Sensory Neuronopathy (SN) represents a distinct peripheral nervous system disorder associated with degeneration of the Dorsal Root Ganglia. We present our retrospective review of 103 patients with an electro-clinical diagnosis of SN. Average age of onset was 54 yr. Aetiologies included Sjogrens (21%), Probable Inflammatory (16%), Idiopathic (29%), Inherited (20%), Toxic (5%) and paraneoplastic (9%). Of those with inherited SN (n=21); CANVAS syndrome 2/21, mitochrondrial cytopathy 9/21 with 4 confirmed POLG1 mutations, 3/21 presumed HSANIIb, Frederich's Ataxia 1/21 and 6/21 unidentified phenotypes. Clinically, acquired causes commonly presented with pain (62%), asymmetrical/non-length dependent sensory disturbance (91%) as compared to the inherited group who are more likely to present with gait disturbance without prominent sensory symptoms (52%). Of the cohort with presumed inflammatory disease, 29 patients were immunosuppressed with 12 patients responding to a combination of steroids and Mycophenolate. IVIG was not found to be beneficial with no sustained benefit in 7 patients. Paraneoplastic causes (n=9) included Breast (n=2), Neuroendocrine tumours (n=2), Carcinoid (n=2), Bowel (n=1), SCLC (n=1) and unknown primary (n=1) with only 4 Hu positive Conclusions Sensory neuronopathy is clinically and aetiologically pleomorphic. In cases with a suspected inflammatory cause it is worthwhile considering a trial of immunomodulatory treatment.


Many manifold embedding algorithms fail apparently when the data manifold has a large aspect ratio (such as a long, thin strip). Here, we formulate success and failure in terms of finding a smooth embedding, showing also that the problem is pervasive and more complex than previously recognized. Mathematically, success is possible under very broad conditions, provided that embedding is done by carefully selected eigenfunctions of the Laplace-Beltrami operator $\Delta$. Hence, we propose a bicriterial Independent Eigencoordinate Selection (IES) algorithm that selects smooth embeddings with few eigenvectors. The algorithm is grounded in theory, has low computational overhead, and is successful on synthetic and large real data.


The solid complexes of Mn(III), VO(IV), MoO2(VI) and UO2(VI) with unsymmetrical dibasic tetradentate ONNO donor Schiff base derived from the condensation of salicylaldenyde, o-hydroxy acetophenone and ethylene diamine have been synthesized and characterized by elemental analysis, magnetic susceptibility measurements, IR and reflectance spectra. The thermal dehydration and decomposition of these complexes were studied kinetically using the Horowitz- Metzger method. The solid state electrical conductivity of complexes has been measured in the temperature range 313 K≤ T ≥403 K and the complexes exhibited semiconducting behavior. Scanning electron micrograph has also been reported and suggested homogeneous phase material. Complexes were used for the catalytic oxidation of styrene.


Rate control plays an important role in video coding and transmission. Current initialization of Quantization Parameter (QP) in H.264 rate control takes the same value for images with different complexity as long as the bit number per pixel is the same which is different from the real-world situation. In this paper, we propose a new R-Q model and QP initializing method to improve the precision of rate control. In this method, the quantization parameter and R-Q model parameters are calculated from the first two frames of video sequence. Some formulas are presented to implement the process in this paper. Experimental results show that the output bit rate achieved by our proposed one is more close to the target bit rate while the reconstructed quality is comparable with low computing complexity.


In order to investigate any size-dependent differences between behavioural patterns, wild-caught Hart's rivulus Rivulus hartii of varying sizes were exposed to chemical alarm cues extracted from the skin of conspecifics or heterospecific Poecilia reticulata, or a tank water control, in a series of laboratory trials. In response to conspecific alarm cues, R. hartii subjects of the range of body sizes tested exhibited consistent, size-independent antipredator behaviours that were characterized by decreased locomotory activity and foraging levels and increased refuging behaviour. Conversely, focal R. hartii demonstrated significant size-dependent trends in response to heterospecific alarm cues, with smaller individuals exhibiting antipredator responses and larger individuals shifting their behaviour to increased levels of activity consistent with a foraging, or predatory, response. These results show that the behavioural responses of individual R. hartii to publicly available chemical alarm cues from heterospecifics are mediated by the size of the receiver.


Experimental data relating to oscillatory flow of hard-metal carbide powders compounded with a polymeric binder are presented. Such powder/binder mixtures are used for the production of sintered cemented carbide components via powder injection moulding. The binder composition tailored to a carbide powder consisted of polyethylene, ethylene/acrylic acid copolymer, and paraffin wax. Four kinds of hard-metal carbide powders differing in their particle size distribution were considered to investigate the structural changes during shear deformation. The obtained results reveal that particle size distribution of powder has a considerable influence on viscoelastic properties of highly filled compounds.


Abstract A new species, Metavermilia arctica, is described from the Arctic Ocean. It differs from all foregoing species by combining characteristically small-pitted tube sculpture with a conical operculum possessing a flat distal plate. The genus is recorded for the first time in the region. Data on ecology and distribution of the new species are given.


We argue the case for abstract document structure as a separate descriptive level in the analysis and generation of written texts. The purpose of this representation is to mediate between the message of a text (i.e., its discourse structure) and its physical presentation (i.e., its organization into graphical constituents like sections, paragraphs, sentences, bulleted lists, figures, and footnotes). Abstract document structure can be seen as an extension of Nunberg's text-grammar it is also closely related to logical markup in languages like HTML and LaTEX. We show that by using this intermediate representation, several subtasks in language generation and language understanding can be defined more cleanly.


Publisher's description: The use of geometric methods in classical mechanics has proven fruitful, with wide applications in physics and engineering. In this book, Professor Marsden concentrates on these geometric aspects, especially on symmetry techniques. The main points he covers are: the stability of relative equilibria, which is analyzed using the block diagonalization technique; geometric phases, studied using the reduction and reconstruction technique; and bifurcation of relative equilibria and chaos in mechanical systems. A unifying theme for these points is provided by reduction theory, the associated mechanical connection and techniques from dynamical systems. These methods can be applied to many control and stabilization situations, and this is illustrated using rigid bodies with internal rotors, and the use of geometric phases in mechanical systems. To illustrate the above ideas and the power of geometric arguments, the author studies a variety of specific systems, including the double spherical pendulum and the classical rotating water molecule.


The ever-growing demands for high-bandwidth data transfer have been pushing towards advancing research efforts in the field of high-performing communication systems. Studies on the performance of single chip, e.g. faster multi-core processors and higher system memory capacity, have been explored. To further enhance the system performance, researches have been focused on the improvement of data-transfer bandwidth for chip-to-chip communication in the high-speed serial link. Many solutions have been addressed to overcome the bottleneck caused by the non-idealties such as bandwidth-limited electrical channel that connects two link devices and varieties of undesired noise in the communication systems. Nevertheless, with these solutions data have run into limitations of the timing margins for high-speed interfaces running at multiple gigabits per second data rates on low-cost Printed Circuit Board (PCB) material with constrained power budget. Therefore, the challenge in designing a physical layer (PHY) link for high-speed communication systems turns out to be power-efficient, reliable and cost-effective. In this context, this dissertation is intended to focus on architectural design, system-level and circuit-level verification of a PHY link as well as system performance optimization in respective of power, reliability and adaptability in high-speed communication systems.
The PHY is mainly composed of clock data recovery (CDR), equalizers (EQs) and high- speed I/O drivers. Symmetrical structure of the PHY link is usually duplicated in both link devices for bidirectional data transmission. By introducing training mechanisms into high-speed communication systems, the timing in one link device is adaptively aligned to the timing condition specified in the other link device despite of different skews or induced jitter resulting from process, voltage and temperature (PVT) variations in the individual link. With reliable timing relationships among the interface signals provided, the total system bandwidth is dramatically improved. On the other hand, interface training offers high flexibility for reuse without further investigation on high demanding components involved in high costs.
In the training mode, a CDR module is essential for reconstructing the transmitted bitstream to achieve the best data eye and to detect the edges of data stream in asynchronous systems or source-synchronous systems. Generally, the CDR works as a feedback control system that aligns its output clock to the center of the received data. In systems that contain multiple data links, the overall CDR power consumption increases linearly with the increase in number of links as one CDR is required for each link. Therefore, a power-efficient CDR plays a significant role in such systems with parallel links. Furthermore, a high performance CDR requires low jitter generation in spite of high input jitter. To minimize the trade-off between power consumption and CDR jitter, a novel CDR architecture is proposed by utilizing the proportional-integral (PI) controller and three times sampling scheme.
Meanwhile, signal integrity (SI) becomes critical as the data rate exceeds several gigabits per second. Distorted data due to the non-idealties in systems are likely to reduce the signal quality aggressively and result in intolerable transmission errors in worst case scenarios, thus affect the system effective bandwidth. Hence, additional trainings such as transmitter (Tx) and receiver (Rx) EQ trainings for SI purpose are inserted into the interface training. Besides, a simplified system architecture with unsymmetrical placement of adaptive Rx and Tx EQs in a single link device is proposed and analyzed by using different coefficient adaptation algorithms. This architecture enables to reduce a large number of EQs through the training, especially in case of parallel links. Meanwhile, considerable power and chip area are saved.
Finally, high-speed I/O driver against PVT variations is discussed. Critical issues such as overshoot and undershoot interfering with the data are primarily accompanied by impedance mismatch between the I/O driver and its transmitting channel. By applying PVT compensation technique I/O driver impedances can be effectively calibrated close to the target value. Different digital impedance calibration algorithms against PVT variations are implemented and compared for achieving fast calibration and low power requirements.


