The dependence of life scientists on software has steadily grown in recent years. For many tasks, researchers have to decide which of the available bioinformatics software are more suitable for their specific needs. Additionally researchers should be able to objectively select the software that provides the highest accuracy, the best efficiency and the highest level of reproducibility when integrated in their research projects. Critical benchmarking of bioinformatics methods, tools and web services is therefore an essential community service, as well as a critical component of reproducibility efforts. Unbiased and objective evaluations are challenging to set up and can only be effective when built and implemented around community driven efforts, as demonstrated by the many ongoing community challenges in bioinformatics that followed the success of CASP. Community challenges bring the combined benefits of intense collaboration, transparency and standard harmonization. Only open systems for the continuous evaluation of methods offer a perfect complement to community challenges, offering to larger communities of users that could extend far beyond the community of developers, a window to the developments status that they can use for their specific projects. We understand by continuous evaluation systems as those services which are always available and periodically update their data and/or metrics according to a predefined schedule keeping in mind that the performance has to be always seen in terms of each research domain. We argue here that technology is now mature to bring community driven benchmarking efforts to a higher level that should allow effective interoperability of benchmarks across related methods. New technological developments allow overcoming the limitations of the first experiences on online benchmarking e.g. EVA. We therefore describe OpenEBench, a novel infra-structure designed to establish a continuous automated benchmarking system for bioinformatics methods, tools and web services. OpenEBench is being developed so as to cater for the needs of the bioinformatics community, especially software developers who need an objective and quantitative way to inform their decisions as well as the larger community of end-users, in their search for unbiased and up-to-date evaluation of bioinformatics methods. As such OpenEBench should soon become a central place for bioinformatics software developers, community-driven benchmarking initiatives, researchers using bioinformatics methods, and funders interested in the result of methods evaluation.


Suppose that we observe a sample of independent and identically distributed realizations of a random variable. Given a model for the data generating distribution, assume that the parameter of interest can be characterized as the parameter value which makes the population mean of a possibly infinite dimensional estimating function equal to zero. Given a collection of candidate estimators of this parameter, and specification of the vector estimating function, we propose crossvalidation criteria for selecting among these estimators. This cross-validation criteria is defined as the Euclidean norm of the empirical mean over the validation sample of the estimating function at the candidate estimator based on the training sample. We establish a finite sample inequality of this method relative to an oracle selector, and illustrate it with some examples. This finite sample inequality provides us with asymptotic equivalence of the selector with the oracle selector under general conditions. We also study the performance of this method in the case that the parameter of interest itself is path-wise differentiable (and thus, in principle, root-$n$ estimable), and show that the cross-validated selected estimator is typically efficient, and, at certain data generating distributions, superefficient (and thus non-regular). Finally, we combine 1) the selection of sequence of subspaces of the parameter space (i.e., a sieve), 2) the estimating equation as empirical criteria to generate a candidate estimator for each subspace, and 3) estimating function based cross-validation selector to select among the candidate estimators, in order to provide a new unified estimating function based methodology. In particular, we formally establish a finite sample inequality for this general estimator in the case that one uses epsilon-nets as sieve, and point out that this finite sample inequality corresponds with minimax adaptive rates of convergence w.r.t. to the norm implied by the estimating function. May 19, 2005 18:50 WSPC/Trim Size: 9in x 6in for Review Volume estfiecrossval2005tech


This article provides a contemporary reading of Euripides' drama, the Alcestis, through the practical application of Wittgenstein's method of Gloss Analysis. The main problem investigated is how Euripides treats the motif of love in the Alcestis. This problem is approached by way of an analysis of the function of language. More specifically, emphasis is placed on the role of metaphorical language in order to show up the tensions in a classical marriage. Through Gloss Analysis the use of metaphors is illuminated, and this reveals the function of the patriarchal value system and how it failed in the classical era.


This talk will present our recent findings and visual (static and animated) maps characterising combinatorial and computer program search spaces. We seek to lay the foundations for a new perspective to understand problem structure and improve heuristic search algorithms: search space cartography. Heuristic methods operate by searching a large space of candidate solutions. The search space can be regarded as a spatial structure where each point (candidate solution) has a height (objective or fitness value) forming a fitness landscape surface. The performance of search algorithms crucially depends on the fitness landscape structure, and the study of landscapes offers an alternative to problem understanding where realistic formulations and algorithms can be analysed. Most fitness landscapes analysis techniques study the local structure of search spaces. Our recently proposed model, Local Optima Networks, helps to study instead their global structure. This graph-based model provides fundamental new insight into the structural organisation and the connectivity pattern of a search space with given move operators. Most importantly, it allows us to visualise realistic search spaces in ways not previously possible and brings a whole new set of network metrics for characterising them.


Shirley Jackson's masterpiece: the deliciously dark and funny story of Merricat, tomboy teenager, beloved sister - and possible lunatic. "Her greatest book ...at once whimsical and harrowing, a miniaturist's charmingly detailed fantasy sketched inside a mausoleum...Through depths and depths and bloodwarm depths we fall, until the surface is only an eerie gleam high above, nearly forgotten; and the deeper we sink, the deeper we want to go". (Donna Tartt, author of The Goldfinch). Living in the Blackwood family home with only her sister Constance and her Uncle Julian for company, Merricat just wants to preserve their delicate way of life. But ever since Constance was acquitted of murdering the rest of the family, the world isn't leaving the Blackwoods alone. And when Cousin Charles arrives, armed with overtures of friendship and a desperate need to get into the safe, Merricat must do everything in her power to protect the remaining family. This Penguin edition includes an afterword by the acclaimed novelist Joyce Carol Oates. All Shirley Jackson's other novels, plus The Lottery and Other Stories, are available in Penguin Modern Classics. Shirley Jackson was born in California in 1916. When her short story The Lottery was first published in The New Yorker in 1948, readers were so horrified they sent her hate mail; it has since become one of the most iconic American stories of all time. Her first novel, The Road Through the Wall, was published in the same year and was followed by five more: Hangsaman, The Bird's Nest, The Sundial, The Haunting of Hill House and We Have Always Lived in the Castle, widely seen as her masterpiece. In addition to her dark, brilliant novels, she wrote lightly fictionalized magazine pieces about family life with her four children and her husband, the critic Stanley Edgar Hyman. Shirley Jackson died in her sleep in 1965 at the age of 48. "The world of Shirley Jackson is eerie and unforgettable...She is a true master". (A. M. Homes). "A masterpiece of Gothic suspense". (Joyce Carol Oates). "If you haven't read We Have Always Lived in the Castle ...you have missed out on something marvellous". (Neil Gaiman).


Understanding the interactive experience of using digital technologies is a complex process. Traditional methods of evaluating interactive technologies originate from usability, which focuses on ease of use, ease of learning and performance. User Experience (UX) emerged from the recognition that usability alone does not account for the more subjective emotional responses experienced when interacting with a product. Although the term UX has become widely accepted within the area of Human Computer Interaction (HCI), its definition still remains unclear, making it difficult to evaluate and design for. This thesis adopts a hybrid perspective by bridging the division between the reductionist and holistic approaches to UX research. Using a multi-methods approach that combine the strengths of both quantitative (objective) and qualitative (subjective) methods, will provide deeper insights into the users? judgement process of interactive products. Various theories have been proposed to understand UX, yet no consensual UX theory or model has emerged. The importance of aesthetics in influencing decisions about a products quality gained much attention in early UX research with conflicting results, sparking a surge of research into understanding the complexities of user quality judgement. Past UX research has focused on the multi-constructs of pragmatics, hedonics and aesthetics, and how these may influence user judgement, which can vary depending on the context, task and user background. However, little attention has been given to the impact of interactive design features upon UX. Findings from this thesis clearly show that interactivity is an important element within UX in both short and long-term usage. This thesis expands the existing process model of user quality judgement, through a series of three studies to reveal the importance of interactivity, and how initial perception and judgement of a products quality can change over time. The first two studies identify the importance of interactivity in positive influencing UX. Both studies revealed that affective and hedonic ratings increased as a result of interaction, demonstrating the powerful effect of interaction, and showed clear differences for websites that contained enhanced interactive features, despite the presence of usability problems. Further exploration using cluster analysis revealed three sub-groups that categorised users not only by their interactive style preferences, but also by their predispositions towards technology. This perspective of user sub-group analysis is a contribution to the field which bridges population-level quantitative analysis with qualitative findings that focuses on the individual ethnographic interpretations of experience. Considerable UX research has focused on short-term evaluations, based on users first impressions pre and post-interaction, with few studies capturing long-term usage. The third study reports on an ecological longitudinal investigation into how UX changes over time and long-term product use. A group of novice iPad users were tracked over six months to reveal that despite poor usability, hedonic ratings remained high, yet over time usefulness and utility were dominating factors affecting UX and product adoption. The influence of both device and app revealed that although users found the device more pleasurable, it was the variety of apps contained on the device that facilitated positive UX. The overall findings from this research provided some valuable methodological insights and aided the creation of set of practical UX heuristics that can be used to inform both future research and design practice.


