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Direct numerical simulations (DNSs) are used to investigate the drag-reducing performance of superhydrophobic surfaces (SHSs) in turbulent channel flow. SHSs combine surface roughness with hydrophobicity and can, in some cases, support a shear-free air?water interface. Slip velocities, wall shear stresses and Reynolds stresses are considered for a variety of SHS microfeature geometry configurations at a friction Reynolds number of Re?? 180. For the largest microfeature spacing studied, an average slip velocity over 75% of the bulk velocity is obtained, and the wall shear stress reduction is found to be nearly 40%. The simulation results suggest that the mean velocity profile near the superhydrophobic wall continues to scale with the wall shear stress but is offset by a slip velocity that increases with increasing microfeature spacing. [ABSTRACT FROM AUTHOR]

Purpose: Mutations in the HRAS (m HRAS ) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M m HRAS HNSCC., Methods: We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m HRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m HRAS variant allele frequency (VAF) data, enrollment was limited to those with a m HRAS VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles., Results: Of the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%)., Conclusion: Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist (NCT02383927)., Competing Interests: Alan L. HoConsulting or Advisory Role: Bristol-Myers Squibb, Eisai, Genzyme, Merck, Novartis, Sun Pharma, Regeneron, TRM Oncology, Ayala Pharmaceuticals, AstraZeneca, Sanofi, CureVac, Prelude Therapeutics, Kura Oncology, McGivney Global Advisors, Rgenta, Exelixis, Genentech/Roche, AffyimmuneSpeakers' Bureau: Medscape, Omniprex America, NovartisResearch Funding: Lilly, Genentech/Roche, AstraZeneca, Bayer, Kura Oncology, Kolltan Pharmaceuticals, Eisai, Bristol-Myers Squibb, Astellas Pharma, Novartis, Merck, Pfizer, Ayala Pharmaceuticals, Allos Therapeutics, Daiichi Sankyo, Elevar TherapeuticsTravel, Accommodations, Expenses: Janssen Oncology, Merck, Kura Oncology, Ignyta, Ayala Pharmaceuticals, Klus Pharma Irene BranaConsulting or Advisory Role: Merck Sharp and Dohme, Rakuten Medical, Sanofi, Achilles Therapeutics, eTheRNA Immunotherapies, Cancer Expert NowSpeakers' Bureau: Bristol-Myers Squibb, Merck Serono, RocheResearch Funding: AstraZeneca, Bristol-Myers Squibb, Celgene, Gliknik, GlaxoSmithKline, Janssen Oncology, Kura Oncology, Merck Sharp and Dohme, Novartis, Orion Pharma GmbH, Pfizer, Roche, Shattuck Labs, Nanobiotix, Seattle GeneticsTravel, Accommodations, Expenses: AstraZeneca Spain, Merck Serono Robert HaddadEmployment: Dana-Farber Cancer InstituteLeadership: NCCNConsulting or Advisory Role: Celgene, Merck, Eisai, Bristol-Myers Squibb, AstraZeneca, Pfizer, Loxo, Genentech, Immunomic Therapeutics, GlaxoSmithKline, Gilead Sciences, Vaccinex, EMD Serono, BioNTech AG, Achilles TherapeuticsResearch Funding: Boehringer Ingelheim, Merck, Bristol-Myers Squibb, Celgene, AstraZeneca, VentiRx, Genentech, Pfizer, Kura OncologyPatents, Royalties, Other Intellectual Property: UpToDateOther Relationship: Nanobiotix, ISA Pharmaceuticals Jessica BaumanConsulting or Advisory Role: Pfizer, Bayer, AstraZeneca, Kura OncologyResearch Funding: Bristol-Myers SquibbTravel, Accommodations, Expenses: Trident Pharmaceuticals Sjoukje OostingResearch Funding: Celldex Deborah J. WongConsulting or Advisory Role: Bristol-Myers Squibb, Genentech/Roche, Sanofi/Aventis, Blueprint MedicinesResearch Funding: BioMed Valley Discoveries, Merck Serono, Merck Sharp and Dohme, ARMO BioSciences, AstraZeneca/MedImmune, Kura Oncology, Regeneron, Genentech/Roche, Bristol-Myers