The epidermis protects the organism from external challenges and from dehydration. The establishment, maintenance and restoration of this epithelial barrier are driven by a balance between self-renewal and differentiation of interfollicular epidermal (IFE) progenitor cells. However, the upstream signals that regulate this balance are largely unknown. The major aim of this thesis was to identify and characterize the in vivo role of epidermal insulin/IGF signaling, which have been identified as key regulators of growth, metabolism and stem cell behavior in other tissues. Inactivating the insulin receptor (IR-/-), the IGF-1 receptor (IGF-1R-/-) or both (dko) specifically in the epidermis resulted in a progressive decrease in the number of suprabasal layers, first obvious at E16.5, although differentiation and apoptosis were unaltered. Instead, the phenotype was directly associated with a strong decrease in proliferative potential in vitro and altered IFE progenitor cell behavior in vivo. Furthermore, rescue experiments identified the small GTPase Rac1 as a key target of IGF-1R/IR signaling that regulates epidermal morphogenesis in vivo and proliferative potential in vitro. To address how IR/IGF-1R regulates epidermal morphogenesis, we focused on E16.5 dko embryos, when the phenotype is first obvious. Whereas no change was observed in expression of the proliferation marker Ki67, a reduced number of anaphase spindles and an increased number of metaphase spindles were found in dko mice compared to control, and in vitro in cultured keratinocytes. This indicated an arrest in the spindle check point of the cell cycle in the absence of IR/IGF-1R. This was associated with disturbed spindle formation in IGF-1R-/- metaphase cells and reduced expression of AuroraB, a key regulator of mitosis, as well as other cell cycle regulators, such as p53 and stratifin (14-3-3σ). Interestingly, the reduction in cell divisions upon loss of IR/IGF-R was predominantly on the expense of asymmetric divisions and correlated with reduced p63 expression, a known regulator of this process. Since asymmetric cell divisions have been implicated in regulating epidermal stratification, the results indicate that epidermal Insulin/IGF1 signaling couples cell cycle progression to asymmetric divisions thereby regulating the number of suprabasal layers in the IFE during morphogenesis. In short, the results in this thesis have identified epidermal IR/IGF-1R as key regulators of epidermal morphogenesis, proliferative potential, IFE progenitor cells and asymmetric cell divisions.


INTRODUCTION
Study objective was to determine feasibility and compliance with a 3-month exercise intervention in older adults, and if peripheral quantitative computed tomography muscle measures and jumping mechanography could detect changes in muscle mass and function.

METHODS
A parallel group, nonblinded, pilot trial with individuals 70 yr or older randomized to control group of walking-only (WALK) or an intervention group of walking combined with exercises to improve balance and strength (W + EX). Both groups attended similar weekly nutrition education sessions. Body composition, muscle density, intramuscular adipose tissue area, and muscle function were assessed before and after the intervention using dual-energy x-ray, peripheral quantitative computed tomography, functional tests, and mechanography.

RESULTS
Eighty-five (90%) of 94 individuals enrolled completed (41WALK, 44W + EX). Eighty-six percent of participants attended seven or more nutrition sessions, and log sheets, used to assess exercise compliance, were returned by 66% of participants, and of those, 88% logged activity on 50%+ days. Sixty-seven percent of participants stated that they increased activity levels, and 82% stated that they felt better overall. Both groups increased lean and lost fat mass, resulting in decreases in fat percentage (all, P < 0.05). Intramuscular adipose tissue area decreased and muscle density increased among WALK (P < 0.05 and P = 0.056, respectively) but were not different between groups. Improvement in force efficiency and chair-rise power were greater among W + EX group than WALK (5.9% ± 1.8% vs -1.2% ± 2.0% [P = 0.01] and 0.25 ± 0.19 W·kg and -0.37 ± 0.23 W·kg [P = 0.04], respectively). Differences in mechanography results became greater in a per-protocol analysis.

CONCLUSIONS
A larger trial is feasible, and the program was well accepted. Both groups showed improvements, the program that included strength and balance lead to greater jump force efficiency and power than walking only. Whether these differences lead to differences in fall rates need to be determined in a larger trial.


The TTE approach to Computable Analysis is the study of so-called representations (encodings for continuous objects such as reals, functions, and sets) with respect to the notions of computability they induce. A rich variety of such representations had been devised over the past decades, particularly regarding closed subsets of Euclidean space plus subclasses thereof (like compact subsets). In addition, they had been compared and classified with respect to both non-uniform computability of single sets and uniform computability of operators on sets. In this paper we refine these investigations from the point of view of computational complexity. Benefiting from the concept of second-order representations and complexity recently devised by Kawamura & Cook (2012), we determine parameterized complexity bounds for operators such as union, intersection, projection, and more generally function image and inversion. By indicating natural parameters in addition to the output precision, we get a uniform view on results by Ko (1991-2013), Braverman (2004/05) and Zhao & Muller (2008), relating these problems to the P/UP/NP question in discrete complexity theory.


Phased array systems, a special case of MIMO systems, take advantage of spatial directivity and array gain to increase spectral efficiency. Implementing a phased array system at high frequency in a commercial silicon process technology presents several challenges. This article focuses on the architectural and circuit-level trade-offs involved in the design of the first silicon-based fully integrated phased array system operating at 24 GHz. The details of some of the important circuit building blocks are also discussed. The measured results demonstrate the feasibility of using integrated phased arrays for wireless communication and vehicular radar applications at 24 GHz.


Recent observations suggest that the vasoactive peptide endothelin-1 (ET-1) may be an important contributor to the etiology of glaucoma. ET-1 administration has been shown to produce optic nerve axonal loss and apoptosis of retinal ganglion cells. Ocular ET-1 levels are elevated in aqueous humor in response to elevated intraocular pressure both in glaucoma patients and in animal models of glaucoma; however, the precise mechanisms by which ET-1 mediates glaucomatous optic neuropathy are not clear. Presently we report that ET-1-mediated apoptosis was markedly attenuated in ETB receptor-deficient rats, suggesting a key role for ETB receptors in apoptosis of retinal ganglion cells by ET-1 treatment. Using virally transformed rat retinal ganglion cells (RGC-5 cells), we found that ET-1 (100 nmol/L) treatment produced apoptotic changes in these cells that was determined by flow cytometric analyses, release of mitochondrial cytochrome c to the cytosol, and increased phosphorylation of c-Jun N-terminal kinase. Pretreatment with the ETB-receptor antagonist BQ788 (1 micromol/L) was able to significantly attenuate ET-1-mediated apoptosis in RGC-5 cells. ET-1-mediated apoptotic changes in RGC-5 cells were associated with ETB-receptor activation and were accompanied by a significant upregulation of ETB-receptor expression. These studies suggest that ocular ET-1 acts through ETB receptors to mediate apoptosis of retinal ganglion cells, a key event in glaucoma and related optic neuropathies.


In this paper, the chemical properties of the transactinide elements rutherfordium, Rf (element 104); dubnium, Db (element 105); and seaborgium, Sg (element 106) are critically reviewed. The experimental methods for performing rapid chemical separations on a time scale of seconds are reviewed, and comments are given on the special situation with the transactinides for which the chemistry has to be studied with single atoms. There follows a systematic description of theoretical predictions and experimental results on the chemistry of Rf, Db, and Sg—their mutual comparison and evaluation. The literature cited has the cutoff date of March 1999. The more recent chemical identification of bohrium, Bh (element 107), and of hassium, Hs (element 108), should be evaluated in a future Part II of this report.


The majority of species are under predatory risk in their natural habitat and targeted by predators as part of the food web. Through the process of evolution by natural selection manifold mechanisms have emerged to avoid predation. As Fisher argued, it is the ubiquitous presence of anti-predator adaptations which shows that predation plays a significant role in the ecology and evolution of ecosystems. These ecosystems are intrinsically complex which derives from the high entanglement of organisms interacting in competitive relationships: the prey is part of the predator's environment and vice versa. As a result, the evolution of predator and prey is best described as a co-evolutionary process of predator-prey systems. It is common to classify anti-predator adaptations into 'primary defences' and 'secondary defences'. Primary defences operate before an attack by reducing the frequency of detection or encounter with predators. Secondary defences, which are used after a predator has initiated prey-catching behaviour, commonly involve the expression of toxins or deterrent substances which are not observable by the predator. Hence, the possession of such secondary defence in many prey species comes with a specific signal of that defence. This pairing of a toxic secondary defence and a conspicuous primary defence is known as aposematism. Previous models mainly focused on questions of the initial evolution of aposematism in ancestrally cryptic populations. However, the field has a renewed interest in questions beyond the initial evolution of aposematism such as: how conspicuous should a signal be, and how much should be invested into secondary defence? Moreover, which factors influence evolutionary stability of aposematic solutions. Within this context, the role of co-evolution and the mechanisms of aversive learning are at the heart of the current research. On the one hand, to explain stability and persistence of aposematic signals requires a theory of co-evolution of defence and signals. On the other hand, the role of the predator and details of the predator's aversive learning process gained renewed interest of the field. As the selective agent, aversive learning is an important aspect of predator avoidance and of the co-evolution of predator-prey systems. In the first chapter, this thesis will review the literature on aposematism and introduce the different selective pressures acting on aposematic prey. The thesis will then identify open questions of interest around aposematism. In the second chapter the thesis will focus on the perspective of the prey. The introduction of a game theoretical model of co-evolution of defence and signal will be followed by an adaptation of the model for finite populations. In finite populations, investigating the co-evolution of defence and signalling requires an understanding of natural selection as well as an assessment of the effects of drift as an additional force acting on stability. In the third chapter the thesis will adopt the perspective of the predator. It will introduce reinforcement learning as an normative framework of rational decision making in a changing environment. An analysis of the consequences of aposematism in combination with aversive learning on the predator's diet and energy intake will be followed by a lifetime model of optimal foraging behaviour in the presence of aposematic prey in the fourth chapter. In the last chapter I will conclude that the predator's aversive learning process plays a crucial role in the form and stability of aposematism. The introduction of temporal difference learning allows for a better understanding of the specific details of the predator's role in aposematism and presents a way to take the discipline forward.