This policy brief summarizes the impact of intimate partner and family violence on the HIV vulnerability of men who have sex with men (MSM), transgender and hijra community members in India. It calls for an end to the denial and acceptance of emotional, physical, sexual and financial violence experienced by these groups and offers recommendations on how HIV interventions can be strengthened to break the cycle between violence and HIV vulnerability. Recommendations include strategies at individual, community, organizational, legal and policy levels towards violence prevention, protection and mitigation.


Three studies were conducted in order to identity factors that impact the likelihood that a witness will lie for a suspect in an alibi corroboration context. Specifically, the level of affinity between a suspect and a witness, the level of social pressure, and gender were investigated as factors impacting the likelihood that a witness would knowingly support a false alibi. During a study session purportedly intended to investigate dyadic problem-solving ability, a mock theft was staged in an adjacent office. When questioned by the experimenter, undergraduate students were provided the opportunity to either corroborate or refute a confederate's false alibi that the latter had been in the testing room during the time of the theft, which participants knew was false. In study 1, participants who were explicitly asked to conceal the confederate's whereabouts during the time of the theft were more likely to lie for him or her by corroborating the false alibi (61% vs. 26% of those who were not asked to lie). In study 2, there was a higher percentage of male participants who corroborated a male confederate's false alibi (41%) compared to female participants who corroborated a female confederate's false alibi (23%). In study 3, participants were found to be more likely to lie for a confederate when the latter was their friend (41%) than when he or she was a stranger (18%). How much a participant liked the suspect (study 1) and whether or not the suspect had previously helped the participant (study 2) did not affect the rates of false alibi corroboration. The results confirm that alibi witnesses often lie, but suggest that investigators and jurors may underestimate the frequency with which strangers and acquaintances lie for one another, and that witnesses who lie do so more often because they trust that the suspect is innocent rather than guilty.


An information-encryption method based on computer-generated hologram (CGH) interference is presented. In this method the original information is decomposed into two parts, and then each part is encoded on a separate CGH. When these two encoded CGHs are aligned and illuminated, a combined interference pattern is formed. The original information is obtained from this pattern. It is impossible to decrypt the original information from one CGH alone; two matched CGHs must be put together to make it available.


This study provides an issue-by-issue analysis of decisions by the Board of Patent Appeals and Interferences (BPAI) of the United States Patent and Trademark Office (USPTO). The study reports that most appeals from examiner rejections focus on two or more issues. Of those, the majority of rejections (61%) are affirmed and the remainder reversed. When more issues are presented, the case as a whole becomes more likely to be affirmed-in-part. In addition, I find that the likelihood that a case is affirmed has increased over time (Jan 2008 - May 2009). By far, the most common issue on appeal is obviousness. I find that 87% - 90% of cases decide an issue of obviousness. Only 4% of appeals consider neither obviousness nor novelty. The major aberration of this trend is for cases involving biotechnology and organic chemistry (TC 1600). 18% of BPAI decisions involving those technologies focus on issues other than obviousness and novelty.In comparing results by issue, I find that obviousness rejections are more likely to be affirmed than are other types of rejections. Cases that discuss neither obviousness nor novelty are reversed in 74% of cases.The BPAI is becoming increasingly important. Over the past several years, the BPAI has seen a dramatic rise in the number of appeals being filed. In addition every recent patent reform legislative proposal has included an increasing role for the Board.


A survey of senior and influential IT managers explored the related questions of why some senior IT professionals perceive organisational issues to be more important than technical issues, and whether this has a concomitant impact on the treatment of organisational issues. An overall response rate of 63 per cent was achieved from a combined survey of two distinct groups. The results show that there are significant differences in managers' perceptions about the importance of organisational issues which can, to some extent, be explained in terms of organisational size, and to a lesser extent by the favoured development approach. However, these differences in perception appear to have no identifiable relation to the significant differences in the approaches adopted for treating organisational issues. It is suggested that this is due to the difficulties in treating such issues and further research to resolve these difficulties is proposed.


In this paper, we consider the problem of determining primary and backup paths for survivable optical wavelength-division multiplexed mesh networks. We propose a distributed routing mechanism, which is called Least Resource Consumption Routing, that tries to minimize the combined cost of the primary and the backup paths. The proposed cost model includes the effect of various factors such as mean load, variance of the load on the route, number of converters required by the route, and the length of the route. Further, we model the route cost in such a way that it is extensible to include any new parameters and vary their relative importance. The performance studies conducted for the 14-node National Science Foundation Network and a 30-node topology show that the proposed scheme leads to significant improvements in blocking probability at low and moderate loads. Further, the proposed cost model also reduces the number of converters required to obtain a target blocking performance as compared to some other techniques proposed in the literature.


This work tries to investigate the use of a Convolutional Neu-ral Network approach and its fusion with more traditional systems such as Total Variability Space for speaker identification in TV broadcast data. The former uses spectrograms for training, while the latter is based on MFCC features. The dataset poses several challenges such as significant class imbalance or background noise and music. Even though the performance of the Convolutional Neural Network is lower than the state-of-the-art, it is able to complement it and give better results through fusion. Different fusion techniques are evaluated using both early and late fusion.


The electrocatalytic conversion of CO2 to energy-rich chemicals or energy vectors is a highly challenging approach to cope with an ever increasing demand for energy storage and valorization of renewable resources. Herein we report on the electrocatalytic reduction of CO2 to CO using covalently N-decorated carbon nanotubes as highly efficient and chemoselective metal-free electrocatalysts. At odds with more conventional synthetic methods for the production of N-doped nanocarbons, chemical functionalization warrants a unique control of "surface N-defects" available for the process, ruling out any synergistic contribution to electrocatalysis coming from other surface or bulk N-containing groups. With a CO faradaic efficiency (FECO) close to 90% and productivity as high as 48 NLCO gN−1 h−1, NH-aziridine functionalized MWCNTs have shown CO2RR performance that is among the highest reported so far for related metal-free systems. At the same time, it has offered a unique view-point for the comprehension of the underlying structure–reactivity relationship.


Histone modifications of nucleosomes distinguish euchromatic from heterochromatic chromatin states, distinguish gene regulation in eukaryotes from that of prokaryotes, and appear to allow eukaryotes to focus recombination events on regions of highest gene concentrations. Four additional epigenetic mechanisms that regulate commitment of cell lineages to their differentiated states are involved in the inheritance of differentiated states, e.g., DNA methylation, RNA interference, gene repositioning between interphase compartments, and gene replication time. The number of additional mechanisms used increases with the taxon's somatic complexity. The ability of siRNA transcribed from one locus to target, in trans, RNAi-associated nucleation of heterochromatin in distal, but complementary, loci seems central to orchestration of chromatin states along chromosomes. Most genes are inactive when heterochromatic. However, genes within β-heterochromatin actually require the heterochromatic state for their activity, a property that uniquely positions such genes as sources of siRNA to target heterochromatinization of both the source locus and distal loci. Vertebrate chromosomes are organized into permanent structures that, during S-phase, regulate simultaneous firing of replicon clusters. The late replicating clusters, seen as G-bands during metaphase and as meiotic chromomeres during meiosis, epitomize an ontological utilization of all five self-reinforcing epigenetic mechanisms to regulate the reversible chromatin state called facultative (conditional) heterochromatin. Alternating euchromatin/heterochromatin domains separated by band boundaries, and interphase repositioning of G-band genes during ontological commitment can impose constraints on both meiotic interactions and mammalian karyotype evolution.


Journals tend to publish only statistically significant evidence, creating a scientific record that markedly overstates the size of effects. We provide a new tool that corrects for this bias without requiring access to nonsignificant results. It capitalizes on the fact that the distribution of significant p values, p-curve, is a function of the true underlying effect. Researchers armed only with sample sizes and test results of the published findings can correct for publication bias. We validate the technique with simulations and by reanalyzing data from the Many-Labs Replication project. We demonstrate that p-curve can arrive at conclusions opposite that of existing tools by reanalyzing the meta-analysis of the "choice overload" literature.


Recent work on infrared stimulated luminescence (IRSL) dating has focussed on finding and testing signals which show less or negligible fading. IRSL signals measured at elevated temperature following IR stimulation at 50°C (post-IR IRSL) have been shown to be much more stable than the low temperature IRSL signal and seem to have considerable potential for dating. For Early Pleistocene samples of both European and Chinese loess natural post-IR IRSL signals lying in the saturation region of the laboratory dose response curve have been observed; this suggests that there is no significant fading in nature. As a contribution to the further testing of post-IR IRSL dating, we have used 18 samples from two Japanese loess profiles for which quartz OSL and tephra ages up to 600 ka provide age control. After a preheat of 320°C (60 s), the polymineral fine grains (4–11 μm) were bleached with IR at 50°C (200 s) and the IRSL was subsequently measured at 290°C for 200 s. In general, the fading uncorrected post-IR IRSL ages agree with both the quartz OSL and the tephra ages. We conclude that the post-IR IRSL signal from these samples does not fade significantly and allows precise and accurate age determinations on these sediments.