The spatial distribution of CaCO 3 polymorphs formed during the experimental carbonation of water saturated Portland-cement cores (30 mm in diameter), with supercritical CO 2 at 90 °C and 30 MPa, has been investigated using Raman microspectrometry on polished sample sections and X-ray microdiffraction. The three calcium carbonate polymorphs (calcite, aragonite and vaterite) were clearly distinguished using both techniques and their distribution along the main CO 2 diffusion direction could be mapped at the millimetre scale using a dynamic line-scanning Raman mapping tool. The calcium carbonate 2D distribution clearly shows that vaterite, the least stable of the three CaCO 3 polymorphs, is mostly located in a 500 μm wide ring ahead of the carbonation zone. This feature indicates that vaterite is the first CaCO 3 polymorph to crystallize within the cement sample in the course of the carbonation process. The presence of a vaterite front indicates that local mineral-solution equilibration can be slower than species transport, even above ambient conditions, and that kinetics cannot be ignored in the cement carbonation process. By using calcite and vaterite precipitation kinetic data from the literature and assuming water-mineral kinetics based on the Transition State Theory, the vaterite front inferred from Raman mapping is reproduced with a purely diffusive 1D transport code.


Abstract. Knowledge about Antarctic sea-ice volume and its changes over the past decades has been sparse due to the lack of systematic sea-ice thickness measurements in this remote area. Recently, first attempts have been made to develop a sea-ice thickness product over the Southern Ocean from space-borne radar altimetry and results look promising. Today, more than 20 years of radar altimeter data are potentially available for such products. However, the characteristics of individual radar types differ for the available altimeter missions. Hence, it is important and our goal to study the consistency between single sensors in order to develop long and consistent time series. Here, the consistency between freeboard measurements of the Radar Altimeter 2 on board Envisat and freeboard measurements from the Synthetic-Aperture Interferometric Radar Altimeter on board CryoSat-2 is tested for their overlap period in 2011. Results indicate that mean and modal values are in reasonable agreement over the sea-ice growth season (May–October) and partly also beyond. In general, Envisat data show higher freeboards in the first-year ice zone while CryoSat-2 freeboards are higher in the multiyear ice zone and near the coasts. This has consequences for the agreement in individual sectors of the Southern Ocean, where one or the other ice class may dominate. Nevertheless, over the growth season, mean freeboard for the entire (regionally separated) Southern Ocean differs generally by not more than 3 cm (8 cm, with few exceptions) between Envisat and CryoSat-2, and the differences between modal freeboards lie generally within ±10 cm and often even below.


Introduction: Mountain biking (MTB) is an adventure sport with an increasing number of participants and competitors. The amount of injuries reported over the last years has grown. Research is needed to identify typical injury patterns and to improve possible preventive measures. This review study discusses the published literature on acute mountain-biking injuries. Methods: An electronical search in Pubmed and Sportdiscus was performed from March 2008 until November 2008. Results: The literature search revealed 23 studies. The review showed, that 50–90 % of the examined mountain bikers had sustained an injury in the past, most of which were minor (ca. 75.4 %), such as lacerations, contusions or abrasions. The review further showed, that the injuries mainly occurred to the upper and to the lower limbs, with a nearly equal distribution (35– 45 % vs. 30–45 %). Head injuries also turned out to be a noticeable component of the sum of injuries (10–20 %), most of which were concussions.Although the biggest amount of injuries occurred to young males aged 20–39 the review showed, that women were nearly twice as likely to be injured and also more likely to sustain fractures. Conclusion: MTB is a popular sport that can result in a wide variety of injuries. Although most traumas were minor, serious injuries (e. g. fractures, concussions) occurred as well and mostly resulted from falls over the handle bar. The injury risk may be reduced by the use of protective devices and appropriate trail selection.


Problem statement: Pseudomonas aeruginosa is an opportunistic pathogen that still
develops life-threatening infections in patients with immunological system defects, like burn patients,
especially in developing countries. Since this bacterium is naturally resistant to many drugs and is able
to get resistance to all effective antibiotics, the infection with this organism is particularly problematic
condition for patients. This study was design to evaluated drug susceptibility for determination of
multidrug-resistant isolates and molecular epidemiology of P. aeruginosa colonization for
investigation of the isolates routes in the burn unit of Shahid Motahhari Hospital in Tehran.
Approach: About 127 clinical and 2 environmental P. aeruginosa isolates were collected during 6
months. All P. aeruginosa isolates were analyzed for drug susceptibility by disk diffusion method and
molecular epidemiology assessment were done by RAPD-PCR analysis. Results: Drug susceptibility
tests were shown high resistance for ceftizoxime (86.8%), aztreonam (80.6%), kanamycin (79.8%) and
tetracycline (78.3%); furthermore, low resistance for some antibiotics like imipenem (30.2%),
piperacillin/tazobactam (34.1%) and amikacin (41.1%) was showed. In addition, 42 multidrug-resistant
P. aeruginosa isolates were recovered from clinical specimens and one isolate from environmental
samples. Molecular typing revealed eight different profiles that include two profiles, RAPD1 and
RAPD4, with environmental resource. The major RAPD profile was RAPD1 profile (n = 64, 50.4%),
which includes 31 (72.1%) multidrug-resistant isolates with an environmental reservoir. Conclusion: In
summery, we were found three different profiles for multidrug-resistant strains. Different RAPD
profiles suggested the different resources of infection, two environmental resources were found, that
one of them was multidrug-resistant strain. These findings highlighted the need for further attention to
disinfection inanimate hospital environment and controlled contact between staff with patients to limit
transfer of P. aeruginosa in this BU; moreover, use of some antimicrobial agents must be restricted
due to existence of high resistance and using of combined effective antibiotics is recommend.


When may physicians refuse to provide medical interventions that might prolong the patient's life? When should they refuse? When must they? Such questions of medical futility remain as much a subject of debate today as in 1995 when the first edition of Wrong Medicine: Doctors, Patients, and Futile Treatment was published. Therefore, it is altogether fitting that Larry Schneiderman (a physician) and Nancy Jecker (a philosopher) have published a second edition of their widely influential book. Schneiderman and Jecker want to foster critical discussion both in the medical profession and in society at large about the goals of medicine and the nature of the physician-patient relationship at the end of life. This materially updated and revised second edition will prompt and richly inform such critical discussion. This review includes definitions of medical futility, a snapshot of the structure and organization of the book, and the major criticism (undefended assumptions) and minor criticism (legal errors).


Although many studies have shown that P450aromatase (P450arom), anti-Mullerian hormone (AMH) and estrogen receptor α (ERα) play pivotal roles in sexual differentiation of the gonads during early embryonic development in chickens and quail, few studies have been reported for other domestic birds. Furthermore, little information is available in relation to the mRNA expression in gonads after sexual differentiation in posthatching birds. The present study was conducted to assay mRNA expression of P450arom, AMH and ERα in gonads at day of hatch in turkey and duck and 2 days after hatching in goose using the real-time PCR. The mRNA expression was also determined at one week of age in gonads of these birds. At the time of collection of the left gonads for total RNA extraction, the external appearance of the left and right gonads of male and female was documented by digital camera. Clear asymmetry was observed in the female ovary in which the right ovary was regressed completely by 1-2 days in posthatching turkey, duck and goose. Although gonadal asymmetry was as remarkable as in females, the left testis was larger than the right one in males. Remarkable expression of P450arom mRNA was observed only in females in all the 3 species but substantially no expression was detected in males. Significantly higher expression of AMH mRNA was detected in males than females only in goose but there was no sex difference in turkey and duck at 1-2 days posthatching and one week of age. Weak ERα mRNA expression without a sex difference was detected in the 3 birds. These results suggest that estrogen plays a key role for ovarian development via P450arom mRNA expression after hatching, whereas absence of its expression in males leads to testis development in turkey, duck and goose.


While expanding federal involvement in the health care system, the Patient Protection and Affordable Care Act (ACA) preserves states' roles as policy laboratories and private providers' roles as health care delivery laboratories. State-based and provider-based laboratories suffer from many shortcomings, however, as mechanisms to develop, evaluate, and facilitate diffusion of reforms within the health system. This Article argues that the federal government can take steps to address these shortcomings. It first briefly reviews ACA provisions that promote policy and delivery experimentation. It then suggests that by tying funding to policy outcomes, making use of regulatory variation and regulatory menus, and conditioning waivers on systematic evaluation, the federal government could further improve the performance of the nation as a laboratory.


INTRODUCTION The organic fraction of a potting mix is subject to decomposition and, therefore, is important in relation to nitrogen (N) immobilisation. Immobilisation of N is the reduction in plant available N (i.e., nitrate or ammonium) as a result ofmicroorganisms using this N as they decompose organic materials with a high carbon (C) content. The organic portion of potting mixes usually constitutes 50% or more of their volume and in New Zealand Pinus radiata bark and sphagnum peat are the most commonly used materials. Pinus radiata sawdust, tree fern fibre, composted mixed vegetation, and other sources of bark or sawdust are also used on a limited scale. Spent mushroom compost has also been successfully used in bark and peat container media overseas although there have been reports ofproblems with its use in New Zealand. It has good physical properties and is a useful source of nutrients except for N (Henny, 1979; Chong et aI., 1991; Chong and Rinker, 1994; Stewart et aI., 1998ab). Spent mushroom compost may cause temporary N immobilisation, after which N is slowly mineralised from it (Stewart et aI., 1998a). Spent mushroom compost also has a highsoluble salt content that can be ameliorated by leaching, and a pH of6.5-8.1 (Henny, 1979; Chong et aI., 1994; Chong and Rinker, 1994; Stewart et aI., 1998b). This paper seeks to review the factors causing decomposition of these organic materials and the implications of these processes on N immobilisation.