Why have decollectivized Romanian lawyers failed to become important actors in the consolidation of their nation's democracy? Interviews of legal professionals in four Romanian cities suggest that their failure to participate in civil society inhibits avocats from becoming agents of change. Notwithstanding the 1990-2002 statutes privatizing the bar, daily Romanian law practice differs little from collectivized practice. A similar resemblance to United States solo and small-firm practice is so striking as to belie the influence of the communist past in determining the behavior of typical Romanian lawyers today. The economics of law practice seem to explain consistent behavior in both countries. Decollectivization has affected avocats' outlook on their profession. Enduring rapidly changing statutes in new fields, avocats yearn for stability and clarity in the law that would diminish the need for interpretation by judges, who are too often corrupt. Privatization has not modified the negative attitudes toward civic engagement generated during the communist era. Romanian lawyers are largely nonparticipants. This is in stark contrast to lawyers in the United States who actively volunteer in organizations to build their careers and out of a sense of social obligation, professional self-image, and response to community expectations. Romanian lawyers lack these non-economic motivations. However, if the financial/careerist justifications for civic activity were stronger, avocats' small but growing sense of professionalism could nudge them into community activities. In that new role they could strengthen Romanian democracy.


Luxury brands are motivated by their long-term vision, where the establishment of relationships with high-net worth customers is essential. Further supported by the fact that it may cost them as much as five times more to acquire new customers than retaining existing new ones. Luxury brands major focus is on providing an exceptional experience, which can arguably be hard to achieve online. Electronic Customer Relationship Management (e-CRM) further puts the focus on the customer interaction with little or no human contact at all. The purpose of this thesis is to examine the practice of Electronic Customer Relationship Management in luxury brands. In particular, how fashion luxury brands communicate the luxury value through e-CRM. The research method of this paper is qualitative, further a multiple case study of six luxury fashion brands. The cases has been observed from annual reports and websites. In order to fulfil the purpose several e-CRM characteristics were investigated, which were connected with the different value dimensions of luxury brands. The main challenge facing luxury brands is the dilemma between accessibility and exclusivity. The brands uses different strategies in order to handle this dilemma. The study shows that it is possible to deliver all four value dimensions online through the use of e-CRM initiatives. Therefore, it could be argued that online interactions would not weakening, but rather strengthening the brand image. This thesis focus the problem from the brands perspective.


Due to the current rates of data acquisition, the growth of data volumes in nearly all domains of our lives is reaching historic proportions [5], [6], [7]. Spatiotemporal data mining has emerged in recent decades with the main goal focused on developing data-driven mechanisms for the understanding of the spatiotemporal characteristics and patterns occurring in the massive repositories of data. This work focuses on discovering spatiotemporal co-occurrence patterns (STCOPs) from large data sets with evolving regions. Spatiotemporal co-occurrence patterns represent the subset of event types that occur together in both space and time. Major limitations of existing spatiotemporal data mining models and techniques include the following. First, they do not take into account continuously evolving spatiotemporal events that have polygon-like representations. Second, they do not investigate and provide sufficient interest measures for the STCOPs discovery purposes. Third, computationally and storage efficient algorithms to discover STCOPs are missing. These limitations of existing approaches represent important hurdles while analyzing massive spatiotemporal data sets in several application domains that generate big data, including solar physics, which is an application of our interdisciplinary research. In this work, we address these limitations by i) introducing the problem of mining STCOPs from data sets with extended (region-based) spatial representations that evolve over time, ii) developing a set of novel interest measures, and iii) providing a novel framework to model STCOPs. We also present and investigate three novel approaches to STCOPs mining. We follow this investigation by applying our algorithm to perform a novel data-driven discovery of STCOPs from solar physics data.


Estimating bacterial growth dynamics The pattern of sequencing read coverage of bacteria in metagenomic samples reflects the growth rate. This pattern is predictive of growth because bacterial genomes are circular, with a single origin of replication. So during growth, copies of the genome accumulate at the origin. Korem et al. use the ratio of copy number at the origin to the copy number at the terminus to detect the actively growing species in a microbiome (see the Perspective by Segre). They could spot the difference between virulent and avirulent strains, population diurnal oscillations, species that are growing in irritable bowel disease, and what happens when a host's diet changes. Results were consistent in chemostats, in mice, and in human fecal samples. Science, this issue p. 1101; see also p. 1058 A new method provides a quantitative measure of the growth rate of multiple gut microbes in one go. [Also see Perspective by Segre] Metagenomic sequencing increased our understanding of the role of the microbiome in health and disease, yet it only provides a snapshot of a highly dynamic ecosystem. Here, we show that the pattern of metagenomic sequencing read coverage for different microbial genomes contains a single trough and a single peak, the latter coinciding with the bacterial origin of replication. Furthermore, the ratio of sequencing coverage between the peak and trough provides a quantitative measure of a species' growth rate. We demonstrate this in vitro and in vivo, under different growth conditions, and in complex bacterial communities. For several bacterial species, peak-to-trough coverage ratios, but not relative abundances, correlated with the manifestation of inflammatory bowel disease and type II diabetes.


Atmospheric noble gases are routinely used as natural tracers to analyze gas transfer processes in aquatic systems. Their isotopic ratios can be employed to discriminate between different physical transport mechanisms by comparison to the unfractionated atmospheric isotope composition. In many applications of aquatic systems molecular diffusion was thought to cause a mass dependent fractionation of noble gases and their isotopes according to the square root ratio of their masses. However, recent experiments focusing on isotopic fractionation within a single element challenged this broadly accepted assumption. The determined fractionation factors of Ne, Ar, Kr and Xe isotopes revealed that only Ar follows the prediction of the so-called square root relation, whereas within the Ne, Kr and Xe elements no mass-dependence was found. The reason for this unexpected divergence of Ar is not yet understood. The aim of our computational exercise is to establish the molecular-resolved mechanisms behind molecular diffusion of noble gases in water. We make the hypothesis that weak intermolecular interactions are relevant for the dynamical properties of noble gases dissolved in water. Therefore, we used ab initio molecular dynamics to explicitly account for the electronic degrees of freedom. Depending on the size and polarizability of the hydrophobic particles such as noble gases, their motion in dense and polar liquids like water is subject to different diffusive regimes: the inter-cavity hopping mechanism of small particles (He, Ne) breaks down if a critical particle size achieved. For the case of large particles (Kr, Xe), the motion through the water solvent is governed by mass-independent viscous friction leading to hydrodynamical diffusion. Finally, Ar falls in between the two diffusive regimes, where particle dispersion is propagated at the molecular collision time scale of the surrounding water molecules.


Lupus nephritis (LN) often results in progressive renal dysfunction. The inactive rhomboid 2 (iRhom2) is a newly identified key regulator of A disintegrin and metalloprotease 17 (ADAM17), whose substrates, such as TNF-&agr; and heparin-binding EGF (HB-EGF), have been implicated in the pathogenesis of chronic kidney diseases. Here, we demonstrate that deficiency of iRhom2 protects the lupus-prone Fcgr2b–/– mice from developing severe kidney damage without altering anti-double-stranded DNA (anti-dsDNA) Ab production by simultaneously blocking HB-EGF/EGFR and TNF-&agr; signaling in the kidney tissues. Unbiased transcriptome profiling of kidneys and kidney macrophages revealed that TNF-&agr; and HB-EGF/EGFR signaling pathways are highly upregulated in Fcgr2b–/– mice, alterations that were diminished in the absence of iRhom2. Pharmacological blockade of either TNF-&agr; or EGFR signaling protected Fcgr2b–/– mice from severe renal damage. Finally, kidneys from LN patients showed increased iRhom2 and HB-EGF expression, with interstitial HB-EGF expression significantly associated with chronicity indices. Our data suggest that activation of iRhom2/ADAM17-dependent TNF-&agr; and EGFR signaling plays a crucial role in mediating irreversible kidney damage in LN, thereby uncovering a target for selective and simultaneous dual inhibition of 2 major pathological pathways in the effector arm of the disease.


Lyrical, dark, comic or iconoclastic, the Irish short story has always punched well above its weight. Anne Enright has brought together a dazzling collection of Irish stories by authors born in the twentieth century - from Mary Lavin and Frank O'Connor to Claire Keegan and Kevin Barry. With a pithy and passionate introduction by Enright, The Granta Book of the Irish Short Story traces this great tradition through decades of social change and shows the pleasure Irish writers continue to take in the short-story form. Deft and often devastating, the short story dodges the rolling mythologies of of Irish life to produce truths that are delightful and real. Also includes stories by: Maeve Brennan, Roddy Doyle, Mary Lavin, Colum McCann, William Trevor, John McGahern, Colm Toibin, Claire Keegan and Kevin Barry.