Squibb, FSTAR, Pfizer, Astellas Pharma, Enzychem Lifesciences, Lilly, Elevar Therapeutics Myung-Ju AhnHonoraria: AstraZeneca, Lilly, MSD, TAKEDAConsulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, TAKEDA, Alpha pharmaceutical Caroline EvenConsulting or Advisory Role: Innate Pharma, Bristol-Myers Squibb, MSD Oncology, Merck Serono Jerome FayetteHonoraria: AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Merck Serono, Innate Pharma, RocheConsulting or Advisory Role: AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Merck Serono, Innate Pharma, RocheResearch Funding: Bristol-Myers SquibbTravel, Accommodations, Expenses: Bristol-Myers Squibb, AstraZeneca, Merck Sharp and Dohme Kevin HarringtonHonoraria: Merck Sharp and Dohme, Amgen, Merck Serono, AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Replimune, Oncolys BioPharma, MersanaConsulting or Advisory Role: Merck Sharp and Dohme, Merck Serono, AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, ReplimuneSpeakers' Bureau: Merck Sharp and Dohme, Merck Serono, Bristol-Myers SquibbResearch Funding: AstraZeneca, Merck Sharp and Dohme, Boehringer Ingelheim, Replimune Sung-Bae KimHonoraria: DAEHWA Pharmaceutical, ISU ABXISConsulting or Advisory Role: Lilly, AstraZeneca, DAEHWA Pharmaceutical, ISU AbxisResearch Funding: Novartis, Dongkook Pharma, Genzyme Lisa LicitraConsulting or Advisory Role: Eisai, Boehringer Ingelheim, AstraZeneca, SOBI, Novartis, Bayer, MSD, Merck Serono, Roche, Bristol-Myers Squibb, Incyte, Doxapharma, GlaxoSmithKline, Nanobiotix, Debiopharm Group, Amgen, IpsenResearch Funding: AstraZeneca, Novartis, Roche, MSD, Eisai, Merck Serono, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Exelixis, IRX Therapeutics, Medpace, Pfizer, Debiopharm Group, RocheTravel, Accommodations, Expenses: Merck Serono, Bayer, Bristol-Myers Squibb, MSD, Eisai, AstraZeneca Nabil F. SabaHonoraria: Merck, Lilly, Pfizer, Bristol-Myers Squibb, CUE Biopharma, GlaxoSmithKline, Aduro Biotech, Kura Oncology, Genentech/RocheConsulting or Advisory Role: Pfizer, Bristol-Myers Squibb, Merck, Lilly, Bluprint, BiontechResearch Funding: Bristol-Myers Squibb, ExelixisTravel, Accommodations, Expenses: Bristol-Myers Squibb, Merck, Pfizer, Lilly, GlaxoSmithKline, Genentech/Roche, Bluprint Francis WordenHonoraria: Merck Sharp & Dohme, Eisai, Bristol-Myers Squibb, Bayer, RegeneronConsulting or Advisory Role: Merck, Loxo, Bristol-Myers Squibb, Eisai, Bayer, CUE Biopharma, Rakuten Medical, RegeneronResearch Funding: Pfizer, Merck, Eisai, Bristol-Myers Squibb, Loxo, Oragenics, LillyTravel, Accommodations, Expenses: Merck Sharp & Dohme, Bayer Binaifer BalsaraEmployment: Kura OncologyStock and Other Ownership Interests: Kura Oncology Mollie LeoniEmployment: Kura Oncology, Kyowa Kirin InternationalStock and Other Ownership Interests: Kura OncologyTravel, Accommodations, Expenses: Kura Oncology, Kyowa Kirin International Catherine ScholzEmployment: Kura Oncology, H3 BiomedicineStock and Other Ownership Interests: Kura OncologyPatents, Royalties, Other Intellectual Property: Methods of Treating Cancer Patients With Farnesyltransferase Inhibitors (FTI treatment of H-Ras mutant cancers), co-Inventor (014168-0011-999), Methods of Treating Cancer With Farnesyltransferase Inhibitors (FTI treatment of a CXCL12-expressing cancer), co-Inventor (014168-0021-999), Methods of Treating Cancer Patients With Farnesyltransferase Inhibitors (FTI treatment of Casitas B cell lymphoma [CBL] mutant cancers), co-Inventor (014168-0024-228), Therapies For Squamous Cell Carcinomas (FTI treatment of SCC with high frequencies of H-Ras mutant allele frequency), co-Inventor (014168-0051-888)Travel, Accommodations, Expenses: Kura OncologyNo other potential conflicts of interest were reported.