Dr. Pliny Smith is the "new kid on the block." The second floor of the Johnson block that is, taking over an office previously occupied by a part-time faculty member. Dr. Smith relocated to Lake Forest College for the start of the fall 2006 semester coming from Salt Lake City, Utah. There he left two part time positions at Huntsmen Cancer Institute and Westminster College. As an undergraduate student, Dr. Smith attended Grinnell College in Iowa, a school similar to Lake Forest College. It was there he obtained his interest in Biology and decided that becoming an undergraduate professor was his calling. He reports that being able to do his own research, interacting with faculty members from different fields, and getting to know students are among the many perks of being a professor. He notes that it is rewarding to see students leave here with a new ideas and that teaching is the best way for him to continue learning. What is he bringing to the table at Lake Forest College? Dr. Smith, in addition to teaching Organismal and Developmental Biology, hopes to one day build a genetics course that can be offered to biology students. Also, in spring 2007 he is teaching a core seminar entitled The Biology of Aging. During this course, although planning is still underway, Dr. Smith hopes to start with the little concepts, like cellular based aging, and work his way up to entire biological explanations for population aging. This core class for biology majors and minors will incorporate concepts ranging from cell biology to evolution. Dr. Smith, as a professor, reports he enjoys teaching at the college level in hopes of turning "undergraduate students into scholars" by teaching them to think critically and providing them a way to apply what they learn to the big picture. In addition, he hopes to get to know a few select students really well, by employing them in his research lab. While the lab is not yet set up, Dr. Smith is already recruiting interested students to help him with his work on C. elegans and cell-fate. C. elegans have been an important organism to Dr. Smith for years and he reports it is because they are the smallest and best specimens to do genetics research. In fact, the Nobel Prize 2006 for biology was given to a scientist for work done with C. elegans and Dr. Smith could only smile. He is proud that the spotlight is on his field of study and model organism. While being a biology professor and scientist takes up most of his time, do not be shocked to see him out on a 30 mile bike ride or roaming around campus with his wife, an immunologist, and two children, Jason, 6, and Gillian, 9. Dr. Smith is eager to find out what Lake Forest College has to offer in the way of extracurriculars, so he can get involved. And because of his late move to campus, don't be surprised to find his office and billboard undecorated. So, if you have any posters lying around, you know where to donate them.


Some analysts lean toward comparative analyses of population aging, then draw potential policy implications. Others lean in the direction of attention to differences in policy regimes and then consider implications of population aging. Key differences among advanced societies may not emanate from demographic aging but from differences in how markets, states, and families work to redistribute societal benefits. In this paper, three countries with contrasting configurations of markets, states, and families, and at different stages of demographic aging, are compared and contrasted: Canada, Japan, and Korea. The paper has three objectives: 1) to outline key changes in population, family, and work in the three countries; 2) to consider how knowledge about these changes, their dynamics and interrelationships, is framed with respect to policy options; and 3) to compare Canada, Japan, and Korea in terms of the framing of policy challenges related to demographic aging. It is found that Canada is joining the longstanding pattern of Japan and Korea of late home-leaving by youth, meaning less effective time in the paid labour force. Little deep connection exists between population aging and economic productivity or labour force shortages. Differential labour market participation of women mediates the effects of population aging.


Currents treatments for obesity have been unsuccessful. It is essential that a patient-centred approach for obesity management is developed and for this to be successful other diet and lifestyle approaches need to be considered. A systematic review comparing low carbohydrate vs. low fat diets for the treatment of obesity was carried out. It found that low carbohydrate/high protein diets are as effective as, if not better, for treating obesity and cardiovascular disease risk factors. A randomised controlled trial investigating dietary approaches for the treatment of obesity and its co morbidities was carried out. Variables including weight and body composition, cardiovascular risk factors, adipokines, liver and kidney function, and health and lifestyle factors were measured. Those with metabolic syndrome were also examined. It was hypothesised that there are alternative ways of treating obese subjects depending on their phenotype. Those with a higher BMI tend to have a higher carbohydrate intake rather that a higher fat intake so may be better suited to a low carbohydrate/high protein diet rather than the conventional low fat/energy reduced diet. Subjects were initially treated with the standard dietary approach for obesity (health eating, HE) and if not successful after 3 months were randomised to either a very low calorie diet (Lighterlife, LL) or a protein sparing modified fast (PSMF). All three groups showed a significant weight loss and reduced risk for CVD at 12 months. Significant improvements were seen for plasminogen-activated receptor-1, adiponectin, leptin and IL-6 on HE and LL, but only adiponectin significantly improved on the PSMF. Neither diet showed any detrimental effects for those with a healthy liver and kidney function. Quality of life and levels of depression improved at 12 months. Of the 54 subjects with metabolic syndrome at baseline, 12 remained on HE and 32 were randomised to LL and PSMF. This indicates that most subjects did not suit a low fat dietary approach. They were successful at losing weight on LL and PSMF and showed improvement in MS risk factors, and adipokine levels at 12 months. In conclusion, the study demonstrates that a low fat diet may not necessarily be the first line of approach to treat obese subjects with a BMI over 35 kg/m2, including those with MS. A very low calorie diet such as LL or a PSMF may be better suited to the subject.


A multimodal network (MMN) is a novel mathematical construct that captures the structure of biological networks, computational network models, and relationships from biological databases. An MMN subsumes the structure of graphs and hypergraphs, either undirected or directed. Formally, an MMN is a triple (V, E, M) where V is a set of vertices, E is a set of modal hyperedges, and M is a set of modes. A modal hyperedge e = (T, H, A, m) ∈ E is an ordered 4-tuple, in which T, H, A ⊆ V and m ∈ M. The sets T, H, and A are the tail, head, and associate of e, while m is its mode. In the context of biology, each vertex is a biological entity, each hyperedge is a relationship, and each mode is a type of relationship (e.g., 'forms complex' and 'is a'). Within the space of multimodal networks M , structural operations such as union, intersection, hyperedge contraction, subnetwork selection, and graph or hypergraph projections can be performed. A denotational semantics approach is used to specify the semantics of each hyperedge in MMN in terms of interaction among its vertices. This is done by mapping each hyperedge e to a hyperedge code algo V (e), an algorithm that details how the vertices in V (e) get used and updated. A semantic MMN-based model is a function of a given schedule of evaluation of hyperedge codes and the current state of the model, a set of vertex-value pairs.
An MMN-based computational system is implemented as a proof of concept to determine empirically the benefits of having it. This system consists of an MMN database populated by data from various biological databases, MMN operators implemented as database functions, graph operations implemented in C++ using LEDA, and mmnsh, a shell scripting language that provides a consistent interface to both data and operators. It is demonstrated that computational network models may enrich the MMN database and MMN data may be used as input to other computational tools and environments. A simulator is developed to compute from an initial state and a schedule of hyperedge codes the resulting state of a semantic MMN model.


Beyond effects on bone health, vitamin D exerts effects on a variety of target organs, including the brain. The discussion herein presents the state of the art in research on the neurological role of vitamin D and clinical implications among older adults, including implications for dementia onset and progression. Some of the neurosteroid actions of vitamin D include regulation of calcium homeostasis, clearance of amyloid‐β peptide, antioxidant and anti‐inflammatory effects, and possible protection against the neurodegenerative mechanisms associated with Alzheimer's disease (AD). The correction of age‐related hypovitaminosis D and cognitive decline has been reported by various cross‐sectional and longitudinal studies reporting associations of lower vitamin D concentrations with brain changes and poorer cognition, specifically with respect to executive dysfunction. Epidemiological studies have consistently shown an association between inadequate dietary intake of vitamin D and cognitive disorders, including greater AD risk. Although there have not been any randomized placebo‐controlled trials conducted to examine the effectiveness of vitamin D supplementation to prevent AD, several nonrandomized controlled studies have found that older adults experienced cognitive improvements after 1–15 months of vitamin D supplementation. Therefore, it appears crucial to maintain vitamin D concentrations at sufficiently high levels in order to slow, prevent, or improve neurocognitive decline.


Glucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteoporosis. However, data are ambiguous. The aim of this study was to assess the regulation of sclerostin by GC using several mouse models with high GC levels and two independent cohorts of patients treated with GC. Male 24-week-old C57BL/6 and 18-week-old DBA/1 mice exposed to GC and 12-week-old mice with endogenous hypercortisolism displayed reduced bone formation as indicated by reduced levels of P1NP and increased serum sclerostin levels. The expression of sclerostin in femoral bone tissue and GC-treated bone marrow stromal cells, however, was not consistently altered. In contrast, GC dose- and time-dependently suppressed sclerostin at mRNA and protein levels in human mesenchymal stromal cells, and this effect was GC receptor dependent. In line with the human cell culture data, patients with rheumatoid arthritis (RA, n = 101) and polymyalgia rheumatica (PMR, n = 21) who were exposed to GC had lower serum levels of sclerostin than healthy age- and sex-matched controls (−40%, P < 0.01 and −26.5%, P < 0.001, respectively). In summary, sclerostin appears to be differentially regulated by GC in mice and humans as it is suppressed by GCs in humans but is not consistently altered in mice. Further studies are required to delineate the differences between GC regulation of sclerostin in mice and humans and assess whether sclerostin mediates GC-induced osteoporosis in humans.


From its birth in the seventh century through modern times, the Islamic religion has inspired glorious works of art. This stunning book includes more than four hundred reproductions of treasures of Islamic art that span the world: from southern Europe along the entire Mediterranean basin to sub-Saharan Africa, through the Middle East, India, and Central Asia. Arranged geographically, the objects include paintings, miniatures, ceramics, calligraphy, textiles, carpets and metal works. Each region is given a thorough introduction that offers historical context and extensive descriptions of its artefacts. Accompanying essays offer guidance in interpreting the many themes that tie these works together, including typology, calligraphy, and religious beliefs. Despite its wide-ranging history and origins, Islamic art is unified by its devotion to faith and beauty. With its large format, exquisite reproductions and extensive research, this book is a thorough introduction to an artistic tradition.