One of the most successful examples of artificial insemination as a conservation management tool has been the production and genetic management of over 87 black-footed ferrets and selected re-introduction into their previous home range (Howard et al., 2001). While AI has the capability to supplement inbred populations, prevent disease transmission associated with the movement of whole animals, and overcome mate incompatibility, little effort has been devoted to this area in Australia. AI into the urogenital sinus has been successful in the koala (Phascolarctos cinereus) with 6 live births from 11 inseminations reported (Johnson et al., 1999 abst.). Super-ovulated brush-tailed possums (Trichosurus vulpecula) and tammar wallabies (Macropus eugenii) inseminated into the uterus resulted in 1-4 cell embryos (Molinia et al., 1998a).

The tammar wallaby (M. eugenii) is one of 56 species of the family Macropodidae (Kirsch and Calaby, 1977), comprising small rat kangaroos, wallabies and large kangaroos. As in all marsupials studied, females have two separate uteri each with a separate cervix that open into the anterior vaginal culs de sac. The vaginal apparatus is made up of two lateral vaginae and a third, in macropodids permanent, median vagina (birth canal) that connects the anterior vaginal culs de sac to a urogenital sinus and opening.

Female reproduction is extremely well characterized in M. eugenii (Tyndale-Biscoe and Renfree, 1987) making it an ideal model to develop AI for application in endangered counterparts including the brush-tailed rock wallaby (Petrogale penicillata) and long-nosed potoroo (Potorous tridactylus). M. eugenii is monovular and polyoestrus, with a breeding season from mid January to mid May. They have a post-partum oestrus, and a multiple male mating strategy. Embryonic diapause is a phenomenon common to many macropodids, and occurs when a developing embryo (conceived post-partum) arrests at the unilaminar blastocyst stage in the uterus for the duration of lactation and suckling by the pouch young on the teat (Sharman, 1959; Tyndale-Biscoe et al., 1974; Renfree, 1981). If the sucking stimulus stops, the embryo reactivates and birth occurs 26.4±0.5 days later (Merchant, 1979; Renfree et al., 1989). Oestrus and mating occur 1-6h post-partum (Rudd, 1994) and ovulation from 37-43h post-partum (Renfree and Lewis, 1996). Sperm are found in the uterus 6-24h post-coitum (Tyndale-Biscoe and Rodger, 1978). Thus by removing the sucking stimulus we can naturally synchronize the birth, oestrus and ovulation in M. eugenii and introduce sperm relative to the time it is found naturally in the tract.
The aim of this study was to develop artificial insemination in M. eugenii. Twenty-four adult females were isolated from males and their reproductive cycles naturally synchronized as described above. Semen was collected from adult males in Ham's F10 +5% fetal calf serum and 50IU/mL penicillin-50±g/mL streptomycin (Life Technologies, Australia) using a 10mm diameter, 3-strip electrode rectal probe with a 20Hz sine wave electro-ejaculation unit (CGS, Australia)(Taggart et al., 1998). Sperm was assessed for motility and concentration, and inseminated within 12h of birth into 4 different regions of the female reproductive tract:
(i) urogenital sinus via modified syringe (n=7)
(ii) anterior vaginal culs de sac via silicon balloon HSG catheter (Cook, Australia)(n=7)
(iii) uterus via a trans-cervical catheter during laparotomy (n=5)
(iv) uterus directly via needle during laparotomy (n=5)
Animals were checked for births from 26 days after AI.

Sperm inseminated had a mean (±SEM) sperm motility index of 245.7±14.9 (0-400 scale), motility of 93.1±0.9%, and concentration of 16.3±2.0x106 sperm/mL across all animals treated. One of the five females (♀0651), inseminated by direct intra-uterine artificial insemination, gave birth (4.2% success across all animals inseminated). This is the first macropodid offspring produced by AI. ANOVA analysis (SYSTAT 9.01) indicated that ♀0651 was an outlier with respect to a later insemination time (~16.5h post-partum), than other animals (10.6±0.7h post-partum). This may be a critical factor that resulted in success in this animal. Sperm used in this female was also of a considerably higher quality with a sperm motility index of 318.2, 96.3% motility and concentration of 10.1x106 sperm/mL.

Based on our findings a second group of females (n=7) was inseminated by intra-uterine AI using insemination times further from oestrus but closer to ovulation in the female. These ranged from approximately 15.5 to 27.5h post-partum. Inseminates had a higher mean concentration of 10.3 ± 4.4x107 sperm/mL, and a sperm motility index of 237.5±7.3 and 83.9±2.6% motility. To date, one of these animals has not been successful but the remaining 6 animals may have undergone seasonal embryonic diapause. Investigations to confirm pregnancies are currently underway.

The ultimate goal of this work is to improve the efficiency of AI in M. eugenii and work toward a non-surgical technique that can be readily adopted in endangered macropodids. We know that sperm capacitation is important in fertilization in marsupials (Mate and Rodger, 1996), and anaesthetic can negatively affect sperm transport (Wildt et al., 1987) and ovulation (Howard et al., 1992). These and other factors need to be taken into consideration to further optimize this technique.


The year 2000 marks the tenth anniversary of the 1990 passage of the Americans with Disabilities Act ("ADA"). It also marks a quarter century since the passage of the Education for All Handicapped Children Act ("EAHCA"). The EAHCA opened the doors for disabled children to receive a free and appropriate education. As a result of this special education law, many disabled young people were able to succeed and are now knocking at law schools' doors seeking admission.On July 26, 1990, Congress enacted the ADA, a landmark civil rights bill designed to open up all aspects of American life to individuals with disabilities. The stated purpose of this federal law is to provide a clear and comprehensive national mandate for the elimination of discrimination against individuals with disabilities. The focus of the ADA is to furnish strong and consistent standards addressing discrimination against individuals with disabilities. Furthermore, Congress bestows on the federal government the primary responsibility for enforcing the standards established by the ADA. Law schools face the challenge of providing disabled students reasonable accommodations in a fair and equitable manner. Disabled law students are demanding academic modifications in course examinations -- claiming to be persons with mental and physical disabilities. Law schools, by virtue of the entitlements under the ADA, are witnessing requests for exam modifications, including: changes in exam format; additional test time to complete an exam; and test relocation for environmental control purposes.This article discusses and analyzes court decisions addressing reasonable accommodations in the academic arena of law school examinations. The text illustrates the impact of the ADA and the direction courts are heading as they tackle this difficult and important area of law. In a prior study, eighty law schools from across the country were surveyed to obtain data and elicit their opinions on questions relating to academic modifications. The empirical data is intended to serve as a backdrop for elaboration and comparison of these and other questions. The significant number of disabled students seeking academic modifications in their law school education warrants such an inquiry. Law schools continue to grapple with claims from disabled students for fair and equitable treatment. An additional concern is the desire to avoid a backlash from the non-disabled students who want to prevent providing disabled students an unfair advantage in the law school setting.


Background There are limited data on the safety of intravenous recombinant tissue plasminogen activator (rtPA) for treating acute ischemic stroke in patients with gastrointestinal malignancy or recent gastrointestinal bleeding within 21 days of their index stroke. Aims To evaluate clinical outcomes in patients treated with rtPA for acute ischemic stroke who had gastrointestinal malignancy or recent gastrointestinal bleeding Methods We identified patients who were treated with rtPA for acute ischemic stroke between 2/2009 and 12/2015 from the Get With The Guidelines-Stroke linked to Medicare claims data. Gastrointestinal malignancy and recent gastrointestinal bleeding were defined as any gastrointestinal malignancy hospitalisation within one year prior to acute ischemic stroke and gastrointestinal bleeding hospitalisation within 21 days prior to acute ischemic stroke, respectively. Outcomes of interest included in-hospital mortality and bleeding complications. Results Among 40,396 patients aged 65 years or older treated with rtPA for acute ischemic stroke from 1522 sites (mean age [SD] 81.0 [8.1] years; 41.9% women), 136 (0.3%) had gastrointestinal malignancy (n = 96) or recent gastrointestinal bleeding (n = 43). Patients with gastrointestinal malignancy or bleeding had more severe stroke than those without (median NIHSS [interquartile range]: 14.0 [8.0–19.0] vs. 11.0 [6.0–18.0]). The rates of in-hospital mortality and life-threatening systemic haemorrhage were not significantly different between those with and without gastrointestinal malignancy or bleeding (mortality: 10.3% vs. 9.0%, adjusted odds ratio [aOR] 1.01, 95%CI 0.58–1.75; bleeding: 2.3% vs. 1.2%, aOR 1.72, 95%CI 0.58–5.11). Conclusions In this observational cohort, we did not find increased risk of in-hospital mortality and bleeding in rtPA-treated patients with gastrointestinal malignancy or recent gastrointestinal bleeding.