The objectives of this work were to evaluate the in vitro release and in vivo pharmacokinetics and local tolerability of a novel, segmented ethylene-vinyl acetate (EVA) intravaginal ring (IVR) delivering progesterone (P) in drug-naïve ovariectomized female Dorset crossbred sheep. Following preparation and assessment of in vitro release of P, animals were randomized into one of six treatment groups: group 1 Crinone® 8% gel (90 mg); group 2 Prometrium® 200-mg capsules; group 3 placebo IVR; group 4 progesterone (P) IVR 4 mg/day; group 5 P IVR 8 mg/day; or group 6 P IVR 12 mg/day. Crinone 8% gel and Prometrium capsules were administered once daily for 28 days. IVRs were inserted vaginally on day 1 and remained in place through day 14; a new ring was administered on day 15 and was removed at day 28. Animals underwent daily examinations to confirm ring placement, and vaginal irritation was scored from 0 (none) to 4 (severe). Blood samples were taken at scheduled times for pharmacokinetic analysis. Postmortem examinations performed on all IVR groups included vaginal irritation, macroscopic, and microscopic evaluations, including irritation scoring and histopathology. Intravaginal rings were retained over 28 days in all animals. Clinical observations showed no significant abnormal findings in any group. Pharmacokinetic analysis in animals showed sustained release of P over from days 0 through 14 of ring use. Irritation scores and microscopic assessments were consistent with the IVRs being well tolerated. These results will guide future human clinical studies to ultimately develop an IVR for use in women for the prevention of preterm birth.

This study reports the preparation, in vitro release, pharmacokinetics, and local tolerability of novel ethylene-vinyl acetate intravaginal rings (IVRs) delivering 17β-estradiol (E 2 ) and progesterone (P), in drug-naïve ovariectomized female Dorset crossbred sheep. After preparation and assessment of in vitro release of E 2 and P, animals were randomized to treatment groups 1 or 2 (comparator rings releasing 50 or 100 μg/d E 2 , respectively), groups 3 or 4 (ethylene-vinyl acetate IVRs, 160 μg/d E 2 with 4 [160/4 IVR] or 8 mg/d P [160/8 IVR], respectively), or group 5 (160 μg E 2 and 10 mg P administered intravenously). IVRs were placed on day 1 and remained in place through day 29. Animals underwent daily examinations to confirm ring placement, and vaginal irritation was scored from 0 (none) to 4 (severe). Blood samples were taken at scheduled times for pharmacokinetic analysis. Postmortem examinations performed on groups 1-4 were macroscopic and microscopic evaluations, including irritation scoring and histopathology. IVRs were retained over 28 days in all but 1 animal (group 4). In all animal groups, clinical observations showed no significant abnormal findings. Pharmacokinetic analysis in the animals showed sustained release of E 2 and P over a 28-day period. Irritation scores and microscopic assessments were consistent with foreign object placement. A novel 2-drug IVR delivery system was well tolerated in a sheep model and pharmacokinetic release was as expected over a 28-day release period. These results will guide future human clinical studies., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate how physicians in the United States (US) screen for, define, and treat a short cervix to prevent preterm birth., Methods: This was a cross-sectional, web-based survey of 500 physicians treating pregnant patients with a short cervix in the US. Respondents' geographic region was monitored to ensure balance across the nine US Census divisions., Results: Respondents were predominantly obstetrician/gynecologists (86%, 429/500; mean age 49 years). Physicians reported that a median of 90% of their pregnant patients undergo cervical length screening; 81% (407/500) use transvaginal ultrasound. Physicians consult multiple evidence sources to inform their patient care, most commonly clinical guidelines (83%; 413/500) and published research (70%; 349/500). Most physicians (98%; 490/500) reported treating pregnant patients with a short cervix; 95% (474/500) use synthetic and/or natural progestogen, alone or in combination with other treatment modalities. If reimbursement was not a concern, 47% of physicians (230/500) would choose vaginal progesterone as their preferred treatment to prevent preterm birth in all patients with a short cervix, and 45% (218/500) would choose a synthetic progestogen., Conclusion: US guidelines recommend transvaginal ultrasound for cervical length screening; 81% of physicians in this study reported using this method. Most physicians surveyed use progestogens to treat a short cervix, with approximately half choosing a synthetic progestin (45%) and half choosing natural progesterone (47%) as their preferred treatment, despite national guidelines recommending only vaginal natural progesterone for this indication. Additional physician education is required to implement current and best practices.