We report here on a study which tests the magnetic field line mapping between geosynchronous orbit and the ionosphere. The mapping is determined both observationally and fiom five magnetospheric magnetic field models. The mapping is tested observationally by comparing electron energy spectra obtained by the Magnetospheric Plasma Analyzer (MPA) at geosynchronous orbit and by the DMSP spacecraft. Because the orbits are nearly perpendicular, in general, the spectra match well for only a few seconds providing a good determination of when DMSP crosses the geosynchronous drift shell. In this way the mapping between geosynchronous orbit and the ionosphere can be determined to better than one degree. We then compare the measured magnetic footpoints of geosynchronous orbit with the footpoints predicted by five magnetospheric field models: Tsyganenko-89, Tsyganenko-87, Tsyganenko-82, Oslen-Pfitzer, and Hilmer-Voigt. Based on a set of over 100 measured magnetic conjunctions we find that, in general, there are significant differences between the mappings predicted by various magnetic field models but that there is no clear "winner" in predicting the observed mapping. We find that the range of magnetic latitudes at which we measure conjunctions is much broader than the range of latitudes which the models can accommodate. This lack of range is common to all magnetic field models tested. Although there are certainly cases where the models are not sufliciently stretched, we find that on average all magnetic field models tested are too stretched. This technique provides a n excellent opportunity for testing future magnetic field models and for determining the appropriate parameterizations for those models.


This qualitative study examined the culture-specific forms of dance talent development. Due to the scant and uneven literature in the field of dance talent development, this study firstly aimed at exploring the various theories and research methodologies underpinning current dance talent development literature. The other aims were to better understand how various catalysts and processes enhanced dancers' development at different stages and helped guide students in actualizing their potential. Hence, mapping the Finnish and Singaporean dancers' and dance students' talent trajectories later became the focus of this study. This dissertation consists of three sections or (dance) "Acts", which are based on three soleauthored publications. Act I introduces the compilation and synthesis of empirically based articles published between 2000–2012 that dealt with the critical issues of developing dance talents across the lifespan of children, adolescents, and adults. Data from 37 accepted studies were abstracted into evidence tables relating to: (a) abilities and traits, (b) creativity, (c) motivation, and (d) social support. Findings and recommendations about future research were useful in clarifying the ontological, epistemological, and methodological lenses adopted in subsequent studies in this dissertation. In particular, definition of dance talents should be addressed using talent development theories, and more retrospective research about successful dancers and more prospective longitudinal research about talented students should be conducted. Act II presents, via retrospective interviews, the key factors that impacted the talent development of the award-winning Singaporean (n = 4) and Finnish (n = 4) ballet and contemporary dancers. Integral to all the eight dancers' success were a high level of abilities, developed psychosocial skills, supportive and knowledgeable people, optimal learning opportunities, and chance. Four dancers' stories titled "Nonconformist," "Exemplary Dancer," "Go-Getter," and "Trailblazer"—revolving around the themes and developmental stages—illustrate the markedly different pathways for achieving success. The talent-development mega-model framed the discussions in Acts I and II. The perspectives of students (n = 4), parents (n = 2), teachers (n = 6), and a sibling were analyzed in Act III in order to clarify how well significant individuals have supported the exceptionally talented dance students across the different stages of their talent development. The four exceptionally talented students were enrolled in their national dance institutions—the Finnish National Opera Ballet School and the Singapore Dance Theatre. Common themes that emerged from this prospective, two-year study were being there, sharing, and knowing that illustrated the types of support—instrumental, emotional, and informational—from families, peers, and teachers that contributed to the students'


The Haiyangsuo area of the NE Sulu ultrahigh-pressure terrane, eastern China, consists of gneisses with minor granulite and amphibolite layers, metagabbros, and granitic dikes. The peak-stage assemblages of the granulites (garnet + orthopyroxene + clinopyroxene + plagioclase ± pargasite ± biotite ± quartz) formed at >750 °C and 9–11 kbar and were overprinted by amphibolite-facies phases characterized by welldeveloped corona layers of ⏐garnet⏐amphibolite + quartz⏐at contacts between plagioclase and clinopyroxene or orthopyroxene, as well as by the exsolution of (orthopyroxene + ilmenite + amphibole) from clinopyroxene. These textures indicate a near-isobaric cooling history of the granulite-bearing gneiss terrane. The metagabbro preserves a relict igneous assemblage (orthopyroxene + clinopyroxene + plagioclase + pargasite ± ilmenite ± quartz) in its core, but in its margins has a metamorphic corona texture similar to the granulite that formed at ~600–700 °C and 7–10 kbar. Sensitive high-resolution ion microprobe (SHRIMP) U-Pb dating of zircons indicates that the protolith age of the garnet-biotite gneiss is older than 2500 Ma, whereas the granulitefacies metamorphism (the first regional metamorphic event) occurred at 1846 ± 26 Ma. Gabbro intrusion took place at 1734 ± 5 Ma, and the formation of amphibolite assemblages in both metagabbro and granulite occurred at ca. 340–370 Ma. Both gneiss and metagabbro were intruded by granitic dikes, with one dated at 158 ± 3 Ma. These data, together with a lack of eclogitic assemblages, suggest that this granuliteamphibolite–facies complex is exotic relative to the Triassic Sulu high-pressure– ultrahigh-pressure terrane; juxtaposition took place in Jurassic time.


Nutraceuticals: Efficacy, Safety and Toxicity brings together all current knowledge regarding nutraceuticals and their potential toxic effects as written by the scientists at the forefront of their study. Users will find an introduction to nutraceuticals, herbal medicines, ayurvedic medicines, prebiotics, probiotics, and adaptogens, along with their use and specific applications. This essential reference then discusses the mechanism of action for the judicious use of these nutraceuticals and the best tools for their evaluation before detailing the safety and toxicity of nutraceuticals and their interactions with other therapeutic drugs. Finally, and crucially, regulatory aspects from around the world are covered, providing a comprehensive overview of the most effective tools for the evaluation, safety, and toxicity of nutraceuticals, prebiotics, probiotics, and alternative medicines.Grants an overview of the current state-of-the-science of nutraceuticals, their use and applications, and known adverse effectsProvides effective tools to evaluate the potential toxicity of any nutraceuticalIncludes details of regulatory issues as written by international experts


Endoscopic retrograde cholangiopancreatography (ERCP) was performed in twenty‐six AIDS patients to evaluate either abdominal pain suggestive of biliary tract disease, fever, serum alkaline phosphatase elevation, or a combination of these findings. Twenty patients (77%) had abnormal cholangiograms and four distinct patterns were identified: (1) papillary stenosis (n = 3); (2) sclerosing cholangitis (n = 4); (3) sclerosing cholangitis with papillary stenosis (n = 10); and (4) long extrahepatic bile duct strictures (n = 3). Ampullary biopsy and culture identified an AIDS‐related pathogen (CMV, MAI and cryptosporidium) or malignancy (lymphoma, Kaposi's sarcoma) in eleven patients (55%). No features differentiated patients with normal from patients with abnormal cholangiograms. Noninvasive biiary tract imaging studies (CT, ultrasound), however, showed ductal dilation in 75% of patients with abnormal cholangiograms compared with 16% in those with normal cholangiograms (p <0.001). Endoscopic sphincterotomy (ES) in 12 patients with either papillary stenosis or the combination of sclerosing cholangitis and papillary stenosis produced a significant reduction in right upper abdominal pain, although serum alkaline phosphatase continued to increase (mean follow‐up = 3.9 months). Ten of the 12 patients undergoing ES had sclerosing cholangitis, perhaps explaining this lack of response of the serum alkaline phosphatase. Of the 12 patients who had ES, five died of AIDS‐related complications within nine months of the procedure (a mean of 4.8 months), four were lost to follow‐up by four months, and three were alive at 12 months. Of the eight patients who did not have ES, five were alive at one to six months and three died within five months (mean 1.7 months) after the procedure. This paper expands our knowledge of biliary tract abnormalities in HIV‐infected individuals and suggests that ES may improve biliary tract associated abdominal pain.


Contemporary policy discussions of taxes in general, and of the estate tax in particular, are often dominated by arguments that start from libertarian premises. However, these libertarian views are rarely fully unpacked, and, as a result, the conclusions of these arguments often extend beyond what can be justified by those libertarian premises. With regard to the estate tax, many libertarians argue that government interference with the free transfer of assets after death is an immoral violation of the property rights of the deceased. In this Article, I work through the libertarian arguments of Robert Nozick in his seminal work, Anarchy, State, and Utopia, with special attention to his views of property and inheritance rights. By demonstrating that libertarianism cannot justify property rights that extend beyond death, I show that, in fact, libertarianism is entirely consistent with a robust estate tax. While this does not mean that the libertarian views of property rights require an estate tax, those views do not, on moral grounds, preclude the imposition of the tax.


RELATIONSHIPS AMONG UNCERTAINTY, COPING, AND PSYCHOLOGICAL DISTRESS IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT Jennifer Sjostedt Avery, MSN, RN, GNP-BC Marquette University, 2014 Mild cognitive impairment (MCI) has an average prevalence of 18.9% and most often affects people 60 years of age or older. It is a cognitive stage between normal functioning and dementia (Petersen, 2003; Petersen, 2011; Petersen et al., 2014). MCI can be broken into two subtypes classified by the presence of memory impairment (amnestic MCI) or the lack thereof (nonamnestic MCI). Medical diagnostic criteria are commonly used to guide research with older adults with MCI. A theoretical framework that addresses the antecedents and consequences of MCI, specifically one examining the relationships among MCI, uncertainty, coping and psychological distress, is essential to guide the development of effective nursing interventions but is unapparent in published literature. The aims of this quantitative, cross-sectional study are to: (1) test select components of a new conceptual framework for MCI by examining the relationships among uncertainty, coping, psychological distress, time since diagnosis, and level of cognitive impairment from MCI; (2) describe the levels of uncertainty, coping, and psychological distress in persons with MCI; (3) examine the differences in scores on uncertainty, coping, and psychological distress between the two subtypes of MCI; and (4) examine the strength and direction of relationships between scores on uncertainty, coping, and psychological distress within the subtypes of MCI. The sample consisted of 91 primarily Caucasian (>85%) older adults receiving care at a neurology clinic, with a relatively even split between genders and MCI subtypes. Positive relationships were found between uncertainty, coping, and psychological distress, supporting the study framework. In addition, subjects reported low to moderate levels of uncertainty and psychological distress, and most often used emotion-focused coping strategies. Subjects with naMCI reported more somatic symptoms than those with aMCI (p<0.05); however, there were no significant relationships between the MCI subtypes or level of cognitive impairment on the other psychological distress subscales, coping instrument, or uncertainty instrument. The long-term goal of this study is to provide a foundation for a program of research centered on the development and evaluation of interventions to assist older adults who have a diagnosis of MCI and their family members with coping and managing their condition.