The global emission of CO2 has increased in the sector of power generation from countries outside the OECD, particularly in China which comprises two-third of the share. Meanwhile, OECD countries focus their effort in reducing their emission, where the industry area declined their emission by a quarter. Consequently, governments set up energy policies where renewable-based energies such as solar or wind energies, are highlighted. The drawback is the dependency of environment factors which generates power variations in the network leading to instabilities and a blackout in the worst case. The use of hydropower is an excellent complement to versatile renewable energy, capable of compensating these fluctuations and even be used as an energy storage. In Switzerland, hydropower is the most available resources and is constantly under development to increase capacity and energy-efficiency. Nevertheless, a lot of effort is put to extend lifetime of power generating equipment as much as possible in order to optimize the best timing for replacement or refurbishment, which requires efficient and flexible tools such as real-time simulations, which are widely used with the rapid development of computation technology. The objective of this present thesis is to study the feasibility of a multi-physics model-based real-time simulation with SIMSEN for an existing hydroelectric power plant. The concept of such system consists of using a validated model and achieves a real-time simulation taking into account boundary conditions such as water level of upstream reservoir, voltage of power network, but also set point of control system including turbine guide vane opening and the excitation system of generator. The system would enable to detect potential dysfunctions if the behavior of the power plant shows significant discrepancies in the simulation-measurement comparison during the real-time simulation. The study is divided into two main parts, which are the set-up of a test bench and the implementation of the real-time system in the power plant. The first part describes the methodology for setting-up a small-scale power unit which simulates similar behavior as a large scale one. The model includes the parameters from experimental tests used for parameters identification of synchronous machine. Two validations tests are presented: (i) a load variation (ii) sudden three-phase short circuit. The model validation is achieved comparing offline simulation results with measurement, followed by a validation in real-time with similar tests. The set-up of the test bench is concluded by a demonstration of feasibility in monitoring application by detection of a dysfunction during an opening failure of a circuit-breaker. The second part explains the modeling of a 72MW hydroelectric power plant, which includes the modeling of hydraulic components such as pipe, surge tank and Pelton turbine besides the modeling of generator. Two measurement campaigns were organized. The first consisted in collecting data in order to validate the present model. The second consisted of implementing the model running in real-time in a general-purpose computer, in the power plant and performed variations of active and reactive powers.


ABSTRACT Inclusions of platinum-group minerals (PGM) within alluvial isoferroplatinum nuggets from the Freetown Peninsula, Sierra Leone, are aligned with their shape determined by the structure of their host. The edges of the majority of the inclusions lie at 0°, 45° or 90° to external crystal edges of the nugget which shows that the inclusions are not randomly oriented earlier minerals incorporated within their host. The inclusions are later infills, probably formed at the surface of the nugget during growth and subsequently enclosed by the growing nugget. PGM on the present surface of the nugget represent the last stage of this partnership. A single nugget containing abundant inclusions is described here but similar features are observed in other nuggets from the same area. The inclusions contain laurite (RuS2), irarsite–hollingworthite (IrAsS–RhAsS), Pd–Te–Bi–Sb phases, Ir-alloy, Os-alloy, Pd-bearing Au, an Rh–Te phase, Pd–Au alloy and Pd–Pt–Cu alloy. PGM found on the nugget surface include laurite, irarsite and cuprorhodsite (CuRh2S4). The Pd–Te–Bi–Sb phases may include Sb-rich keithconnite (Pd20S7) and compositions close to the kotulskite–sobolevskite solid-solution series (PdTe–BiTe). Textural evidence suggests that formation of the nuggets began with the isoferroplatinum host and the voids were filled starting intergrowths of laurite and irarsite–hollingworthite with both laurite and irarsite–hollingworthite often showing compositional zonation and each of them replacing the other. Filling of the voids probably continued with Pd-Cu-bearing gold, Sb-rich keithconnite (Pd,Pt)20.06(Te,Sb,Bi)6.94, keithconnite, telluropalladinite Pd9(Te,Bi)4, RhTe and finally Ir-alloy and then Os-alloy. The nuggets are thought to be neoform growths in the organic- and bacterial-rich soils of the tropical rain forest cover of the Freetown intrusion. The mineralogical assemblage in the layered gabbros of the intrusion has been previously shown to differ from the alluvial assemblage in the rivers and these inclusions, not seen in Pt3Fe in the unaltered rocks, add a further item to the catalogue of differences.


Aims: A nested case-control study of 75 patients with cardiac device infections (CDI) and 75 matched controls was conducted to evaluate time course, risk factors, culture results and frequency of CDI. Methods and results: CDI occurred in 75/3410 (2.2%) device implantation and revision procedures, performed between 2000 and 2007. The time delay between device procedure and infection ranged from 0 to 64 months (mean 14 (SD 16)), 21 patients (28%) had an early infection (<1 month), 26 (35%) a late infection (1–12 months) and 28 (37%) a delayed infection (>12 months). Of interest, 18 (24%) patients presented with an infection >24 months after the device-related procedure. Time delay until infection was significantly shorter when cultures were positive for micro-organisms compared to negative cultures (8 (12) vs 18 (18) months, p = 0.03). Pocket cultures in delayed infections remained more often negative (61% vs 23%, p = 0.01). Independent CDI risk factors were: device revision (odds ratio (OR) 3.67; 95% confidence interval (CI), 1.51 to 8.96), renal dysfunction defined as glomerular filtration rate <60 ml/min (OR 4.64; CI, 1.48 to 14.62) and oral anticoagulation use (OR 2.83; CI 1.20 to 6.68). Conclusion: CDI occurred in 2.2% of device procedures, with 24% occurring more than two years after the device-related procedure. Renal dysfunction, device revisions and oral anticoagulation are potent risk factors for CDI.


ABSTRACT Sandstone reservoirs from the Norwegian continental shelf commonly show varying degrees of postdepositional fractionation of Sm/Nd ratio, apparently due to preferential incorporation of Sm in the crystal lattice of diagenetic apatite. Based on data from leaching experiments, an apatite mineral separate, and petrography, it is proposed that fractionation occurred mainly during closed-system burial diagenesis, as phosphate deposited on the sea floor recrystallized to apatite and incorporated rare earth elements (REE) from the surrounding rock matrix. As a result, the Sm-Nd model age parameter in general contains two components of information: A) the true crustal age of the sediment and B) a secondary component of Sm/Nd fractionation, which can be either negligible or dominant. It is difficult to separate these components and thus correct for component B. Even in data showing no obvious signs of postdepositional fractionation, model ages may be variably disturbed by subordinate amounts of diagenetic alteration. However, the isotope ratio 143Nd/144Nd is expected to be relatively resistant to alteration by secondary Sm/Nd fractionation and should therefore be used rather than model age as the principal correlation parameter in stratigraphic studies. In this way, Nd-isotope stratigraphy can still be used as a valuable and unique tool for studies of provenance and correlation, even in strata showing strong Sm/Nd fractionation effects. Strongly Sm/Nd-fractionated horizons (recognized by bulk-rock Sm/Nd ratios > 0.23) may also be useful for stratigraphic correlation, but it is clear that their occurrence reflects special depositional conditions rather than shifts in sediment provenance.


Does the embryological state of genital undifferentiation suggest the possibility of a collapse of gender from male and female singularities to a more complex, layered concept of sexuality where each of the sexes can be seen one within the other? Could the sexual body be represented as an ontologically transparent skin through which art and science are mutually visible? These questions are posed by the author in the form of cross-disciplinary works: original biologicakisual research into the development of the genitals in the human embryo, 3D models, drawings, videos, paintings on the body and didactic lecture-performances. The works draw upon disparate fields of knowledge-linguistics, psychoanalysis, the histories of visual art and biological science, the subjectivity of the artist—to propose alternative terms for the construction of sex, sexuality and gender during this time of crisis in sexual difference as it stands at the intersection of feminism, science, art and politics.


Why did Turkish policies toward Syria and Egypt in 2011-15 largely fail? At the individual level, the leadership of Recep Tayyip Erdogan was plagued by populism in the sense that he uses foreign policy issues for the sake of domestic party politics without pursuing long-term international strategies. At the state level, Turkey's military and diplomatic capacity was not sufficient to shape the political transformations in Syria and Egypt. At the international level, Turkey could not effectively respond to the challenges of the Iranian-led and Saudi Arabian-led blocs. The former supported the regime of Bashar al-Assad and the latter backed the military coup in Egypt. Turkey needed the support of its North Atlantic Treaty Organization allies against these two rival blocs. However, Erdogan's populist discourse and tendency toward Islamist authoritarianism further deteriorated Turkey's relations with its Western allies.


Richard Abel's magisterial new book radically rewrites the history of French cinema between 1896 and 1914, particularly during the years when Pathe-Freres, the first major corporation in the new industry, led the world in film production and distribution. Based on extensive investigation of rare archival films and documents, and drawing on recent social and cultural histories of turn-of-the-century France and the United States, his book provides new insights into the earliest history of the cinema. Abel tells how early French film entertainment changed from a cinema of attractions to the narrative format that Hollywood would so successfully exploit. He describes the popular genres of the era - comic chases, trick films and feeries, historical and biblical stories, family melodramas and grand guignol tales, crime and detective films - and shows the shift from short subjects to feature-length films.Cinema venues evolved along with the films as live music, color effects, and other new exhibiting techniques and practices drew larger and larger audiences. Abel explores the ways these early films mapped significant differences in French social life, helping to produce thoroughly bourgeois citizens for Third Republic France. "The Cine Goes to Town" recovers early French cinema's unique contribution to the development of the mass culture industry. As the one-hundredth anniversary of cinema approaches, this compelling demonstration of film's role in the formation of social and national identity will attract a wide audience of film scholars, social and cultural historians, and film enthusiasts.


Due to globalization and relaxed market regulation, we have assisted to an increasing of extremal dependence in international markets. As a consequence, several measures of tail dependence have been stated in literature in recent years, based on multivariate extreme-value theory. In this paper we present a tail dependence function and an extremal coefficient of dependence between two random vectors that extend existing ones. We shall see that in weakening the usual required dependence allows to assess the amount of dependence in $d$-variate random vectors based on bidimensional techniques. Simple estimators will be stated and can be applied to the well-known stable tail dependence function. Asymptotic normality and strong consistency will be derived too. An application to financial markets will be presented at the end.


Importance
The incidence of rhegmatogenous retinal detachment (RRD) is partly determined by its risk factors, such as age, sex, cataract surgery, and myopia. Changes in the prevalence of these risk factors could change RRD incidence in the population.

Objective
To determine whether the incidence of RRD in the Netherlands has changed over recent years and whether this change is associated with an altered prevalence of RRD risk factors.

