Objective This retrospective study describes procedures of choice in management of patients with primary prolapse compared with recurrence prolapse patients by fellowship-trained surgeons. Methods Surgically managed primary and recurrent prolapse cases from 2012 to 2015 at Houston Methodist Hospital were reviewed. Baseline characteristics, compartment defects, and stage were compared. Mean interval from the index surgeries to management of prolapse recurrence was recorded. In recurrence cases, mesh complaints were noted if present. Primary outcome was the procedure type used to manage cases of recurrence and primary prolapse. Logistic regression was used to determine odds ratio (OR) for the procedure of choice in recurrence and primary repairs of prolapse. Results Of 386 cases reviewed, 379 met criteria for inclusion; 25.8% of repairs were for recurrence. Recurrence patients were significantly older than primary cases (mean, 63.6 vs 60.5; P = 0.03) and had been postmenopausal for longer (P = 0.004). Median time interval to surgical management of recurrence was 8 years. Thirty percent of recurrence patients treated previously by mesh had mesh complaints. There was no difference in the distribution of defects or stage. Sacrocolpopexy was more frequently used to manage recurrent prolapse (OR, 2.6334; P < 0.0005). Vaginal mesh repairs showed no difference in utilization. Uterosacral ligament fixation (OR, 0.347; P = 0.002) was used more often in primary prolapse. Anterior colporrhaphy (OR, 0.398; P = 0.0005) and uterosacral ligament fixation (OR, 0.347; P = 0.002) were performed less in recurrence cases. Conclusion Fellowship-trained urogynecologists at this institution utilize sacrocolpopexy mesh more frequently in recurrent prolapse, and uterosacral ligament fixation was used more frequently in primary prolapse cases.


Radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan or 131I-tositumomab combines a radiation-emitting radionuclide with an antibody targeting CD20 to treat B-cell non-Hodgkin lymphoma. Multiple studies demonstrate favorable RIT efficacy and safety profiles in follicular lymphoma (FL). The primary toxicity is reversible myelosuppression. Various FL treatment options include single-agent immunotherapy, radiation, chemoimmunotherapy, and RIT. Examining RIT clinical effects and position within treatment algorithms is important to optimal patient benefit. Clinical studies support using single-agent RIT in relapsed/refractory FL, in selected patients with new, untreated FL, and as consolidation after induction chemotherapy or chemoimmunotherapy. RIT as consolidation enhances response rates (with conversion of partial to complete responses following induction therapy) and prolongs disease control versus observation. The overall response rate is 60–80% in the relapsed setting. Time to progression is longer with low-bulk disease, fewer prior therapies, and retained rituximab sensitivity. RIT apparently does not preclude subsequent therapies or increase risk of secondary malignancies compared with chemotherapy's known risk. This article summarizes consensus recommendations for RIT and presents RIT treatment algorithms developed by hematologists/oncologists who regularly treat patients with FL. Maximizing RIT benefit requires healthcare providers to utilize algorithms assisting with treatment decisions.


A field trial was carried out in a drip irrigated Dan-ben-Hannah/Ramsey table grape vineyard near Paarl in the Berg River Valley region of South Africa to compare three fertigation strategies. Fertilisers were applied (i) two weeks after bud break, fruit set and post-harvest (LF), (ii) weekly from two weeks after bud break until ten weeks after harvest, except during berry ripening (WF), and (iii) in daily fertigation pulses (DF). Grapevines of all treatments received c. 116 kg/ha N, 22 kg/ha P and 92 kg/ha K per season. Grapevines of all the fertigation strategies were thinned to obtain a normal and high crop load, which is 26 and 36 bunches per grapevine respectively for Dan-ben-Hannah under the given conditions. In the case of DF, the soil directly beneath the drippers became acidic after three years. Salt also accumulated on the perimeter of the wetted soil volumes. Petiole P of the DF grapevines was 77% higher than that of the LF and WF grapevines. Daily fertigated grapevines bearing normal crop loads had 20% to 30% higher leaf blade P than the LF or WF grapevines. Leaf blade K of the WF grapevines was lower than in the grapevines bearing a normal crop load of the LF and DF strategies. Grapevines bearing high crop loads tended to have lower juice N than grapevines with a normal crop load. Juice P of the DF grapevines was higher than that of the LF and WF grapevines, regardless of crop load. Daily pulse fertigation promoted the accumulation of N, P and K in the berry skins.


Various hardware and software technologies are transforming datacentre management into a programming problem. Network booting and virtualization allow dynamic allocation of hardware resources. Virtual machine mobility helps to optimize hardware utilization, to support maintenance, and to minimize power consumption. Virtual networking isolates mutually distrustful workloads, and allows test to proceed concurrently with production. These technologies reduce the need for human intervention – indeed, virtual machines can even be rented by the hour over the web, eliminating physical configuration altogether. These hardware and software trends support the abstraction that a datacentre (or even a collection of datacentres) is a single programmable computer, made up of many individual servers managed in software. Going by different names – compute fabric, grid, utility computing, autonomous computing, dynamic systems, cloud – this abstraction has arisen in different research communities, albeit with varying emphases. To help identify discussion topics at the workshop we invited participants to contribute short (unrefereed) position papers about their insights into the problems of managing this kind of system. This elicited an exciting response from a wide range of disciplines – covering, amongst other topics, practical experiences working with today's datacentres, foundational aspects of security and service design, technology trends, and performance modelling.


In Turkey, as a developing country, environmental impact assessment (EIA) is a critical key for environmental protection. EIA is not regulated in Turkey by means of law, but through a decree put into force on the basis of the relevant provision of the Environmental Law. The EIA Regulation that is currently in effect was rearranged to eliminate operational problems and ensure harmony with European Standards and was put into practice in 2003. In the paper, EIA system is studied under certain headlines and the weak points are determined. Necessary precautions are suggested to strengthen these weak points.


We present the study of stellar populations in the central 5.5' (~1.2 kpc) of the M31 bulge by using the optical color magnitude diagram derived from HST ACS WFC/HRC observations. In order to enhance image quality and then obtain deeper photometry, we construct Nyquist-sampled images and use a deconvolution method to detect sources and measure their photometry. We demonstrate that our method performs better than DOLPHOT in the extremely crowded region. The resolved stars in the M31 bulge have been divided into nine annuli and the color magnitude diagram fitting is performed for each of them. We confirm that the majority of stars (> 70%) in the M31 bulge are indeed very old (>5 Gyr) and metal-rich ([Fe/H] > 0.3). At later times, the star formation rate decreased and then experienced a significant rise around 1 Gyr ago, which pervaded the entire M31 bulge. After that, stars formed at less than 500 Myr ago in the central 130". Through simulation, we find that these intermediate-age stars cannot be the artifacts introduced by the blending effect. Our results suggest that although the majority of the M31 bulge are very old, the secular evolutionary process still continuously builds up the M31 bulge slowly. We compare our star formation history with an older analysis derived from the spectral energy distribution fitting, which suggests that the latter one is still a reasonable tool for the study of stellar populations in remote galaxies.


There was once a group of trees who were fed up with living in a deep, dark and crowded valley - so they moved to the enchanted forest. But as everybody knows, trees cannot walk without magic. This is the story of how Jack, the small boy with the frozen touch, wanders in to the forest and ends up saving the magic from the greedy goblins outside. An exquisitely illustrated and beautifully told story.


Background The adverse effects of maternal and paternal smoking on child health have been studied. However, few studies demonstrate the interaction effects of maternal/paternal smoking, and birth outcomes other than birth weight have not been evaluated. The present study examined individual effects of maternal/paternal smoking and their interactions on birth outcomes. Methods A follow‐up hospital‐based study from pregnancy to delivery was conducted from 1997 to 2010 with parents and newborn infants who delivered at a large hospital in Hamamatsu, Japan. The relationships between smoking and growth were evaluated with logistic regression. Results The individual effects of maternal smoking are related to low birth weight (LBW), short birth length and small head circumference. The individual effects of paternal smoking are related to short birth length and small head circumference. In the adjusted model, both parents' smoking showed clear associations with LBW (odds ratio [OR] = 1.64, 95% confidence interval [CI] 1.18‐2.27) and short birth length (‐1 standard deviation [SD] OR = 1.38, 95% CI 1.07‐1.79; ‐2 SD OR = 2.75, 95% CI 1.84‐4.10). Conclusions Maternal smoking was significantly associated with birth weight and length, but paternal smoking was not. However, if both parents smoked, the risk of shorter birth length increased.


In this short note, we show how to quickly verify the correctness of the estimates of the PML risk on natalizumab established in [Borchardt 2015]. Our approach is simple and elementary in that it requires virtually no knowledge of either statistics or probability theory. For a Kaplan-Meier curve of the PML incidence may be found in [O'Connor et al 2014], based on postmarketing data as of early August 2013, and just using the information from that chart, it is possible to directly derive estimates of the risk of PML in JCV-seropositive natalizumab-treated patients according to prior or no prior immunosuppression. Actually, the resulting figures are almost identical to the ones in [Borchardt 2015], even though the latter were obtained in a very different fashion.


