John F. Sonnett Memorial Lecture Series: Advocacy: Has It a Future?

Lecture introduction to Chief Justice Thomas A. Finlay of the Supreme Court of Ireland (1985-1994). Handwritten notes are included.https://ir.lawnet.fordham.edu/events_programs_sonnet_lectures/1023/thumbnail.jp

Invitation to the Fifteenth Annual John F. Sonnett Memorial Lecture Series: Advocacy Has It a Future?

Invitation to Advocacy: Has It a Future? by Chief Justice Thomas A. Finlay of the Supreme Court of Ireland (1985-1994).https://ir.lawnet.fordham.edu/events_programs_sonnett_miscellaneous/1021/thumbnail.jp

Исследование фармакокинетики 1% крема Ламизил®при местном применении

Twenty volunteers were entered into a study to investigate the pharmacokinetics of Lamisil® 1% cream. The subjects were randomized to receive Lamisil® 1% cream applied to the skin on the back on 1 day, or on 3, 5 or 7 consecutive days. Up to five biopsies were taken at a site on the upper back at various time-points both during treatment and after treatment. Lamisil® levels in the biopsies were analyzed using HPLC. The study showed that increasing the number of applications from one to seven did not significantly increase the peak concentration (Cmax) in the stratum corneum. However, there was an increase in the total amount of Lamisil® found in the stratum corneum resulting in Lamisil® being detected for longer periods after cessation of therapy. Treatment for 7 days resulted in Lamisil® still being detectable 7 days after cessation of therapy, and the drug concentration was significantly higher than the concentration killing the common causative organisms of superficial dermatomycoses. This study indicates a significant potential for short-term treatment with Lamisil® 1% cream in superficial dermatomycoses.Для оценки фармакокинетики 1% крема Ламизил® проведено исследование с участием 20 добровольцев. Испытуемых рандомизировали на группы получающих лечение 1% кремом Ламизил® путем нанесения препарата на кожу спины в течение 1 дня либо 3, 5 или 7 дней подряд. В одном из обработанных участков кожи верхней части спины брали до 5 биоптатов в разное время, в том числе во время лечения и после терапии. Уровень препарата Ламизил® в этих биоптатах анализировали с помощью высокоэффективной жидкостной хроматографии. Исследование показало, что увеличение числа нанесений крема от 1 до 7 не вызывало значительного увеличения его максимальной концентрации (Cmax) в роговом слое. Однако при этом возрастало общее количество препарата Ламизил® в роговом слое, в результате чего Ламизил® сохранялся в коже в течение более продолжительного периода после прекращения лечения. При 7-дневной терапии Ламизил® выявлялся в течение 7 дней после прекращения нанесения крема, при этом концентрация препарата была значительно выше концентрации, вызывающей гибель обычных возбудителей поверхностных дерматомикозов. Это исследование показало значительные возможности дерматомикозов 1% кремом Ламизил

Mountains Without End

Monograph/artist book exploring my relationship to landscape and mountains within my art practice. Includes essays from Thomas A Clark, (UK) Dr David Watson (Australia), introduction from Sandie Macrae (UK) and a contribution from Alec Finlay (UK). This book was a monograph featuring recent works that explored how we experience and participate in the experience of landscape, and in particular, remote, wild landscapes and mountainous terrain. Both Thomas A Clark and Dr David Watson wrote essays on my practice, Alec Finlay contributed a poem "Pataphysical Cuillin" and Sandie Macrae wrote an introduction. The book was published by ROOMBOOKS - I am represented in the UK by ROOM (now called Roaming ROOM). The book features works made over the last 4 years, including drawings, text based drawings, photographs, paintings, and digitally altered images. It ended with a selection of my on writings on my experiences of different landscapes, texts that emerged initially through my blog "living mountains". The book was published by ROOMBOOKS in 2013, ISBN 978-0-95499-156-2

Hypoxia Promotes Atrial Tachyarrhythmias via Opening of ATP-Sensitive Potassium Channels