Pavel Palazchenko has been an advisor and translator for Mikhail Gorbachev since 1985. During perestroika, he worked out of the foreign ministry and later the presidential office and also advised and interpreted for Foreign Minister Eduard Shevardnadze. He currently is a consultant at the Gorbachev Foundation in Moscow. His memoirs appeared as My Years with Gorbachev and Shevardnadze (University Park: Pennsylvania State University, 1997). In this interview, he speaks about the origins of new political thinking, of the Kremlin's reaction to the 1989 revolutions in Eastern Europe and German reunification, of relations with President George H. W. Bush, and the ability of Gorbachev to "frame issues in ways that made people think realistically and responsibly." Demokratizatsiya: Gorbachev has admitted many mistakes in economic reforms, in cadre policies, and in other fields. But in foreign policy, I get the sense that he is proud of what he achieved. But if he could do it all over again in this field, what would he do differently? Palazchenko: That's an interesting question that perhaps we should ask him directly. But I sense that you are right. Of those various aspects of perestroika that you mention, it is foreign policy that he would probably change the least. My feeling is that on subtler, finer points, such as whether it was wise in Reykjavik to tie together the entire package of nuclear issues--including ABMs [antiballistic missiles], strategic weapons, and INF [intermediate range nuclear forces]--there would be some rethinking. Or whether it was such a good idea when President George Bush senior started his reassessment of policy towards the USSR--which took six to eight months and which, in my opinion, was a waste of time--whether perhaps it would have been better for Gorbachev to insist that they should hit the ground running, to find a way to compel Bush to act more swiftly. Perhaps he should have looked into that possibility. Or, perhaps, whether after the Soviet withdrawal from Afghanistan there should have been an effort made to continue to work together with the Americans, Pakistanis, Indians, and others, to put together some coalition government in order to prevent the Taliban from taking over the country. Whether it was wise to let the Afghans, after our withdrawal, to just simmer in their own juices. So, there were a number of things that he may have wanted to reconsider, but they were not, I believe, of fundamental importance, and certainly different decisions could have been taken on each one of those three issues, and I suspect there could be more. But that would not change the overall direction, and I believe that this overall direction was very important and did a lot to really establish a pattern of cooperative security, of partnership, of addressing issues and not letting go, not allowing the disagreements on peripheral issues and sometimes very important issues to affect the overall attitude of cooperation. I believe that all of those things were established at that time--and they weren't in the subsequent years. And even now when, for example, during the war in Iraq it turned out that Russia and the United States had very substantial differences on a major issue, I think it is in part because of the Gorbachev-Reagan example that Russia and the United States did not allow that issue to overwhelm the entire relationship, even to set the tone for the entire relationship. Again, I think the roots of that go back to the years of perestroika and I think the pattern was set at that time. And I think that our leaders including, by the way, Yeltsin and Clinton, including Putin and Bush, showed that they are sticking to that general approach that was developed during those years at the end of the cold war and the establishment of a pattern of cooperation. Demokratizatsiya: You mentioned Bush senior and the reassessment of policy towards the USSR when he came to power. Reagan even came out and criticized Bush, saying he should speed things up. …


OBJECTIVE
To compare outcomes between increasing versus maintaining the dose of mirtazapine in patients with depression without initial improvement.

METHOD
Data from a 6-week double-blind randomized placebo-controlled trial of mirtazapine in major depressive disorder (DSM-IV) conducted from November 2004 to December 2005 were used. Percentages of remitters (ie, a score of ≤ 7 in the 17-item Hamilton Depression Rating Scale [HDRS-17]) and HDRS-17 score changes from baseline to week 6 were compared in the following 2 pairs, using Fisher exact test or mixed-effects model for repeated measures: (1) subjects who failed to show a ≥ 20% decrease in the HDRS-17 total scores at week 1 but were assigned to continue 15 mg/d (stay(15) group) versus those who were assigned to increase the dose to 30 mg/d (increase(30) group) and (2) subjects who failed to show a ≥ 20% decrease in the HDRS-17 total scores with 30 mg/d at week 2 but were assigned to continue 30 mg/d (stay(30) group) versus those who were assigned to increase the dose to 45 mg/d (increase(45) group).

RESULTS
The increase(30) group showed a numerically but not significantly higher remission rate and a significantly greater decrease in the HDRS-17 total score at week 6 than the stay(15) group (34.7% [8 of 23 patients] vs 14.3% [3 of 21 patients], P = .2; least squares mean, -15.8 vs -10.9, P = .003). No significant differences were found between the increase(45) and stay(30) groups.

CONCLUSIONS
Dose increase of mirtazapine from 15 mg/d to 30 mg/d may be effective for patients with depression without initial improvement. However, effectiveness may not be the case beyond 30 mg/d.

TRIAL REGISTRATION
JapicCTI identifier: 152830.


A unilateral double testicle is a rare anomaly characterized by migration of one testicle towards the opposite inguinal canal. The commonest erratic development is the more or less incomplete descent of the testicle along the normal route of descent, which is known as cryptorchidism. In ectopia of the testicles, as opposed to cryptorchidism, the displaced testicle does not descend along the usual route but as it migrates downwards it moves into an entirely abnormal position. Usually the migrating testicle remains on its own side of the body but may end up in an unusual position e.g. in the superficial tissue of the inguinal region above the external ring, in the area of the base of the penis, in the upper part of the thigh, in the region of perineum or in the pelvic cavity. In this case, the right and left testicles were found to descend together on the right side, whereas the left side of the scrotum was entirely empty. The case was treated with 'Bilateral Transeptal Subdartos Orchidopexy'. The case reported here is evidently one of extreme rarity as there are about 148 reported cases since the first described by Von Lenhossek in1886. Key words: Cryptorchidism; Testicle; Ectopia; Orchidopexy; CTE. DOI: http://dx.doi.org/10.3329/fmcj.v6i2.9214 FMCJ 2011; 6(2): 110-112


Upscaling water use of individual trees to stands using sap flux techniques is a common method for partitioning site water balance, but few such studies have occurred in the tropics. Increasing interests in the role of tropical forests in global cycles have spurred upscaling studies in natural tropical forests, which present challenges from greater tree species and functional diversity, and potential factors that would reduce transpiration, such as frequent cloud cover and wet canopy conditions. In a premontane wet tropical forest in central Costa Rica, sap flow was measured in 15 trees stratified into 5 size classes based on tree diameters. None of the trees belonged to the same species, genus, or even family. We also accounted for potential radial variation in sap flux density. Data were scaled to estimate transpiration within a small 2.2‐ha watershed using stand surveys of sapwood area. Stand transpiration averaged only 1.4 ± 0.7 mm day−1 within this forested watershed due to persistent low radiation, evaporative demand, and frequent wet canopy conditions. Our systematic approach used tree size attributes to scale water use to the stand, given difficulties to quantify species differences in such a diverse ecosystem. Contrary to previous evidence on temperate trees, the large trees sampled did not exhibit flow reductions in deeper sapwood, which warrants further study. These results highlight some unique aspects of measuring transpiration in wet tropical forests that are important to consider for future studies in diverse stands.


Objective To examine herpes simplex virus 2 (HSV-2)/HIV co-infection as a contributing factor in the increase in HIV infection among non-injecting heroin and cocaine users in New York City. Methods Subjects were recruited from the Beth Israel Medical Center drug detoxification and methadone maintenance programs in New York City in 1995–1999 and 2005–2011. All reported current heroin and/or cocaine use and no injection drug use. A structured questionnaire was administered and serum samples collected for HIV and HSV-2 testing. Population-attributable risk percentages (PAR%s) were estimated for associations between HSV-2 and increased susceptibility to and increased transmissibility of HIV among female NIDUs. Results 785 subjects were recruited from 1995–1999, and 1764 subjects from 2005–2011. HIV prevalence increased from 7% to 13%, with nearly uniform increases among all demographic subgroups. HSV-2/HIV co-infection was common in both time periods, with an average (over the two time periods) of 80% of HIV negative females infected with HSV-2, an average of 43% of HIV negative males infected with HSV-2; an average of 97% of HIV positive females also infected with HSV-2 and an average of 67% of HIV positive males also infected with HSV-2. The increase in HIV prevalence was predominantly an increase in HSV-2/HIV co-infection, with relatively little HIV mono-infection in either time period. The estimated PAR%s indicate that approximately half of HIV acquisition among females was caused by HSV-2 infection and approximately 60% of HIV transmission from females was due to HSV-2 co-infection. Conclusions The increase in HIV infection among these non-injecting drug users is better considered as an increase in HSV-2/HIV co-infection rather than simply an increase in HIV prevalence. Additional interventions (such as treatment as prevention and suppressing the effects of HSV-2 on HIV transmission) are needed to reduce further HIV transmission from HSV-2/HIV co-infected non-injecting drug users.


Magnetic excitations in copper pyrimidine dinitrate, a spin-1/2 antiferromagnetic chain with alternating g-tensor and Dzyaloshinskii-Moriya interactions that exhibits a field-induced spin gap, are probed by means of pulsed-field electron-spin-resonance spectroscopy. In particular, we report on a minimum of the gap in the vicinity of the saturation field H-sat = 48.5 T associated with a transition from the sine-Gordon region (with soliton-breather elementary excitations) to a spin-polarized state (with magnon excitations). This interpretation is fully confirmed by the quantitative agreement over the entire field range of the experimental data with the density matrix renormalization group calculations for a spin-1/2 Heisenberg chain with a staggered transverse field.