SUMMARY When a new drug is introduced to the market, the availability of head-to-head data for comparisons of annual cost and health outcomes with other drugs already on the market is usually insufficient. When only limited head-to-head data are available, one alternative is to perform preliminary modeling using data from the best available studies. In this paper, we synthesise data from the most comparable available studies to create a model to compare the annual costs and health outcomes when initiating treatment for schizophrenia with one of two antipsychotic drugs: olanzapine, which was launched in the United States (US) market in September 1996, and ziprasidone, which was approved by the US Food and Drug Administration (FDA) in February 2001. Annual treatment costs were determined by response and relapse rates as well as acquisition costs. The results indicate similar annual treatment costs (US$48,676 for olanzapine; US$48,873 for ziprasidone), despite the lower drug acquisition cost for ziprasidone. Annual health outcomes differed between the olanzapine and ziprasidone groups with 23.5% and 25.2% relapsed, 36.7 and 37.4 hospital days, and 60.0 and 60.1 EPS days in the olanzapine and ziprasidone groups respectively. A head-to-head naturalistic trial is needed to validate the results of this modeling exercise.


Sexual assault is a traumatic experience for any woman. Furthermore, many victims who tell others about their assault must endure a 'second assault' in the form of negative reactions, such as victim blaming and disbelief. One third to two thirds of victims may experience such reactions, which have negative mental and physical health effects on the victims. This book provides a comprehensive look at women's rape disclosure, addressing such issues as why, how often, and to whom women disclose their sexual assault; how people respond to disclosures; what factors influence how they respond to disclosures; and how these responses affect survivors. With an ecological approach, the book considers the social context of rape, arguing that negative social reactions emanate from broader social norms and attitudes about rape. Multiple perspectives are considered, including those of survivors, informal support providers (family, friends, and intimate partners), and formal support providers (therapists, victim advocates, and others). Finally, recommendations for research, treatment, and intervention are provided. Powerful, insightful, and provocative, this book is essential reading for everyone who works with sexual assault victims, including therapists, health care workers, victim advocates, rape researchers, policy makers, and students in any of these fields.


This report discusses the minimum separation distance in a near midair collision report which the event must meet in order to be classified a "near miss." If a pilot of flight crew member subjectively believes that the near miss occurred, the report of that event is accepted by the Federal Aviation Administration (FAA) and counts as a near miss in the FAA data base regardless of the actual separation distance. While no proximity limits are placed on near midair collision reports, the agency does attempt to categorize each reported encounter by degree of hazard represented from an aviation safety perspective.


The crystal structure of the mutant deoxyhemoglobin in which the beta-globin Val67(E11) has been replaced with threonine [Fronticelli et al. (1993) Biochemistry 32, 1235-1242] has been determined at 2.2 A resolution. Prior to the crystal structure determination, molecular modeling indicated that the Thr67(E11) side chain hydroxyl group in the distal beta-heme pocket forms a hydrogen bond with the backbone carbonyl of His63(E7) and is within hydrogen-bonding distance of the N delta of His63(E7). The mutant crystal structure indicates only small changes in conformation in the vicinity of the E11 mutation confirming the molecular modeling predictions. Comparison of the structures of the mutant beta-subunits and recombinant porcine myoglobin with the identical mutation [Cameron et al. (1993) Biochemistry 32, 13061-13070] indicates similar conformations of residues in the distal heme pocket, but there is no water molecule associated with either of the threonines of the beta-subunits. The introduction of threonine into the distal heme pocket, despite having only small perturbations in the local structure, has a marked affect on the interaction with ligands. In the oxy derivative there is a 2-fold decrease in O2 affinity [Fronticelli et al. (1993) Biochemistry 32, 1235-1242], and the rate of autoxidation is increased by 2 orders of magnitude. In the CO derivative the IR spectrum shows modifications with respect to that of normal human hemoglobin, suggesting the presence of multiple CO conformers. In the nitrosyl derivative an interaction with the O gamma atom of Thr67(E11) is probably responsible for the 10-fold increase in the rate of NO release from the beta-subunits. In the aquomet derivative there is a 6-fold decrease in the rate of hemin dissociation suggesting an interaction of the Fe-coordinated water with the O gamma of Thr67(E11).


The main purposes of this research were to investigate factors for the development of basic Dharma
traits (BDT) in preschool children and to promote the BDT which is one of a number of identified topics
concerning ethics and morality targeted for urgent presentation to children and youth in Thailand. The
study was conducted in two phases using kindergarten students aged 5 and 6. In Phase 1, teachers
evaluated the BDT in 1,088 preschool children throughout Thailand using cluster sampling. The
confirmatory factor analysis found that the preschool children showed BDT in eight areas of Diligence,
Saving, Honesty, Discipline, Politeness, Cleanliness, Unity, and Kindness. Most of the preschool
children could express examples of each area by themselves or with the assistance of teachers or friends.
In Phase 2, a model for promoting the BDT of preschool children was developed through learning
activities using sets of fables. These learning activities comprised fable books, storytelling activities, and
supplementary Dharma activities and were used by the teachers with 326 students selected from the
sample of Phase 1 by purposive sampling. The results showed that the model for promoting the BDT
could obviously promote higher scores both in general and for all the specific areas.


Research on migrant fertility has often found differences between the childbearing of migrants and natives. These 'differentials' are important because they demonstrate how migrants contribute towards population change. They can be also used to investigate how living in a new destination affects the fertility of immigrants and their descendants. This is especially true when demographers study how differentials change over time as a process of convergence. Unfortunately, the literature on migrant fertility differentials suffers from a number of limitations. Firstly, existing definitions of migrant fertility convergence are ambiguous. It is unclear what the concept means, and how it should be tested. Secondly, researchers have limited knowledge about variation in differentials over the life course, in particular for women who have completed childbearing. Thirdly, there is a lack of empirical research that examines why differentials exist, and whether they can be explained by exposure to cultural norms. This thesis responds to these issues with four papers, one that critically evaluates convergence, and three that analyse migrant fertility in the UK. The results show evidence of generational convergence for some descendants of immigrants, notably those with Irish and Jamaican ancestry, but evidence against convergence for the descendants of immigrants from Pakistan and Bangladesh. These results are partly explained by childhood socialisation and culturally entrenched fertility norms, such that differentials are lower for child migrants who grow up in areas where they are more likely to be exposed to native cultural norms. Overall, the results show that differentials vary considerably over the life course, and follow very different patterns for different migrant groups. The findings suggest that researchers must be careful when trying to make generalisations about migrant fertility behaviour. They also highlight the immigrants, descendants, life course stages, and explanations of migrant fertility that may be most fruitfully studied by future research.


We demonstrate that the non-steady-state photoelectromotive force induced by a vibrating Ronchi grating has a very complicated but deterministic dependence on the propagation distance. The characteristic minima of this dependence are found at fractional values of the Talbot distance, and their width is determined by the maximal transversal spatial frequency resolved by the system. This permits high accuracy in the determination of the Talbot distance.


Epistemology is the study of knowledge – of what is known and how we know it. Organizational epistemology is dominated by the dualist opposition of objectivist and subjectivist philosophies of science. Objectivists accept knowledge claims as potentially true and warranted on objective evidence, whereas subjectivists ground knowledge in perception, phenomenology and social construction. Though these two perspectives differ in their ontologies (the reality of constructs and relations) and methodologies (how these relations can be observed), both views accept that reliable organizational knowledge is possible. This paper introduces a third epistemological perspective fallibilism - and shows how neglect of this third epistemology has constrained advance in the objectivist-subjectivist debate. Fallibilism, which challenges the foundations and reliability of knowledge claims, occupies a significant place in every major philosophical tradition, but contradicts the prevailing rhetoric of knowledge-claiming in organizational research, and has been systematically excluded from the debate. In this article we present the foundations and precepts of fallibilism, show how its absence has invited divisive and sectarian dogmatism, and explore its potential contributions to organizational research.


The first ammonoids from the Lower Emsian (Devonian) of Belgium are described. They belong to the Anetoceratinae, which show the most plesiomorphic characters of all ammonoids. This is the second report of Early Emsian ammonoids within the Rhenish facies of the Rhenish Slate Mountains (Belgium, Germany), in this case from the Belgian part of the Eifel (Burg Reuland). It highlights the possible importance of ammonoids for the correlation of the Emsian in its traditional German sense and the Emsian in the global sense as delimited by the GSSPs. Newly collected, age-significant brachiopods of the genera Arduspirifer and Euryspirifer and other previously reported fossils indicate a middle or late Early Emsian (Singhofen or Vallendar) age (in German sense) for this locality. We extend the range of Ivoites schindewolfi outside of the Hunsruck Basin and further corroborate an age younger than Ulmen for parts of the Hunsruck Slate.


In the field of facade engineering, structural silicone sealants have been used in adhesively bonded connections since the 1960s. The low strength and stiffness of silicone rubber compared to other types of adhesives are compensated by the excellent adhesion properties and the good resistance against ageing and environmental influences, like UV radiation. Silicone sealants show a pronounced nonlinear material behaviour. The applicable design concepts in civil engineering propose simplified design equations, which are based on the assumption of a linear material law. Due to the current state of knowledge and to compensate the simplified model assumptions in the design concept, high reduction factors on the material strength and many restrictions on applications are defined. In order to overcome these drawbacks, the stress state within the sealant is increasingly described using the Finite Element Method. Considering the results of these analysis, the assessment of both the complex stress states with a suitable failure criterion and the influence of stress singularities on the failure behaviour constitute inevitable questions.