BACKGROUND: Hypoxia-ischemia predisposes to atrial arrhythmia. Atrial ATP-sensitive potassium channel (KATP) modulation during hypoxia has not been explored. We investigated the effects of hypoxia on atrial electrophysiology in mice with global deletion of KATP pore-forming subunits. METHODS: Whole heart KATP RNA expression was probed. Whole-cell KATP current and action potentials were recorded in isolated wild-type (WT), Kir6.1 global knockout (6.1-gKO), and Kir6.2 global knockout murine atrial myocytes. Langendorff-perfused hearts were assessed for atrial effective refractory period (ERP), conduction velocity, wavefront path length (WFPL), and arrhymogenicity under normoxia/hypoxia using a microelectrode array and programmed electrical stimulation. Heart histology was assessed. RESULTS: Expression patterns were essentially identical for all KATP subunit RNA across human heart, whereas in mouse, Kir6.1 and SUR2 (sulphonylurea receptor) were higher in ventricle than atrium, and Kir6.2 and SUR1 were higher in atrium. Compared with WT, Kir6.2 global knockout atrial myocytes had reduced tolbutamide-sensitive current and action potentials were more depolarized with slower upstroke and reduced peak amplitude. Action potential duration was prolonged in 6.1-gKO atrial myocytes, absent of changes in other ion channel gene expression or atrial myocyte hypertrophy. In Langendorff-perfused hearts, baseline atrial ERP was prolonged and conduction velocity reduced in both KATP knockout mice compared with WT, without histological fibrosis. Compared with baseline, hypoxia led to conduction velocity slowing, stable ERP, and WFPL shortening in WT and 6.1-gKO hearts, whereas WFPL was stable in Kir6.2 global knockout hearts due to ERP prolongation with conduction velocity slowing. Tolbutamide reversed hypoxia-induced WFPL shortening in WT and 6.1-gKO hearts through ERP prolongation. Atrial tachyarrhythmias inducible with programmed electrical stimulation during hypoxia in WT and 6.1-gKO mice correlated with WFPL shortening. Spontaneous arrhythmia was not seen. CONCLUSIONS: KATP block/absence leads to cellular and tissue level atrial electrophysiological modification. Kir6.2 global knockout prevents hypoxia-induced atrial WFPL shortening and atrial arrhythmogenicity to programmed electrical stimulation. This mechanism could be explored translationally to treat ischemically driven atrial arrhythmia

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Impedance spectroscopy of epitaxial multiferroic thin films

Temperature dependent impedance spectroscopy enables the many contributions to the dielectric and resistive properties of condensed matter to be deconvoluted and characterized separately. We have achieved this for multiferroic epitaxial thin films of BiFeO3 (BFO) and BiMnO3 (BMO), key examples of materials with strong magneto-electric coupling. We demonstrate that the true film capacitance of the epitaxial layers is similar to that of the electrode interface, making analysis of capacitance as a function of film thickness necessary to achieve deconvolution. We modeled non-Debye impedance response using Gaussian distributions of relaxation times and reveal that conventional resistivity measurements on multiferroic layers may be dominated by interface effects. Thermally activated charge transport models yielded activation energies of 0.60 eV +- 0.05 eV (BFO) and 0.25 eV +- 0.03 eV (BMO), which is consistent with conduction dominated by oxygen vacancies (BFO) and electron hopping (BMO). The intrinsic film dielectric constants were determined to be 320 +- 75 (BFO) and 450 +- 100 (BMO)

Acceleration of relativistic beams using laser-generated terahertz pulses

Dielectric structures driven by laser-generated terahertz (THz) pulses may hold the key to overcoming the technological limitations of conventional particle accelerators and with recent experimental demonstrations of acceleration, compression and streaking of low-energy (sub-100 keV) electron beams, operation at relativistic beam energies is now essential to realize the full potential of THz-driven structures. We present the first THz-driven linear acceleration of relativistic 35 MeV electron bunches, exploiting the collinear excitation of a dielectric-lined waveguide driven by the longitudinal electric field component of polarization-tailored, narrowband THz pulses. Our results pave the way to unprecedented control over relativistic electron beams, providing bunch compression for ultrafast electron diffraction, energy manipulation for bunch diagnostics, and ultimately delivering high-field gradients for compact THz-driven particle acceleration.Comment: 8 pages, 4 figure

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

Prediction of mosquito species and population age structure using mid-infrared spectroscopy and supervised machine learning

Despite the global efforts made in the fight against malaria, the disease is resurging. One of the main causes is the resistance that Anopheles mosquitoes, vectors of the disease, have developed to insecticides. Anopheles must survive for at least 10 days to possibly transmit malaria. Therefore, to evaluate and improve malaria vector control interventions, it is imperative to monitor and accurately estimate the age distribution of mosquito populations as well as their population sizes. Here, we demonstrate a machine-learning based approach that uses mid-infrared spectra of mosquitoes to characterise simultaneously both age and species identity of females of the African malaria vector species Anopheles gambiae and An. arabiensis. mid-infrared spectroscopy-based prediction of mosquito age structures was statistically indistinguishable from true modelled distributions. The accuracy of classifying mosquitoes by species was 82.6%. The method has a negligible cost per mosquito, does not require highly trained personnel, is rapid, and so can be easily applied in both laboratory and field settings. Our results indicate this method is a promising alternative to current mosquito species and age-grading approaches, with further improvements to accuracy and expansion for use with other mosquito vectors possible through collection of larger mid-infrared spectroscopy data sets