We show that on graphs with n vertices the 2-dimensional Weisfei-ler-Leman algorithm requires at most O(n2/log(n)) iterations to reach stabilization. This in particular shows that the previously best, trivial upper bound of O(n2) is asymptotically not tight. In the logic setting this translates to the statement that if two graphs of size n can be distinguished by a formula in first order logic with counting with 3 variables (i.e., in C3) then they can also be distinguished by a C3-formula that has quantifier depth at most O (n2/log(n)).To prove the result we define a game between two players that enables us to decouple the causal dependencies between the processes happening simultaneously over several iterations of the algorithm. This allows us to treat large color classes and small color classes separately. As part of our proof we show that for graphs with bounded color class size, the number of iterations until stabilization is at most linear in the number of vertices. This also yields a corresponding statement in first order logic with counting.Similar results can be obtained for the respective logic without counting quantifiers, i.e., for the logic L3.


Visual place recognition is essential for large-scale simultaneous localization and mapping (SLAM). Long-term robot operations across different time of the days, months, and seasons introduce new challenges from significant environment appearance variations. In this paper, we propose a novel method to learn a location representation that can integrate the semantic landmarks of a place with its holistic representation. To promote the robustness of our new model against the drastic appearance variations due to long-term visual changes, we formulate our objective to use non-squared ℓ2-norm distances, which leads to a difficult optimization problem that minimizes the ratio of the ℓ2,1-norms of matrices. To solve our objective, we derive a new efficient iterative algorithm, whose convergence is rigorously guaranteed by theory. In addition, because our solution is strictly orthogonal, the learned location representations can have better place recognition capabilities. We evaluate the proposed method using two large-scale benchmark data sets, the CMU-VL and Nordland data sets. Experimental results have validated the effectiveness of our new method in long-term visual place recognition applications.


The Juncker Commission has recently indicated that the experienced gained from the Cooperation and Verification Mechanism (CVM) is relevant when addressing rule of law challenges in all Member States. It has also proposed to monitor the rule of law in all Member States. Bulgaria and Romania are the only EU members which are subjected to the CVM because they did not fully fulfill the accession criteria on the rule of law when they acceded to the Union in 2007. In 2018, the Juncker Commission identified important progress in Bulgaria and promised to lift the mechanism for the country before the end of its term. Yet, has the CVM helped Bulgaria strengthen its rule of law? By using Bulgaria's CVM as a case study, this article showcases some of the pitfalls of this mechanism, including the quality of the Commission's monitoring – namely, that Bulgaria's rule of law declined despite the CVM. Dissecting this phenomenon is important not just in light of the Commission's own call to study the experience gained from the CVM, but also in view of growing concerns about dual standards in enforcing EU values in the Union.
Rule of law, EU values, European Convention on Human Rights, Cooperation and Verification Mechanism (CVM), Romania, Bulgaria, Law reform, Judicial independence, Political judicial council, Political Prosecutor's Office


Forecasts from a vector autoregressive model indicate that the substantial cuts in defense spending proposed by the Bush Administration in 1991 are likely to reduce GNP in both the short run and the long run. These forecasts hold even if proceeds from the spending cuts are used to reduce the federal debt. The long-range VAR forecasts, in particular, contrast markedly with those of the large-scale econometric models employed by the Congressional Budget Office.


This article, utilizing a postmodern mediated cultural framework, critically situates the sociopolitical context of public education within the constructs of a lost ship at sea. Seeking to rupture false assumptions of popular culture and its impact on the learning community, I further explore critical possibilities regarding the intersection of popular culture and educational leader-"ship."


How to design a city more legible is one of the main problems in urban design. To define the parameters that are crucial in designing legible cities is the main debate of this article. The research methodology was studying mental maps of the city dwellers and comparing the group image of the city with the pattern of continuity of salient elements and integration of the urban axes using Space Syntax theory. It was found out that to make a city more legible there should be continuity between salient elements of the city; between main integrators and visible fields of the landmarks, to form a coherent structure, or these elements should overlap to emphasize each other to make the city more legible. The relationship of these two elements in the city structure depends on the degree of irregularity of the layout and the presence of the rules of Gestalt of "good configuration". Each urban morphology according to its degree of irregularity and presence or absence of Gestalt rules can be categorized as organized, semi-organized and unorganized. The role of landmarks or visual clues according to the type of morphology differs from one type to another. To make a legible city, there should be a coincidence between the maps of main integrators to the landmark setting to emphasize the main structure of the city in regular settings (organized and semi organized structures). In irregular layouts, there should be continuity between pattern of visible fields of landmarks and main integrators of the city to form a coherent whole. The hierarchy of the urban axes in global and local levelmost integrated and least integrated axeswill be followed by the hierarchy of the visual clues in global and local levels, which defines the nature of systems of reference in the structure of the city. The aim of the study presented by this article is to show how the interaction of landmarks and pathway configuration influence the legibility of the city and make the image group of the city.


Tracer testing was undertaken from sinking streams feeding the Chalk, a porous limestone aquifer characterised by frequent small-scale surface karst features. The objective was to investigate the nature and extent of sub-surface karstic development in the aquifer. Previous tracer testing has demonstrated rapid flow combined with low attenuation of tracer. In this study, at two sites rapid groundwater flow was combined with very high attenuation and at two other sites no tracer was detected at springs within the likely catchment area of the stream sinks tested, suggesting that tracer was totally attenuated along the flowpath. It is proposed that the networks beneath stream sinks in the Chalk and other mildly karstic aquifers distribute recharge into multiple enlarged fractures that divide and become smaller at each division whereas the networks around springs have a predominantly tributary topology that concentrates flow into a few relatively large cavities, a morphology with similarities to that of the early stages of karstification. Tracer attenuation is controlled by the degree to which the two networks are directly connected. In the first state, there is no direct linkage and flow between the two networks is via primary fractures in which tracer attenuation is extreme. The second state is at a percolation threshold in which a single direct link joins the two networks. A very small proportion of tracer reaches the spring rapidly but overall attenuation is very high. In the third state, the recharge and discharge networks are integrated therefore a large fraction of tracer reaches the spring and peak concentrations are relatively high. Despite the large number of stream sinks that recharge the Chalk aquifer, these results suggest that sub-surface conduit development may not always be continuous, with flow down smaller fissures and fractures causing high attenuation of solutes and particulates providing a degree of protection to groundwater outlets that is not seen in more highly karstic aquifers. Bacteriophage tracers that can be detected at very large dilutions (10) are recommended for investigating groundwater pathways where attenuation may be high.


In the early weeks of January 2012, a report of four cases of tuberculosis from Mumbai, India, stirred up a storm.1 India bears a giant's share of the world's multidrug-resistant tuberculosis (MDR-TB) burden, but these cases were different even though they came from a centre (Hinduja Hospital and Research Center) which has been reporting on the alarming escalation in drug-resistant TB in Mumbai over the last two decades. The four patients described in this report were resistant to all first-line (isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin) and second-line drugs (kanamycin, amikacin, capreomycin, ofloxacin, moxifloxacin, ethionamide and para-amino salicylic acid) to which they were tested. That the report came from Mumbai's most reputed mycobacterial laboratory, accredited for drug susceptibility testing (DST) by the Revised National TB Control Program (RNTCP), and serving as the de facto reference mycobacterial laboratory for the city added to the veracity of this report. The choice of the term 'Totally Drug-Resistant' for these four cases was found unpalatable by the Indian health authorities, who initially denied the very existence of 'totally drug-resistant tuberculosis (TDR-TB)'. This, despite there being reports of strains with similar extreme patterns of resistance, from Italy and Iran in the past, none, however, having stirred up the hornet's nest of attention among media and health organisations as the Indian report did.2 ,3 The government's response of initial denial served only to stir up matters further. WHO, though more measured in its response, at a meeting of experts (TDR-TB: a WHO consultation on the diagnostic definition and treatment options) on March 20-21st, 2012, in Geneva, decided that there was not enough evidence to support the creation of yet another category of resistance (TDR), but admitted that patterns of resistance even more extreme than Extensively Drug-Resistant TB (XDR-TB) were being encountered, and were …


We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 +/‐ 0.8 pc cm(‐3), a pulse duration of 2.8(‐0.5)(+1.2) ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7(‐0.1)(+0.2) Jy. The FRB originated at a Galactic longitude and latitude of 24.66 degrees, 5.28 degrees and 25 degrees away from the Galactic Center. The burst was found to be 43 +/‐ 5 per cent linearly polarized with a rotation measure (RM) in the range ‐9 < RM < 12 rad m(‐2) (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X‐ray, gamma‐ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.


