control of the disease. Conclusion Stepped care, as outlined in this model treatment algorithm for the managed care setting, is an effective method to achieve the fundamental goal of MS treatment, that is, to delay disease progression and the associated disability and cognitive impairment.

Various organic acids, ultrasonic instruments, and lasers have been used to remove the smear layer from the surface of instrumented root canals. The purpose of this study was to investigate the effect of a mixture of a tetracycline isomer, an acid, and a detergent (MTAD) as a final rinse on the surface of instrumented root canals. Forty-eight extracted maxillary and mandibular single-rooted human teeth were prepared by using a combination of passive step-back and rotary 0.04 taper nickel-titanium files. Sterile distilled water or 5.25% sodium hypochlorite was used as intracanal irrigant. The canals were then treated with 5 ml of one of the following solutions as a final rinse: sterile distilled water, 5.25% sodium hypochlorite, 17% EDTA, or a new solution, MTAD. The presence or absence of smear layer and the amount of erosion on the surface of the root canal walls at the coronal, middle, and apical portion of each canal were examined under a scanning electron microscope. The results show that MTAD is an effective solution for the removal of the smear layer and does not significantly change the structure of the dentinal tubules when canals are irrigated with sodium hypochlorite and followed with a final rinse of MTAD.