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Integrating Artificial Intelligence (AI) has opened up new possibilities for enhancing patient outcomes, diagnostic accuracy, and advancing medical research. In particular, the integration of AI in pediatric surgery has broadened the horizons of the field. However, with these developments come important ethical considerations that must be at the forefront of AI integration into medicine. While AI is crucial for innovative developments, it brings with it the potential for ethical conundrums associated with its use in patient care. There have been advancements in the use of AI, including its incorporation with surgical robots to its utilization with (electronic medical record) EMR for data comparisons, AI is undoubtedly beneficial in many regards. However, particular considerations are specific to the field of pediatric surgery, including the consent process. Obtaining informed consent and guardian/ parental permission for child’s intervention is of utmost importance. It involves the patient (a minor with variable capacity to comprehend the indications or procedures), the parents or guardians, and the provider(s). Given that AI may play a significant role in the care provided, discussion of this involvement of AI in the generation of treatment plans or delivery of procedures, adds a layer of complexity to the consent process. This complexity should be considered through the lens of the ethical principles commonly associated with the practice of medicine such, justice, non-maleficence, beneficence and patient autonomy. Herein we explore the impact of AI into medicine and pediatric surgery from an ethical standpoint. We seek to critically evaluate the interplay of ethical principles with technological advancements while considering the implications for providers and patients.

Microbial food spoilage is a major contributor to food waste and, hence, to the negative environmental sustainability impacts of food production and processing. Globally, it is estimated that 15–20% of food is wasted, with waste, by definition, occurring after primary production and harvesting (for example, in households and food service establishments). Although the causative agents of food spoilage are diverse, many microorganisms are major contributors across different types of foods. For example, the genus Pseudomonascauses spoilage in various raw and ready-to-eat foods. Aerobic sporeformers (for example, members of the genera Bacillus, Paenibacillusand Alicyclobacillus) cause spoilage across various foods and beverages, whereas anaerobic sporeformers (for example, Clostridiales) cause spoilage in a range of products that present low-oxygen environments. Fungi are also important spoilage microorganisms, including in products that are not susceptible to bacterial spoilage due to their low water activity or low pH. Strategies that can reduce spoilage include improved control of spoilage microorganisms in raw material and environmental sources as well as application of microbicidal or microbiostatic strategies (for example, to products and packaging). Emerging tools (for example, systems models and improved genomic tools) represent an opportunity for rational design of systems, processes and products that minimize microbial food spoilage.

AbstractSeveral configurations for the core and pedestal plasma are examined for a predefined tokamak design by implementing multiple heating/current drive (H/CD) sources to achieve an optimum configuration of high fusion power in a noninductive operation while maintaining an ideally magnetohydrodynamic (MHD) stable core plasma using the IPS-FASTRAN framework. IPS-FASTRAN is a component-based lightweight coupled simulation framework that is used to simulate magnetically confined plasma by integrating a set of high-fidelity codes to construct the plasma equilibrium (EFIT, TOQ, and CHEASE), calculate the turbulent heat and particle transport fluxes (TGLF), model various H/CD systems (TORIC, TORAY, GENRAY, and NUBEAM), model the pedestal pressure and width (EPED), and estimate the ideal MHD stability (DCON). The TGLF core transport model and EPED pedestal model are used to self-consistently predict plasma profiles consistent with ideal MHD stability and H/CD (and bootstrap) current sources. In order to evaluate the achievable and sustainable plasma beta, varying configurations are produced ranging from the no-wall stability to with-wall stability regimes, simultaneously subject to the self-consistent TGLF, EPED, and H/CD source profile predictions that optimize configuration performance. The pedestal density, plasma current, and total injected power are scanned to explore their impact on the target plasma configuration, fusion power, and confinement quality. A set of fully noninductive scenarios are achieved by employing ion-cyclotron, neutral beam injection, helicon, and lower-hybrid H/CDs to provide a broad profile for the total current drive in the core region for a predefined tokamak design. These noninductive scenarios are characterized by high fusion gain (Q ~ 4) and power (Pfus~ 600 MW), optimum confinement quality (H98~ 1.1), and high bootstrap current fraction (fBS~ 0.7) for Greenwald fraction below unity. The broad current profile configurations identified are stable to low-n kink modes either because the normalized pressure βis below the no-wall limit or a wall is present.

Black yeasts can survive extreme conditions in food production because of their polyextremotolerant character. However, significant strain-to-strain variation in black yeast thermoresistance has been observed. In this study, we assessed the variability in tolerance to nonthermal interventions among a collection of food-related black yeast strains. Variation in tolerance to UV light treatment, high pressure processing (HPP), sanitizers, and osmotic pressure was observed within each species. The two strains previously shown to possess high thermotolerance, Exophiala phaeomuriformisFSL-E2-0572 and Exophiala dermatitidisYB-734, were also the most HPP tolerant but were the least halotolerant. Meanwhile, Aureobasidium pullulansFSL-E2-0290 was the most UV and sanitizer tolerant but had been shown to have relatively low thermoresistance. Fisher's exact tests showed that thermoresistance in black yeasts was associated with HPP tolerance and inversely with halotolerance, but no association was found with UV tolerance or sanitizer tolerance. Collectively, the relative stress tolerance among strains varied across interventions. Given this variation, different food products are susceptible to black yeast spoilage. In addition, different strains should be selected in challenge studies specific to the intervention.

In 2019, Vancouver International Airport conducted a precast concrete panel replacement pilot project on Taxiway Victor to establish whether precast concrete was a viable option for a planned runway repair project. This was the first major use of precast airfield pavement in North America in nearly 20 years. Twelve panels measuring 6 m × 7.5 m with a thickness of 360 mm and weighing up to 43 metric tons each were installed to demonstrate the viability of in-situ concrete panel replacement in 8-h night work windows. The panels were designed as heavily reinforced “ductile slabs”; conventional pavement design procedures would have required much greater slab thickness and removal/replacement of base material, which would have greatly slowed panel replacements. Load transfer was provided by 38-mm diameter galvanized steel dowels, which were spaced nonuniformly along each panel edge. The use of bottom slots presented a clean surface with minimal potential for foreign object damage. Five of the panels included embedded airfield light cans, which required great placement precision to ensure their proper alignment and function. Seven of the panels were nonplanar, requiring a special first-of-its-kind warped casting bed that was large enough to produce nonplanar airfield-sized panels to the specified fabrication tolerances. Many valuable lessons were learned during this pilot project, which confirmed that long-life jointed precast concrete pavement repairs could be successfully constructed in 8-h overnight work windows on an active airfield using large repair panels and doweled joints, while adhering to strict panel-to-panel elevation tolerances.