Design, Setting, and Participants
This cohort study included data from all 14 vitreoretinal clinics in the Netherlands, as well as a large Dutch population-based cohort study. All patients who underwent surgical repair for a primary RRD in the Netherlands from January 1 to December 31, 2009, and January 1 to December 31, 2016, were analyzed, in addition to all participants in the population-based Rotterdam Study who were examined during these years. Analysis began February 2018 and ended November 2019.

Exposures
RRD risk factors, including age, male sex, cataract extraction, and myopia.

Main Outcomes and Measures
Age-specific RRD incidence rate in the Dutch population, as well as change in RRD incidence and risk factor prevalence between 2009 and 2016.

Results
In 2016, 4447 persons (median [range] age, 61 [3-96] years) underwent surgery for a primary RRD within the Netherlands, resulting in an RRD incidence rate of 26.2 per 100 000 person-years (95% CI, 25.4-27.0). The overall RRD incidence rate had increased by 44% compared with similar data from 2009. The increase was observed in both phakic (1994 in 2009 to 2778 in 2016 [increase, 39%]) and pseudophakic eyes (1004 in 2009 to 1666 in 2016 [increase, 66%]), suggesting that cataract extraction could not solely account for the overall rise. Over the same period, the prevalence of mild, moderate, and severe myopia among persons aged 55 to 75 years had increased by 15.6% (881 of 4561 [19.3%] vs 826 of 3698 [22.3%]), 20.3% (440 of 4561 [9.6%] vs 429 of 3698 [11.6%]), and 26.9% (104 of 4561 [2.3%] vs 107 of 3698 [2.9%]), respectively, within the population-based Rotterdam Study.

Conclusions and Relevance
In this study, an increase was observed in primary RRD incidence in the Netherlands over a 7-year period, which could not be explained by a different age distribution or cataract surgical rate. A simultaneous myopic shift in the Dutch population may be associated, warranting further population-based studies on RRD incidence and myopia prevalence.


Climate change is increasingly being framed as a "climate crisis." Such a crisis could be viewed both to unfold in the climate system, as well as to be induced by it in diverse areas of society. Following from current understandings of modern crises, it is clear that climate change indeed can be defined as a "crisis." As the Intergovernmental Panel on Climate Change 1.5oC special report elaborates, the repercussions of a warming planet include increased food insecurity, increased frequency and intensity of severe droughts, extreme heat waves, the loss of coral reef ecosystems and associated marine species, and more. It is also important to note that a range of possible climate-induced crises (through, e.g., possible increased food insecurity and weather extremes) will not be distributed evenly, but will instead disproportionally affect already vulnerable social groups, communities, and countries in detrimental ways.
 The multifaceted dimensions of climate change allow for multiple interpretations and framings of "climate crisis," thereby forcing us to acknowledge the deeply contextual nature of what is understood as a "crisis." Climate change and its associated crises display a number of challenging properties that stem from its connections to basically all sectors in society, its propensity to induce and in itself embed nonlinear changes such as "tipping points" and cascading shocks, and its unique and challenging long-term temporal dimensions. The latter pose particularly difficult decision-making and institutional challenges because initial conditions (in this case, carbon dioxide emissions) do not result in immediate or proportional responses (say, global temperature anomalies), but instead play out through feedbacks among the climate system, oceans, the cryosphere, and changes in forest biomes, with some considerable delays in time. Additional challenges emerge from the fact that early warnings of pending so-called "catastrophic shifts" face numerous obstacles, and that early responses are undermined by a lack of knowledge, complex causality, and severe coordination challenges.


In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.


The Irish Diaspora is a series of transnational networks connecting emigrant communities with the homeland and each other. Such connections had long historical roots and a broad geographical extent. This chapter demonstrates the range of movements adhered to by a wide range of Irish emigrants in the long nineteenth century, from early republican and trades' union movements, to modern nationalist groups and labour institutions. The discussion is shaped by the concept that transnationalism extends beyond the migration of Irish culture and has meaning primarily as a method of demonstration consciousness and action beyond Ireland. Transnationalism is a method for analysing a mosaic of individuals, groups and activities connected and sustained across national borders. Its value is predicated upon the existence of sources which enable the study of multiple locations: not as isolated instances of culture and behaviour, but as a genuine set of connected communities whose transnationalism lies in their communication across space, their coordination of activity or their exampling of each other's strategies. The chapter seeks to highlight how immigrants brought modes of behaviour and forms of action that were Irish in character and had a distinct effect on host institutions. Irish nationalist movements provide the clearest examples of this continuing importance of Ireland in the immigrant's sense of identity; while labour organisations, such as trades' unions and working-class political parties felt the impact of Irish modes of behaviour beyond innate nationalism. Ultimately, we make the case for transnational connections between Irish people and non-Irish actors, and for the blending and blurring of modes of activity, thus moving away from the idea that the nationalist struggle at home was somehow divorced from other movements for political and social change.


Light is the ultimate energy source for photo-autotrophs on earth. For green plants, however, it can also be toxic under certain stressful environmental conditions and at critical developmental stages. Anthocyanins, a class of flavonoids, act as an effective screening mechanism that allows plant survival and proliferation under occasional periods of harmful irradiation through modulation of light absorption. Apart from light-sensing through photoreceptors such as phytochrome and cryptochrome, plants use the photosynthetic electron transfer (PET) chain to integrate light information. The redox status of the plastoquinone (PQ) pool of the PET chain regulates anthocyanin biosynthesis genes, together with the plant hormone ethylene and plant hormone-like sugars. A complex signaling apparatus in acyanic cells appears to transduce information to cyanic cells to regulate anthocyanin production through an intercellular signaling pathway that remains largely uncharacterized. This review will highlight recent advances in this field and their implications for the regulation of anthocyanin pigmentation.


The influence of different bacterial phenotypic traits on the feeding selectivity of a bac- terivorous nanoflagellate was investigated in laboratory experiments. Twelve bacterial isolates from freshwater habitats were characterized in terms of cell size, morphology, capsule formation, surface hydrophobicity and charge, and swimming behavior. Mechanisms of differential flagellate feeding on these isolates were studied in short-term grazing experiments by high-resolution video microscopy using the nanoflagellate Spumella sp. as a model interception-feeding predator. The dif- ferentiation into distinct stages of the feeding process (contact, capture, ingestion) revealed a com- plex selection behavior illustrated by the relatively small proportion of ingested bacteria over cell contacts. We found that bacterial swimming speed increased contact rates but also decreased flagel- late capture efficiency, which had a compensating effect on overall ingestion rates. Bacterial cell size revealed no correlation with flagellate contact rates but an effective inhibition of ingestion rates when exceeding a critical size limit. Correlation analysis presented no bacterial property to account for the residual variability of flagellate ingestion efficiencies. Experiments with specifically coated artificial particles provided evidence for the relative importance of the biochemical surface composi- tion in flagellate food selection compared to physicochemical interaction forces. Only extreme charges beyond -45 mV reduced flagellate ingestion rates. Our results reinforce the idea that bacte- rial cell size strongly affects the feeding success of bacterivorous flagellates, and further implicates size-independent bacterial traits such as swimming speed and biochemical surface composition in this feeding success.


Intrusion detection is a relatively mature domain. Network Intrusion Detection Systems have been used for over a long period of time for detecting potential intruders or attackers in a network or similar environment. Detecting and eliminating such threats is essential for the growth of any company in this cashless economy era where more and more users are moving to online banking, ecommerce and other related domains. With new technologies such as machine learning, neural networks, the advancements in computers such as processors and memory, and programming languages and libraries custom tailored for machine learning such as R, Python, matplotlib, scikit-learn etc. NIDS instead of being a vague Intrusion detection approach is now an accurate Intrusion detection system. The anomalies in network data are effectively predicted using such machine learning and neural network algorithms. In this project we are trying to create a model which works with a classic NIDS benchmark dataset in its backbone to create an accurate system which predicts network anomalies. Here we are using ensembled approaches for both sampling and for prediction phases for getting a superior result. For the sampling process we are using SMOTETomek algorithm which combine regular SMOTE for over-sampling and Tomek link for under-sampling. For the classification approach we are using Support Vector Machines (SVM), K-Nearest Neighbors, Nave Bayes. The method is not claiming an absolute accuracy or performance, and it can be still be improved upon with better resources and tools.


In this paper a new tool for estimation of the radio performance of terminal antennas in terms of Total Radiated Power, TRP is tested and evaluated. The tool is known as Lab Express and is developed by the Canadian company EMSCAN. The results from measurements performed with the Lab Express are compared with of the radiation patterns and total radiated power (TRP) estimates, measured with a CTIA approved Satimo SG24 chamber. The TRP and radiation pattern measurements are performed on 10 commercially available mobile phones at GSM 900 and GSM 1800 frequency bands. The dependency of the measured TRP on the positioning of the mobile phone on EMSCAN is also tested. Our results indicate that the TRP measured with Lab Express is well correlated with the results obtained from the Satimo SG24 chamber even though the Lab Express equipment seem to over estimate the TRP with on average about 4dB at 900MHz and about 1.3dB at 1800MHz.


BACKGROUND
Pediatric phase I oncology trials have historically focused on safety and toxicity, with objective response rates (ORRs) <10%. Recently, with an emphasis on targeted approaches, response rates may have changed. We analyzed outcomes of recent phase I pediatric oncology trials.

MATERIALS AND METHODS
This was a systematic review of phase I pediatric oncology trials published in 2012-2017, identified through PubMed and EMBASE searches conducted on March 14, 2018. Selection criteria included full-text articles with a pediatric population, cancer diagnosis, and a dose escalation schema. Each publication was evaluated for patient characteristics, therapy type, trial design, toxicity, and response.