The present work addresses these two questions. In the first step, the strain magnitude has been determined as a suitable failure criterion for the defect-free bulk material of the considered Dow Corning® 993 structural silicone sealant, subjected to a quasi-static loading. The failure criterion has been calibrated using the results of uniaxial tension as well as circular shear tests and validated with the results of compression tests. The strain magnitude is a strain-based failure criterion, which can be seen as a measure for the distortion of the molecular chains.

In a second step, the stress distribution of the single-lap shear joint has been investigated in detail. For the assessment of the singular stresses and strains at the edge area of the interface between the adhesive and the substrate, referred to as two-material wedge, the so-called coupled stress and energy criterion, a concept of Finite Fracture Mechanics, was extended to nonlinear elastic material behaviour. Based on results of conduced simple shear tests on small bonded connections with varying adhesive thicknesses and overlap lengths, the coupled criterion was used to predict the crack initiation loads and a good agreement with the experimentally recorded values was obtained. Knowing the strength and the critical energy release rate of the material, the crack initiation load and the corresponding crack length are determined in the coupled criterion by solving an optimisation problem based on a Finite Element Analysis. The stress partial criterion has been modified to consider the strain magnitude as a failure criterion. In order to analyse the energy partial criterion, the critical energy release rate of Dow Corning® 993 structural silicone sealant has been determined in Double Cantilever Beam tests using the evaluation method based on the J-integral approach. Furthermore, concepts of the Theory of Critical Distances were used to determine the failure loads of the small scale tests. Unlike as for the notched circular shear tests and the tension tests on small scale bonded connections, good predictions were found in the Finite Element Analysis for the simple shear specimens, when a constant element size and formulation at the vicinity of the two-material wedge were used. Similar results were obtained with the point method and the control volume approach. These findings indicate that the characteristic material length for silicone rubber is not constant.


Environmental, social and economic concerns linked to the sustainable development of the built-up environment are increasingly calling into question models of territorial development based on urban sprawl. This is because the process of dispersed urbanization generates social inequalities; it is based on the extensive use of automobiles, and leads to increased spending on infrastructure networks. This phenomenon tends to be explained by the search for a combination of life in the city and life in the wide-open which creates new life-styles based on the extensive use of transportation and communication systems. The analysis of these emerging practices indicates that they arise from a double pressure exerted on the population: on one hand, attraction to rural and mountain areas, and on the other hand the economic and cultural dependency vis-a-vis the large urban centers. In this context, the regeneration of urban wasteland areas appears to be a strategy capable of favoring a better anchoring between urbanization and public transport. The dynamics of off-shoring enterprises has freed up a large number of plots that are however connected to existing networks, and benefit from good accessibility and sometimes enviable centrality. The requalification of industrial wasteland has been the object of much research in the nineties, which has led to establish as principles density, mixed use and the preservation of the industrial heritage (for instance Escher-Wyss in Zurich-West, Sulzer in Winterthur, ABB in Baden, SIP in Plainpalais-Geneva). In the same way, following the abandonment of some mobility structures, research has started to focus on the fate of urban railroad wastelands. These are considered to be strategic locations to develop "compact cities", attractive for habitat and favorable for the development of social and cultural activities. Several examples in Switzerland illustrate these attempts: Ecoparc in Neuchâtel, Zurich HB, La Praille in Geneva, etc. Today, in order to offer alternatives to the urban paradigm of the compact city we focus our attention on a different type of railroad wasteland. By regional railroad wasteland we refer to areas located close to a train station, either abandoned or in the process of being abandoned, and situated in suburban or periurban zones. Though these regional railroad wastelands present advantages similar to those of the urban wastelands in terms of accessibility to public transport, they are very different by their relationship to the landscape and nature. In addition, much more affordable land prices than in city centers allow more flexibility in the choice of programs and target users. In line with the thinking led by Thomas Sieverts among others, we attempt to go beyond the antagonisms between city and country, by formulating the hypothesis that these regional railroad wastelands bring an answer that is able to reconcile the aspirations to life in the country with the requirements of sustainable territorial development. The present research aims to explore a series of urbanism strategies induced by the simultaneous and inseparable presence of the railroad and natural dimensions, which constitutes the specificity of these periurban and suburban sites. In a first phase, in order to reveal these specific characteristics we conducted a typology exercise on a sample of thirty railroad sites located on the Geneva to Sankt-Gallen axis. It extends the whole length of the country from Lake Geneva in the southwest to Lake Constance in the northeast and goes through the main city areas of the country as well as several so-called calm areas. These thirty wastelands were measured, photographed, described, analyzed and finally represented according to an innovative methodology that combines architectural, urbanism and sociological approaches. This first phase concludes with the construction of the "face" of each site; beyond the fundamental distinction between urban and regional wastelands, it leads to the identification of six individual types. In a second phase, the focus moves to the project process. In order to understand precisely the mechanisms and the stakes at play, we have analyzed several case studies of urban wastelands in various stages of advancement, going from construction finished (Zurich-West), to the beginnings of the launch of a project (Fribourg), the first stages of construction (Zurich Stadtraum-HB) and planning in the course of development (Lausanne-Malley). We thus show the main obstacles to development, then the levers, triggers or planning instruments capable of surmounting them. Finally, in the last part, we elaborate development scenarios up to 2025 for three regional wastelands of the Lake Geneva urban hub, which come from a distinct group within the typology: Versoix, La Plaine and Palezieux. The project recognizes two scales of intervention: the train station and its immediate surroundings on one hand, and the extended perimeter on the other hand, which includes land within a 500 meter radius around the station. The developments of these two perimeters are intimately linked: the creation of a pole of urbanization may induce an improvement of the rail service and vice-versa. These two embedded scales thus constitute a complex dynamic system, within which specific, though coordinated urbanism strategies are implemented, and the stakes proper to each perimeter dictate these. For the station and its immediate surroundings, the goal is primarily to increase the hospitability of the site, that is principally to increase the symbolic role of the station, to plan the equipment and infrastructure necessary in view of the increased flows of travelers, and arranging the external space by accentuating the presence of vegetation, in agreement with the local character. All of these interventions lead to the creation of a "railroad landscape" which is the regional counterpart to the urban public space. Within the extended perimeter, the project strategy rests upon the recognition of five complementary qualities: inhabited, equipped, wild, productive, to be contemplated, whose proportions vary according to the territorial insertion of the wasteland. Densification is then effected in a punctual and targeted manner, in coherence with the logic resulting from the encounter between rail and nature.


The pattern of life is a discontinuous one: both fossils and modem taxa show a clustering of forms separated by gaps. Evolutionary theory explains these gaps by relatively rapid transitions happening long ago, leaving few identifiable intermediates. One mechanism for this 'punctuated equilibrium' process suggests that these dramatic changes take place in small isolated populations at the edges of a species' range. This notion was tested in the land snail Cepaea nemoralis in the French and Spanish Pyrenees. Geographical patterns of genetic differentiation in enzyme polymorphisms ('molecular area effects') suggest that the population was once fractured into smaller units which, after a process of genetic disruption, recolonised their original range. The interface between two of these areas was mapped by an analysis of enzyme polymorphisms. Pure populations and their hybrids were then compared for adaptational differences (shell and body colour, thermal behaviour and mortality rates), and for reproductive isolation (as calculated by estimates of selection against hybrids from the enzyme dine width using field determinations of dispersal rate). No significant adaptive differentiation or reproductive barrier could be established between the two molecular areas. Instead, the same processes of adaptation seem to have taken place within the areas, in response to altitude and insolation. Furthermore, I investigated the possibility of a hybrid advantage effect taking place within the zone of hybridisation, where mean shell size is larger, resulting in more eggs being laid. Hybrid genotypes are thus likely to disperse faster than those of the pure types, dissipating the genetic differentiation between area effects more quickly than by random mixing. Present day selection is unlikely to determine the pattem of molecular area effects, as they do not coincide with geological, climatic, and vegetational discontinuities. Rather, they are relics of history, arising from the expansion of glacial refuges. The dynamics of this process were investigated by tracking vegetation patterns from ancient pollen cores, and by an analysis of mtDNA and enzyme variant distribution. The results of this study counter the expectations of the proposed mechanism of punctuated equilibrium. They are a reminder that, for most of the time, living organisms are robust to dramatic evolutionary change.