Black yeasts are a functional group that has caused spoilage in cold-filled and hot-filled beverages, as well as other water activity–controlled food products. We established quantitative thermoresistance parameters for the inactivation of 12 Aureobasidiumand Exophialaisolates through isothermal experiments and a challenge study. Culture age (2 versus 28 days) variably affected the thermoresisitance among the black yeast strains. Variation in thermoresistance exists within each genus, but the two most resistant strains were the Exophialaisolates. The two most heat-resistant isolates were Exophiala phaeomuriformisFSL-E2-0572, with a D60-value of 7.69±0.63 min in 28-day culture and Exophiala dermatitidisYB-734, with a D60-value of 16.32±2.13 min in 28-day culture. Although these thermoresistance levels were, in some cases, greater than those for conidia and vegetative cells from other common food spoilage fungi, they were much more sensitive than the ascospores of heat-resistant molds most associated with spoilage of hot-filled products. However, given that black yeasts have caused spoilage in hot-filled products, we hypothesized that this intermediate degree of thermoresistance may support survival following introduction during active cooling before package seals have formed. A challenge study was performed in an acidic (apple cider) and water activity–controlled (maple syrup) product to evaluate survival. When apple cider was hot filled at 82°C, black yeast counts were reduced by 4.1 log CFU/mL 24 h after the heat treatment, but the survivors increased up to 6.7 log CFU/mL after 2 weeks. In comparison, the counts were below the detection limit after both 24 h and 14 days of shelf life in both products when filled at the boiling points. This suggests that ensuring water microbial quality in cooling tunnels and nozzle sanitation may be essential in mitigating the introduction of these fungi.

A data set consisting of 376 broadband and long‐period MT measurements was used to generate the first ever 3D resistivity model of the Archean western Superior Craton. The modeled resistivity structure is compared to coincident seismic reflection data. The observed geophysical signatures are interpreted within the context of the late stages of crustal growth and cratonization of the region via the progressive accretion of terranes against the initial cratonic core. The northern‐most terranes comprising the cratonic core exhibit a nearly homogenous highly resistive crust. The lower crust of the southern terranes contains largely continuous low resistivity bands which run subparallel to major terrane boundaries and corresponding fault systems. In some cases, low resistivity features are coincident with dense packages of sub‐horizontal to listric reflections within the mid‐ to lower crust. These resistivity structures are inferred to represent preserved geoelectric signatures of late to post‐orogenic magmatic pulses likely related to delamination of locally overthickened crust. Increased mantle heat flow resulted in partial melting of the lower crust and upper mantle and upward migration of CO2‐rich melts and fluids through crustal weak zones corresponding to shear and/or suture zones formed during terrane amalgamation. Thermal softening of the mid‐ to lower crust led to orogenic collapse and reactivation of the crustal shear zones, resulting in formation and interconnection of graphitic films which were preserved within the stable craton. These results have implications for the tectono‐magmatic history of the western Superior Craton, as well toward the understanding of the geodynamic regime of the Archean Earth. The present day geophysical signatures of cratons, ancient continents which formed and have remained stable since the Archean roughly 2.5–4.0 billion years ago, may be used to investigate the tectonic processes that were active during their formation. Here, we combine magnetotelluric (MT) and seismic data to investigate the crust and upper‐most mantle structure of the western Superior Craton of Canada. A 3D resistivity volume of the region derived from the MT data maps electrically conductive zones within the lower crust which overlap with zones of high seismic reflectivity, and are spatially correlated with major geological terrane boundaries. These signatures are interpreted as representing electrically conductive graphite and/or sulphidic films emplaced within deep crustal shear zones as a result of crustal collapse and magmatic activity during the late stages of construction and stabilization of the Superior Craton. Our results have implications for our understanding of the processes responsible for the formation of these ancient continents. First large‐scale 3D resistivity model of the Archean western Superior Craton reveals ∼east‐west trending low resistivity features at lower‐crustal depthsConductive features coincident with listric to sub‐horizontal seismic reflections, suggestive of mid‐ to lower crustal shear zonesPreserved geophysical signatures are indicative of late Archean tectono‐magmatic processes First large‐scale 3D resistivity model of the Archean western Superior Craton reveals ∼east‐west trending low resistivity features at lower‐crustal depths Conductive features coincident with listric to sub‐horizontal seismic reflections, suggestive of mid‐ to lower crustal shear zones Preserved geophysical signatures are indicative of late Archean tectono‐magmatic processes

AbstractWith his administration’s shift away from reactionary anti-communism, concern about American support for right-wing dictators, and expressed commitment to welcome nationalist movements rooted in in self-determination, John F. Kennedy had the potential to be the first US president to prioritize human rights abroad. He had spoken out against colonialism and in favor of human rights as a member of Congress and a presidential candidate. In office, however, he yielded to other foreign policy priorities. Analyzing his administration’s record on human rights reveals the Cold War utility of human rights rhetoric and the limits to US support for human rights in these years.

ABSTRACTNeolocalism has much to offer the local development literature. Highly discussed in the food and beverage tourism literature, neolocalism has shown merits for marketing place-based aspects of craft beverages to tourists and locals alike; however, few offer cautions against neolocalism, its limits, and its dark side. This article specifically examines how neolocalism is expressed among 41 breweries in the Finger Lakes region of New York. This article employs accessible research methods to identify expressions of neolocalism and to create a rubric to assess neolocalism, including location, naming, and storytelling. Using an online platform for consumer ratings, neolocalism correlated with brewery ratings in addition to other brewery attributes and beer ratings evaluated. Exemplars of neolocalism are featured, so others can see more in-depth examples of how it is expressed. Finally, implications for future research, policy, and practice are shared highlighting the merits and cautions regarding neolocalism.

•We update the national estimates of emergency department (ED) visits for sickle cell disease in the U.S.•Overall volume of ED visits increased by nearly 13% from prior national estimates.•Pain remains the top patient-cited reason for visiting the ED.•Medicaid and Medicare covered most (72%) ED visits.•Average time spent in the ED increased by about an hour from prior estimates.

Psychrotolerant growth of Listeria monocytogenesin ready-to-eat (RTE) foods increases the risk to food safety, particularly when spoilage does not occur prior to L. monocytogenesgrowth of >1 log CFU/g. The purpose of this study was to evaluate the relative rates of quality deterioration and L. monocytogenesgrowth in six product systems (tomatoes, apples, fresh-cut cantaloupe, fresh-cut lettuce, baby spinach, and commercially processed turkey slices) under various conditions of refrigeration temperatures, atmospheres, and quality. Cantaloupe and spinach leaves supported >1 log CFU/g growth of L. monocytogenesbefore product spoilage at both 4 and 9°C. In some cases, conditions that improved microbial quality by extending shelf life also allowed L. monocytogenesgrowth of >1 log CFU/g before deterioration due to microbial spoilage. For example, storage with modified atmosphere packaging enhanced L. monocytogenesgrowth relative to spoilage microbiota in lettuce leaves (1.0-log increase 7 days before spoilage). In contrast, the use of secondary quality produce (i.e., apples, tomatoes, and lettuce with physical damage) reduced shelf life and, consequently, limited the time for L. monocytogenesproliferation. Therefore, spoilage cannot be considered a fail-safe indicator or proxy for limitation of shelf life across refrigerated RTE products.