Lidocaine vaginal bioadhesive gel is being developed as a local anesthetic for use in minimally invasive outpatient gynecological procedures and was investigated in single-dose and multiple-dose studies in healthy young adult women. Lidocaine doses of 2.5%, 5%, and 10% (w/w) were administered, and parent drug and metabolites monoethylglycinexylidide and glycinexylidide were measured in plasma. Lidocaine was absorbed through vaginal tissue and into the systemic circulation in a dose-proportional manner, and there was little systemic accumulation. Plasma concentrations were 10- to 20-fold lower than concentrations obtained after administration of intravenous lidocaine used to treat arrhythmic activity, thus demonstrating a wide safety margin for a vaginal lidocaine product., (© 2016, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.)

Background: Suicides among men aged 35-64 years increased by 27% between 1999 and 2013, yet little research exists to examine the nature of the suicide risk within this population. Many men do not seek help if they have mental health problems and suicides may occur in reaction to stressful circumstances., Aims: We examined the precipitating circumstances of 600 suicides without known mental health or substance abuse (MH/SA) problems and with a recent crisis. Whether these suicides occurred within the context of an acute crisis only or in the context of chronic circumstances was observed., Method: Using data from the National Violent Death Reporting System and employing mixed-methods analysis, we examined the circumstances and context of a census of middle-aged male suicides (n = 600) in seven states between 2005 and 2010., Results: Precipitating circumstances among this group involved intimate partner problems (IPP; 58.3%), criminal/legal problems (50.7%), job/financial problems (22.5%), and health problems (13.5%). Men with IPP and criminal/legal issues were more likely than men with health and/or job/financial issues to experience suicide in the context of an acute crisis only., Conclusion: Suicides occurring in reaction to an acute crisis only or in the context of acute and chronic circumstances lend themselves to opportunities for intervention. Further implications are discussed.

Background: We retrospectively analyzed sunitinib outcome as a function of age in metastatic renal cell carcinoma (mRCC) patients., Methods: Data were pooled from 1059 patients in six trials. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were compared by log-rank test between patients aged <70 (n=857; 81%) and ≥70 (n=202; 19%) years., Results: In first-line patients, median PFS was comparable in younger and older patients, 9.9 vs 11.0 months, respectively (HR, 0.89; 95% CI: 0.73-1.09; P=0.2629), as was median OS, 23.6 vs 25.6 months (HR, 0.93; 95% CI: 0.74-1.18; P=0.5442). Similarly, in cytokine-refractory patients, median PFS was 8.1 vs 8.4 months (HR, 0.79; 95% CI: 0.49-1.28; P=0.3350), while median OS was 20.2 vs 15.8 months (HR, 1.14; 95% CI: 0.73-1.79; P=0.5657). Some treatment-emergent adverse events were significantly less common in younger vs older patients, including fatigue (60% vs 69%), cough (20% vs 29%), peripheral edema (17% vs 27%), anemia (18% vs 25%), decreased appetite (13% vs 29%), and thrombocytopenia (16% vs 25%; all P<0.05). Hand-foot syndrome was more common in younger patients (32% vs 24%)., Conclusions: Advanced age should not be a deterrent to sunitinib therapy and elderly patients may achieve additional clinical benefit.