Boolean Satisfiability (SAT) is a fundamental NP-complete problem of determining whether there exists an assignment of variables which makes a Boolean formula evaluate to True. SAT is a convenient representation for many naturally occurring optimization and decisions problems such as planning and circuit verification. SAT is most commonly solved by a form of backtracking search which systematically explores the space of possible variable assignments. We show that the order in which variable polarities are assigned can have a significant impact on the performance of backtracking algorithms. We present several ways of transforming SAT instances into non-linear objective functions and describe three value-ordering methods based on iterative optimization techniques. We implement and test these heuristics in the widely-recognized MiniSAT framework. The first approach determines polarities by applying Newton's Method to a sparse system of non-linear objective functions whose roots correspond to the satisfying assignments of the propositional formula. The second approach determines polarities by minimizing an objective function corresponding to the number of clauses conflicting with each assignment. The third approach determines preferred polarities by performing stochastic gradient descent on objective functions sampled from a family of continuous potentials. The heuristics are evaluated on a set of standard benchmarks including random, crafted and industrial problems. We compare our results to five existing heuristics, and show that MiniSAT equipped with our heuristics often outperforms state-of-the-art SAT solvers.


In 1849, the German mathematician Gauss large average distribution density of primes near x. Based on the density of the Gauss proposed regional distribution of prime numbers theorem. And regional distribution of prime numbers theorem proved easy to understand way. The fundamental theorem to obtain the distribution of prime numbers. Thus proving that a new prime number theorem. Therefore gives the details of the calculation.


Accurately understanding the thoughts and feelings of romantic partners, termed empathic accuracy, is critical for optimal relationship functioning. Empathic failure is linked to common reasons couples seek therapy (Doss, Simpson, & Christensen, 2004; Jacobson & Christensen, 1996) and is either implicitly or explicitly a target of many couple therapies (e.g., Jacobson & Christensen, 1996). More specifically, couple therapies target partners' abilities to accurately understand one another preceding and during conflict, periods characterized by high levels of stress. The current study tests the hypothesis that acute stress can be harmful for empathic accuracy in romantic couples, and tests two competing path models of the impact of stress on accuracy. Results show that an acute stressor affected accuracy of men and women differently, impairing accuracy in women but not observably affecting men's accuracy. The effect of the stressor on empathic accuracy for women was mediated by curvilinear arousal, and men's accuracy was also associated with curvilinear arousal. This pattern of results suggests that moderate arousal is optimal for empathic accuracy for both men and women, but this effect was twice as large for women relative to men. These findings point toward potential avenues to improve existing couple therapies by incorporating strategies to mitigate the effects of stress, thereby increasing couples' ability to accurately understand one another in therapy. These findings also suggest strategies for couples to be optimally productive when having important relationship conversations by attending to their level of arousal.


Abstract Social capital appears to be an important determinant of health production and health utilization and demand. However, there is limited evidence on the mechanisms underlying this relationship. In this article we draw on the evidence and insights reported in this special issue along with findings from the economic and other social science literature to develop a discussion on the explanations of the likely (behavioural) mechanisms that underpin the connection between social capital and health. An important and under-explored influence mediating the relationship between social capital and health (behaviour) lies in the 'social formation of health preferences and constraints' individuals face in determining their life-styles and in using health care. In particular, we point to the interdependence in how individuals in the first place perceive and also respond to common health risks and the role of cultural transmission and social identity as conveyors of this process. We argue that an emerging body of evidence suggesting that interdependent preferences influence health calls for further re-formulation of traditional demand for and production of health models. Additionally, methodological problems are highlighted and possible ways forward suggested.


The date was January 8, 1997, I was on the witness stand at the Palm Beach Court, (401) and Judge Joseph Davis asked me: "Doctor, can you imagine some special circumstances in which you would help a patient to end his life?" "No, Your Honor." "How so? Never?" asked the judge, and his incredulous surprise reminded me how much the world has changed. But has it? Our hopes and fears, and the necessity to face our destiny have not changed, nor has, I deeply believe, the calling of physicians. In this chapter I shall try to explain why the traditional clinician rejects euthanasia and physician-assisted suicide: * His attitude had been primarily shaped by his upbringing and traditions but had been ultimately determined by medical considerations. * As a young doctor, he had accepted the Hippocratic ethics on faith, but his life's experience, and the centuries long experience of his profession, have confirmed the soundness of this ethical code. * Knowing how dependent and vulnerable the patients are, the traditional clinician is skeptical about the voluntariness of euthanasia. * He would never draw fatal and irreversible conclusions from his diagnoses and prognoses because diagnoses are fallible and prognoses notoriously unreliable. * He is worried about the future of the medical profession, and foresees the paralyzing effect of euthanasia on the professional performance of doctors and nurses, (402) * And he is convinced that confusing the role of a healer with that of a killer must lead to disaster. The Physician, the Patient, and "Voluntary" Euthanasia. At the time when so often the courts intervene in medical practices, it will be useful to realize how different are the images of a sick person as seen by Medicine and by the Law. The Law sees the patient as he should be, as he has the right to be: an autonomous being, able to make independent, rational, and sovereign decisions. The Physician sees a very different person: weakened by the disease, dimmed by the sedatives and painkillers, euphoric after some reassurance, but depressed when the news is not so good, fully dependent on the information given by the doctor, easily influenced not only by the content, but also by the way the information is presented. In the view of the traditional clinician, if a patient is asking for death, probably the doctor induced him to make such request. Euthanasia, Assisted Suicide, and the Uncertainties of Medicine. A high degree of certainty, or rather, a complete certainty should be required when an irreparable step is considered, and human life is at stake. Yet the present tendency to regard medical diagnoses as certainties, and medicine as exact science, is obviously mistaken. On the contrary, the traditional clinician's view of medicine as the art of dealing with uncertainties has been right in the past and remains valid at present. Now as in the past, 20 to 40 percent of clinical diagnoses prove wrong in confrontation with the ultimate diagnostic standard, the post-mortem findings. In spite of all precision tools which have been introduced, the accuracy of medical diagnoses has not improved in the last fifty years, which has led to the notion of necessary fallibility of medical diagnoses. (403) An erroneous diagnosis of fatal disease remains a real possibility. In their efforts to improve a patient's condition or save his life, doctors have to rely on diagnoses that are only probable. To cause a patient's death on the grounds of a diagnosis that may prove faulty is as evil as it is mindless. How Well Can Doctors Predict the Future? Doctors' predictions that the patients will die within so many weeks or months thrust some sick persons into such a psychologically intolerable situation that suicide or euthanasia may be seen as a way out. Death is then sought, and perhaps granted, on the grounds of a false certainty. …


The goal of the Infrastructure Safety Assessment in a Connected Vehicle (CV) Environment project was to develop a method to identify infrastructure safety "hot spots" using CV data. Using these basic safety messages to detect hot spots may allow for quicker discovery than traditional methods, such as police-reported crashes. The basic safety message may be able to detect events that police normally cannot obtain, including unreported crashes and near-crashes. The project successfully explored some models and algorithms to detect crashes and near-crashes and also designed a methodology to apply to hot spot identification. With the data available, conclusive results were not achieved; however, the models showed some potential. Three techniques were tested to predict crashes using vehicles' kinematic data. To predict where a crash was occurring, multivariate adaptive regression splines, classification and regression trees, and a novel pattern matching approach were all tested. The models were able to identify the majority of 13 known crashes with different amounts of false positives. The pattern matching approach outperformed a simple acceleration threshold by identifying nearly 70% of crashes in a crash-only test set and 74% of near-crashes in a near-crash only test set. On the training set, it was able to identify more crashes than the thresholds without increasing the number of false positives observed. Based on the work described in this report, the CVI-UTC is fully prepared to apply the methodology to data collected on the field test bed.


For over two decades, studies on task planning and its role in second language learners' oral performance have shown that the opportunity to plan for a task generally improves learners' speech (Ellis, 2005). It has been hypothesized that the opportunity to plan for a task reduces cognitive load during language processing, thus allowing learners to attend to various aspects of language, and that this enhanced attention, in turn, results in more successful task performance. However, one limitation to this task planning research to date it that most studies have examined the effects of planning before task performance, while largely ignoring the effects of planning that occur during task performance (Yuan & Ellis, 2003). Another limitation in planning research is that findings have been based exclusively on external observation and measurement of learners' oral production; we know little about what strategies learners use that may result in higher-quality speech. The participants in this study were intermediate and high-intermediate learners of Japanese. They were divided into experimental groups and performed a narrative task under different task conditions. Participants received a set of pictures and were asked to retell the story in Japanese. To examine the effects of planning on task performance, fluency, complexity, and accuracy in the participants' speech were analyzed. For the analysis of planning strategies, retrospective interviews were given to a group of participants from each planning group immediately after the task performance. The results revealed that there were no significant differences in participants' oral production across planning conditions, except in the area of lexical complexity (participants without a pre-task planning opportunity produced narrative stories with a greater variety of vocabulary than those who planned before the task). A trade-off effect between lexical complexity and accuracy was found when participants planned either before or during the task. Another trade-off effect was found between lexical complexity and fluency for the participants with on-line planning only. The analyses of strategy use showed that second language learners generally selected similar strategies regardless of planning conditions. These results provided important pedagogical implications and suggested useful future research directions.


The new high-temperature (T), high-pressure (P), body-centered cubic (bcc) phase of iron has probably already been synthesized in recent diamond anvil cell (DAC) experiments (Mikhaylushkin et al 2007 Phys. Rev. Lett. 99 165505). These DAC experiments on iron revealed that the high-PT phase on quenching transforms into a mixture of close-packed phases. Our molecular dynamics simulation and structural analysis allow us to provide a probable interpretation of the experiments. We show that quenching of the high-PT bcc phase simulated with the embedded-atom model also leads to the formation of the mixture of close-packed phases. Therefore, the assumption of the stability of the high-PT bcc iron phase is consistent with experimental observation.