Objective: Several states are building infrastructure and data collection methods for longitudinal, population-based surveillance systems for selected hemoglobinopathies. The objective of our study was to improve an administrative case definition for sickle cell disease (SCD) to aid in longitudinal surveillance.Methods: We collected data from 3 administrative data sets (2004-2008) on 1998 patients aged 0-21 in Georgia who had ≥1 encounter in which an SCD International Classification of Diseases, Ninth Revision, Clinical Modification(ICD-9-CM) code was recorded, and we compared these data with data from a laboratory and medical record review. We assessed performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of case definitions that differed by number and type of SCD-coded encounters; addition of SCD-associated treatments, procedures, and complications; and length of surveillance (1 vs 5 years). We identified correct diagnoses for patients who were incorrectly coded as having SCD.Results: The SCD case definition of ≥3 SCD-coded encounters in 5 years simplified and substantially improved the sensitivity (96.0% vs 85.8%) and NPV (68.2% vs 38.2%) of the original administrative case definition developed for 5-year, state-based surveillance (≥2 encounters in 5 years and ≥1 encounter for an SCD-related treatment, procedure, or complication), while maintaining a similar PPV (97.4% vs 97.4%) and specificity (76.5% vs 79.0%).Conclusions: This study supports an administrative case definition that specifies ≥3 ICD-9-CM–coded encounters to identify SCD with a high degree of accuracy in pediatric patients. This case definition can be used to help establish longitudinal SCD surveillance systems.

Machinery mold is a foodborne fungus associated with spoilage of fruit and vegetable products, as well as colonization of the food production environment. Galactomycesspp. are not considered heat-resistant molds, although their sensitivity to mild heat treatments, like blanching and pasteurization, as well as to nonthermal treatments, like high pressure processing (HPP), remains unknown. Cultures of two Galactomycesspp. isolates, Galactomyces geotrichumand Galactomyces candidum,were heat treated at 50, 53, and 55°C and HPP treated at 4°C for 90 s at 300, 400, and 600 MPa. The 2-day-old G. geotrichumhad a D-value of 0.99±0.04 min and 28-day-old G. geotrichumhad a D-value of 1.28±0.07 min at 55°C. Meanwhile, 2-day-old G. candidumhad a D-value of 3.13±0.20 min and 28-day-old G. candidumhad a D-value of 1.60±0.01 min at 55°C. Overall, the significant differences in D-values between the two cultivation times were modest, and statistical significance was not consistent across all three temperatures. However, the differences were more pronounced at higher processing temperatures. G. geotrichumwas only reduced by 0.32±0.07 log CFU/mL after 90 s at 300 MPa. However, increasing the treatment level to 400 MPa for 90 s decreased the counts for G. geotrichumto below the limit of detection (<1 log CFU/mL) following HPP treatment. Meanwhile, the counts for G. candidumsurvivors at 400 MPa were 1.36±0.08 log CFU/mL and were under the limit of detection at 600 MPa for 90 s. Based on the findings in this study, machinery mold contaminants would be readily inactivated by the processing conditions used to target a 5-log reduction in the bacterial pathogen of concern.

Bonded concrete overlays of asphalt pavements (BCOA) consist of a concrete overlay placed on an existing asphalt or composite pavement. This technique is intended as a cost-effective rehabilitation solution for marginally distressed in-service asphalt or composite pavements. BCOA with panel sizes between 4.5 ft and 8.5 ft have become popular as they reduce curling stresses while keeping the longitudinal joints out of the wheelpath. The BCOA-ME (mechanistic empirical) design procedure and Pavement ME short jointed plain concrete pavement (SJPCP) module can both be used to design BCOA with mid-size panels. However, these design procedures differ in the assumptions used to develop the mechanistic computational model, fatigue models used to predict failure, treatment of environmental conditions, estimate of asphalt stiffness, consideration of structural fibers, the application of traffic loading, and the calibration process. This results in the procedures producing different overlay thicknesses and predicted distresses. The strengths and limitations of each procedure are evaluated and comparisons are made between the design thicknesses obtained from them.

Food processing, packaging, and formulation strategies are often specifically designed to inhibit or control microbial growth to prevent spoilage. Some of the most restrictive strategies rely solely or on combinations of pH reduction, preservatives, water activity limitation, control of oxygen tension, thermal processing, and hermetic packaging. In concert, these strategies are used to inactivate potential spoilage microorganisms or inhibit their growth. However, for select microbes that can overcome these controls, the lack of competition from additional background microbiota helps facilitate their propagation.

ABSTRACTMilitary personnel frequently report various physical and psychological complaints including somatic symptoms, bodily pain, depression, posttraumatic stress disorder, and physical role limitation. This study aimed to identify how psychological symptoms, somatic complaints, and physical role limitations are associated with each other in a sample of 207 male Air Force pararescue personnel and combat rescue officers. Results of a moderated mediation model indicated that the interaction of depression and somatic symptoms was associated with significantly more severe pain, which was, in turn, associated with greater physical role limitations. Pathways from posttraumatic stress disorder and the depression-by-somatic symptoms interaction to physical role limitation were both fully mediated by bodily pain. These findings (a) highlight the importance of assessing physical and psychological symptoms when individuals report impaired physical role limitation and (b) help to clarify the complex interplay of emotional and physical health conditions among elite military personnel.

Some species of Alicyclobacillusspoil beverages by producing guaiacol. Current culture-based methods detect the presence of Alicyclobacillusspp. and a subsequent peroxidase assay determines if the isolate can produce guaiacol. However, these methods are time consuming and can yield false negatives due to differences in growth optima among species. The purpose of this study was to compare a RT-PCR-based method, the GENE-UP® PRO ACB assay, to the IFU Method No. 12 Enumeration and Enrichment methods. Ten species of Alicyclobacilluswere detected using the tested RT-PCR assay, while A. dauciand A. kakegewensiswere not detected using either IFU protocol. Low concentrations (1-10, 10-100, and 100-1,000 CFU/10 ml) of A. acidoterrestris, A. suci, and A. acidocaldariuswere tested in five matrices. The proportion of positive samples identified using the tested RT-PCR assay (62/84) or the IFU Enrichment protocol (62/84) did not differ significantly from the proportion of inoculated samples (63/84). However, the IFU Enumeration method (32/84) detected statistically fewer positives. Additionally, methods identifying guaiacol production were compared. The proportion of correctly identified guaiacol producers using the tested RT-PCR assay (51/63) was not significantly different than those identified using the 3 h Cosmo Bio assay (54/63). Finally, four commercial samples of orange juice and sucrose solution were tested. Alicyclobacillusspp. were identified in all four samples using the IFU Enrichment method and in two samples using the tested RT-PCR assay. However, Alicyclobacilluswas not detected in any sample using the IFU Enumeration method. Overall, this study showed consistent detection of Alicyclobacillusspp. using either the IFU Enrichment protocol or the tested RT-PCR assay, which both outperformed the IFU Enumeration protocol. Both the 3 h guaiacol bioassay and the tested RT-PCR assays consistently differentiated guaiacol producing and non-producing strains.