Virtual Learning Environments (VLEs) are increasingly being used by colleges and universities to deliver and/or complement traditional face-to-face courses. The range of learning technologies available for use within these virtual platforms is considerable, but how confident are we that these learning tools support the learning process for students? It is crucial that the learning tools utilised in virtual platforms do not cause additional barriers for the online and distant learner. This Survey research study is designed to determine if rapid authoring tools can meet the needs of a variety of learning preferences of adult learners. The study focuses specifically on the use of virtual tutorials, created using the rapid authoring tool Articulate Presenter 2007, to establish the learning preferences of the students as represented by Fleming's (2011) VARK model. In total, ten variations of the VARK learning preferences were represented across respondents, with the majority indicating a uni-modal preference in an online self-administered questionnaire. Overall, the majority of students responded positively in relation to their experience of the virtual tutorial.


This paper examines two opposing theories of disbelief in evolution. One, the "bounded rationality" account, attributes disbelief to the inability of individuals to suppress the strongly held intuition that all functional systems, including living beings, originate in intentional agency. The other, the "expressive rationality" account, holds that positions on evolution arise from individuals' tendency to form beliefs that signal their membership in and loyalty to identity-defining cultural groups. To assess the relative plausibility of these theories, the paper analyzes data on the relationship between study subjects' beliefs in evolution, their religiosity, and their scores on the Cognitive Reflection Test (CRT), a measure of critical-reasoning proficiencies including the disposition to interrogate intuitions in light of available evidence. Far from uniformly inclining individuals to believe in evolution, higher CRT scores magnified the division between relatively religious and relatively nonreligious study subjects. This result was inconsistent with the bounded rationality theory, which predicts that belief in evolution should increase in tandem with CRT scores for all individuals, regardless of cultural identity. It was more consistent with the expressive rationality theory, under which individuals of opposing cultural identities can be expected to use all the cognitive resources at their disposal to form identity-congruent beliefs. The paper discusses the implications for both the study of public controversy over evolution and the study of rationality and conflicts over scientific knowledge generally.


ABSTRACT This article examines the responses made by the Baltic States to the threat they face from Russian hybrid warfare. It looks first at the nature of this threat and at the many modes of warfare that are being employed by Russia, including, and in particular, information warfare. The article then goes on to examine the way in which this threat is viewed in the Baltic States and the debate over how it can best be countered. Raising defenses, though, as is made clear here, is not easy. Indeed, this article argues that the defenses that are being raised by the Baltic States will prove largely ineffective and possibly counterproductive.


The following work. is an investigation into methods of Cluster Analysis and Ordination. The main objective of this thesis has been to investigate the capabilities of these methods for practical usage. An important subsidiary aim has been to collect together related work which has been carried out in many different areas - ecology, biology, archaeology, psychology, etc.., into, one work. After a_ brief introduction to the general concepts of multivariate analysis in Section A of the thesis, Section B gives an introductory account of the methods of Clustering, Ordination and Seriation, putting them into the context of the by now better established multivariate techniques. Section C considers Cluster Analysis in depth, explaining and examining various methods reported in the literature, together with methods developed by the author. The suitability of the methods for practical use is discussed and, decision rules are set out for the choice of method to be used in any particular study, based on the results of extensive comparative tests of the methods. In Section D the various ordination methods are. considered, giving an, overall viere and relating the methods to each other. Particular emphasis is paid to the rather neglected metric methods. Section E, after a survey of published applications of the methods, suggests new areas where the methods previously discussed could be valuable aids for data investigation and problem solving. An Addenda is included which describes several operational research case studies using these methods. Computer programs are given for the most successful of the newly introduced cluster methods, and an extensive reference section is also included.


Buying a property is one of the most important decisions people make in their lives. This thesis investigates customer behaviour in the real estate market of Cyprus. As it was revealed from the literature review carried out in this research project there is lack of studies of this nature especially for investigating the Cyprus real estate market. At a time of a world financial crisis, but most importantly, scrutinize over the declining period in the real estate market of Cyprus the need for identifying customer needs and attracting those with suitable approach and offer the right products become even more challenging. Thus the aim of this study is to identify the key factors influencing customers buying behaviour in the Cyprus real estate market. In 2000, foreign buyers, mostly British, began purchasing properties III Cyprus. Under such ongoing circumstances, the real estate market was affectcd positively, showing an increase in numbers of home buyers up to the year 2007 (Hill , 2013). It was during this period that a great lot of amateur companies, attracted by easy money regardless of profession, experience or knowledge-, joined the real estate business. As of it, mistakes were to be made in a lot of aspects. The main objective of this study is to investigate the residential property buyer's behaviour in the real estate market. By investigating the influential factors determining buyer's decision making in real estate market in Cyprus. A key element of this research is the identification from the prospective buyers the real factors that cause them not buying now. In this study a methodical investigation have been done through targeted questionnaires and interviews. The results exhibit the ten key influential factors that can affect customer buying


Simulation and experimental results of grating couplers composed of arrays of nanoholes are presented. The use of an array of holes instead of a conventional waveguide grating provides an additional degree of freedom in the design of the coupler, thus enabling fabrication using the same photolithography mask and etching process as used for the silicon-on-insulator (SOI) waveguides. A grating coupler with coupling efficiency as high as 34% for coupling between the TE mode of the silicon nanophotonic wire waveguide and a single-mode optical fiber and with 3-dB bandwidth of 40 nm was fabricated. A theoretical model is presented, and 3-D finite-difference time-domain simulations are used to optimize the coupler design.


OBJECTIVE
To assess the discriminative ability of several fitness dimensions and anthropometric attributes for forecasting competitive success in female karate athletes.

METHODS
Fitness and anthropometric data from 98 female junior karatekas obtained during the training camps of the Spanish National Karate Federation between 1999 and 2012 were used. Binary logistic-regression models were built to ascertain whether the set of fitness and anthropometric variables could predict future sporting-performance levels. For this purpose, participants were classified as elite (medalist in World or European Championships in the senior category) or subelite (at least a medalist in Spanish National Championships in cadet or junior but not included in the elite group), according to the results achieved up to 2019.

RESULTS
Participants who were subsequently classified as elite karatekas showed significant differences in agility, upper- and lower-body muscle power, and general fitness in comparison with those who were classified as subelite in the senior category. A total of 57 junior female karatekas who were subsequently classified as elite (7) or subelite (50) were included in the binary logistic-regression analysis. Resultant models showed significant capacity to predict karate performance.

CONCLUSIONS
Assessing physical fitness in junior categories can be a useful resource to determine future karate success. Coaches in this sport should pay special attention to the levels of muscle power and agility shown by their athletes, as both fitness dimensions could be indicators of future sportive success.


In 2008, the world produced approximately 87 gigaliters of liquid biofuels, which is roughly equal to the volume of liquid fuel consumed by Germany that year. Essentially, all of this biofuel was produced from crops developed for food production, raising concerns about the net energy and greenhouse gas effects and potential competition between use of land for production of fuels, food, animal feed, fiber, and ecosystem services. The pending implementation of improved technologies to more effectively convert the nonedible parts of plants (lignocellulose) to liquid fuels opens diverse options to use biofuel feedstocks that reach beyond current crops and the land currently used for food and feed. However, there has been relatively little discussion of what types of plants may be useful as bioenergy crops.


The study of the neurobiology of spatial navigation provides a neural model for a complex form of learning that is likely to be highly conserved across evolution. Single cell recordings from rats as they forage through spatially extended environments have revealed that salient spatial, movement, and reinforcement information become incorporated into local computational networks across multiple brain structures in a context-specific manner. The hippocampus is thought to evaluate the extent to which the current spatial context is different from the one expected based on past experience. This information may be passed on to update long term memory representational systems. Also, hippocampal contextual information may inform behavioral expression systems of the frontal cortex and striatum such that appropriate behavioral responses and strategies are employed. Together, the continuous evaluation of, and responses to, changes in current sensory and reinforcement conditions allow animals to flexibly adapt to ever changing environmental demands. Chapter Outline & Navigation


The purpose of this study was to construct a scale to measure the attitudes of women coaches toward the conduct of intercollegiate athletics for women. The situation-response technique was selected as the method for measuring attitudes. The procedure for constructing the attitude scale involved the identification of areas and sub-areas which served as guides in the development of situation-response items. Five judges assisted in the revision of these areas and sub-areas. The thirteen areas were (1) place of athletics in education and physical education, (2) leadership, (3) financing, (4) public relations, (5) general philosophy, (6) ethics, (7) methods of coaching, (8) team selection, (9) scheduling of events, (10) standards and eligibility, (11) rules and officials, (12) health and safety, and (13) equipment and facilities. The investigator devised one hundred items to represent these areas and sub-areas. Each item contained a brief description of a situation and five alternative responses representing different degrees of attitude toward the situation.


We present a novel unsupervised learning scheme that simultaneously clusters variables of several types (e.g., documents, words and authors) based on pairwise interactions between the types, as observed in co-occurrence data. In this scheme, multiple clustering systems are generated aiming at maximizing an objective function that measures multiple pairwise mutual information between cluster variables. To implement this idea, we propose an algorithm that interleaves top-down clustering of some variables and bottom-up clustering of the other variables, with a local optimization correction routine. Focusing on document clustering we present an extensive empirical study of two-way, three-way and four-way applications of our scheme using six real-world datasets including the 20 News-groups (20NG) and the Enron email collection. Our multi-way distributional clustering (MDC) algorithms consistently and significantly outperform previous state-of-the-art information theoretic clustering algorithms.