This work is concerned with the use and further development of acomputer program to determine displacement vector fields fromsequential satellite images. The work was carried out as part of aGerman-Chinese joint venture between the Institute for Meteorology ofthe Free University Berlin (FU Berlin) and the Second Institute ofOceanography at Hangzhou, Peoples Republic of China.The modified computer program is based on a functional analyticapproach after Horn and Schunk (1981). From the resulting vectorfields, kinematic fields were determined using the image processingtool IDL (Interactive Data Language). In order to compute kinematicfields (e.g., vorticity and divergence), a two dimensionaldistribution of direction and velocity of the shifting grey-valuestructure was assigned to the corresponding physical quantities (e.g.,sea surface temperature) as needed. Alternatively, grey value imagesdisplaying spectral albedo can be utilized.This study tests the ability of information from the visible spectrum toyield reliable results employing data from NOAA-AVHRR (NationalOceanic and Atmospheric Administration - Advanced Very High ResolutionRadiometer). Receiving, processing (geo-correction) and archiving wasdone at the Institute for Meteorology, FU Berlin, as part of theEROS-project (European River and Ocean System) of the EuropeanUnion. Atmospheric and sunglint correction was computed to gaindisplacement vector fields using NOAA-11 data of the Black Sea, fromearly August 1993. Direct verification of displacement vector fieldswas difficult due to lack of in-situ measurements, however the resultsmay be evaluated as a useful approximation. At the times ofobservation, the displacement vector fields correlated well with thekinematic fields of the uppermost water layer.


The Semantic Web and Linked Data movements with the aim of creating, publishing and interconnecting machine readable information have gained traction in the last years. However, the majority of information still is contained in and exchanged using unstructured documents, such as Web pages, text documents, images and videos. This can also not be expected to change, since text, images and videos are the natural way in which humans interact with information. Semantic structuring of content on the other hand provides a wide range of advantages compared to unstructured information. Semantically-enriched documents facilitate information search and retrieval, presentation, integration, reusability, interoperability and personalization. Looking at the life-cycle of semantic content on the Web of Data, we see quite some progress on the backend side in storing structured content or for linking data and schemata. Nevertheless, the currently least developed aspect of the semantic content life-cycle is from our point of view the user-friendly manual and semi-automatic creation of rich semantic content. In this thesis, we propose a semantics-based user interface model, which aims to reduce the complexity of underlying technologies for semantic enrichment of content by Web users. By surveying existing tools and approaches for semantic content authoring, we extracted a set of guidelines for designing efficient and effective semantic authoring user interfaces. We applied these guidelines to devise a semantics-based user interface model called WYSIWYM (What You See Is What You Mean) which enables integrated authoring, visualization and exploration of unstructured and (semi-)structured content. To assess the applicability of our proposed WYSIWYM model, we incorporated the model into four real-world use cases comprising two general and two domain-specific applications. These use cases address four aspects of the WYSIWYM implementation: 1) Its integration into existing user interfaces, 2) Utilizing it for lightweight text analytics to incentivize users, 3) Dealing with crowdsourcing of semi-structured e-learning content, 4) Incorporating it for authoring of semantic medical prescriptions.


Abstract. This work quantifies the spatial distribution of different aerosol types, their seasonal variability and sources.The analysis of four years of CALIOP (Cloud–Aerosol LIdar with Orthogonal Polarization) vertically resolved aerosol data allows the identification of spatial patterns of desert dust and carbonaceous particles in different atmospheric layers. Clusters of Lagrangian back trajectories highlight the transport pathways from source regions during the dusty spring season. The analysis shows a prevalence of dust; at low heights it occurs frequently (up to 70% of available observations) and is distributed north of the Tibetan Plateau with a main contribution from the Gobi and Taklamakan deserts, and west of the Tibetan Plateau, originating from the deserts of southwest Asia and advected by the Westerlies. Above the Himalayas the dust amount is minor but still not negligible (occurrence around 20%) and mainly affected by the transport from more distant deserts sources (Sahara and Arabian Peninsula). Carbonaceous aerosol, produced mainly in northern India and eastern China, is subject to shorter-range transport and is indeed observed closer to the sources, while there is a limited amount reaching the top of the plateau. Data analysis reveals a clear seasonal variability in the frequencies of occurrence for the main aerosol types; dust is regulated principally by the monsoon dynamics, with maximal occurrence in spring. We also highlight relevant interannual differences, showing a larger presence of aerosol in the region during 2007 and 2008. The characterization of the aerosol spatial and temporal distribution in terms of observational frequency is a key piece of information that can be directly used for the evaluation of global aerosol models.


Objectives Quick service restaurant (QSR) television advertisements for children's meals were compared with adult advertisements from the same companies to assess whether self-regulatory pledges for food advertisements to children had been implemented. Methods All nationally televised advertisements for the top 25 US QSR restaurants from July 1, 2009 to June 30, 2010 were obtained and viewed to identify those advertising meals for children and these advertisements were compared with adult advertisements from the same companies. Content coding included visual and audio assessment of branding, toy premiums, movie tie-ins, and depictions of food. For image size comparisons, the diagonal length of the advertisement was compared with the diagonal length of salient food and drink images. Results Almost all of the 92 QSR children's meal advertisements that aired during the study period were attributable to McDonald's (70%) or Burger King (29%); 79% of 25,000 television placements aired on just four channels (Cartoon Network, Nickelodeon, Disney XD, and Nicktoons). Visual branding was more common in children's advertisements vs. adult advertisements, with food packaging present in 88% vs. 23%, and street view of the QSR restaurant present in 41% vs. 12%. Toy premiums or giveaways were present in 69% vs. 1%, and movie tie-ins present in 55% vs. 14% of children's vs. adult advertisements. Median food image diagonal length was 20% of the advertisement diagonal for children's and 45% for adult advertisements. The audio script for children's advertisements emphasized giveaways and movie tie-ins whereas adult advertisements emphasized food taste, price and portion size. Conclusions Children's QSR advertisements emphasized toy giveaways and movie tie-ins rather than food products. Self-regulatory pledges to focus on actual food products instead of toy premiums were not supported by this analysis.


A five-year trial (2009 to 2013) was executed in a drip-irrigated seven-year-old Shiraz/101-14 Mgt vineyard established on a sandy to sandy clay loam soil at Blaauwklippen Farm (33°58'S, 18°50'E) near Stellenbosch, South Africa. Fourteen treatments, consisting of two management practices applied to five cover crop species, as well as winter-growing weeds (no cover crop) and winter-growing weeds (no cover crop) with nematicide applied in the vine row, were applied. The weeds and cover crop species were eithercontrolled chemically (CC) or mechanically (MC) during grapevine bud break, followed by full-surface chemical control during berry set (for both CC and MC treatments). Rhynchelytrum repens (Natal redtop)dominated the post-harvest pre-treatment weed spectrum in all the treatments except Eruca sativa cv. Nemat (Nemat) (MC). This species lost its post-harvest dominance from 2010 onwards. It seems that the relatively low summer rainfall during the 2010/2011 season allowed Anagallis arvensis to appear in April 2011 and dominate some of the treatments, which coincided with the disappearance of Cynodon dactylon (common couch) and Polygonum aviculare (prostrate knotweed). Digitaria sanguinalis, common couch and prostrate knotweed seemed to establish better during late summer where MC was applied. The pre-treatment average post-harvest weed stand of 5.53 t/ha was reduced to 0.53 t/ha within one season, illustrating the benefit of full-surface chemical weed control applied during grapevine berry set.


This banded dissertation is an examination of simulation as a pedagogy for social work education. While the Council of Social Work Education recognizes simulation as an accepted pedagogy, there remains little research on its use in social work education. To effectively utilize and structure simulation within the curriculum, more needs to be understood about its influences on social work student development and its fit within the social work educational context. The first product of this dissertation, a conceptual paper, presents a framework for the use of simulation in social work education. The framework consists of three elements: holistic competency as the aim of social work education, a model of curriculum as engagement for the vehicle through which programmatic culture is established, and experiential learning theory as a foundational learning theory. The author demonstrates alignment between the pedagogy of simulation with the aims, culture, and theory which inform social work education. The second product is a research study, examining the influence of participation in repeated simulations on social work student development in clinical skills. Addressing a gap in the literature, this study utilized a nine-month qualitative design to explore student experiences with three simulations over the course of two semesters. Based on the findings, the author proposes a conceptual model for student growth in metacognition and self-regulation, utilizing multiple simulation experiences. The third product is an interactive eposter presentation given at the Council on Social Work Education 2018 Annual Program Meeting. This eposter summarizes research findings from the second banded dissertation product and incorporates practice experience in simulations for interprofessional education. Conclusions address the need for alignment between simulation learning objectives and simulation frequency. SIMULATION AS PEDAGOGY iii Simulation is a strong pedagogy for social work education, allowing for holistic engagement in learning. A better understanding of its influence on social work students allows educators to leverage the benefits of the pedagogy to align with identified learning objectives. Further research can build on the proposed conceptual model in Product Two as well as explore the use of simulation in an online environment.


Five Scolelepis species from the Gulf of Mexico and Western Atlantic Ocean are reported and certain species previously synonymized with Scolelepis (S.) squamata are revised. Four species are reinstated: S. (S.) goodbodyi (Jones, 1962), S. (S.) minuta (Treadwell, 1939), S. (S.) acuta (Treadwell, 1914), and S. (S.) agilis (Verrill, 1873); and two are described as new: S. (S.) lighti n. sp., and S. (S.) vossae n. sp. Scolelepis (Scolelepis) goodbodyi (Jones, 1962) n. comb., S. (S.) minuta (Treadwell, 1939) n. comb., S. (S.) acuta (Treadwell, 1914), and S. (S.) agilis (Verrill, 1873) are removed from synonymy with S. (S.) squamata Muller, 1806. The record of Scolelepis (P.) texana Foster, 1971 from the Grand Caribbean region is confi rmed. A key to all Scolelepis species from the Grand Caribbean is provided.