•Emergency department overcrowding is a worldwide problem.•Over 40% of emergency department patients require specialty consultations.•Consultation to decision time increases wait times significantly.•A completed workup prior to consultation decreases wait times significantly.

Breast cancer is the leading cause of cancer-related deaths among women. Approximately 75% of breast cancers are estrogen receptor-a (ERa) positive, underscoring the dependence of cancer cells on estrogen for growth and survival. Patients treated with endocrine therapy often develop resistance, either de novoor acquired, which in some cases is caused by aberrations within the growth factor signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) has emerged as a critical node in estrogenic signaling. We have previously shown that mTORC1 can phosphorylate and activate ERa on S167 via its effector—the 40S ribosomal S6 kinase 1 (S6K1). Presently, we have uncovered a direct link between mTORC1 and ERa. We found that ERa binds to regulatory-associated protein of mTOR (Raptor) and causes it to translocate to the nucleus upon estrogen stimulation. In addition, we identified mTOR as the kinase that phosphorylates ERa on S104/106 and activates transcription of ER target genes. Our findings show a direct link between mTORC1 and ERa, which further implicates mTORC1 signaling in the pathogenesis of ER-positive breast cancer and provides rationale for FDA-approved use of mTORC1 inhibitors in combination with endocrine agents for treatment of this disease.

Bupivacaine appears to have a duration of action longer than previously reported. Results of this study demonstrate that the addition of buprenorphrine may enhance the analgesic duration of effect for bupivacaine regional nerve blocks. In addition, the use of bupivacaine alone may have analgesia that exceeds 24 hours in many cases. Although not statistically significant based on sample size, 50% of dogs receiving the bupivacaine/buprenorphine regional anesthetic block demonstrated a decreased anesthetic requirement 48 hours postadministration when compared to 25% of dogs receiving the bupivacaine anesthetic. No adverse cardiorespiratory effects were noted secondary to either local anesthetic treatment. Use of bupivacaine may have analgesic effects extending greater than 24 hours (24-72) when used in regional anesthetic blocks in veterinary dental patients with acute dental pain. The addition of buprenorphine to bupivacaine may extend the duration of analgesia (48-96 h). The limited sample size, in addition to patient variability in response to medications, may account for the fact that no differences were detected between the treatments administered.

Objective. Population-based surveillance data from California and Georgia for years 2004 through 2008 were linked to state death record files to determine the all-cause death rate among 12,143 patients identified with sickle cell disease (SCD).Methods. All-cause death rates, by age, among these SCD patients were compared with all-cause death rates among both African Americans and the total population in the two states. All-cause death rates were also compared with death rates for SCD derived from publicly available death records: the compressed mortality files and multiple cause of death files.Results. Of 12,143 patients identified with SCD, 615 patients died. The all-cause mortality rate for the SCD population was lower than the all-cause mortality rate among African Americans and similar to the total population all-cause mortality rates from birth through age 4 years, but the rate was higher among those with SCD than both the African American and total population rates from ages 5 through 74 years. The count of deceased patients identified by using population-based surveillance data (n=5615) was more than twice as high as the count identified in compressed mortality files using SCD as the underlying cause of death alone (n=5297).Conclusion. Accurate assessment of all-cause mortality and age at death requires long-term surveillance via population-based registries of patients with accurately diagnosed SCD.

AASHTOWare Pavement ME Design, software developed from the AASHTO Mechanistic–Empirical Pavement Design Guide(MEPDG), uses performance data extracted primarily from the long-term pavement performance database to calibrate the performance prediction models for rigid pavements. In this study, factorial designs were generated as a subset of the national rigid pavement database for calibration of the MEPDG rigid pavement performance models. Three separate factorial designs were included for each rigid pavement performance model for (a) jointed plain concrete pavement (JPCP) transverse cracking, (b) JPCP faulting (doweled and undoweled), and (c) continuously reinforced concrete pavement punchouts. Experimental design variables for each model were selected to provide the broadest possible representation of key design, construction, and environmental features. The three performance models were then calibrated with the developed factorial matrices. The results were presented along with the calibration procedure. A validation of the calibrated models was then conducted with sites not included in the factorial matrices. An evaluation compared design slab thicknesses required to meet specified performance criteria determined with these and other previously established calibration coefficients. Finally, conclusions and recommendations based on the experiences gained conducting this study are provided.

A recent medicinal chemistry campaign to identify positive allosteric modulators (PAMs) of metabotropic glutamate receptor subtype 5 (mGluR5) led to the discovery of potent compounds featuring an oxazolidinone structural core flanked by biaryl acetylene and haloaryl moieties. However, biotransformation studies of some of these mGluR5 PAMs demonstrated the formation of glutathione (GSH) conjugates. The conjugates in question were formed independently of NADPH as the main products in liver microsomes and liver cytosol (rat and human) and exhibited masses that were 307 u greater than their respective substrates, indicating the involvement of a reductive step in the formation of these metabolites. To further characterize the relevant metabolic sequences, GSH conjugates of (4R,5R)-5-(3-fluorophenyl)-4-(5-(pyrazin-2-ylethynyl)pyridin-3-yl)oxazolidin-2-one and (4R,5R)-5-(4-fluorophenyl)-4-(6-((3-fluoropyridin-2-yl)ethynyl)pyridin-2-yl)oxazolidin-2-one were biosynthesized and isolated. Subsequent analysis by NMR showed that GSH had reacted with the acetylene carbon atoms of these mGluR5 PAMs, suggesting a conjugate addition mechanism and implicating cytosolic and microsomal GSH S-transferases (GSTs) in catalysis. Interestingly, five closely related mGluR5 PAMs were not similarly prone to the formation of GSH conjugates in vitro. These compounds also featured acetylenes, but were flanked by either phenyl or cyclohexyl rings, which indicated that the formation of GSH conjugates was influenced by proximal functional groups that modulated the electron density of the triple bond and/or differences in enzyme-substrate specificity. These results informed an ongoing drug-discovery effort to identify mGluR5 PAMs with drug-like properties and a low risk of reactivity with endogenous thiols.