Cross-national research is a research methodology that aims to make comparisons across countries. Nowadays, cross-national research is growing, especially in some social science disciplines such as sociology, political science, geography, and economics. However, it has not yet steadily entered the field of audiovisual translation (AVT). Despite its theoretical and methodological challenges (Hoffmeyer-Zlotnik & Harkness, 2005), cross-national research could be used successfully in AVT to investigate long-debated issues. These issues include, but are not restricted to, the reception of a given AVT method or strategy, and the different ways in which the translation process is accomplished in different countries. In this contribution, I will outline both theoretical and methodological debates in comparative cross-national research and apply them to AVT. After that, I will briefly present the results of a cross-national study (Perego et. al, 2016) designed to analyse the subtitle reception comparing the way the process takes place in different countries with different AVT traditions. The discussion of the study will contribute to assessing the potential strengths of cross-national research in AVT, thus offering indications on future methodological developments and enabling future and more rigorous international comparisons.


The paper advances a new architecture for seamless roaming, which is implemented at the application layer. This architecture is subject for the research projects PERIMETER and MOBICOME, recently granted by the EU STREP FP7 and EUREKA, respectively. The research challenges are on mobility management, security, QoE management, overlay routing, node positioning, mobility modeling and prediction, middleware and handover. The foundation of seamless handover is provided by several components, the most important ones being the handover, mobility management, connectivity management and Internet mobility. The paper provides an analysis of these components as well.


Purpose – Despite growing scholarly v interest in social entrepreneurs and the social enterprises which they create, few studies have examined the hybridity of social enterprises including, surprisingly, whether they adoption an entrepreneurial orientation (EO) One explanation for this may be the continuing lack of an appropriate scale measuring a social entrepreneurship orientation. This paper seeks to address this research gap by proposing an initial social entrepreneurship orientation (SEO) scale based on input from scholars in the fields of entrepreneurship and social entrepreneurship. Design/methodology/approach – This study presented employed mixed-methods and a two stage design. In stage one a Delphi study with 18 researchers with expertise of investigating entrepreneurship and social entrepreneurship was used to generate constructs combining aspects of both social and entrepreneurial orientations. In stage two, we assessed the face validity of the derived items from the Delphi study by conducting a survey with 82 such experts. Findings – The paper provides empirical insights into how SEO can be measured by proposing, for the first time, a 12-item scale with 4 dimensions that allows the measurement of a social entrepreneurship orientation for the first time. Research limitations/implications – We recommend that future studies employ quantitative methods, particularly with firms exhibiting differing levels of the 'socialness' dimension which we propose and that such studies involve a variety of research informants. Statistical analysis of data collected across large sample sizes will help evaluate the reliability and validity of the scale which we propose. Practical implications – The paper includes implications for future research based on the proposed social entrepreneurship orientation measurement scale. Originality/value – This paper develops the first SEO scale based on empirical data collected from experts in the fields of entrepreneurship and social entrepreneurship.


Operation of a district heating system is accomplished via a sequence of decisions by the operators controlling the system. These decisions are based on expectations of conditions in the system that are not known at decision time. The operators could be helped by a decision support system that computes predictions of future system variables and suggests appropriate control actions given the available information.

This thesis presents a new model that gives a both physical and stochastic description of a district heating system. The model describes both technical and economical information of the system that are important for the control decisions. It is easy to calculate predictions based on this model as well as performing simulations.

The ambient temperature is the single most important explanatory variable for the heat demand in a district heating network. A model that can be used to calculate reliable temperature predictions are presented where the full advantage of both local measurements and forecasts from a meteorological institute are utilized.

A heuristic approach to the operational optimization problem is presented and it is shown in simulations to be superior to a traditional control, based on a priority scheme. The operational optimization problem is a complex stochastic optimization problem and the heuristic approach gives a solution that can be calculate instantly.

An online computer program, EnerPlan, is developed where the described models are used to calculate predictions and simulate alternative future scenarios. The program is currently used in the control room at the Heleneholm power plant in Malmo, Sweden.


Partitioning graphs into equally large groups of nodes while minimizing the number of edges between di(cid:11)erent groups is an extremely important problem in parallel computing. For instance, e(cid:14)ciently paralleliz-ing several scienti(cid:12)c and engineering applications requires the partitioning of data or tasks among processors such that the computational load on each node is roughly the same, while communication is minimized. Obtaining exact solutions is computation-ally intractable, since graph-partitioning is an NP-complete. For a large class of irregular and adaptive data parallel applications (such as adaptive meshes), the computational structure changes from one phase to another in an incremental fashion. In incremental graph-partitioning problems the partitioning of the graph needs to be updated as the graph changes over time; a small number of nodes or edges may be added or deleted at any given instant. In this paper we use a linear programming-based method to solve the incremental graph partitioning problem. All the steps used by our method are inherently parallel and hence our approach can be easily parallelized. By using an initial solution for the graph partitions derived from recursive spectral bisection-based methods, our methods can achieve repartitioning at considerably lower cost than can be obtained by applying recursive spectral bisection from scratch. Fur-ther, the quality of the partitioning achieved is comparable to that achieved by applying recursive spectral bisection to the incremental graphs from scratch.


Abstract : In an era of sequestration and austerity, the federal government is seeking software reuse strategies that will allow them to move away from stove-piped development toward open, reusable architectures. The government is also motivated to explore reusable architectures for purposes beyond fiscal constraints: to leverage existing technology, curtail wasted effort, and increase capabilities rather than reinventing them. An open architecture in a software system adopts open standards that support a modular, loosely coupled, and highly cohesive system structure that includes the publication of key interfaces within the system and full design disclosure. One area where the Department of Defense (DoD) is concentrating on the development of service-oriented architectures and common technical frameworks is in the intelligence community, specifically the Defense Intelligence Information Enterprise (DI2E). As this blog post details, a team of researchers at the SEI Emerging Technology Center (ETC) and the Secure Coding Initiative in the SEI s CERT Division, are working to help the government navigate these challenges in building the DI2E framework, which promotes reuse in building defense intelligence systems.


Spatial light interference microscopy (SLIM) is a new optical microscopy technique, capable of measuring nanoscale structures and dynamics in live cells via interferometry. SLIM combines two classic ideas in light imaging: Zernike's phase contrast microscopy, which renders high contrast intensity images of transparent specimens, and Gabor's holography, where the phase information from the object is recorded. Thus, SLIM reveals the intrinsic contrast of cell structures and, in addition, renders quantitative optical path-length maps across the sample. The resulting topographic accuracy is comparable to that of atomic force microscopy, while the acquisition speed is 1,000 times higher. We illustrate the novel insight into cell dynamics via SLIM by experiments on primary cell cultures from the rat brain. SLIM is implemented as an add-on module to an existing phase contrast microscope, which may prove instrumental in impacting the light microscopy field at a large scale.


The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.


Acetylated oligosaccharides are common in nature. While they are involved in several biochemical and biological processes, the role of the acetyl groups and the complexity of their migration has largely gone unnoticed. In this work, by combination of organic synthesis, NMR spectroscopy and quantum chemical modeling, we show that acetyl group migration is a much more complex phenomenon than previously known. By use of synthetic oligomannoside model compounds, we demonstrate, for the first time, that the migration of acetyl groups in oligosaccharides and polysaccharides may not be limited to transfer within a single monosaccharide moiety, but may also involve migration over a glycosidic bond between two different saccharide units. The observed phenomenon is not only interesting from the chemical point of view, but it also raises new questions about the potential biological role of acylated carbohydrates in nature.


Bedrock weathering runs to the hills Fractures in bedrock drive the breakdown of rock into soil. Soil makes observations of bedrock processes challenging. St. Clair et al. combined a three-dimensional stress model with geophysical measurements to show that bedrock erosion rates mirror changes in topography (see the Perspective by Anderson). Seismic reflection and electromagnetic profiles allowed mapping of the bedrock fracture density. The profiles mirror changes in surface elevation and thus provide a way to study the critical zone between rock and soil. Science, this issue p. 534; see also p. 506 Geophysical survey data and stress modeling connect surface topography to Earth's critical zone. [Also see Perspective by Anderson] Bedrock fracture systems facilitate weathering, allowing fresh mineral surfaces to interact with corrosive waters and biota from Earth's surface, while simultaneously promoting drainage of chemically equilibrated fluids. We show that topographic perturbations to regional stress fields explain bedrock fracture distributions, as revealed by seismic velocity and electrical resistivity surveys from three landscapes. The base of the fracture-rich zone mirrors surface topography where the ratio of horizontal compressive tectonic stresses to near-surface gravitational stresses is relatively large, and it parallels the surface topography where the ratio is relatively small. Three-dimensional stress calculations predict these results, suggesting that tectonic stresses interact with topography to influence bedrock disaggregation, groundwater flow, chemical weathering, and the depth of the "critical zone" in which many biogeochemical processes occur.