RESULTS
Of 3,431 citations, 109 studies (2,713 patients) met eligibility criteria. Of these, 78 (72%) trials incorporated targeted therapies. Median age at enrollment/trial was 11 years (range 3-21 years). There were 2,471 patients (91%) evaluable for toxicity, of whom 300 (12.1%) experienced dose-limiting toxicity (DLT). Of 2,143 patients evaluable for response, 327 (15.3%) demonstrated an objective response. Forty-three (39%) trials had no objective responses. Nineteen trials (17%) had an ORR >25%, of which 11 were targeted trials and 8 were combination cytotoxic trials. Targeted trials demonstrated a lower DLT rate compared with cytotoxic trials (10.6% vs. 14.7%; p = .003) with similar ORRs (15.0% vs. 15.9%; p = .58).

CONCLUSION
Pediatric oncology phase I trials in the current treatment era have an acceptable DLT rate and a pooled ORR of 15.3%. A subset of trials with target-specific enrollment or combination cytotoxic therapies showed high response rates, highlighting the importance of these strategies in early phase trials.

IMPLICATIONS FOR PRACTICE
Enrollment in phase I oncology trials is crucial for development of novel therapies. This systematic review of phase I pediatric oncology trials provides an assessment of outcomes of phase I trials in children, with a specific focus on the impact of targeted therapies. These data may aid in evaluating the landscape of current phase I options for patients and enable more informed communication regarding risk and benefit of phase I clinical trial participation. The results also suggest that, in the current treatment era, there is a rationale to increase earlier access to targeted therapy trials for this refractory patient population.


Chile pepper (Capsicum annuum L.) yields are highly variable and are strongly influenced by disease and weather. The goal of two field experiments was to evaluate crop management factors, especially planting date, that could contribute to improved and more consistent crop production. Current practice in New Mexico is to direct seed the crop from 13 to 27 Mar. In the first experiment, chile pepper was direct seeded on three planting dates, 13, 20, and 27 Mar. 2000, without or with a fungicide treatment of pentachloronitrobenzene and mefenoxam for the control of damping off. The results in- dicate planting date had no effect on stand establishment or yield. Fungicide treatment, significantly reduced stand, but had no effect on yield. In the second experiment, chile pepper was direct seeded on six planting dates, 13, 20, 27 Mar. and 3, 10, 17, Apr. 2001, with or without an application of phosphorus fertilizer, P at 29.4 kg·ha -1 , banded beneath the seed row. During the growing season, this experimental planting suffered, as did com- mercial plantings in New Mexico, from high mortality and stunting due to beet curly top virus, a disease transmitted by the beet leafhopper. The results indicate planting date had a significant effect on crop performance. The best stand establishment and highest yield were associated with the earliest planting date, 13 Mar. This date also resulted in the least viral disease damage. Phosphorus fertilizer had no effect on stand establishment or yield. Chemical names used: pentachloronitrobenzene (PCNB); (R)-2-((2,6-dimethylphenyl)- methoxyacetylamino)-propionic acid methyl ester (mefenoxam).


We address the generation of fully inseparable three-mode entangled states of radiation by interlinked nonlinear interactions in χ(2) media. We show how three-mode entanglement can be used to realize symmetric and asymmetric telecloning machines, which achieve optimal fidelity for coherent states. An experimental implementation involving a single nonlinear crystal in which the two interactions take place simultaneously is suggested. Preliminary experimental results showing the feasibility and the effectiveness of the interaction scheme with a seeded crystal are also presented.


Third-party funding in international commercial arbitration is one of the most current and controversial issues in international arbitration. Third-party funding is the system whereby a third-party funder finances, partly or fully, one of the parties' arbitration costs. In case of a favourable award, the third-party funder is generally remunerated by a previously agreed percentage of the amount of the award. In case of an unfavourable award, the funder's investment is lost. One of the numerous issues raised by the involvement of third-party funders in international commercial arbitration proceedings is arbitrator conflict of interest due to nondisclosure of the involvement of the third-party funder in the process. In this article, we first explain the concept of 'third-party funding in international commercial arbitration.' Then we examine arbitrator conflict of interest implicating third-party funders. Finally, we discuss the need to create an obligation to disclose the involvement of third-party funders in arbitral proceedings as a predicate for arbitrator conflict of interest.


Estimates of recovery from oil fields are often found to be significantly in error, and the multidisciplinary SAIGUP modelling project has focused on the problem by assessing the influence of geological factors on production in a large suite of synthetic shallow-marine reservoir models. Over 400 progradational shallow-marine reservoirs, ranging from comparatively simple, parallel, wave-dominated shorelines through to laterally heterogeneous, lobate, river-dominated systems with abundant low-angle clinoforms, were generated as a function of sedimentological input conditioned to natural data. These sedimentological models were combined with structural models sharing a common overall form but consisting of three different fault systems with variable fault density and fault permeability characteristics and a common unfaulted end-member. Different sets of relative permeability functions applied on a facies-by-facies basis were calculated as a function of different lamina-scale properties and upscaling algorithms to establish the uncertainty in production introduced through the upscaling process. Different fault-related upscaling assumptions were also included in some models. A waterflood production mechanism was simulated using up to five different sets of well locations, resulting in simulated production behaviour for over 35 000 full-field reservoir models. The model reservoirs are typical of many North Sea examples, with total production ranging from c. 15×106 m3 to 35×106 m3, and recovery factors of between 30% and 55%. A variety of analytical methods were applied. Formal statistical methods quantified the relative influences of individual input parameters and parameter combinations on production measures. Various measures of reservoir heterogeneity were tested for their ability to discriminate reservoir performance. This paper gives a summary of the modelling and analyses described in more detail in the remainder of this thematic set of papers.


This work relates to the development of a method of preparing a filled phenolic resin, for use particularly, but not exclusively, in building materials. The method includes mixing filler and micro-filler, a catalyst, resin and a hetrocyclic alcohol (i.e. furfuryl alcohol) at a stable temperature, compacting the mixture and allowing the mixture to set and cure. The condition for setting may be with heat and pressure, with heat and/or pressure, or at ambient temperature and pressure. To design a particular grading from the various numbers of filler components available, a computer program was produced permitting up to 14 components of known grading to be combined into the closest possible approximation to a defined target grading. This was compared to the grading obtained using a combination of trial and error and graphical procedures. In developing the Phenolic Concrete mixes, initially, the cold set resol phenolic systems were used which resulted in products with low strength as a result of insufficient bond development between the inert granular or powder like materials (fillers) and the resin. Consequently, modified resins were developed which resulted in the production of high strength Phenolic Concrete systems. The determination of the Phenolic Concrete properties was used in describing the indicative inter-relation between the mix constituents, mix proportioning, and criteria of both strength and economy. In addition, Phenolic Concrete mixes were designed with optimization of the mix matrix resin in developing highly fillable media and defining its macro- properties affecting the strength of the end product. Its material properties as a function of its microstructure was investigated using fracture mechanics. The maximum mix ratio devised was 9:1 weight by weight of filler to resin. Maximum compressive cylinder strength obtained was 88.3 N/mrn(^2) and maximum disc tensile strength was 8.85 N/mm(^2) with maximum flexural strength being 30.5 N/mm(^2). The unit weights ranged from 2.08 to 2.28 g/cm(^3), modulus of elasticity ranged from 14.64 X 10(^9) to 19.6 X 10(^9) N/m(^2) and flexural modulus ranged from 17.4 x 10(^9) to 32.4 X 10(^9) N/m(^2). Maximum fracture toughness obtained was 2.12 N/m(^3/2), and maximum fracture energy was 220.7 J/m(^2). The development, construction techniques and properties of various phenolic resin concretes were investigated and described. Using the modified resin systems and the techniques developed here, filled phenolic resin concrete was produced cheaply without sacrificing strength and stiffness. The use of wet or dry fibre glass laminates as primary reinforcement resulted in exceptionally strong composite systems. Alternatively, or in addition, the filled phenolic resin systems were combined with further reinforcing materials such as profiled high yield steel bars. These were then used in manufacturing box beams, bridge deck panels, (and subsequently, access floor tiles). The technique by which these components were constructed proved to be reliable and repeatable. The structural behaviour of these Phenolic Concrete components was studied and proved to be predictable applying elastic theory and ultimate load analysis.


As data centers grow larger and strive to provide tight performance and availability SLAs, their monitoring infrastructure must move from passive systems that provide aggregated inputs to human operators, to active systems that enable programmed control. In this paper, we propose Trumpet, an event monitoring system that leverages CPU resources and end-host programmability, to monitor every packet and report events at millisecond timescales. Trumpet users can express many *network-wide events*, and the system efficiently detects these events using *triggers* at end-hosts. Using careful design, Trumpet can evaluate triggers by inspecting every packet at full line rate even on future generations of NICs, scale to thousands of triggers per end-host while bounding packet processing delay to a few microseconds, and report events to a controller within 10 milliseconds, even in the presence of attacks. We demonstrate these properties using an implementation of Trumpet, and also show that it allows operators to describe new network events such as detecting correlated bursts and loss, identifying the root cause of transient congestion, and detecting short-term anomalies at the scale of a data center tenant.