This thesis is concerned with understanding the psychosocial effects of aphasia for partners, and with the outcomes and processes of group programmes of support and conversation training. It comprises three studies, each of which builds upon the other in method and depth. Study One utilised the quantitative, idiographic Personal Questionnaire Rapid Scaling Technique (Mulhall, 1978) to examine the psychosocial issues of 12 partners of people with aphasia (PWA) before and throughout the programmes. Individual statistical analysis suggested that the scores of four partners showed significant positive change as a result of the support programme, and two changed as a result of the conversation training programme. Results were achieved by considerable data reduction, so changes in individual issues could not be determined. Study Two therefore shifted from the quantitative, researcher's perspective to a method able to capture more fully insider perspectives. The Framework Method (Ritchie and Spencer, 1994) was used to analyse semi-structured interview data from the programme participants. This highlighted, within broad themes, varied and interacting factors that influenced participation and psychosocial change: programme content and organisation, individual circumstances, group and personal processes. The predominant focus of Study Two's findings was the process of intervention, leaving the essential question of how partners really experience psychosocial life with PWA unanswered. By taking a further qualitative shift, Study Three answers that question for one woman. An interpretative phenomenological analysis (Smith, 1996) of her in-depth interview suggests her experience was a complicated process of accommodation linked to life pre-stroke and post-stroke. This process featured complex phases labelled as 'rescue mission and hope', 'endurance, loss and hopelessness' and, finally, 'regeneration'. These phases were linked to her changing perception of her relationship with her husband, her role and her self-image. The thesis concludes with a discussion of methodology, theoretical findings and avenues for further research.


In this paper, an axis-symmetric contact finite element analysis (FEA) model of resistance spot welding (RSW) for aluminum alloys was developed using ANSYS. It provided effective analysis of contact behavior in the pre-squeeze stage of aluminum alloys RSW. The computational simulation interpreted the reason leading to contact pressure distribution shape and contact area size at the faying interface between workpieces. And the factors and rules affecting contact behavior were also discussed in this paper.


Abstract The Cenomanian–Turonian interval of the Sevier foredeep, western U.S.A., is examined in order to (1) establish a high-resolution stratigraphic framework for marginal-marine strata of this interval and (2) test for the existence of high-frequency (tens of kyr-scale) cycles of continental runoff or sea-level change predicted by the hemipelagic record and climate models. High rates of sediment accumulation in marginal-marine environments of southwestern Utah (up to 210 m/Myr, compacted) and a northward translation of the major Sevier thrusting made possible the preservation of a highly detailed record of shoreline movements. The coeval Bridge Creek Limestone, linked with the study interval using biostratigraphic and bentonite-stratigraphic data of previous authors, provides an unprecedented, high-resolution orbital time scale. Three orders of transgressive–regressive cycles defined as genetic sequences are identified in the upper Cenomanian (S. gracile and N. juddii Zones) through lower Turonian (W. devonense through M. nodosoides Zones). The longest sequence (S. gracile Zone through V. birchbyi Zone) spans approximately 800 kyr and is penecontemporaneous with the δ13Corg positive excursion that defines Oceanic Anoxic Event II (OAE II). Medium-term and short-term sequences show durations of c. 65–160 kyr and c. 20–40 kyr, respectively. Features suggesting regression due to relative sea-level fall are described from some of the 20–40 kyr cycles in the lowermost S. gracile Zone (possibly including the uppermost M. mosbyense Zone). The data provide the first physical evidence globally of Cenomanian–Turonian changes in shoreline position and relative sea level, whose recurrence interval was as short as a few tens of kyr. These processes provide a viable depositional link between the rhythmic deposition of the Bridge Creek Limestone and the primary orbital forcing of insolation and climate. Although the possible tectonic influence is difficult to unravel, the study area represents an important reference point for climate and oceanographic modeling of the Cenomanian–Turonian greenhouse and OAE II.


The paper presents platform one4all uses several computer products implementing as services for realization of the basic/fundamental business processes, communication and workflow management, project management, or the analysis of business activities. The newly presented the foundations of building the systems of Service Oriented Architecture, SOA, their conception and influence on functioning of the whole enterprise.


Whole‐body polychlorinated biphenyls (ΣPCBs) and plasma hydroxylated PCBs (OH‐PCBs) concentrations were determined in brown bullhead (Ameiurus nebulosus) from Wheatley Harbour, Ontario, Canada. Elevated ΣPCBs in Wheatley Harbour are suspected to have originated from industrial waste disposal and/or discharges from nearby fish processing through discarding of fish remains. Mean ΣPCB concentrations in brown bullhead from Wheatley Harbour were approximately 250 ng/g wet weight compared with approximately 40 ng/g wet weight for brown bullhead from the reference sites, Hillman Marsh and Turkey Creek (both in Ontario, Canada). A significant relationship was found between the concentrations of non‐ortho and mono‐ortho PCB concentrations (toxic equivalents) and liver mixed‐function oxygenase in brown bullhead (r = 0.74, p < 0.001). Plasma OH‐PCB concentrations were greater in Wheatley Harbour brown bullhead than in those from Hillman Marsh (3.6 vs 1.5 ng/g wet wt, p < 0.01), and were detected infrequently in those from Turkey Creek (0.1 ng/g wet wt, n = 2). The OH‐PCB congeners most frequently detected were 4′‐OH‐CB172, 3′‐OH‐CB180, 4‐OH‐CB187, 4‐OH‐CB146, 3‐OH‐CB138, and 4‐OH‐CB130, which are structurally similar to the thyroid hormones. To test the hypothesis of fish waste as the cause of the observed PCB contamination of Wheatley Harbour brown bullhead, a principal component analysis (PCA) was used to compare the brown bullhead PCB congener data with equivalent data for Lake Erie walleye, Lake Erie sediment, and industrial Aroclor mixtures. The relative proportions of each Aroclor mixture were estimated using the conjugated gradient method. The high similarity between the congener signatures for Lake Erie walleye and Wheatley Harbour brown bullhead supports the hypothesis of contamination from the fish processing industry. Environ. Toxicol. Chem. 2012;31:2788–2797. © 2012 Crown in the Right of Canada


Abstract : Predatory bacteria are ubiquitous in aquatic environments and may be important players in the ecology and biogeochemistry of microbial communities. Three novel strains belonging to two genera of marine flavobacteria, Olleya and Tenacibaculum, were cultured from coastal sediments and found to be predatory on other bacteria on surfaces. Two described species of the genus Tenacibaculum were also observed to grow by lysis of prey bacteria, raising the possibility that predation may be a widespread lifestyle amongst marine flavobacteria, which are diverse and abundant in a variety of marine environments. Strains from the two genera were found to exhibit divergent prey specificities and predatory growth yields. An investigation of the minimum number of predatory cells needed to generate clearings of prey cells found that the inoculation of individual predatory flavobacteria cells can result in dense lytic swarms. A novel methodology for the experimental study of biofilms was used to assess the impact of exposure to predatory marine flavobacteria on the release of macronutrients from prey biofilms. The Olleya sp. predator had a stimulative effect on macronutrient release while the Tenacibaculum sp. did not, further suggesting the two groups of predators are adapted to different ecological niches.


This paper examines the effect of fall 2020 school reopenings in Texas on county-level COVID-19 cases and fatalities. Previous evidence suggests that schools can be reopened safely if community spread is low and public health guidelines are followed. However, in Texas, reopenings often occurred alongside high community spread and at near capacity, making it difficult to meet social distancing recommendations. Using event-study models and hand-collected instruction modality and start dates for all school districts, we find robust evidence that reopening Texas schools gradually but substantially accelerated the community spread of COVID-19. Results from our preferred specification imply that school reopenings led to at least 43,000 additional COVID-19 cases and 800 additional fatalities within the first two months. We then use SafeGraph mobility data to provide evidence that spillovers to adults' behaviors contributed to these large effects. Median time spent outside the home on a typical weekday increased substantially in neighborhoods with large numbers of school-age children, suggesting a return to in-person work or increased outside-of-home leisure activities among parents.


ICD Connection contains a collection of stories from patients and their families who are living with an implantable cardioverter defibrillator. The inspiration for the book stemmed from an annual University of Michigan Young ICD patient and family support conference. This event, "The Young ICD Connection Conference," is a multidisciplinary collaboration and is coordinated and hosted by the University of Michigan Samuel and Jean Frankel Cardiovascular Center and Congenital Heart Center cardiology staff. ¶ Patient and family stories highlight how the ICD implant affected their life, their challenges and struggles along the way, and share what was and wasn't helpful to their moving forward and adjusting to life with an ICD. The opportunity for these patients to share their experiences and interact with peers who have had similar experiences can facilitate personal growth and wellness on their life journey with an ICD.


With the implementation of the National Council of Teachers of Mathematics recommendations and the adoption of the Common Core State Standards for Mathematics, modeling has moved to the forefront of K–12 education. Modeling activities not only reinforce purposeful problem-solving skills, they also connect the mathematics students learn in school with the mathematics they will use outside of school. Instructors have found mathematical modeling difficult to teach. To successfully incorporate modeling activities I believe that curricular changes should be accompanied by professional development for curriculum developers, classroom teachers, and higher education professionals. This article serves as an introduction to modeling by defining mathematical modeling, outlining the steps to construct a model, and providing an example that illustrates the iterative non-linear process. Key to teaching modeling is the ability to understand how the modeling process differs from problemsolving activities, which this article discusses. This article describes the benefits and challenges of incorporating mathematical models. The overarching aim of this article is to serve as a primer to aid with the implementation of curricular reforms that call for an increased focus on modeling activities.