Emotional neglect is one of the five sub-types of childhood mistreatment that has been classified by practitioners in the fields of psychology, psychiatry and education. The other four are sexual abuse, physical abuse, emotional abuse and physical neglect. Perhaps unsurprisingly, it is the least studied area from these five despite being commonly cited by research as being the most likely to occur. Contrary to what one might guess, numerous studies have in fact reported that emotional neglect can have an even greater negative impact upon individuals than the other types of mistreatment, particularly in regards to how individuals view themselves and their place in the world. Emotional neglect can broadly be defined as repeated and consistent caregiver-child interactions that are characterized by emotional unavailability, withdrawal, lack of reciprocity, disinterest or disengagement which lead to the child feeling that s/he is worthless, flawed, unloved, unwanted, endangered, or only of value in meeting another's needs. Previous research has published findings strongly associating childhood emotional neglect with a range of cognitive and behavioral outcomes including but not limited to; depression, anxiety, low self-compassion, shame, guilt, sexually risky behavior, self-destructive behavior, negative schemas, poor emotional regulation, Machiavellianism and so on. Given what we know in relation to the sheer importance of the interactions between primary caregivers and the child, namely by way of Bowlby's attachment theory, it is unsurprising to find that emotional neglect has many detrimental consequences. The reasons for emotional neglect can be numerous. One of the more common reasons behind it include it being passed on from generation to generation (as is also often the case with other types of abuse/neglect); indeed, social learning theory would support the idea that we take a lot of our parenting skills and styles directly from our own parents, even if we perceive them to be negative. Another source may be familial adversity, such as poverty, living within a conflict, or living during a time of persecution. Emotional neglect may also ensue due to the sickness of a sibling or parent, as the physically sick family member often can receive all attention and emotional capital of the family unit. Parental drug or alcohol abuse would place a child at risk of experiencing emotional neglect as would the seemingly more benign yet often just as threatening driven parental styles within which all love is contingent upon meeting pre-set academic or, later in life, professional goals. In the context of Qatar, it is also worth noting that emotional neglect often occurs within family units within which material wealth is abundant, however there is physical or psychological distance between the child and the primary caregiver, say due to a large number of siblings, half-siblings or maid/nursing staff being employed to take on child-rearing duties. Our emotional development, and being raised within a context in which we feel loved and cared for, is vital to the healthy development of the self. Accordingly, I have been looking at how emotional neglect impacts upon the self, that part of us that is believed to be the source of our consciousness and the core of our being. Two specific aspects of the self which I intend to include in my research are self-esteem and memory recall. Both of these areas have not been looked at in the context of emotional neglect research yet both may hold valuable findings that will then allow practitioners to be able to design interventions that will aide individuals in overcoming their emotional neglect. This will also be the first reported study that has used qualitative interviews to assess the impact of emotional neglect. This was also a key for me; through all the research I had reviewed, the emotion in emotional neglect was not being conveyed in the numbers and the statistics. Being a student of science though I know the value of these constructs and it was with both of these ideas in mind that I decided to use mixed methods for this doctorate study. This Ph.D. is currently being carried out by me at Queen's University Belfast, and is being supervised by, Dr Teresa Rushe.


A standard introduction to online learning might place Online Gradient Descent at its center and then proceed to develop generalizations and extensions like Online Mirror Descent and second-order methods. Here we explore the alternative approach of putting exponential weights (EW) first. We show that many standard methods and their regret bounds then follow as a special case by plugging in suitable surrogate losses and playing the EW posterior mean. For instance, we easily recover Online Gradient Descent by using EW with a Gaussian prior on linearized losses, and, more generally, all instances of Online Mirror Descent based on regular Bregman divergences also correspond to EW with a prior that depends on the mirror map. Furthermore, appropriate quadratic surrogate losses naturally give rise to Online Gradient Descent for strongly convex losses and to Online Newton Step. We further interpret several recent adaptive methods (iProd, Squint, and a variation of Coin Betting for experts) as a series of closely related reductions to exp-concave surrogate losses that are then handled by Exponential Weights. Finally, a benefit of our EW interpretation is that it opens up the possibility of sampling from the EW posterior distribution instead of playing the mean. As already observed by Bubeck and Eldan, this recovers the best-known rate in Online Bandit Linear Optimization.


Neonatal hypoxia-ischemia (HI) is a severe condition and defined as a period of insufficient blood gas exchange before, during or early after birth. It is one of the primary causes of neonatal mortality. In this thesis we study the contribution of apoptotic cell death and inflammation to the development of HI brain damage in neonatal rodent models.

In the first part of this thesis, we demonstrate the potent neuroprotective effects of three small peptides (D-JNKi, Sabkim1, TAT-P7-pi) that prevent mitochondrial outer membrane permeabilization after neonatal HI by targeting the MAP kinase c-Jun N-terminal kinase (JNK) and the tumor suppressor p53, two proteins that control the apoptotic balance at the mitochondrial membrane.

Inhibition of mitochondrial JNK activation by D-JNKi protected the neonatal brain after HI by preserving mitochondrial integrity and reducing apoptotic cell death. Upregulation of mitochondrial anti-apoptotic proteins was crucial for maintaining neuroprotection after D-JNKi treatment after the initial protective effects on mitochondrial integrity. The importance of mitochondrial JNK activation was further underlined by the fact that treatment with SabKIM1, a peptide that prevents JNK binding to the mitochondrial scaffold Sab, also protected the brain after HI. Furthermore JNK can induce apoptosis via phosphorylation of p53, which results in an increased stability and half-life of p53. We describe for the first time that treatment with TAT-P7-pi, a peptide that prevents binding of JNK to p53, resulted in a profound reduction in infarct volume and improvement in sensorimotor and cognitive function after neonatal HI. We emphasize the importance of early protection of the mitochondria to convey efficient long-term neuroprotection after neonatal HI.

In the second part of this thesis we focused on the role of inflammation in the development of neonatal HI brain damage. We demonstrate that neonatal HI induces an early cerebral inflammatory response with polarization of microglia/macrophages towards a pro-inflammatory M1 and later to anti-inflammatory M2 phenotype. Cerebral HI reduces the peripheral hepatic inflammatory response, except from a potent upregulation of hepatic CINC-1 expression.
Furthermore, we show that a systemic inflammation induced by LPS aggravates the severity of HI-induced brain damage. LPS-sensitized HI results in a gradual increase of neuronal damage, with strong effects on white matter integrity and an increased and prolonged cerebral inflammatory response. Systemic inflammation not only exacerbates HI-induced brain damage, but fundamentally changes some molecular pathways involved in the development of HI brain damage. When HI was preceded by LPS, cell death was mainly regulated via the extrinsic instead of the intrinsic apoptotic pathway. We further illustrate the clinical relevance of these changes by demonstrating that two important treatment strategies (D-JNKi and etanercept) in the neonatal HI model lose their neuroprotective effect when inflammation precedes HI. We emphasize that clinicians and scientists have to be aware of the fact that treatment strategies might not be effective or require modifications in therapeutic window, dose or combination of different treatments to achieve efficacious neuroprotection when neonates face a HI insult in combination with inflammation.


Like voters (the represented), politicians (the representees) are the heart and soul of representative democracy. But isnt being a politician just like any other job? After we get past the rhetoric, is politics any different than other occupations? In the political sector, voters, parties and politicians represent the counterparts of consumers, firms and workers/managers in the market sector. In fact, the analogy is much deeper than it may appear at first sight. In the market sector, consumers determine to a large extent the success of a firm and ultimately the managements fate. However, managers are chosen by the firms, which typically have an objective that is different from those of consumers and managers. Likewise, while in all democratic systems the voters ultimately determine who is elected, it is typically the case that political parties nominate candidates for public office. Furthermore, the objectives of voters and parties with respect to the selection of candidates may differ, and are constrained by the career ambitions of individuals with political aspirations. But then, what really makes a career in the political sector different from a career in any other economic sector? There are at least three distinctive features that characterize the labor market in the political sector. First, politicians are typically under the spotlight, receiving the attention of the media and of a variety of citizens organizations. This makes politics a showcase, where politicians in office can display their political skills, while it might be more difficult for individuals working in the market sector to reveal their market ability. Second, inter-party competition for potential politicians is likely to be of secondary importance, as ideological preferences are more likely to attract individuals toward specific parties at the beginning of their political careers. Third, it is often the case that political parties take care of their losers by reserving partys positions to defeated incumbents. As a result, while individual careers within the political sector are inevitably linked to the opportunities available within parties, the extent to which individual endowments of political and market skills are correlated, or experience in the political (market) sector is also valuable in the market (political) sector, links the labor markets of the two sectors. This link affects the selection of politicians, the politicians careers, and the relationship between parties and voters.


The study analyzes which forms opinion leadership takes in contemporary media environments where communication channels have increased and started to permeate interpersonal interaction. Some scholars assume that opinion leadership becomes more important under these conditions, as more media are available to enact it, and that more orientation is needed. Others argue that opinion leadership loses its importance as online media target audiences directly without interaction from opinion leaders. This study demonstrates that opinion leadership still exists in contemporary media environments. Using a cluster analysis of German online survey data, three clusters were identified that resemble communicative roles from earlier studies: Opinion Leaders, Followers, and Inactives. An additional fourth cluster, Mediatized Opinion Leaders, was also found. Individuals in this cluster exhibit the strongest and most diverse use of media and communication channels both for informing themselves and for communicating with followers.