The identification of transient or readily reversible interactions between proteins is a difficult problem that has been addressed with various methods. Ruotolo et al. have now applied mass spectrometry to the problem to exploit its advantages of sensitivity and speed. They show that the trp RNA binding attenuation protein (TRAP) maintains its 11-membered ringlike structure in the gas phase and that binding of RNA and tryptophan influences the shape and stability of the ring in a fashion consistent with its known behavior in aqueous solution. B. T. Ruotolo, K. Giles, I. Campuzano, A. M. Sandercock, R. H. Bateman, C. V. Robinson, Evidence for macromolecular protein rings in the absence of bulk water. Science 310, 1658-1661 (2005). [Abstract] [Full Text]


Optical communications based on fiber optics and the associated technologies have seen remarkable progress over the past two decades. Widespread deployment of optical
fiber has been witnessed in backbone and metro networks as well as access segments connecting to customer premises and homes. Designing and developing a reliable, robust and efficient end-to-end optical communication system have thus
emerged as topics of utmost importance both to researchers and network operators. To fulfill these requirements, various problems have surfaced and received attention,
such as network planning, capacity placement, traffic grooming, traffic scheduling, and bandwidth allocation. The optimal network design aims at addressing (one or more of) these problems based on some optimization objectives. In this thesis, we consider two of the most important problems in optical networks; namely the survivability in optical long-haul networks and the problem of bandwidth allocation and scheduling in optical access networks. For the former, we present efficient and accurate models for availability-aware design and service provisioning in p-cycle based survivable networks. We also derive optimization models for survivable network design based on p-trail, a more general protection structure, and compare its performance with p-cycles. Indeed, major cost savings can be obtained when the optical access and long-haul subnetworks become closer to each other by means of consolidation of access and metro networks. As this distance between long-haul and access networks reduces, and the need and expectations from passive optical access networks (PONs) soar, it becomes crucial to efficiently manage bandwidth in the access while providing the desired level of service availability in the long-haul backbone. We therefore address in this thesis the problem of bandwidth management and scheduling in passive optical networks; we design efficient joint and non-joint scheduling and bandwidth allocation methods for multichannel PON as well as next generation 10Gbps Ethernet PON (10G-EPON) while addressing the problem of coexistence between 10G-EPONs
and multichannel PONs.


Aluminium (Al 99.99 % purity) and aluminium alloy Al-5.7Ni and Al-5Mg (wt.%) open-cell foams made by replication processing are creep-tested in the temperature range T/Tm=0.5-0.8, varying the relative density between 0.10 and 0.25. Steady state creep rates are measured and interpreted on the basis of analytical models developed using the variational estimate of Ponte Castaneda and Suquet, as well as the beam engineering model developed by Andrew-Gibson-Ashby. The steady state creep rate, in foams produced of pure aluminium show a strong sensitivity to the volume fraction: for instance, in the case of the 400 µm pore size pure Al it varies as. The present experiments are therefore conducted on foams produced of two metals having a substructural scale much smaller than the pore size (the Al3Ni rod spacing and the average dislocation spacing, for Al-5.7Ni and Al-5Mg respectively), with a goal to probe whether this behaviour should be attributed to the material constituting the foam (microscopic scale) or to the foam architecture (mesoscopic scale). The creep behaviour is examined in light of the pure aluminium data, and interpreted in terms of the possible influence of the damage, the presence of internal stress or the substructure-invariant model of Sherby et al.


We provide a database of transit times and updated ephemerides for 382 planets based on data from the NASA Transiting Exoplanet Survey Satellite (TESS) and previously reported transit times, which were scraped from the literature in a semiautomated fashion. In total, our database contains 8667 transit-timing measurements for 382 systems. About 240 planets in the catalog are hot Jupiters (i.e., planets with mass >0.3 M Jup and period <10 days) that have been observed by TESS. The new ephemerides are useful for scheduling follow-up observations and searching for long-term period changes. WASP-12 remains the only system for which a period change is securely detected. We remark on other cases of interest, such as a few systems with suggestive (but not yet convincing) evidence for period changes, and the detection of a second transiting planet in the NGTS-11 system. The compilation of light curves, transit times, ephemerides, and timing residuals are made available online, along with the Python code that generated them (visit https://transit-timing.github.io).


BACKGROUND
Traditional contrast media containing iodine remain the gold standard for vessel visualization during endovascular procedures. On the other hand, their use has several side effects and implications and may cause contrast medium-induced nephropathy. Carbon dioxide (CO2) angiography is an old alternative technique used only for critical patients in order to prevent kidney damages or allergic reactions. Zero contrast procedure: The availability of automated CO2 injectors has led to a spread of the use of CO2 angiography, giving an option for zero contrast interventions, preserving patient renal function and saving costs for hospital facility. Taking advantage of the properties of CO2 gas, it is possible to improve the performance of some complex procedures such as atherectomy and the detection of type II endoleaks after EVARs. However, a learning curve is needed to get good imaging, and learn about the qualities and limitations of the technique.

CONCLUSIONS
The use of automatic delivery systems for CO2 angiography appears to be a good choice for the use of CO2 as first imaging option. The standardization of injection protocols as well as the extensive use of this technique could lead to significant benefits both for the patient's prospects and health facilities.


This paper presents a mathematical decision-making tool that is easy to use and express mathematically, requires only a little mathematical expertise, and gives results that are easy to interpret. The tool has been used extensively as part of a term project in a precalculus class. The decision-making process forces students to consider the Christian ideals of faith, morals, and ethics, and to use them in a quantitative form in order to make their decision. The overall success of the tool comes from the integration of several different kinds of student learning experiences in a properly designed project. That is to say, the student must look deeply into his or her own core values in an effort to quantify his or her feelings toward God, faith, morals, and ethics. This decision-making mathematical tool is something that students can take with them as they journey through life. It is the primary objective of this paper to identify the tool, to show how it is used, and to encourage other Christian educators to use it in their classes too.


Storm-driven overwash is a sediment-transport process fundamental to the evolution of low-lying coastal environments. Physical insight into overwash morphodynamics is crucial for improved risk assessment and hazard forecasting in vulnerable coastal zones. Spatially extended observations of washover deposits have shown that back-barrier shoreline planforms can be quasi-periodic. These rhythmic patterns have been attributed to the influence of a forcing template in bathymetry or topography, or as inherent in the forcing itself. With an alternative to this prevailing explanation, we present results of a physical experiment and numerical model in which quasi-periodic patterns in washover deposits are self-organized, arising from interactions between barrier topography, routing of overwash flow, and sediment flux.


■ ABSTRACT Introduction: Video endoscopy has become a procedure of choice for the treatment of eyebrow ptosis and forehead wrinkles. This minimally invasive technique has several advantages over traditional coronal incision. Several fixation methods are reported in the literature, with similar results. In this study, we describe direct needle fixation. Objective: To evaluate the prognosis of video endoscopic surgery using a direct needle technique. Method: Computerized photographic evaluations of 37 patients undergoing video endoscopy of the frontal region with needle direct fixation were conducted in two private hospitals in the city of Porto Alegre in Rio Grande do Sul, Brazil. Results: The mean eyebrow elevations were 5.7 and 4.4 mm in the lateral and middle third measurements. After a small dip in elevation in the first month after surgery, the repositioning of the eyebrow remained unchanged in subsequent measurements up to 24 months later. Conclusion: Direct needle fixation produced lasting, reliable, and reproducible results during the period in which measurements were made.


This article critically examines the purposes and objectives of the Organisation internationale de la Francophonie (OIF). While analysts debate whether the OIF is a hegemonic or counter-hegemonic instrument of statecraft, we argue that it is an institution founded upon the principle of geopolitical ownership of a distinctive geocultural space. Its prime task, with regard to conflict resolution, is to help transfer responsibilities and capabilities from northern to southern member states. From this perspective, we contend that the OIF has progressively taken charge of a distinct and necessary geocultural role with regard to international security.


In this article, we address the problem of realizing a complete efficient system for automated management of fleets of autonomous ground vehicles in industrial sites. We elicit from current industrial practice and the scientific state of the art the key challenges related to autonomous transport vehicles in industrial environments and relate them to enabling techniques in perception, task allocation, motion planning, coordination, collision prediction, and control. We propose a modular approach based on least commitment, which integrates all modules through a uniform constraint-based paradigm. We describe an instantiation of this system and present a summary of the results, showing evidence of increased flexibility at the control level to adapt to contingencies.


Abstract An evolutionary model of the bank size distribution is presented based on the exchange and creation of deposit money. In agreement with empirical results the derived size distribution is lognormal with a power law tail. The theory is based on the idea that the size distribution is the result of the competition between banks for permanent deposit money. The exchange of deposits causes a preferential growth of banks with a fitness that is determined by the competitive advantage to attract permanent deposits. While growth rate fluctuations are responsible for the lognormal part of the size distribution, treating the mean growth rate of banks as small, large banks benefit from economies of scale generating the Pareto tail.


Worldwide there is a big need for affordable livingspace. Globalization leads to a connection of development and ideas in the field of building. Open Source communities could improve and accelerate this development. The potential of theses communities lies in the connection of different diciplines. Especially for building projects with a small budget and a willingness to participate in the work process open source do-it-yourself constructions are a great opportunity to help cover the need of affordable work and living space. Renewable materials such as wood offer great potential here. New, standardised technologies make a decentralised production possible.