China's emergence as an economic power and its sheer size have put it firmly at the center of the global economic stage. Its remarkable pace of growth has attracted a lot of attention, with some observers speculating that it could become the world's second-largest economy if this rate of growth were to be sustained for the next two or three decades. Furthermore, in light of China's trade expansion and rapidly rising stock of international reserves, discussions of global current account imbalances invariably put the spotlight on Beijing. At the same time, the possibilities of overheating and excessive investment in China are raising concerns, because a downturn in its growth could reverberate not just domestically but also in the Asian region and beyond.


All transfer pricing regimes give priority to the comparable uncontrolled price (CUP) method. Despite declarations that transfer pricing is a search for the "best method" or "most appropriate method," all systems concede that the search is over when an exact comparable is found because a CUP is preferred over all methods. The best CUP is an exact CUP because it provides an arm's length price that is not calculated. The price emerges directly from the comparison. CUPs have traditionally been the most commonly applied method for both taxpayers and the government. They are the judicial gold standard. They hold sway even when they are constructed. Whenever constructed CUPs are involved trial argumentation invariably centers on the adjustments. While exact CUPs require no adjustments, the constructed CUP's persuasive value is based on the quality of the adjustments made. Constructed CUPs produce calculated results, and so the concern is with the precision of the calculation. This paper aligns five cases, each from a different country, to paint a multi-jurisdictional picture of the continuing importance of CUPs in transfer pricing. Australia – SNF (Australia) Pty. Ltd. v. Commissioner of Taxation. The court is very receptive to the taxpayer's effort to construct a CUP at trial in support of a filing position that was explained as not much more than an educated guess. US – Compaq Computer Corporation v. Commissioner. The taxpayer filed under a traditional cost-plus method, but at trial to a constructed CUP. UK – DSG Retail Ltd. v. Commissioners for Her Majesty's Revenue and Customs. This case demonstrates what happens when a court is convinced that adjustments are needed to inexact comparables, but when well-reasoned adjustments are not offered. Norway – ConocoPhillips Skandinavia AS and Norske ConocoPhillips AS v. Oljeskattekontoret. The CUP proposed is illusory. This case, like in DSG, results in a profit split. Canada – Alberta Printed Circuits Ltd. v. Her Majesty the Queen. The Canadian Revenue Authority (CRA) in this case cannot overcome the authority of an exact CUP, and missed the business restructuring adjustment. The traditional preference for CUPs in resolving transfer pricing disputes is alive and well in the courts. Courts give just as much authority to constructed CUPs (Compaq, and SNF) as are given exact CUPs (Alberta). The only requirement is that considerable time and effort is needed to prove comparability (DSG). CUPs do not answer all transfer pricing questions. There are clearly cases where exact CUPs are impossible (ConocoPhillips).


Studies concerning speech recognition in noise constitute a very broad spectrum of work including aspects like the cocktail party effect or observing performance of individuals in different types of speech-signal or noise as well as benefit and improvement with hearing aids. Another important area that has received much attention is investigating the inter-relations among various auditory and non-auditory capabilities affecting speech intelligibility. Those studies have focussed on the relationship between auditory threshold (hearing sensitivity) and a number of suprathreshold abilities like speech recognition in quiet and noise, frequency resolution, temporal resolution and the non-auditory ability of cognition. There is considerable discrepancy regarding the relationship between speech recognition in noise and hearing threshold level. Some studies conclude that speech recognition performance in noise can be predicted solely from an individual's hearing threshold level while others conclude that other supra-threshold factors such as frequency and/or temporal resolution must also play a role. Hearing loss involves more than deficits in recognising speech in noise, raising the question whether hearing impairment is a uni- or multi-dimensional construct. Moreover, different extents of hearing loss may display different relationships among measures of hearing ability, or different dimensionality. The present thesis attempts to address these three issues, by examining a wide range of hearing abilities in large samples of participants having a range of hearing ability from normal to moderate-severe impairment. The research extends previous work by including larger samples of participants, a wider range of measures of hearing ability and by differentiating among levels of hearing impairment. Method: Two large multi-centre studies were conducted, involving 103 and 128 participants respectively. A large battery of tests was devised and refined prior to the main studies and implemented on a common PC-based platform. The test domains included measurement of hearing sensitivity, speech recognition in quiet and noise, loudness perception, frequency resolution, temporal resolution, binaural hearing and localization, cognition and subjective measures like listening effort and self-report of hearing disability. Performance tests involved presentation of sounds via circum-aural earphones to one or both ears, as required, at intensities matched to individual hearing impairments to ensure audibility. Most tests involved measurements centred on a low frequency (500 Hz), high frequency (3000 Hz) and broadband. The second study included some refinements based on analysis of the first study. Analyses included multiple regression for prediction of speech recognition in stationary or fluctuating noise and factor analysis to explore the dimensionality of the data. Speech recognition performance was also compared with that predicted using the Speech Intelligibility Index (SII). iii Findings: Findings from regression analysis pooled across the two studies showed that speech recognition in noise can be predicted from a combination of hearing threshold at higher frequencies (3000/4000 Hz) and frequency resolution at low frequency (500 Hz). This supports previous studies that conclude that resolution is important in addition to hearing sensitivity. This was also confirmed by the fact that SII (representing sensitivity rather than resolution) underpredicted difficulties observed in hearing-impaired ears for speech recognition in noise. Speech recognition in stationary noise was predicted mainly by auditory threshold while speech recognition in fluctuating noise was predicted by a combination having a larger contribution from frequency resolution. In mild hearing losses (below 40 dB), speech recognition in noise was predicted mainly by hearing threshold, in moderate hearing losses (above 40 dB) it was predicted mainly by frequency resolution when combined for two studies. Thus it can be observed that the importance of auditory resolution (in this case frequency resolution) increases and the importance of the audiogram decreases as the degree of hearing loss increases, provided speech is presented at audible levels. However, for all degrees of hearing impairment included in the study, prediction based solely on hearing thresholds was not much worse than prediction based on a combination of thresholds and frequency resolution. Lastly, hearing impairment was shown to be multi-dimensional; main factors included hearing threshold, speech recognition in stationary and fluctuating noise, frequency and temporal resolution, binaural processing, loudness perception, cognition and self-reported hearing difficulties. A clinical test protocol for defining an individual auditory profile is suggested based on these findings. Conclusions: Speech recognition in noise depends on a combination of audibility of the speech components (hearing threshold) and frequency resolution. Models such as SII that do not include resolution tend to over-predict somewhat speech recognition performance in noise, especially for more severe hearing impairments. However, the over-prediction is not great. It follows that for clinical purposes there is not much to be gained from more complex psychoacoustic characterisation of sensorineural hearing impairment, when the purpose is to predict or explain difficulty understanding speech in noise. A conventional audiogram and possibly measurement of frequency resolution at 500 Hz is sufficient. However, if the purpose is to acquire a detailed individual auditory profile, the multidimensional nature of hearing loss should not be ignored. Findings from the present study show that, along with loss of sensitivity and reduced frequency resolution ability, binaural processing, loudness perception, cognition and self-report measures help to characterize this multi-dimensionality. Detailed studies should hence focus on these multiple dimensions of hearing loss and incorporate measuring a wide variety of different auditory capabilities, rather than inclusion of just a few, in order gain a complete picture of auditory functioning. Frequency resolution at low frequency (500 Hz) as a predictive factor for speech recognition in noise is a new finding. Few previous studies have included low-frequency measures of hearing, which may explain why it has not emerged previously. Yet this finding appears to be robust, as it was consistent across both of the present studies. It may relate to differentiation of vowel components of speech. The present work was unable to confirm the suggestion from previous studies that measures of temporal resolution help to predict speech recognition in fluctuating noise, possibly because few participants had extremely poor temporal resolution ability.


This paper describes a symbolic representation of the data provided by the stereo-vision system of a mobile robot. The representation proposed is constructed from qualitative descriptions of transitions in the depth information given by the stereograms. The goal of this paper is to investigate the consequences in the depth transitions of qualitative spatial events such as the relative motion between objects, spatial occlusion and object's deformation (expansion and contraction). This causal relationship between spatial events and depth transitions forms a background theory for an abductive process of sensor data assimilation.


Annelids are a phylum of segmented bilaterian animals that have become important components of ecosystems spanning terrestrial realms to the deep sea. Annelids are remarkably diverse, possessing high taxonomic diversity and exceptional morphological disparity, and have evolved numerous feeding strategies and ecologies. Their interrelationships and evolution have been the source of much controversy over the past century with the composi- tion of the annelid crown group, the relationship of major groups and the body plan of the ancestral annelid having undergone major recent revisions. There is a convincing body of molecular evidence that polychaetes form a paraphyletic grade and that clitellates are derived polychae- tes. The earliest stem group annelids from Cambrian Lagerst€atten are errant, epibenthic polychaetes, confirming that biramous parapodia, head appendages and diverse, simple chaetae are primitive for annelids. Current evidence from molecular clocks and the fossil record suggest that crown group annelids are a Late Cambrian - Ordovician radiation, with clitellates radiating in the Late Palaeozoic. Their body fossil record is largely confined to deposits showing exceptional preservation and is punctuated by the acquisition of hard parts in major groups. The discovery of an Ordovician fossil with soft tissues has shown that machaeridians are in fact a clade of crown polychaetes. They were in existence for more than 200 million years and possess unique calcitic dorsal armour, allowing their mode of life and phylogeny to be interpreted in the context of the annelid body plan. We identify a novel clade of machaeridians, the Cuniculepadida, which exhibit a series of adaptations for burrowing.