Plants release volatiles induced by herbivore feeding that may affect the diversity and composition of plant-associated arthropod communities. However, the specificity and role of plant volatiles induced during the early phase of attack, i.e. egg deposition by herbivorous insects, and their consequences on insects of different trophic levels remain poorly explored. In olfactometer and wind tunnel set-ups, we investigated behavioural responses of a specialist cabbage butterfly (Pieris brassicae) and two of its parasitic wasps (Trichogramma brassicae and Cotesia glomerata) to volatiles of a wild crucifer (Brassica nigra) induced by oviposition of the specialist butterfly and an additional generalist moth (Mamestra brassicae). Gravid butterflies were repelled by volatiles from plants induced by cabbage white butterfly eggs, probably as a means of avoiding competition, whereas both parasitic wasp species were attracted. In contrast, volatiles from plants induced by eggs of the generalist moth did neither repel nor attract any of the tested community members. Analysis of the plant's volatile metabolomic profile by gas chromatography-mass spectrometry and the structure of the plant-egg interface by scanning electron microscopy confirmed that the plant responds differently to egg deposition by the two lepidopteran species. Our findings imply that prior to actual feeding damage, egg deposition can induce specific plant responses that significantly influence various members of higher trophic levels.


Abstract. Stable isotope ratios δ18O and δD in polar ice provide a wealth of information about past climate evolution. Snow-pit studies allow us to relate observed weather and climate conditions to the measured isotope variations in the snow. They therefore offer the possibility to test our understanding of how isotope signals are formed and stored in firn and ice. As δ18O and δD in the snowfall are strongly correlated to air temperature, isotopes in the near-surface snow are thought to record the seasonal cycle at a given site. Accordingly, the number of seasonal cycles observed over a given depth should depend on the accumulation rate of snow. However, snow-pit studies from different accumulation conditions in East Antarctica reported similar isotopic variability and comparable apparent cycles in the δ18O and δD profiles with typical wavelengths of  ∼  20 cm. These observations are unexpected as the accumulation rates strongly differ between the sites, ranging from 20 to 80 mm w. e.  yr−1 ( ∼  6–21 cm of snow per year). Various mechanisms have been proposed to explain the isotopic variations individually at each site; however, none of these are consistent with the similarity of the different profiles independent of the local accumulation conditions. Here, we systematically analyse the properties and origins of δ18O and δD variations in high-resolution firn profiles from eight East Antarctic sites. First, we confirm the suggested cycle length (mean distance between peaks) of  ∼  20 cm by counting the isotopic maxima. Spectral analysis further shows a strong similarity between the sites but indicates no dominant periodic features. Furthermore, the apparent cycle length increases with depth for most East Antarctic sites, which is inconsistent with burial and compression of a regular seasonal cycle. We show that these results can be explained by isotopic diffusion acting on a noise-dominated isotope signal. The firn diffusion length is rather stable across the Antarctic Plateau and thus leads to similar power spectral densities of the isotopic variations. This in turn implies a similar distance between isotopic maxima in the firn profiles. Our results explain a large set of observations discussed in the literature, providing a simple explanation for the interpretation of apparent cycles in shallow isotope records, without invoking complex mechanisms. Finally, the results underline previous suggestions that isotope signals in single ice cores from low-accumulation regions have a small signal-to-noise ratio and thus likely do not allow the reconstruction of interannual to decadal climate variations.


The parapharyngeal space is a virtual pyramidal space that extends from the skull base to the hyoid bone. There are numerous risk entities to cross the parapharyngeal space. It may be the site for primary tumors originating in the structures it contains, metastases or large tumors from adjacent structures. Parapharyngeal tumors are characterized by a nonspecific symptomatic pattern and should be evaluated by imaging investigations (CT, MRI). The main treatment is surgical and presents great complexity due to difficult access and the risk elements it contains.


Southeast Asia is the rising star of the global market, however, contrary to its impressive economic achievements, many countries in the region have suffered diverse social problems because of economic growth. Given that a key mechanism to hold businesses accountable is their disclosure practices, this study is looking to expand the understanding of the influences of institutional environment and corporate governance on Corporate Social Responsibility Disclosure (CSRD) in six Southeast Asian countries: Thailand, Singapore, Malaysia, Indonesia, Philippines and Vietnam. A multi-theoretical framework, including institutional theory, agency theory, stakeholder theory and legitimacy theory, was applied. For the purpose of this study, 2013 annual reports of 30 largest companies in the stock exchanges of the six countries were collected. The final sample consists of 171 companies.

Firstly, empirical findings of CSRD levels across the countries showed that Thailand has the highest level of disclosure, followed by Indonesia, Malaysia, Singapore, Philippines and finally Vietnam. There were significant differences between the extent of CSRD of the two countries with highest disclosure (Thailand and Indonesia) and the lowest disclosure group (Philippines and Vietnam). The findings are interesting in a sense that the levels of CSRD do not reflect the stages of economic development, and therefore, the differences in CSRD levels could be attributable to the impact of other institutional factors.

Secondly, in relation to internal determinants and based on the existing literature and the context of Southeast Asia, six corporate governance practices were identified to examine the impact of corporate governance on CSRD. The results of OLS regression supported the negative impact of block ownership and the positive impact of board size as well as the presence of CSR committee on CSRD. Contrary to the theoretical and empirical expectations, board gender diversity was found to have significantly negative relationship with CSRD, and board independence had no impact on CSRD. These differences could be explained by the context of the study where the presentation of women on board is very low and independent directors might not be wholly independent.

Thirdly, in order to examine the impact of the institutional environment on CSRD in a comprehensive way, institutional theory, the Scott's institutional framework (1995) and existing literature are used to identify relevant institutional factors that potentially influence CSRD. The effect of six institutional factors representing the three pillars, regulative (legal origin and mandatory disclosure), cultural-cognitive (uncertainty avoidance and masculinity cultural dimensions), and normative (the adoption of GRI standard and membership of CSR-related associations), were evaluated in this study. The empirical results indicate that mandatory disclosure, uncertainty avoidance dimension and the adoption of GRI standard have positive impact on CSRD, while the masculinity dimension has negative relationship with CSRD. The findings imply that institutional environment influences CSRD through all the three pillars with some institutional factors have greater impact than others.

The study, therefore, has contributed empirically to the existing literature by providing deeper insights into CSRD levels in Southeast Asia, identifying the effectiveness of corporate governance practices in emerging economies and the Asian context, particularly in relation to CSRD, including further examination of the role of diverse external determinants on CSRD. Theoretically, the study is one of a few that have attempted to quantify institutional environment into measurable institutional factors. These factors, hence, could be re-used in future research to advance understanding on the role of institutional environment in shaping a country's CSRD practice.


Discoveries of hominid, or apeman, fossils in the twentieth century have brought human evolution into the scientific spotlight. It is important that ages are assigned to such hominids so that their place in human evolution can be established. South African hominids are found in cave sites that are complex in terms of their stratigraphy.
Dating methods previously applied at the caves include faunal, palaeomagnetic, electron-spin resonance and cosmogenic isotope methods. These have been unable to give conclusive ages to the fossils. South African hominids are therefore poorly dated in comparison to their East African counterparts, which lie in volcanic deposits that are more simply stratified and more simply dated.

U-Pb dating is a radiogenic method proven to be applicable to carbonate deposits. More recently it has been applied to young speleothem deposits with sufficiently high concentrations of U and low levels of common Pb. In this study U-Pb dating is applied to speleothern deposits in stratigraphic context with the South African hominid fossils.

Samples were taken from the Silberberg Grotto at Sterkfontein. The hominid fossil, StW 573, was found here in 1998. Three layers of flowstone were sampled, two
from above the skeleton and one from below. The combined results indicate an age for StW 573 of ≈
2.2Ma. This is considerably younger than previous age estimates have inferred. Samples from three other caves were analysed - Kromdraai, Swartkrans and the Limeworks - but these did not produce reliable ages.

Within the samples both U and Pb were found to vary spatially over small scales in quantity, and Pb in composition too. Published studies in the area have revealed a major 234U excess in groundwater and speleothem. Where conventional age calculations are used this effect could result in an age much greater than the true age. After the sample analyses presented here, 234U excess analyses of some samples became available and these were used to calculate corrected ages. Variations in initial Pb composition introduced scatter on the age plots but this was
not investigated further here.

The results are presented firstly as maximum ages and following correction for 234U excess, as best estimates. The flowstone layers immediately above - layer 2C - and
below - layer 2B - StW 573 gave maximum abg es of 3.04 ± 0.08Ma (SK3 result) and 2.97 ± 0.13Ma respectively. Layer 2C was corrected for disequilibrium and gave a
best estimate age of 2.17 ± 0.17Ma using a weighted average of three results. The corrected age for Layer 2B was 2.24 + 0.09/ - 0.07.