Hudson Bay Lithospheric Experiment (HuBLE) was designed to understand the processes that formed Laurentia and the Hudson Bay basin within it. Receiver function analysis shows that Archaean terranes display structurally simple, uniform thickness, felsic crust. Beneath the Palaeoproterozoic Trans-Hudson Orogen (THO), thicker, more complex crust is interpreted as evidence for a secular evolution in crustal formation from non-plate-tectonic in the Palaeoarchaean to fully developed plate tectonics by the Palaeoproterozoic. Corroborating this hypothesis, anisotropy studies reveal 1.8 Ga plate-scale THO-age fabrics. Seismic tomography shows that the Proterozoic mantle has lower wavespeeds than surrounding Archaean blocks; the Laurentian keel thus formed partly in post-Archaean times. A mantle transition zone study indicates ‘normal’ temperatures beneath the Laurentian keel, so any cold mantle down-welling associated with the regional free-air gravity anomaly is probably confined to the upper mantle. Focal mechanisms from earthquakes indicate that present-day crustal stresses are influenced by glacial rebound and pre-existing faults. Ambient-noise tomography reveals a low-velocity anomaly, coincident with a previously inferred zone of crustal stretching, eliminating eclogitization of lower crustal rocks as a basin formation mechanism. Hudson Bay is an ephemeral feature, caused principally by incomplete glacial rebound. Plate stretching is the primary mechanism responsible for the formation of the basin itself.

AbstractThe advanced physics and advanced technology tokamak power plant ARIES-ACT1 has a major radius of 6.25 m at an aspect ratio of 4.0, toroidal field of 6.0 T, strong shaping with elongation of 2.2, and triangularity of 0.63. The broadest pressure cases reached wall-stabilized βN ∼ 5.75, limited by n = 3 external kink mode requiring a conducting shell at b/a = 0.3, requiring plasma rotation, feedback, and/or kinetic stabilization. The medium pressure peaking case reaches βN= 5.28 with BT= 6.75, while the peaked pressure case reaches βN< 5.15. Fast particle magnetohydrodynamic stability shows that the alpha particles are unstable, but this leads to redistribution to larger minor radius rather than loss from the plasma. Edge and divertor plasma modeling shows that 75% of the power to the divertor can be radiated with an ITER-like divertor geometry, while =95% can be radiated in a stable detached mode with an orthogonal target and wide slot geometry. The bootstrap current fraction is 91% with a q95of 4.5, requiring ∼1.1 MA of external current drive. This current is supplied with 5 MW of ion cyclotron radio frequency/fast wave and 40 MW of lower hybrid current drive. Electron cyclotron is most effective for safety factor control over ρ ∼ 0.2 to 0.6 with 20 MW. The pedestal density is ∼0.9×1020/m3, and the temperature is ∼4.4 keV. The H98factor is 1.65, n/nGr= 1.0, and the ratio of net power to threshold power is 2.8 to 3.0 in the flattop.

AbstractTokamak power plants are studied with advanced and conservative design philosophies to identify the impacts on the resulting designs and to provide guidance to critical research needs. Incorporating updated physics understanding and using more sophisticated engineering and physics analysis, the tokamak configurations have developed a more credible basis compared with older studies. The advanced configuration assumes a self-cooled lead lithium blanket concept with SiC composite structural material with 58% thermal conversion efficiency. This plasma has a major radius of 6.25 m, a toroidal field of 6.0 T, a q95of 4.5,a βtotalNof 5.75, an H98of 1.65, an n/nGrof 1.0, and a peak divertor heat flux of 13.7 MW/m2. The conservative configuration assumes a dual-coolant lead lithium blanket concept with reduced-activation ferritic martensitic steel structural material and helium coolant, achieving a thermal conversion efficiency of 45%. The plasma has a major radius of 9.75 m, a toroidal field of 8.75 T, a q95of 8.0, a βtotalNof 2.5, an H98of 1.25, an n/nGrof 1.3, and a peak divertor heat flux of 10 MW/m2. The divertor heat flux treatment with a narrow power scrape-off width has driven the plasmas to larger major radius. Edge and divertor plasma simulations are targeting a basis for high radiated power fraction in the divertor, which is necessary for solutions to keep the peak heat flux in the range 10 to 15 MW/m2. Combinations of the advanced and conservative approaches show intermediate sizes. A new systems code using a database approach has been used and shows that the operating point is really an operating zone with some range of plasma and engineering parameters and very similar costs of electricity. Other papers in this issue provide more detailed discussion of the work summarized here.

AASHTOWare Pavement ME Design, software developed from the AASHTO Mechanistic–Empirical Pavement Design Guide (MEPDG), uses performance data extracted primarily from the long-term pavement performance database to calibrate the performance prediction models for rigid pavements. In this study, factorial designs were generated as a subset of the national rigid pavement database for calibration of the MEPDG rigid pavement performance models. Three separate factorial designs were included for each rigid pavement performance model for (a) jointed plain concrete pavement (JPCP) transverse cracking, (b) JPCP faulting (doweled and undoweled), and (c) continuously reinforced concrete pavement punchouts. Experimental design variables for each model were selected to provide the broadest possible representation of key design, construction, and environmental features. The three performance models were then calibrated with the developed factorial matrices. The results were presented along with the calibration procedure. A validation of the calibrated models was then conducted with sites not included in the factorial matrices. An evaluation compared design slab thicknesses required to meet specified performance criteria determined with these and other previously established calibration coefficients. Finally, conclusions and recommendations based on the experiences gained conducting this study are provided.

Health-related technology, its relevance, and its availability are rapidly evolving. Technology offers great potential to minimize and/or mitigate barriers associated with achieving optimal health, performance, and readiness. In support of the U.S. Army Surgeon General's vision for a "System for Health" and its Performance Triad initiative, the U.S. Army Telemedicine and Advanced Technology Research Center hosted a workshop in April 2013 titled "Incentives to Create and Sustain Change for Health." Members of government and academia participated to identify and define the opportunities, gain clarity in leading practices and research gaps, and articulate the characteristics of future technology solutions to create and sustain real change in the health of individuals, the Army, and the nation. The key factors discussed included (1) public health messaging, (2) changing health habits and the environmental influence on health, (3) goal setting and tracking, (4) the role of incentives in behavior change intervention, and (5) the role of peer and social networks in change. This report summarizes the recommendations on how technology solutions could be employed to leverage evidence-based best practices and identifies gaps in research where further investigation is needed.