Objective: The present study was undertaken to explore multilevel determinants of planning to continue to drink alcohol after leaving public drinking events. We assessed whether individual-level factors, group-related factors, or event-level bar characteristics were associated with post-bar drinking., Method: We recruited a total of 642 participants from 30 participating bars in urban Southern California. Groups who arrived to patron a bar were interviewed upon their entrance and exit. Given data nesting, we employed a multilevel modeling approach to data analysis., Results: More than one-third (40%) of our sample reported the intention to continue drinking as they exited the bar. Results of our multilevel model indicated eight individual-level variables significantly associated with intending to continue to drink. Time of night moderated the relationship between BrAC change and intentions to continue to drink. Although none of the group factors were significant in our model, a significant cross-level interaction between BrAC change and number of group members indicated the effect of intoxication on planning to continue to drink increases as group members increase. At the bar level, the presence of temporary bars and server offers of non-alcoholic drinks significantly decreased intentions to continue to drink., Conclusions: Given the large percentage of participants who reported the intention to continue drinking after exiting a bar, this study draws attention to the fact that field studies of drinking behavior may assess drinking mid-event rather than at the end of a drinking event., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: This exploratory study examined the ability of young adults to purchase alcoholic beverages through self-checkout lanes without being asked for age verification. Although the minimum drinking age in all 50 U. S. states is 21 years of age, drinking among underage persons (ages 12-20) remains a serious public health concern. Self-checkout options in off-sale alcoholic beverage outlets (e.g., grocery store chains, liquor stores) may represent a potential source of illicit access to alcohol compared with traditional checkout purchases., Method: A total of 216 stores with self-checkout lanes were randomly selected in five Southern California counties. Pseudo-patrons independently judged to be 23 years of age or younger purchased alcohol in each store., Results: Overall, 8.8% of all purchase observations resulted in a failure to ask for identification to purchase alcohol., Conclusions: The growing number of self-checkout options at supermarkets can be a potential source of alcohol for minors; however, the risk they pose is similar to that of traditional checkout purchases. Policies relating to the purchase of alcohol at any store, regardless of checkout type, should be modified so that every purchase of alcohol requires an identification card to be swiped regardless of age.

Purpose: Sunitinib has shown antitumor activity with a manageable safety profile as metastatic renal cell carcinoma (RCC) treatment, when given by the standard intermittent schedule as well as a continuous daily dosing (CDD) schedule. A trial was conducted to compare the schedules., Patients and Methods: Patients with treatment-naive, clear cell advanced RCC were randomly assigned 1:1 to receive sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment (schedule 4/2; n = 146) or 37.5 mg/d on the CDD schedule (n = 146) for up to 2 years. The primary end point was time to tumor progression., Results: Median time to tumor progression was 9.9 months for schedule 4/2 and 7.1 months for the CDD schedule (hazard ratio, 0.77; 95% CI, 0.57 to 1.04; P = .090). No significant difference was observed in overall survival (23.1 v 23.5 months; P = .615), commonly reported adverse events, or patient-reported kidney cancer symptoms. Schedule 4/2 was statistically superior to CDD in time to deterioration, a composite end point of death, progression, and disease-related symptoms (P = .034). CONCLUSION; There was no benefit in efficacy or safety for continuous dosing of sunitinib compared with the approved 50 mg/d dose on schedule 4/2. Given the numerically longer time to tumor progression with the approved 50 mg/d dose on schedule 4/2, adherence to this dose and schedule remains the treatment goal for patients with advanced RCC.

Despite the therapeutic use and abuse potential of gamma-hydroxybutyrate (GHB or Xyrem), relatively few studies have examined the behavioral effects of GHB in humans under controlled laboratory conditions. Thus, this eight-session study examined in 10 non-substance-abusing volunteers the behavioral effects of GHB at each of the following doses: 0, 0.32, 0.56, 0.75, 1.0, 1.8, 2.4, 3.2 g/70 kg, orally. Order of dose testing was random, except that the first two participants received active doses in ascending order and 2.4 g/70 kg was always tested before 3.2 g/70 kg. Before drug administration and at several postdrug time points, self-report, observer report, physiological, and psychomotor performance measures were obtained. Analyses based on area under the curve showed that GHB produced dose-related increases in subjective ratings of sedative-like, stimulant-like, positive mood, and dissociative effects, but no changes in psychomotor performance measures or blood pressure. Analyses based on peak effects generally showed dose-related increases in ratings indicating sedative-like, dissociative, and drug liking, although some measures showed U-shaped dose-related changes. These initial findings suggest that GHB at doses of 0.32-3.2 g/70 kg produces dissociative, sedating and some stimulant-like effects in humans without a history of sedative abuse.