Midwater acoustic backscatter measurements collected by multibeam sonar offer
new opportunities and challenges for fisheries applications. A scientific data mining
technique to handle midwater multibeam backscatter data is presented. Most of the earlier
research on multibeam echosounding for fisheries has focused on the core basic technologies
of multibeam transducers, the associated signal processing, and calibration. Some work has
been done with post-processed data, but no systematic methodology for post-processing of
midwater multibeam backscatter data has emerged. In this paper, the problem is placed in a
data mining framework. A model inversion technique is utilized, by applying the inverse of an
approximation to the multibeam echosounding model. The proposed approach leads to a data
product consisting of a collection of midwater soundings. A multibeam midwater sounding is
the equivalent of the standard multibeam soundings as obtained from hydrographic
multibeam instruments. These soundings can be visualized directly, allowing for exploratory
data analysis in a 3d or 4d interactive environment. A sounding is a measurement in space
and time, and has associated attributes or features, such as the backscatter value. Other
features can be tagged to the soundings, forming generalised data nodes. Advanced spatiotemporal
data mining techniques can now be applied to this set of nodes. Some further
clustering techniques are presented, clustering the soundings into groups representing
coherent objects in the water column, or, more specifically, fish schools. Global properties of
clusters can be derived from the individual feature tags of the soundings, thus allowing for
classification of schools into classes of similar types. The latest developments of this research
are presented.


By incorporating predicted secondary and tertiary restraints derived from multiple sequence alignments into ab initio folding simulations, it has been possible to assemble native-like tertiary structures for a test set of 19 nonhomologous proteins ranging from 29 to 100 residues in length and representing all secondary structural classes. Secondary structural restraints are provided by the PHD secondary structure prediction algorithm that incorporates multiple sequence information. Multiple sequence alignments also provide predicted tertiary restraints via a two-step process: First, seed side chain contacts are selected from a correlated mutation analysis, and then an inverse folding algorithm expands these seed contacts. The predicted secondary and tertiary restraints are incorporated into a lattice-based, reduced protein model for structure assembly and refinement. The resulting native-like topologies exhibit a coordinate root-mean-square deviation from native for the whole chain between 3.1 and 6.7 A, with values ranging from 2.6 to 4.1 A over approximately 80% of the structure. Overall, this study suggests that the use of restraints derived from multiple sequence alignments combined with a fold assembly algorithm is a promising approach to the prediction of the global topology of small proteins.


Analyses of text corpora over time can reveal trends in beliefs, interest, and sentiment about a topic. We focus on views expressed about artificial intelligence (AI) in the New York Times over a 30-year period. General interest, awareness, and discussion about AI has waxed and waned since the field was founded in 1956. We present a set of measures that captures levels of engagement, measures of pessimism and optimism, the prevalence of specific hopes and concerns, and topics that are linked to discussions about AI over decades. We find that discussion of AI has increased sharply since 2009, and that these discussions have been consistently more optimistic than pessimistic. However, when we examine specific concerns, we find that worries of loss of control of AI, ethical concerns for AI, and the negative impact of AI on work have grown in recent years. We also find that hopes for AI in healthcare and education have increased over time.


We propose a simple yet robust stochastic answer network (SAN) that simulates multi-step reasoning in machine reading comprehension. Compared to previous work such as ReasoNet which used reinforcement learning to determine the number of steps, the unique feature is the use of a kind of stochastic prediction dropout on the answer module (final layer) of the neural network during the training. We show that this simple trick improves robustness and achieves results competitive to the state-of-the-art on the Stanford Question Answering Dataset (SQuAD), the Adversarial SQuAD, and the Microsoft MAchine Reading COmprehension Dataset (MS MARCO).


Providing consistent, individualized feedback to teachers is essential for improving instruction but can be prohibitively resource-intensive in most educational contexts. We develop M-Powering Teachers, an automated tool based on natural language processing to give teachers feedback on their uptake of student contributions, a high-leverage dialogic teaching practice that makes students feel heard. We conduct a randomized controlled trial in an online computer science course (N = 1,136 instructors), to evaluate the effectiveness of our tool. We find that M-Powering Teachers improves instructors' uptake of student contributions by 13% and present suggestive evidence that it also improves students' satisfaction with the course and assignment completion. These results demonstrate the promise of M-Powering Teachers to complement existing efforts in teachers' professional development.


The reduction of carbon dioxide (CO2) released from industry can help to reduce the emissions of greenhouse gases (GHGs) to the atmosphere while at the same time producing value-added chemicals and contributing to carbon fixation. Microbial electrosynthesis (MES) is a recently developed process which accomplishes this idea by using cathodic bacteria at the expense of only minimum energy. In this study, enriched mixed homoacetogenic bacteria as cathodic biocatalysts for the reduction of CO2 with five different concentrations were evaluated to produce acetate at a constant potential. Increasing the carbon concentration showed an improved acetate production rate and carbon conversion efficiency. A maximum acetate production rate of 142.2 mg L per day and a maximum carbon conversion efficiency of 84% were achieved, respectively, at 4.0 and 2.5 g HCO3− L−1. The changes in pH due to interactive reactions between the bicarbonate (substrate) and acetate (products) were able to create a buffering nature in the catholyte controlling the operating parameters of the MES process, such as pH and substrate specificity. A higher acetate production shifted the catholyte pH toward acidic conditions, which further triggered favorable conditions for the bioelectrochemical reduction of acetate to ethanol.


The question of sustainability of agricultural production especially animal production and events leading to its development can be dated back to the second part of the last century. Sustainability is a priority subject matter as it is a core element in our existence and in the survival of the forthcoming generations. The notion of sustainability comprises three aspects: ecological, social and political and economic target systems, which by now have been supplemented with cultural and regional elements including the protection of environment, local traditions, scale of values, cultural and historical heritage. The principles of sustainable development also include the improvement of human and animal health and the maintenance of vital rural communities. The priority notion of sustainability of agricultural production refers also to animal husbandry and especially sheep production. Sheep have contributed substantially to the grassland-based agricultural production in Hungary for centuries. Sheep sector is important in rural areas as the tool of sustainability of animal production. It should also be highlighted that contrary to numerous efforts, the globally difficult process of sustainable development poses almost unsolvable problems for implementers even on local and regional levels. This paper will review briefly the levels of sustainability in the Hungarian animal production with a special regard to sheep production and their content and then points out the most significant economic issues by the application of "SWOT†– analysis, "problem tree' and "structure of objectives†methods, on the grounds of the received findings.


Concerns with the final destination of organic solid waste (OSW) generated in rural areas originate from the possibility of this waste harming the environment, in addi tion to producing bad smell and attracting pests, when improperly disposed of in the soil. In this sense, composting might be a suitable way of dealing with this residue. This chapter presents the advantage of treating rural OSW through composting in reactors. Facultative reactors present the advantage of not requiring handling or large areas for the waste processing, and they do not generate bad smell and do not attract pests, which represent common drawbacks of the conventional windrow composting process. The final product of this composting process can be used as fertilizer for crops, resulting in the economy, since commercial fertilizers do not have to be bought. Works carried out by the Analytical and Environmental Chemistry Research Group at the State University of Ponta Grossa—Brazil have reported important results regarding the use of facultative reactors with different OSW mixtures. From the monitoring of physical, chemical, bio - logical and spectroscopic parameters, it was seen that composting in facultative reactors produced stable compost matured in a short period of time.


It has been found that translation is an efficient means to teach/learn grammar, syntax, and lexis of a foreign language. Meanwhile, translation is good for beginners who do not still enjoy the critical level of proficiency in their target language for expression.  This study was conducted to examine the teachers and learners' perceptions of employing translation in the foreign language classroom; i.e., the effects, merits, demerits, limitations, as well as its use as a method, strategy or technique. Both quantitative and qualitative methods were used to collect and analyze the data from graduate and undergraduate learners (n=56) and teachers (n=44), male and female, who responded to two questionnaires. Additionally, only the teachers were interviewed to gain richer insight into their perceptions and attitudes. According to the results of independent samples t-test, there was no significant difference between teachers and learners' attitude to applying translation as a method, strategy, or technique in learning a foreign language.  Based on the interview results, some teachers believed that employing translation in the foreign language context was helpful but not constantly. They claimed that translation was only effective in teaching vocabulary and grammar apart from leaners' proficiency level as it can clarify meaning. But some other teachers noted that mother tongue would interfere with learning foreign language; they considered translation as a time-consuming activity through which students cannot capture the exact meaning.


1. Propagation along the mid-latitude trough Abstract The propagation characteristics of radio signals are important parameters to consider when designing and operating radio systems. From the point of view Working Group 2 of the COST 296 Action, interest lies with effects associ- ated with propagation via the ionosphere of signals within the HF band. Several aspects are covered in this paper: a) The directions of arrival and times of flight of signals received over a path oriented along the trough have been examined and several types of propagation effects identified. Of particular note, combining the HF obser- vations with satellite measurements has identified the presence of irregularities within the floor of the trough that result in propagation displaced from the great circle direction. An understanding of the propagation effects that result in deviations of the signal path from the great circle direction are of particular relevance to the operation of HF radiolocation systems. b) Inclusion of the results from the above mentioned measurements into a propagation model of the norther- ly ionosphere (i.e. those regions of the ionosphere located poleward of, and including, the mid-latitude trough) and the use of this model to predict the coverage expected from transmitters where the signals impinge on the northerly ionosphere. c) Development of inversion techniques enabling backscatter ionograms obtained by an HF radar to be used to estimate the ionospheric electron density profile. This development facilitates the operation of over the hori- zon HF radars by enhancing the frequency management aspects of the systems. d) Various propagation prediction techniques have been tested against measurements made over the trough path mentioned above, and also over a long-range path between Cyprus and the UK. e) The effect of changes in the levels of ionospheric disturbances on the operational availability at various data throughput rates has been examined for the trough path mentioned earlier. The topics covered in this paper are necessarily brief, and the reader is referred to full papers referenced herein on individual aspects.