Background:In a previously reported split‐mouth, randomized controlled trial, Miller Class II gingival recession defects were treated with either a connective tissue graft (CTG) (control) or recombinant human platelet‐derived growth factor‐BB + β‐tricalcium phosphate (test), both in combination with a coronally advanced flap (CAF). At 6 months, multiple outcome measures were examined. The purpose of the current study is to examine the major efficacy parameters at 5 years. Methods:Twenty of the original 30 patients were available for follow‐up 5 years after the original surgery. Outcomes examined were recession depth, probing depth, clinical attachment level (CAL), height of keratinized tissue (wKT), and percentage of root coverage. Within‐ and across‐treatment group results at 6 months and 5 years were compared with original baseline values. Results:At 5 years, all quantitative parameters for both treatment protocols showed statistically significant improvements over baseline. The primary outcome parameter, change in recession depth at 5 years, demonstrated statistically significant improvements in recession over baseline, although intergroup comparisons favored the control group at both 6 months and 5 years. At 5 years, intergroup comparisons also favored the test group for percentage root coverage and change in wKT, whereas no statistically significant intergroup differences were seen for 100% root coverage and changes to CAL. Conclusions:In the present 5‐year investigation, treatment with either test or control treatments for Miller Class II recession defects appear to lead to stable, clinically effective results, although CTG + CAF resulted in greater reductions in recession, greater percentage of root coverage, and increased wKT.

Objective The purpose of this study was to assess the feasibility of an endoscopic, optical-fiber-based, laser delivery system (LDS) developed to perform sole-therapy transmyocardial revascularization (TMR) in a totally endoscopic, robotically assisted operation.Methods Forty-two patients were enrolled in a multicenter, prospective, single-arm clinical trial conducted at four US centers between 2005 and 2007. Transmyocardial revascularization was performed completely endoscopically with robotic assistance, introducing the Holmium:Yttrium aluminum garnet (YAG) LDS via a 5-mm port. Completion of the operation endoscopically defined procedural success. Clinical data were recorded before, during, and at least 30 days after the procedure.Results All patients had Canadian Cardiovascular Score angina class IV at baseline. The mean ejection fraction was 49% (range [R], 28–71), the mean age was 59.1 years (R, 36–80), 71% (30/42) were men, 86% (36/42) underwent previous coronary artery bypass grafting surgery, and 76% (32/42) underwent prior coronary stenting. Procedural success was accomplished in 93% (39/42). For the procedural successes, the mean number of TMR channels was 32 (R, 16–50), the median operative time was 88 minutes (R, 48–250 minutes), and the median length of stay postoperatively was 2.5 days (R, 1–10). There was no operative or 30-day mortality, and no patient received any transfusion. At 30 days, freedom from major adverse cardiac events was 95% (two patients had transient congestive heart failure). At the median 6-month follow-up (single-center data, n = 12), the mean (SD) Canadian Cardiovascular Score angina score was 1.3 (0.05) (P< 0.001 vs baseline).Conclusions Robotically assisted TMR can be performed using an endoscopic, optical-fiber-based LDS, with high procedural success, avoidance of early adverse clinical events, and potential for successful angina relief.

Objective The purpose of this study was to assess the feasibility of an endoscopic, optical-fiber-based, laser delivery system (LDS) developed to perform sole-therapy transmyocardial revascularization (TMR) in a totally endoscopic, robotically assisted operation.Methods Forty-two patients were enrolled in a multicenter, prospective, single-arm clinical trial conducted at four US centers between 2005 and 2007. Transmyocardial revascularization was performed completely endoscopically with robotic assistance, introducing the Holmium:Yttrium aluminum garnet (YAG) LDS via a 5-mm port. Completion of the operation endoscopically defined procedural success. Clinical data were recorded before, during, and at least 30 days after the procedure.Results All patients had Canadian Cardiovascular Score angina class IV at baseline. The mean ejection fraction was 49% (range [R], 28–71), the mean age was 59.1 years (R, 36–80), 71% (30/42) were men, 86% (36/42) underwent previous coronary artery bypass grafting surgery, and 76% (32/42) underwent prior coronary stenting. Procedural success was accomplished in 93% (39/42). For the procedural successes, the mean number of TMR channels was 32 (R, 16–50), the median operative time was 88 minutes (R, 48–250 minutes), and the median length of stay postoperatively was 2.5 days (R, 1–10). There was no operative or 30-day mortality, and no patient received any transfusion. At 30 days, freedom from major adverse cardiac events was 95% (two patients had transient congestive heart failure). At the median 6-month follow-up (single-center data, n = 12), the mean (SD) Canadian Cardiovascular Score angina score was 1.3 (0.05) (P< 0.001 vs baseline).Conclusions Robotically assisted TMR can be performed using an endoscopic, optical-fiber-based LDS, with high procedural success, avoidance of early adverse clinical events, and potential for successful angina relief.

An essay is presented that discusses academic research published on the history of the relation between human rights and U.S. foreign relations. Topics include opposition to international human rights treaties in relation to opposition to civil rights for African Americans, the foreign policy positions of former U.S. President Jimmy Carter, and anti-communist motivations in U.S. foreign policy.

The article discusses the tribal law of the Ho-Chunk Nation, which had the fifth largest population among Wisconsin tribes in 2009. Folkways and mores are the basis of the tribe's traditional law and their government structure is composed of 12 clans, which are provided responsibilities over their members. A detailed discussion on the four branches of their government as mandated by their new Constitution is included. The process observed by the tribe in hearing cases is also included.

ABSTRACTThe exceptional in vitropotency of the hepatitis C virus (HCV) NS5A inhibitor BMS-790052 has translated into an in vivoeffect in proof-of-concept clinical trials. Although the 50% effective concentration (EC50) of the initial lead, the thiazolidinone BMS-824, was ∼10 nM in the replicon assay, it underwent transformation to other inhibitory species after incubation in cell culture medium. The biological profile of BMS-824, including the EC50, the drug concentration required to reduce cell growth by 50% (CC50), and the resistance profile, however, remained unchanged, triggering an investigation to identify the biologically active species. High-performance liquid chromatography (HPLC) biogram fractionation of a sample of BMS-824 incubated in medium revealed that the most active fractions could readily be separated from the parental compound and retained the biological profile of BMS-824. From mass spectral and nuclear magnetic resonance data, the active species was determined to be a dimer of BMS-824 derived from an intermolecular radical-mediated reaction of the parent compound. Based upon an analysis of the structural elements of the dimer deemed necessary for anti-HCV activity, the stilbene derivative BMS-346 was synthesized. This compound exhibited excellent anti-HCV activity and showed a resistance profile similar to that of BMS-824, with changes in compound sensitivity mapped to the N terminus of NS5A. The N terminus of NS5A has been crystallized as a dimer, complementing the symmetry of BMS-346 and allowing a potential mode of inhibition of NS5A to be discussed. Identification of the stable, active pharmacophore associated with these NS5A inhibitors provided the foundation for the design of more potent inhibitors with broad genotype inhibition. This culminated in the identification of BMS-790052, a compound that preserves the symmetry discovered with BMS-346.