Fluidized bed reactor technology has been widely adopted within the industry as vital component for numerous manufacturing, power generation and gasification processes due to its enhanced mixing characteristics. Computational modeling of fluidized bed hydrodynamics is a significant challenge that has to be tackled for increasing predictive accuracy. The distributor plate of a fluidized bed is typically modeled using a uniform inlet condition, when in reality the inlet is non-uniform inlet. The regions of bed mass that do not fluidize because of the non-uniform inlet conditions form deadzones and remain static between the jets. A new model based on the mass that contributes to the pressure drop is proposed to model a fluidized bed, and has been investigated for a cylindrical reactor for glass beads, ceramic single solids particles, and glass-ceramic, and ceramic-ceramic binary mixtures. The adjusted mass model was shown to accurately predict fluidization characteristics such as pressure drop and minimum fluidization velocity. The effectiveness of the adjusted mass model was further illustrated by applying it to fluidized beds containing coal, switchgrass, poplar wood, and cornstover biomass particles and coalbiomass binary mixtures. The adjusted mass model was further analyzed for bed expansion heights of different mixtures, and for solids distribution by analyzing the solids volume fraction. The effect of increasing the percent biomass in the mixture was also investigated. To further model the non-uniform inlet condition, two different distributor configurations with 5 and 9 jets was considered for a quasi-2D bed, and simulations were performed in both 2D and 3D. Fluidization characteristics and mixing of the bed were analyzed for the simulation. Furthermore, the deadzones formed due to multiple jet configurations of the distributor are quantified and their distributions over the plate were analyzed.


This paper examines the prevailing cultural practices that lead to poor infant growth and poor maternal and lactating mothers' nutritional status in sub-Saharan African region (SSAR). The paper reveals that SSAR has the highest maternal, infant and under five mortality rates and protein energy malnutrition (PEM). None of the countries in this region has made any remarkable improvement in reducing these mortality rates and PEM. Contrary to previous and recent investigations that ignorance and poverty are the two major etiologies of PEM and poor growth in SSAR, cultural food habits and infant feeding practices have been identified as major causes of childhood malnutrition. For instance, from cultural point of view, among some major ethnic groups, the concept of healthy child is taking to mean 'fat baby'. In view of this, food items that are believed will increase the size and weight of the baby such as cassava, maize and yam flour are considered good. Because of traditional cultural food practices, legumes and oil seeds such as beans, groundnuts and mellon seeds are sparingly consumed. Nursing mothers in most of the countries in the region have not been making use of existing local food sources as complementary feeds not because of poverty but traditional beliefs and cultural food practices. Unfortunately, the unrestricted and longer duration of breastfeeding that protects infants from early onset of kwashiorkor, strictly adhered to in the past has drastically reduced mainly because of nursing mothers' need to augment family income. The paper recognized that PEM could be prevented in SSAR when food habits are modified or changed. Pregnant and nursing mothers could be encouraged to consume and feed their growing infants with locally available foodstuffs that are cheap and highly nutritious.


Understanding microhabitat requirements for species vulnerable to anthropogenic threats can provide important information to conservation managers. This may be particularly true for ectotherms, where behaviour and physiology (e.g. digestion, responsiveness and activity patterns) are strongly influenced by thermal conditions of microhabitat retreat sites. Retreat sites selected by south-west carpet pythons (Morelia spilota imbricata) were identified through radiotracking 46 pythons over 3 years. Tree hollows appear to be a very important resource for pythons: 61% (22 of 36 individuals tracked over winter) used tree hollows as retreat sites (56% of all observations in winter), and remained in hollows for an average of 124 ± 49 (range 34 to 210) days. If pythons did not use tree hollows over winter, they found refuge in one of four alternative microhabitats: low vegetation cover (26% of winter observations), ground cover (10%), on tree branches (6%) or in hollow logs on the ground (2%). We tested whether tree hollows provide a thermally distinct environment compared with alternative microhabitats, but found no difference in minimum, average, maximum or range of temperatures recorded between microhabitats. When within tree hollows over winter, pythons had colder daily average and maximum body temperatures (cf. pythons that used other microhabitats), but this did not give them an energy saving (in terms of body condition scores). Pythons ate very little over winter and we predict that animals sequestered within tree hollows do not access prey at this time. Tree hollows provide a critical refuge over winter when python body temperature is low, and their responsiveness is limited, rendering individuals vulnerable to predation by terrestrial predators (e.g. introduced red fox). Destruction of hollows through fire, land clearing, competition with other fauna species and the significant age required for hollows to form in trees all contribute to the decline in availability of this important microhabitat.


This paper describes a recently created image database, TID2013, intended for evaluation of full-reference visual quality assessment metrics. With respect to TID2008, the new database contains a larger number (3000) of test images obtained from 25 reference images, 24 types of distortions for each reference image, and 5 levels for each type of distortion. Motivations for introducing 7 new types of distortions and one additional level of distortions are given; examples of distorted images are presented. Mean opinion scores (MOS) for the new database have been collected by performing 985 subjective experiments with volunteers (observers) from five countries (Finland, France, Italy, Ukraine, and USA). The availability of MOS allows the use of the designed database as a fundamental tool for assessing the effectiveness of visual quality. Furthermore, existing visual quality metrics have been tested with the proposed database and the collected results have been analyzed using rank order correlation coefficients between MOS and considered metrics. These correlation indices have been obtained both considering the full set of distorted images and specific image subsets, for highlighting advantages and drawbacks of existing, state of the art, quality metrics. Approaches to thorough performance analysis for a given metric are presented to detect practical situations or distortion types for which this metric is not adequate enough to human perception. The created image database and the collected MOS values are freely available for downloading and utilization for scientific purposes. & 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). er B.V. This is an open acce


Countering Violent Extremism ("CVE") is a counterterrorism strategy ostensibly aimed at preventing "radicalization" through risk assessment and intervention. CVE involves recruitment of helping professionals, including mental health care providers, to monitor their patients for signs of "vulnerability to radicalization," make referrals to "de-radicalization" programs, and participate in multidisciplinary intervention teams. Broad national security and public safety exceptions within existing privacy laws allow mental health professionals participating in CVE to make potentially harmful disclosures of private patient information. This Note argues that professional associations representing mental health care providers should develop policies to limit and regulate members' participation in CVE.


The indexing systems used to systematise our knowledge about a domain tend to have an evaluative character: they represent some things as more important, general, complex, or central than others. They are also imperfect and can misrepresent something as more or less important, etc., than it really is. Such distortions mostly result from mistakes made due to lack of time or resources. In some cases they follow systematic patterns which can reveal the implicit judgements and values shared within a community who maintains and uses an index. I focus on the example of PhilPapers, the largest database of philosophy texts available, to show how the arrangement of categories and the way items are assigned to them, can effectively marginalise certain topics, authors, and entire traditions. I draw attention to such issues as: ordering, size and depth of categories, the use of miscellaneous categories, localising indexes in category names, and assigning items to some but not other categories. I suggest that such structuring of the index can have an impact on users, normalising marginalisation and contributing to the perpetuation of inequalities. I conclude by offering some suggestions for improvement which might help our databases flourish and become even more useful.


The planets of the Solar System grew by collisions, starting with the aggregation of tiny dust particles within the solar nebula and culminating in giant collisions between large planetary bodies. These giant impacts occasionally caused the formation of satellites such as the Earth's Moon. Our understanding of planet formation is based on information from various sources, including meteorites - leftovers from the earliest stages of planet formation - and samples from the Earth and Moon. By combining results from isotopic dating of these materials with dynamic modelling of the solar nebula and planet formation, researchers can reconstruct the accretion and early evolution of planetary bodies during the first [~]100 million years of Solar System history.


Abstract In his influential paper 'The Conscience of Huckleberry Finn', Jonathan Bennett suggests that Huck's failure to turn in the runaway slave Jim as his conscience – a conscience distorted by racism – tells him he ought to is not merely right but also praiseworthy. James Montmarquet however argues against what he sees here as Bennett's 'anti-intellectualism' in moral psychology that insofar as Huck lacks and so fails to act on the moral belief that he should help Jim his action is not praiseworthy. In this paper I suggest that we should reject Montmarquet's claim here; that the case of Huck Finn indicates rather how many of our everyday moral responses to others do not and need not depend on any particular moral beliefs we hold about them or their situation.


BACKGROUND
Autoimmune hepatitis (AIH) is a chronic inflammatory disease that is successfully treated with prednisone and/or azathioprine immunosuppressive therapy in 70% to 80% of patients. The remaining patients are intolerant or refractory to these standard medications. Budesonide, a synthetic glucocorticoid, undergoes a high degree of first-pass metabolism, reducing its systemic bioavailability, and has a 15-fold greater affinity for the glucocorticoid receptor than prednisolone. Budesonide may be a potentially useful systemic steroid-sparing immunosuppressive agent in the treatment of AIH.

OBJECTIVE
To review the Canadian experience using budesonide to treat AIH.

METHODS
Patients with AIH currently or previously treated with budesonide were identified through the Canadian Association for the Study of the Liver membership. Data were collected regarding their clinical and treatment history.

RESULTS
A total of nine patients were identified. All patients were female, with an average age of 39 years (range 12 to 66 years). The indications for budesonide were adverse side effects of prednisone in two patients, noncompliance with prednisone and azathioprine in one patient and intolerance to azathioprine resulting in prednisone dependence in the remaining six patients. Patients were treated in doses ranging from 9 mg daily to 3 mg every other day for 24 weeks to eight years. Seven of nine patients had a complete response, defined as sustained normalization of the aminotransferase levels. The remaining two patients were classified as nonresponders (less than a 50% reduction in pretreatment aminotransferase levels).

CONCLUSIONS
In Canada, budesonide has been successfully used in seven of nine patients with autoimmune hepatitis who were either intolerant to prednisone and azathioprine or prednisone-dependent. No adverse effects were reported with budesonide. Budesonide is potentially a valuable treatment option for AIH patients refractory or intolerant to standard therapy, and is deserving of further study.