In this essay I explore the connections between public choice and originalism, arguing that public choice is crucial to development of the originalism both in its diffuse popular and more academic form. As Robert Bork's famous article, Neutral Principles and Some First Amendment Problems, illustrates, originalism begins as a reaction to the Warren Court, but it is a reaction that largely accepts the primacy of democratic majoritarianism that had begun in the Progressive era. It is public choice more than any other theory of politics that loosens the straightjacket that majoritarianism has on constitutional theory. In its more diffuse form, public choice with its emphasis on the self- interested nature of politicians, the power of interest groups, and the pathologies of collective choice made majority rule less attractive. James Buchanan's contribution with Gordon Tullock in The Calculus of Consent has particular relevance to originalism, because it decisively breaks from the idea that majority rule should be the presumptive norm in constitutional republics. If constitutions are best made by supermajority rules, as Buchanan and Tullock imply, originalism can be justified as a way of protecting the results of supermajoritarian constitutionmaking from change by either majorities or the peculiar submajorities that are comprised by the justices of the Supreme Court. As important as are the interpretive disputes within originalism, like that between original intent and public meaning, public choice's inflection point may be more important because it moves originalism from a theory that was concerned primarily with protecting democratic majorities to a theory that was concerned with preserving a republican regime that was in its formation and essence nonmajoritarian. That shift in turn empowered originalism to become a much more aggressive theory of judicial review of legislation, creating more potential conflict between the judiciary and legislative majorities. The essay also briefly critiques some constitutional theorists who have stayed within the Progressive Paradigm, because their theories fail to solve the countermajoritarian difficulty at its heart. It ends with a description of four problems that public choice originalism has yet fully to address.


The authors empirically analyze the price-setting behaviour of the major Canadian banks in the residential mortgage market over the period 1991–2007. They use weekly posted prices of the major mortgage providers to study the degree of competition in mortgage price setting. Their results suggest that the residential mortgage market is imperfectly competitive. They find distinct price leaders and that, as market concentration increases, so does price dispersion - helped by the increased use of discounting from posted prices. The authors also find that, although banks' pass-through of input price changes to mortgage prices is complete in the long run under reasonable assumptions regarding discounting, there exists some level of pricing asymmetry in the short run.


On 24 May 2006, Professor Emeritus of History Albert Adu Boahen passed away on the evening of his 74th birthday. The first Ghanaian to receive a Ph.D. in African history from the School of Oriental and African Studies (SOAS) in 1959, and the first African to chair the Department of History at the University of Ghana in 1967, Adu Boahen was without a doubt Ghana's foremost historian and a distinguished statesman. His publishing career spanned some forty years, his works ranging from standard textbooks in use in Africa and the West to major interpretations of African history such as African Perspectives on Colonialism (1987), Mfantsipim and the Making of Ghana: A Centenary History, 1876–1976 (1996) and Yaa Asantewaa and the Asante–British War of 1900–1 (2003). A scholar–activist, he demonstrated a consistent opposition to dictatorial rule and military regimes that earned him stints in prison. In February 1988, on the platform of the Ghana Academy of Arts and Sciences, of which he was a fellow, he delivered three lectures under the title of 'The Ghanaian Sphinx: Reflections on the Contemporary History of Ghana, 1972–1987' that broke the 'Culture of Silence' of the oppressive Rawlings regime and inaugurated what has been termed the 'second independence of Ghana'. Posthumously awarded the Order of the Star of Ghana on 30 June 2006 for distinguishing himself in academia and statesmanship, Boahen was given a grand state burial in July 2006. He served on the editorial board of the Journal of African History.


Background and aims Non-alcoholic steatohepatitis (NASH) – a progressive subset of non-alcoholic fatty liver disease (NAFLD) – is a chronic liver disease that can progress to advanced fibrosis, cirrhosis, and end-stage liver disease (ESLD) if left untreated. Early-stage NASH is usually asymptomatic, meaning a large proportion of the prevalent population are undiagnosed. Receiving a NASH diagnosis increases the probability that a patient will receive interventions for the purpose of managing their condition. The purpose of this study was to estimate the disease burden and economic impact of diagnosed NASH in the United Kingdom (UK) adult population in 2018. Methods The socioeconomic burden of diagnosed NASH from a societal perspective was estimated using cost-of-illness methodology applying a prevalence approach. This involved estimating the number of adults with diagnosed NASH in the UK in a base period (2018) and the economic and wellbeing costs attributable to diagnosed NASH in that period. The analysis was based on a targeted review of the scientific literature, existing databases and consultation with clinical experts, health economists and patient groups. Results Of the prevalent NASH population in the UK in 2018, an estimated 79.8% were not diagnosed. In particular, of the prevalent population in disease stages F0 to F2, only 2.0% (F0), 2.0% (F1) and 16.5% (F2), respectively, were diagnosed. Total economic costs of diagnosed NASH in the UK ranged from £2.3 billion (lower prevalence scenario, base probability of diagnosis scenario) to £4.2 billion (higher prevalence scenario, base probability of diagnosis scenario). In 2018, people with NASH in the UK were estimated to experience 94,094 to 174,564 disability-adjusted life years (DALYs) overall. Total wellbeing costs associated with NASH in 2018 were estimated to range between £5.6 to £10.5 billion. Conclusion The prevention and appropriate management of adult NASH patients could result in reduced economic costs and improvements in wellbeing.


This paper begins with the proposition that most project managers are dealing with complex systems. Complex systems are defined as systems with numerous stakeholders, nonlinearities, multiple interdependencies and feedback systems. Typical nonlinearities are often unanticipated changes in the scope of the project, the dismissal of project managers, shedding people with critical labour skills or the termination of credit arrangements with banks. The interdependencies are the relationships between project management, the suppliers and contractors, the clients and the other stakeholders. The feedback systems most common to the success and failure of project management are the rework cycles and their impact on both the demand for labour and the final budget and completion date. The paper outlines a methodology for project management that integrates a number of systems thinking tools into the project management process.


Abstract : This technical note describes the results of a preliminary investigation into measures for software architecture. It focuses on measures that directly indicate the health of, or detect a problem with, the software architecture of an up-and-running software system. Defining these architectural measures is very difficult. The software architecture deeply affects subsequent development and project management decisions, such as the breakdown of the coding tasks and the definition of the development increments. Most existing measures for up-and-running software systems capture the cumulative results of architectural, developmental, and managerial decisions and do not directly address the health of the software architecture. The investigation into measures requires the joint participation of the software architecture and measurement communities. Since the software architecture community has made such rapid progress over the past 10 years, this report first describes what the measurement community needs to know about software architecture to understand the difficulty of defining architectural measures. The current relevant literature is then described in terms of its potential contribution to this research. Finally, the report identifies areas for future research into the application of measurement technology to software architectures. The ultimate goal of this body of work is to provide measurement guidance and quantitative decision support to software practitioners, including software architects and project managers.


The Hikurangi Plateau having anomalously thick oceanic crust subducts under the Australian plate along the Hikurangi subduction zone offshore the North Island of New Zealand. The plate interface is shallow and some characteristics on the plate interface such as seamounts and seismic high reflectivity zones were identified by seismic surveys (Bell et al., 2010). At the Hikurangi subduction margin, slow slip events (SSEs) occur at intervals of 18 to 24 months with durations of 1 to 2 weeks. From May, 2014, to June, 2016, the Hikurangi Ocean Bottom Investigation of Tremor and Slow Slip (HOBITSS) observation was conducted in the northern Hikurangi margin. During this observation, Mw 6.8 SSE occurred in September through October, 2014, directly beneath the ocean bottom seismometer (OBS) network. In this study, we used continuous waveform data recorded by these OBSs, and applied a shear wave splitting analysis (Ando et al., 1983) and a polarization analysis for monitoring shear wave signals. These methods have been successfully applied to waveform data from onshore seismic networks in Cascadia subduction zone by Bostock and Christensen (2012) and in Shikoku Island, Japan, by Ishise and Nishida (2015). As a result, we detected continuous arrival of shear wave signals that appeared to have started in the later half of the SSE duration reported by Wallace et al. (2016). Parts of the continuous signals were identified as tremors and their source locations have been determined by the envelope cross-correlation method (Todd et al., 2016). Our result, however, suggests that the transmission of the signals were rather continuous than sporadic as individual events, and they appeared to last for more than two weeks. Polarization direction became stable in synchronous with the continuous signals and its orientation is different from that in the other times. Arrivals of such continuous long-duration signals with a stable polarization direction are only seen during this period through the year-long OBS records. Our analysis requires less OBSs than envelope cross-correlation methods for monitoring such shear wave signals, which may enable us to detect as yet to be unidentified continuous signals in the Hikurangi margin where seismic attenuation has been known to be large. Distribution of the OBS stations detecting such continuous signals infers that they were generated only around the subducted seamount adjacent to the slow slip area. A previous study on distribution of this SSE obtained by inversion of seafloor vertical displacement data from ocean bottom absolute pressure gauges (Wallace et al., 2016) showed that the fault slip along the plate interface circumvented the subducted seamount. By combining these results about slip distribution and the origin of continuous shear wave signals, we can put more constraints on relationship between frictional properties along the plate interface and its topographic features.