By participating in some form of professional development, medical radiation technologists can increase their skill, knowledge, and competence, leading to improved quality, safety, and standards of practice. Participation will also demonstrate acceptance of the responsibility for medical radiation technologists' own professional development. Over the past 10 years, the profession of medical radiation technology has progressed dramatically, with many changes in technology. The need for medical radiation technologists to keep up-to-date on these advancements is evident. Many medical radiation technologists participate in some form of professional development, and the decision to do so is either mandated at the provincial level or it remains a personal one. Because education is a provincial matter, the continuity of professional development or continuing education for medical radiation technologists across the country does not exist. The purpose of this directed reading is to review the options available to medical radiation technologists for professional development, to provide an overview of professional development programs from various health care professional groups, to outline how to effectively introduce a professional development program to medical radiation technologists, and to recommend the most appropriate program to implement for medical radiation technologists., (Copyright © 2010 Elsevier Inc. All rights reserved.)

We studied the origins of ectopic beats during low-flow reperfusion after acute regional ischemia in excised rat hearts. The left anterior descending coronary artery was cannulated. Perfusate was delivered to the cannula using an high-performance liquid chromatography pump. This provided not only precise control of flow rate but also avoided mechanical artifacts associated with vessel occlusion and deocclusion. Optical mapping of epicardial transmembrane potential served to identify activation wavefronts. Imaging of NADH fluorescence was used to quantify local ischemia. Our experiments suggest that low-flow reperfusion of ischemic myocardium leads to a highly heterogeneous ischemic substrate and that the degree of ischemia between adjacent patches of tissue changes in time. In contrast to transient ectopic activity observed during full-flow reperfusion, persistent ectopic arrhythmias were observed during low-flow reperfusion. The origins of ectopic beats were traceable to areas of high spatial gradients of changes in NADH fluorescence caused by low-flow reperfusion.

We describe a new approach that combines several techniques to allow abnormal electrical and calcium activity to be visualized within hypoperfused myocardial tissue. A flexible microcannula was inserted into the left anterior descending artery of Langendorff perfused rat hearts, an air-tight seal between the coronary artery and the cannula was created, and an HPLC pump was used to deliver a specified flowrate through the microcannula. High resolution optical mapping of NADH/calcium, NADH/voltage or calcium/voltage was then conducted using a dual camera system. The ECG was acquired using surface electrodes. This perfusion technique is superior to occluding a vessel by either a tie or a clamp because it allows precise control of the composition and amount of flow to a defined ischemic bed. Another advantage is that flow can be stopped and resumed remotely, without touching the heart. This allows ectopic beats, or other arrhythmogenic activity, such as alternans, to be recorded immediately after changes in flow are imposed. Altogether, the described method provides a powerful new tool to assess how coronary flow rate affects the degree of local ischemia by the ability to record abnormal patterns of electrical activity and associated intracellular calcium transients with high spatiotemporal resolution from epicardial areas as small as 100 x 100 microm.

Context: No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy., Objective: To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals., Design: This 25-week, placebo-controlled, double-blind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB)., Setting: Outpatient clinic at the Veterans Affairs Connecticut Healthcare System., Participants: A total of 106 opiate-dependent, cocaine-abusing individuals., Interventions: All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study., Main Outcome Measure: Thrice-weekly urine toxicologic test results for cocaine and heroin., Results: Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (P<.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (P<.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (P<.001). In contrast, by treatment end, the VCB and VCP groups showed no significant improvement in cocaine use., Conclusion: These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone.

Objective: The purpose of this study was to assess three modern root-end restorative materials with electrical and dye leakage tests., Method and Materials: Thirty-three human canine teeth were prepared and filled with gutta-percha and sealer. Stainless steel rods were inserted into the root canals as anodes, and the teeth were varnished. The apical 3 mm of each tooth was resected, and 3-mm root-end preparations were made ultrasonically. Mineral trioxide aggregate, Super EBA, and IRM were used to restore 10 teeth each, and three teeth were varnished as controls. Following 24 hours' setting in blood, the specimens were placed in 1% potassium chloride electrolyte, and leakage was recorded electrically for 70 days. The teeth were then submerged in methylene blue dye for 72 hours, sectioned longitudinally, and scored for leakage by six examiners., Results: In both tests, the mineral trioxide aggregate restorations leaked significantly less than the IRM and Super EBA restorations. Super EBA showed significantly less leakage than did IRM restorations in the electrochemical test but not in the dye leakage experiment. The teeth sealed with mineral trioxide aggregate performed similarly to the varnished negative control teeth., Conclusion: The results of this study indicated that mineral trioxide aggregate provides a superior seal in root-end-restorations.