Stereotypically, marketing is mainly concerned about satisfying customers and manufacturing is mainly interested in factory efficiency. Using the principal-agent agency paradigm, which assumes that the marketing and manufacturing managers of the firm will act in their self-interest, we seek incentive plans that will induce those managers to act so that the owner of the firm can attain as much as possible of the residual returns. One optimal incentive plan can be interpreted as follows: The owner subcontracts to pay the manufacturing manager a fixed rate for all capacity he delivers. Each marketing manager receives all of the returns from his product. In turn, all managers pay a fixed fee to the owner. Under this plan, the marketing managers will often complain about the stock level decisions, even though these levels are announced in advance. Under a revised plan, the owner can eliminate such complaints by delegating the stocking decisions to the respective marketing managers, without any loss. This plan is interpreted as requiring the owner to make a futures market for manufacturing capacity, paying the manufacturing manager the expected marginal value for each unit of capacity delivered, receiving the realized marginal value from the marketing managers, and losing money on average in the process.


Congestion in the Internet results in wasted bandwidth and also stands in the way of guaranteeing QoS. The effect of congestion is multiplied many fold in satellite networks, where the resources are very expensive. Thus congestion control has a special significance in the performance of satellite networks. In today's Internet, congestion control is implemented mostly using some of the de facto standard, RED. We have proposed previously a new scheme called the multi-level explicit congestion notification (MECN), which works with the framework of ECN, but enhances the performance using multiple level congestion feedback from the network. But like RED, the tuning of MECN could be a problem. Tuning of parameters is necessary for achieving high throughput with corresponding low delays. Also it is desirable to keep the oscillations in the queue low to reduce jitter, which is the major concern in real-time applications such as voice or video over IP. In this paper, we use a linearized fluid flow model of TCP-MECN to study the performance and stability of the queue in the router. We use classical control tools such as delay margin and tracking error to provide guidelines for optimizing satellite IP networks, which use MECN. We apply our results for optimizing the performance of satellite networks. We use ns simulator to validate the results of our analysis.


This Paper describes the research centered on the Charm Parallel Programming System. Charm is a portable parallel programming system under development at the University of Illinois for the past six years. The system enhances latency tolerance via message driven execution, supports dynamic load balancing for medium grain tasks, and provides innovative language features such as speciically shared variables and \branch ooce" processes. The paper describes the philosophy behind the system, and elaborates on its features and their motivation. Completed and ongoing related projects are summarized, including: Dagger, a textual notation and a corresponding visual language for simplifying expression of split-phase communication that is necessary in message driven execution; A subset of the High Performance Fortran that demonstrates superior latency tolerance; Performance feedback and debugging tools that exploit the speciicity of information available to the runtime system to give the user a highly reened and usable feedback; strategies for parallel execution of speculatively parallel computations; and a summary of preliminary applications.


This thesis examines the problems of health financing and the emergence of Mutual Health Organisations under the health sector reforms in Ghana. Governments of sub-Saharan Africa region have embraced the Community-based health insurance schemes concept under the health sector reforms, with momentous enthusiasm. They believe that these newly emerging health financing arrangements could easily be utilised as platforms for initiating Social Health Insurance strategies to reach the economically deprived people. Without such schemes, citizens would become poorer because they would have had to dispose of their family's wealth in order to treat a member who falls sick. Ghana, a developing country in West Africa has introduced a National Health Insurance Scheme, which is fused with Social health insurance and Community-based health insurance schemes. This study examines pro-active plans to address the financial viability of the schemes, to prevent them from going insolvent. The study generally, investigates health sector reforms in the context of Ghana. Four operating District Mutual Health Insurance Schemes (MHOs) were selected using geographical locations, among other criteria, as case studies. Data was gathered through interviews. The findings of the empirical study were analysed and interpreted using social policy and community field theories with the support of available documents. The evidence from the study concludes that government's intervention (implementation of NIH Act 650) has increased and expanded the membership base of the schemes: from small group-based to district-wide schemes under the ambit of the District Assemblies. However, such intervention has equally led to diminished community initiatives in establishing, and the complete collapse of the original small group-based schemes. The study also finds among other things that:

 The financial viability of the schemes depends on the provision of long-term government subsidy. However, they may not be financially viable beyond subsidy-funding due to uncontrollable high utilisation rate, occurrence of health insurance fraud, moral hazard and associated exorbitant claims made on them by health care providers. There are problems with late release of reimbursement funds for discharging with claims by the central government. This has impacted heavily on the financial and strategic management and decision making processes of health institutions in the operating districts. Health managers are unable to fulfil their contractual obligations to their suppliers as their capital funds are locked up with the Mutual Health Organisations that arc also unable to provide front loading for the health providers even up to a period of three (3) months of their financial operational requirements. There is therefore. a perceived tension between the schemes and the health institutions as the health institutions prefer to treat clients who come under the 'cash and carry' group since they provide prompt payment to the detriment of insured clients whose reimbursement is delayed causing the institutions to be cash-trapped. This is recommended for immediate attention.


The levels of tobacco-related DNA adducts in human tissues reflect a dynamic process that is dependent on the intensity and time of exposure to tobacco smoke, the metabolic balance between activation of detoxification mechanisms, and the removal of adducts by DNA repair and/or cell turnover. Urinary 8-hydroxydeoxyguanosine (8-OHdG) is probably 1 of the most abundant DNA lesions formed during oxidative stress and is proposed as a sensitive biomarker of the overall oxidative DNA damage and repair. We performed this study to determine whether there were differences in increased oxidative stress susceptibility to smoking within the combined GSTM1 and hOGG1 genotypes and the impact of green tea drinking on this. We completed a Phase II randomized, controlled, 3-arm tea intervention trial to study the effect of high consumption of decaffeinated green or black tea or water on urinary 8-OHdG among heavy smokers and to evaluate the roles of GSTM1 and hOGG1 genotypes as effect modifiers. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed a significant effect of green tea consumption (P = 0.001). The change from baseline was significant in all GSTM1-positive smokers regardless of their hOGG1 genotype. Our data show that consumption of 4 cups (960 mL) of tea/d is a feasible and safe approach and was associated with a significant decrease in urinary 8-OHdG among green tea consumers. Our finding also suggests that green tea intervention might be effective in decreasing DNA damage in the subgroup of smokers who are GSTM1 positive regardless of their hOGG1 genotype.


This article seeks to examine two inter-related dynamics, the relationship between the international dispersion of apparel production and labor control regimes, and the relationship between labor control regimes and patterns of worker resistance. The article argues that where apparel production has concentrated in the last decade has as much to do with labor control regimes as with wages and other economic factors. It suggests that there are three main labor control regimes in the sector: state control, market despotism, and employer repression. The article then argues that these systems of labor control are conducive to three patterns of worker resistance: wildcat strikes, international accords, and cross-border campaigns. The article explores these arguments by examining examples of apparel global supply chains in Vietnam, Bangladesh, and Honduras.


In 1999, ACRL convened a national task force to draft Information Literacy Competency Standards for Higher Education. ACRL has recently launched a revision to those standards. The original standards were influential because they helped advance a national need in higher education at the time: a shift to outcomes based learning. Fourteen years later, information literacy stands alongside oral and written communication, critical thinking and ethical reasoning as learning outcomes broadly acknowledged as needing to be integrated, with disciplinary content, into the curriculum. This author believes that, in contrast to the first process, the current recommendations for revision are focused on the wrong question and include the wrong people to address it. The point isn't to further define, redefine and write more, less or different learning outcomes. The challenge now is to move ahead and address the current concerns of education reform: vertical integration with disciplinary knowledge, curriculum mapping, and assessment. There are a host of challenges and libraries and librarians are perfectly poised to help.


Abstract A review of composite product data interoperability and product life-cycle management challenges is presented, which addresses "Product Life-cycle Management", developments in materials. The urgent need for this is illustrated by the life-cycle management issues faced in modern military aircraft, where in-service failure of composite parts is a problem, not just in terms of engineering understanding, but also in terms of the process for managing and maintaining the fleet. A demonstration of the use of ISO 10303-235 for a range of through-life composite product data is reported. The standardization of the digital representation of data can help businesses to automate data processing. With the development of new materials, the requirements for data information models for materials properties are evolving, and standardization drives transparency, improves the efficiency of data analysis, and enhances data accuracy. Current developments in Information Technology, such as big data analytics methodologies, have the potential to be highly transformative.


Despite the vast amount of molecular data obtained from classical pain studies, there is an ongoing translational pain model crisis reflected by the reduced amount of new effective and safe compounds developed to treat chronic pain in humans. Naturally occurring chronic pain in animals may offer some advantages over induced models of chronic pain, including a natural development of the condition that induces pain, the heterogenicity of the population that affects, and the chronologic age in which they develop, among others. The identification and study of naturally occurring painful diseases that resemble a particular chronic painful condition in humans has been proposed as a potential tool to investigate the molecular mechanisms and thus, accelerating drug development at the preclinical and clinical level. Currently, certain types of chronic pain in companion and large animals have gained attention as potential translational models of chronic pain. Examples of these include canine and feline osteoarthritis, neoplastic diseases as osteosarcoma and bovine and equine lameness. The present review describes the limitations of animal models of chronic pain and briefly enters in how naturally occurring pain models could represent a translational approach to chronic pain.