Hummocky cross-stratification is recorded from the classic Upper Silurian Whitcliffe Group (Ludlow Series)/Downton Group (Pridoli Series) boundary section at Ludlow, Shropshire. This necessitates a revision of previous interpretations of palaeoenvironments which infer either a tidal mudflat depositional setting. Evidence for tidal influence is lacking. Instead the importance of storm activity, probably on a shoreface, is emphasized. The absence of articulate brachiopods and other open marine faunal elements in the Downton strata is attributed to changes in salinity in the restricted Downton sea shortly before its elimination by Acadian uplift. The boundary between the Upper Whitcliffe Formation (Ludlow) and the overlying Downton Castle Sandstone Formation (Pridoli), formerly proposed as the stratotype section for the base of the fourth Series of the Silurian System, is designated at Ludford Corner, Ludlow, Shropshire [SO 51237413] (Fig. 1, Bassett et al. 1982 and references therein). It has received considerable attention, with particular emphasis on faunal changes through the section. In addition to its stratigraphic significance, the section occurs at a crucial position in the transition from marine to non-marine environments associated with the Acadian (late Caledonian) inversion of the Welsh Basin (Woodcock et al. 1988). The Downton Castle Sandstone Formation in the Ludlow area overlies shelly calcareous siltstones of the top Ludlow, Upper Whitcliffe Formation and comprises a coarsening and cleaning-upward sequence, about 15 to 20 m thick (Bassett et al. 1982). Coastal mudflat deposits of the Temeside Shale Formation lie directly above but are not seen at Ludford corner. The basal part of the


Cotton processing efficiency is dependent on the degree of friction between fibers and their processing environment as the fibers are subjected to the various pieces of equipment involved in converting fiber to yarn. This frictional behavior is a function of both fiber morphology and fiber surface characteristics. In this study, fiber surface electrolyte content and the moisture associated with the fiber were investigated to determine their potential role in the conversion of fiber to yarn. A single cultivar of cotton grown in Georgia during the 2003 crop year was treated with different electrolyte solutions at various concentrations, and then the frictional behavior of the cottons was examined using the Rotorring measurement. Results indicated that a coating of electrolyte on the surface of the cotton fiber may lead to either an increase or a decrease in fiber friction. The more hygroscopic electrolytes in general were responsible for increases in fiber-to-metal friction. Fiber-to-fiber friction was increased by all surface electrolyte treatments, which lead to the conclusion that the electrolyte content in conjunction with surface moisture confers anti-electrostatic properties that increases the coherence between individual fibers. Knowledge of this property will aid in predicting the processing performance of cotton fiber and the possibility of adjusting that performance through the application of electrolyte solutions to the fiber.


This paper explores a new phase of urban development based on a case study of Dallas, Texas. The key feature of the North American metropolitan areas is the relatively weak CBD core. Many issues related to social problems, for example increasing number of immigrant shares or more non-English speaking people, often push the major urban functions out toward the suburbs and many high-density office complexes are found separate and far from the CBD as a result. In this paper, the authors examine the new efforts by city councils and other related organizations to reorganize suburbanized functions around a new public transportation system, the light rail transit (LRT). After the completion of the LRT in 1996, a new pattern of commuter flows and an increased urban development close to the newly opened stations occurred.


We describe here a novel footprinting technique to probe the in vivo structural dynamics of membrane protein. This method utilized in situ generation of hydroxyl radicals to oxidize and covalently modify biomolecules on living Escherichia coli cell surface. After enriching and purifying the membrane proteome, the modified amino acid residues of the protein were identified with tandem mass spectrometry to map the solvent-accessible surface of the protein that will form the footprint of in vivo structure of the protein. Of about 100 outer membrane proteins identified, we investigated the structure details of a typical β-barrel structure, the porin OmpF. We found that six modified tryptic peptides of OmpF were reproducibly detected with 19 amino acids modified under the physiological condition. The modified amino acid residues were widely distributed in the external loop area, β-strands, and periplasmic turning area, and all of them were validated as solvent-accessible according to the crystallography data. We further extended this method to study the dynamics of the voltage gating of OmpF in vivo using mimic changes of physiological circumstance either by pH or by ionic strength. Our data showed the voltage gating of porin OmpF in vivo for the first time and supported the proposed mechanism that the local electrostatic field changes in the eyelet region may alter the porin channels to switch. Thus, this novel method can be a potentially efficient method to study the structural dynamics of the membrane proteins of a living cell.


We have proposed neuro-fuzzy (NF) based flood warning system in this paper. The input data have been collected using wireless sensor network (WSN). The proposed model has collected input parameters, such as rainfall, river water level and river water flow, from a specific site and send the data to decentralized node. Based on the inputs, Adaptive Neuro-Fuzzy Inference System (ANFIS) model has determined the flood possibility index. All the decentralized nodes forward the pre-processed information to the centralized node for further processing. Depending on the last ten years data, The centralized node has compared the flood possibility index with the last ten years data stored in a database and then calculated flood persistence index by linguistic term Red, Yellow or Green on a GIS map. This model may also serve as a tool for real time flood monitoring and flood warning.


The relationship between high school mathematics curricula and the likelihood of students who enroll in a developmental (non-credit bearing) course in college taking additional mathematics courses was studied. The results showed that high school mathematics curriculum, years of high school mathematics completed, and ACT mathematics scores were related to developmental mathematics course-taking, but curriculum was not related to the subsequent mathematics course-taking of students who began college with developmental mathematics. The results have important implications for educational researchers and policymakers at the college and high school levels.


Gender mainstreaming is one of the Indonesian central government's alternative programs to achieve gender equality. Gender inequality is experienced by women, especially in underprivileged conditions. Gender mainstreaming to address environmental concerns and the lagging and oppression of the environment's development. Moreover, women, as pioneers of their households, must find ways to survive in environments where massive exploitation has drastically reduced the ability to access natural resourses as a daily support system. It is important that equitable development for all genders to provide a sound environment and create a creative economy to improve living standards takes place. This research employs a qualitative method, an interview conducted with one informant from Deputy Assistant of Gender Equality in Infrastructure and Environment, Ministry of Women's Empowerment and Child Protection of the Republic of Indonesia, as well as literature research. This approach discusses the correlation between women and the environment in development to reduce poverty. Ecofeminist theory is used as a foundation to guide this research; therefore, this theoretical base provides a general description of the results regarding the correlation between women and the environment in terms of reducing poverty towards sustainable development in Indonesia. The Ministry of Environment and Forestry, the Ministry of Women's Empowerment and Child Protection of the Republic of Indonesia, NGOs and communities (women) are involved in increasing gender participation to reduce poverty in several Indonesian districts. Nevertheless, it must be emphasized that each stakeholder has a role in development, including in monitoring law enforcement and related policy instruments. In this case the ecofeminism perspective is seen as an alternative to rehabilitating the environment to create a sustainable way of living, especially in terms of reducing poverty, in Indonesia. Aligned with gender mainstreaming in social capital, ecofeminism aims to empower women to preserve the natural environment or natural resources that will be managed by women in the local community.


1. Homologous angiotensin-I was added to untreated plasma. Angiotensin-II which is formed by plasma converting enzyme and subsequently degradated by angiotensinases was determined as a function of time by using radioimmunoassay. Having determined the kinetics, the activities of converting enzyme and angiotensinases were calculated by a least-square fit of the theoretical curve to the experimentally measured values. 2. The method gives a simple measurement of converting-enzyme activity in untreated plasma; in plasma from salt-depleted and renal hypertensive rats this was found to be slightly increased but was normal in plasma from nephrectomized rats. 3. The half-lives for angiotensin-I in normal rat and human plasma were found to vary between 0·8 and 2·1 min, and the possibility that plasma converting enzyme participates in the regulation of the formation of angiotensin-II in vivo cannot be excluded. 4. The angiotensinase activity in rat plasma gave half-lives for angiotensin-II between 1·5 and 3·3 min; the half-life in normal human plasma was 10 min.


OBJECTIVES
Cost-effectiveness analyses are routinely based on data from group averages, restricting its generalizibility to those with below- or above-average risk. A pharmaco-economic model that used individualized risks for fractures was developed in order to take into account patient heterogeneity.

METHODS
Data were obtained from The Health Improvement Network research database of general practitioners, comprising a UK general population of women aged more than 50 years (N = 330,000). Mortality and hip, vertebral, and other osteoporotic fracture risks for each individual were estimated by age, body mass index (BMI), smoking, and other clinical risk factors. Estimates on costs, EuroQol (EQ-5D) utilities, and treatment efficacy were obtained from a UK national report (the National Institute for Clinical Excellence) and outcomes were simulated over a 10-year period.

RESULTS
It was found that the cost per quality-adjusted life-year (QALY) gained was lower in elderly women and in women with fracture history. There was a large variability in the cost-effectiveness with baseline fracture risk and with clinical risk factors. Patients with low BMI (<20) had considerable better cost-effectiveness than patients with high BMI (>or=26). Using a cost-acceptability ratio of 30k pounds per QALY gained, bisphosphonate treatment became cost-effective for patients with a 5-year risk of 9.3% (95% confidence interval [CI] 8.0-10.5%) for osteoporotic fractures and of 2.1% (95% CI 1.5-2.7%) for hip fractures. Including bone mineral density in the risk assessment, the cost per QALY gained was 35k pounds in women at age 60 with a fracture history and a T-score of -2.5 (at age 80, this was 3k pounds).

CONCLUSION
A pharmacoeconomic model based on individual long-term risks of fracture improves the selection of postmenopausal women for cost-effective treatment with bisphosphonates.