The epidermal growth factor receptor (EGFR) and the type I insulin-like growth factor receptor (IGF-1R) are two cell surface receptor tyrosine kinases known to cooperate to promote tumor progression and drug resistance. Combined blockade of EGFR and IGF-1R has shown improved anti-tumor activity in preclinical models. Here, we report the characterization of a stable IgG-like bispecific antibody (BsAb) dual-targeting EGFR and IGF-1R that was developed for cancer therapy. The BsAb molecule (EI-04), constructed with a stability-engineered single chain variable fragment (scFv) against IGF-1R attached to the carboxyl-terminus of an IgG against EGFR, displays favorable biophysical properties for biopharmaceutical development. Biochemically, EI-04 bound to human EGFR and IGF-1R with sub nanomolar affinity, co-engaged the two receptors simultaneously, and blocked the binding of their respective ligands with similar potency compared to the parental monoclonal antibodies (mAbs). In tumor cells, EI-04 effectively inhibited EGFR and IGF-1R phosphorylation, and concurrently blocked downstream AKT and ERK activation, resulting in greater inhibition of tumor cell growth and cell cycle progression than the single mAbs. EI-04, likely due to its tetravalent bispecific format, exhibited high avidity binding to BxPC3 tumor cells co-expressing EGFR and IGF-1R, and consequently improved potency at inhibiting IGF-driven cell growth over the mAb combination. Importantly, EI-04 demonstrated enhanced in vivo anti-tumor efficacy over the parental mAbs in two xenograft models, and even over the mAb combination in the BxPC3 model. Our data support the clinical investigation of EI-04 as a superior cancer therapeutic in treating EGFR and IGF-1R pathway responsive tumors.

AbstractTo move to a fusion DEMO power plant after ITER, a Fusion Nuclear Science Facility (FNSF) is needed in addition to ITER and research in operating tokamaks and those under construction. The FNSF will enable research on how to utilize and deal with the products of fusion reactions, addressing such issues as how to extract the energy from neutrons and alpha particles into high-temperature process heat streams to be either used directly or converted to electricity, how to make tritium from the neutrons and lithium, how to deal with the effects of the neutrons on the blanket structures, and how to manage the first wall surface erosion caused by the alpha particle heat appearing as low-energy plasma fluxes to those surfaces. Two candidates for the FNSF are considered in this paper: normal and low aspect ratio copper magnet tokamaks. The methods of selecting optimum machine design points versus aspect ratio are fully presented. The two options are compared and contrasted; both options appear viable.

Distributed energy resources (DER) are relatively small-scale generators or energy storage units that are located in close proximity to load centers. The DERs that are integrated to the grid with the power electronic converter interfaces are capable of providing nonactive power in addition to active power. Hence, they are capable of regulating the voltages of weak electrical buses in distribution systems. This paper discusses voltage control capability of photovoltaic (PV) systems as compared to the traditional capacitor banks. The simulation results prove the effectiveness of dynamic voltage control capability of inverter-based PVs. With proper control algorithms, active and nonactive power supplied from DERs (e.g., solar PVs or micro-turbines) can be controlled independently. This paper also presents the scenario of controlling active and nonactive power supplied from a PV array to track and supply the local load.

AbstractThe objective of the Fusion Development Facility (FDF) under consideration is to carry forward advanced tokamak physics for optimization of fusion reactors and enable development of fusion’s energy applications. A concept of FDF based on the tokamak approach with conservative expressions of advanced physics and nonsuperconducting magnet technology is presented. It is envisioned to nominally provide 2 MW/m2of neutron wall loading and operate continuously for up to 2 weeks as required for fusion nuclear component research and development. FDF will have tritium breeding capability with a goal of addressing the tritium self-sufficiency issue for fusion energy. A zero-dimensional system study using extrapolations of current physics and technology is used to optimize FDF for reasonable power consumption and moderate size. It projects a device that is between the DIII-D tokamak (major radius 1.8 m) [J. L. Luxon, Nucl. Fusion, Vol. 42, p. 614 (2002)] and the Joint European Torus (major radius 3 m) [P. H. Rebut, R. J. Bickerton, and B. E. Keen, Nucl. Fusion, Vol. 25, p. 1011 (1985)] in size, with an aspect ratio Aof 3.5 and a fusion gain Qof 2 to 5. Theory-based stability and transport modeling is used to complement the system study and to address physics issues related to specific design points. It is demonstrated that the FDF magnetohydrodynamic stability limits can be readily met with conservative stabilizing conducting wall placement. Transport analysis using a drift-wave-based model with an edge boundary condition consistent with the pedestal stability limit indicates that the FDF confinement requirement can also be readily satisfied. A surprising finding is that the toroidal Alfvén eigenmodes are stabilized by strong ion Landau damping. Analysis of vertical stability control indicates that the basis configuration with an elongation κx[approximately] 2.35 can be controlled using a power supply technology similar to that used in DIII-D. Peak heat fluxes to the divertor are somewhat lower than those of ITER [R. Aymar, P. Barabaschi, and Y. Shimomura, Plasma Phys. Control. Fusion, Vol. 44, p. 519 (2002)], but FDF will operate with a higher duty factor.

Although public service announcements (PSAs) are used extensively in social marketing campaigns, few studies have examined the overall landscape of PSAs. This article presents a comprehensive analysis of all PSAs aired on national television from 2001–2006. Data are from an all-inclusive industry database. Units of analysis were the number of ads, estimated amount of airtime, and estimated dollar value of airtime. Over 183,000 PSAs aired on average each year from 2001–2006, estimated to be worth about $1.6 billion per year. PSAs represented 2% of advertisements on national television, with more (30.5%) PSAs airing overnight between 1:00 am and 5:00 am than at other times of the day, and more appearing in the fall than other times of the year. The most common topic of PSAs was health. Sports programs contained a smaller percentage of PSAs than other types of programs. The results can help policymakers ensure that PSAs air in sufficient quantity and at effective times, inform campaign decisions about allocation of funds and placements of PSAs, and point to the need to monitor PSAs for each campaign.

Bispecific antibodies (BsAbs) represent an emerging class of biologics that achieve dual targeting with a single agent. Recombinant DNA technologies have facilitated a variety of creative bispecific designs with many promising therapeutic applications; however, practical methods for producing high quality BsAbs that have good product stability, long serum half-life, straightforward purification, and scalable production have largely been limiting. Here we describe a protein-engineering approach for producing stable, scalable tetravalent IgG-like BsAbs. The stability-engineered IgG-like BsAb was envisioned to target and crosslink two TNF family member receptors, TRAIL-R2 (TNF-Related Apoptosis Inducing Ligand Receptor-2) and LTβR (Lymphotoxin-beta Receptor), expressed on the surface of epithelial tumor cells with the goal of triggering an enhanced anti-tumor effect. Our IgG-like BsAbs consists of a stability-engineered anti- LTβR single chain Fv (scFv) genetically fused to either the N- or C-terminus of the heavy chain of a full-length anti-TRAIL-R2 IgG1 monoclonal antibody. Both N- or C-terminal BsAbs were active in inhibiting tumor cell growth in vitro, and with some cell lines demonstrated enhanced activity relative to the combination of parental Abs.  Pharmacokinetic studies in mice revealed long serum half-lives for the BsAbs. In murine tumor xenograft models, therapeutic treatment with the BsAbs resulted in reduction in tumor volume either comparable to or greater than the combination of parental antibodies, indicating that simultaneously targeting and cross-linking receptor pairs is an effective strategy for treating tumor cells. These studies support that stability-engineering is an enabling step for producing scalable IgG-like BsAbs with properties desirable for biopharmaceutical development.

The relationship between stress-tolerance mechanisms (cell-wall structure, metabolism, morphology, etc.) of individual fungi and the physiochemistry of their food environment selects for a small group of specific spoilage organisms (SSOs). However, common process deviations and post-processing contamination widen the lens of potentially relevant spoilage fungi. For example, although heat-resistant molds are considered the SSOs in thermally processed foods, unintended events (deviations, post-processing contamination) lead to spoilage by other propagules, notably yeast. The frequency of these unintended events changes our assessments of which spoilage fungi are relevant to a given food system. Consequently, a framework using probabilistic and systems-based thinking is needed to understand spoilage risk. Toward that goal, simple molecular tools for identification and subtyping are required.

Quiescent double barrier (QDB) conditions often form when an internal transport barrier is created with high-power neutral-beam injection into a quiescent H-mode (QH) plasma. These QH-modes offer an attractive, high-performance operating scenario for burning plasma experiments due to their quasi-stationarity and lack of edge localized modes. Our initial experiments and modelling using ECH/ECCD in QDB shots were designed to control the current profile and, indeed, we have observed a strong dependence on the q-profile when EC-power is used inside the core transport barrier region. While strong electron heating is observed with EC power injection, we also observe a drop in the other core parameters, namely ion temperature and rotation, electron density and impurity concentration. At onset and termination of the EC pulse, dynamically changing conditions are induced that provide a rapid evolution of Te/Tiprofiles accessible with 0.3 < (Te/Ti)axis< 0.8 observed in QDB discharges. We are exploring the correlation and effects of observed density profile changes with respect to these time-dependent variations in the temperature ratio. Increases in the measured ion thermal and particle diffusivities inside the barrier region during an ECH pulse correlate with electron heating and a rise in the core Te/Tiratio as the ion temperature and density profiles flatten with this change in transport. The change in transport is consistent with a destabilization of ITG turbulence as inferred from the reduction of the stability threshold due to the change in Te/Ti.

This report summarizes Type I edge localized mode (ELM) dynamics measurements from a number of tokamaks, including ASDEX-Upgrade, DIII-D, JET, JT-60U and MAST, with the goal of providing guidance and insight for the development of ELM simulation and modelling. Several transport mechanisms are conjectured to be responsible for ELM transport, including convective transport due to filamentary structures ejected from the pedestal, parallel transport due to edge ergodization or magnetic reconnection and turbulent transport driven by the high edge gradients when the radial electric field shear is suppressed. The experimental observations are assessed for their validation, or conflict, with these ELM transport conjectures.

The progress that has been made in understanding the processes responsible for edge localized modes is reviewed. Attention is restricted to the role of ideal magneto-hydrodynamics and extensions of this model. As well as reviewing the current understanding, future research needs are discussed and speculative ideas for further development are proposed.

OBJECTIVE To test whether alcohol advertising expenditures and the degree of exposure to alcohol advertisements affect alcohol consumption by youth. DESIGN Longitudinal panel using telephone surveys. SETTING Households in 24 US media markets, April 1999 to February 2001. PARTICIPANTS Individuals aged 15 to 26 years were randomly sampled within households and households within media markets. Markets were systematically selected from the top 75 media markets, representing 79% of the US population. The baseline refusal rate was 24%. Sample sizes per wave were 1872, 1173, 787, and 588. Data on alcohol advertising expenditures on television, radio, billboards, and newspapers were collected. MAIN EXPOSURES Market alcohol advertising expenditures per capita and self-reported alcohol advertising exposure in the prior month. MAIN OUTCOME MEASURE Self-reported number of alcoholic drinks consumed in the prior month. RESULTS Youth who saw more alcohol advertisements on average drank more (each additional advertisement seen increased the number of drinks consumed by 1% [event rate ratio, 1.01; 95% confidence interval, 1.01-1.02]). Youth in markets with greater alcohol advertising expenditures drank more (each additional dollar spent per capita raised the number of drinks consumed by 3% [event rate ratio, 1.03; 95% confidence interval, 1.01-1.05]). Examining only youth younger than the legal drinking age of 21 years, alcohol advertisement exposure and expenditures still related to drinking. Youth in markets with more alcohol advertisements showed increases in drinking levels into their late 20s, but drinking plateaued in the early 20s for youth in markets with fewer advertisements. Control variables included age, gender, ethnicity, high school or college enrollment, and alcohol sales. CONCLUSION Alcohol advertising contributes to increased drinking among youth.--

Using resonant magnetic perturbations with toroidal mode number n= 3, we have produced H-mode discharges without edge localized modes (ELMs) which run with constant density and radiated power for periods up to about 2550?ms (17 energy confinement times). These ELM suppression results are achieved at pedestal collisionalities close to those desired for next step burning plasma experiments such as ITER and provide a means of eliminating the rapid erosion of divertor components in such machines which could be caused by giant ELMs. The ELM suppression is due to an enhancement in the edge particle transport which reduces pedestal current density and maximum edge pressure gradient below the threshold for peeling-ballooning modes. These n= 3 magnetic perturbations provide a means of active control of edge plasma transport.

AbstractStudies of the H-mode pedestal in the DIII-D tokamak are presented. The global energy confinement increases as the plasma pressure on top of the pedestal increases. The best empirical description for a pedestal width parameter is Δpe∝ (βpolPED)0.4, where Δpeis the width of the electron pressure pedestal and βpolPEDis the poloidal beta at the top of the pedestal. The edge profiles of electron density ne, electron temperature Te, and ion temperature Tican all have different shapes. Thus, a simple width scaling for the edge might not exist, and studies of the physics of individual profiles have been initiated. A model for the neprofile, based on self-consistent treatment of edge particle sources and edge particle transport, agrees with several experimental observations. The steep gradient region for the Teprofile often extends farther into the plasma than the nepedestal step. Magnetohydrodynamic stability provides the ultimate limits to the evolution of the pedestal and usually leads to edge instabilities called edge-localized modes (ELMs). However, the absence of ELMs in a regime called the Quiescent H-mode shows that large pedestals can be produced without ELMs.