There are important implications for the U-Pb age of StW 573. Firstly it provides evidence as to the age and formation of the Sterkfontein cave and therefore other hominid bearing caves with comparable faunal assemblages. The cave sediments exhibit complex stratigraphic relationships that render chronostratigraphy uncertain. More importantly it lends further information on how South African hominids fit into the family tree. At 2.2Ma StW 573 may come under the classification of Australopithecus africanus and be contemporaneous with the fossil Sts 5, also from Sterkfontein, which had previously been considered to postdate StW 573. It also confirms that the South African branch of this genus is probably not
as ancient as the East African and that these hominids were not widespread in Africa at 4Ma. With the first evidence for the genus Homo at 2.5Ma, StW 573 is unlikely to be a direct ancestor of modern humans.

Beyond their implications for human evolution, these results confirm the applicability of U-Pb dating to carbonates, and more specifically to young carbonates.


Abstract:This review article considers two lecture courses by Michel Foucault (1972–73, 1979–80) and two books relating to the whole series of lectures (1970–84) by Stuart Elden. Foucault's lecture courses can be divided into three phases, the first focused on the difference between sovereign and disciplinary power; the second on biopower, security, and liberalism; and the third on the government of the self and others. Foucault in 1976–79 altered his earlier frame by introducing the concept of governmentality and security dispositif and identified a missing, fourth type of power-governmentality called "socialism," around which his concerns revolved for the remaining courses. Today there is a new Foucault effect, which has arisen around the courses on governmentality, neoliberalism, and biopower. The two courses by Foucault are situated in relation to the complete set of courses, and Elden's books are welcomed critically as throwing light on the background to the lectures and Foucault's main publications in this period but are problematic with respect to Foucault's theoretical framework.


Published in 2011 as a crime sequel to Pride and Prejudice, Death Comes to Pemberley was adapted for BBC One and first aired on Christmas Day 2013. It subsequently aired on PBS in the United States in November 2014 and has had several re-runs on the British based free to view Drama channel. P.D. James, one of the most successful and revered British crime writers of the twentieth century, produced a worthy homage to her favourite writer (James 1999: 227), published in time to celebrate the two-hundred-year anniversary of Pride and Prejudice in 2013.

As a multi-genre sequel, P.D. James's novel mixes Austen's comedy of manners and love story with a crime caper and whodunit, police procedural and journalistic court reporting, infused with Gothic elements and fan fiction tributes. The result is a multi-authored fluid text that should be read in the context of authorship and genre polygamy, whereby both novels, together with their adaptations for television and cinema, co-exist and travel in multiple fields of meaning, defined by in-betweenness. Although the ensuing analysis will focus on Death Comes to Pemberley and its screen adaptation for the BBC, we will inevitably and simultaneously also refer implicitly or explicitly to Austen's work and its numerous television and film adaptations, thus offering a contextualised socio-historical approach.

Any text that has endured various adaptations, sequels, and mash-ups, can be considered a migrant on a journey of exile, resettlement, adaptation, and cultural translation, resulting in "contrapuntal"(Said 1994: 36) co-presences, multiple embodiments and shifting identities. It is therefore appropriate to use diasporic theory, as described in the following section, to better understand the text's journey of migration from one space to another, from page to screen and back again. Identities are shaped by departures and arrivals, emigration and immigration, and in-between experiences, and we borrow from the arsenal of diasporic theory concepts such as alienation-adaptation, journey-capital, multiplicity-hybridity, change, place polygamy, symbolic geography, homeness, trauma, and memory. These concepts expand on already existing theories in adaptation studies, such as Stam (2005), Hutcheon (2006), and Sanders (2006), who examine hybridity and transtextuality through authors from Bakhtin to Kristeva and Deleuze to Genette. However, while these approaches still put the text at the centre of a mainly literary analysis, diasporic concepts offer new tools for a socio-historical analysis and a sociology of adaptation, which is a more fitting method of investigating identity, change, and multiplicity.


This report reviews Argentina's financial crisis, the bond exchanges of 2005 and 2010, ongoing litigation, prospects for a final solution, related U.S. legislation, and broader policy issues. These include lessons on the effectiveness and cost of Argentina's default strategy, the ability to force sovereigns to meet their debt obligations, and ways to avoid future defaults like Argentina's.


This work looks at the consequences of the development of information technology and the information society for consumers and for consumer law. While the new technological environment has been greeted with enthusiasm by many, citing the improvement in consumer choice, convenience, and the accessibility of information, there have also been calls to focus on the needs of those consumers who cannot easily gain access to the benefits associated with the new technology. This collection of papers examines developments in consumer protection legislation around the world in response to the technological advances, and focuses on issues such as electronic marketing, electronic commerce, financial services, product liability, intellectual property and rights of access to information. Issues such as how and to what extent the new environment should be regulated, as well as the impact of changes in the globalized information market, are also discussed. This volume arose from the 7th International Consumer Law Conference, held in Helsinki in 1999 under the auspices of the International Association for Consumer Law.


The vast differences in summer learning activities among children present a substantial challenge to providing equal educational opportunity in the United States. Most initiatives aimed at reversing summer learning loss focus on school- or center-based programs. This study explores the potential of enabling parents to provide literacy development opportunities at home as a low-cost alternative. We conduct a randomized field trial of a summer text-messaging pilot program for parents focused on promoting literacy skills among first through fourth graders. We find positive effects on reading comprehension among third and fourth graders, with effect sizes of .21 to .29 standard deviations, but no effects for first and second graders. Texts also increased attendance at parent-teacher conferences but not at other school-related activities. Evidence to inform future efforts to reverse summer learning loss is provided by parents' responses to a follow-up survey.


A significant amount of research has been done in the area of understanding how people use technology in the workplace. Included in this research is how social and technical systems of an organization interact and influence one another. Previous work in both Management of Information Systems and Computer Supported Cooperative Work show how the interaction between the social and technical systems of a workplace can lead to new technology uses and requirements, as well as adoption issues like resistance. One area that has not been extensively studied is how organizations select technologies to begin with. To understand how an organization makes a choice on technology, one has to investigate the underlying organizational decision-making processes. The subject of this research is a case study of a government IT project. Data on the decision-making that led to the selection of the IT solution is gathered through elite and specialized interviews of government officials who were involved in the selection. The data collected in the case study supports three conclusions about decision-making for organizational systems: 1.) sociopolitical dynamics constrain the design space, 2.) emergent requirements are likely and 3) organizational systems can have different levels of stakeholders and the levels reflect the power structure within the organization. Finally, general guidelines for conducting decision-making analysis are provided so that data from decision-making activities of other organizations can be collected and analyzed by researchers and practitioners.


We show how to generate "really hard" random instances for subgraph isomorphism problems. For the non-induced variant, we predict and observe a phase transition between satisfiable and unsatisfiable instances, with a corresponding complexity peak seen in three different solvers. For the induced variant, much richer behaviour is observed, and constrainedness gives a better measure of difficulty than does proximity to a phase transition. We also discuss variable and value ordering heuristics, and their relationship to the expected number of solutions.


Received: 27 October 2010 Revised: 27 November 2010 Accepted 02 December 2010 Abstract The purpose of this study was to examine the effect of certain variables chosen (gender, financial state of the family, educational background of the parents, a computer available for use at home and the number of siblings) and technology-supported project-based learning approach applied in the physics course on 11-grade students' attitudes towards computers and to evaluate the participating students' views at the end of the study about the applications they actively took part in. In order to determine the students' attitudes towards computers, the computer attitude scale was used. The study was carried out with thirty two 11-grade students in the academic year of 2009-2010. Before starting the applications, the computer attitude scale was applied to the students as a pre-test. The three-hour physics courses were executed with simulations and animations in two course-hours and with the project-based learning approach in the other course-hour. At the end of the applications, the computer attitude scale was applied to the students as a post-test. In order to determine the students' views about the process as well as about computers, semi-structured interviews were held with them. The results of the analysis demonstrated that there was a significant difference between the computer attitude mean scores of the students before and after the experimental process in favor of the post-test mean scores. But, there were no differences among their attitude scores according to certain variables. The interviews held with the students revealed that the students had positive views about the process and computers.


Geographic Information Systems (GIS) can assist in using information from census data to investigate questions for national and local government planning purposes, such as socio-economic profiles and needs of communities. I will be doing this on the data from the Ethiopian census, scheduled for 2006. . As no Ethiopian geo-referenced data is available at this stage. I am using the 10% sample of the South African Census 2001 data for KwaZulu-Natal (KZN), as a hypothetical population. KZN was chosen as this provides a setting with urban and rural populations, as well as mountainous and flat areas, and so is in some ways similar to Ethiopia. The questions to be asked of the Ethiopian census data are of the form: • What exists at a specific location or in a specific area? (eg what health facilities are there, what is the population)? • What access does the population have to facilities in the area? Does the road network need to be improved to resolve the problem of access • Where are groups of people in greatest need of ... (eg where are there clusters of people with disabilities, and are there facilities for them) • What are the characteristics of ... (eg female headed households) and what are these related to (eg HIV/AIDS or migrant labour?) • What changes need to be made to infrastructure to increase service to communities in need? The results for the hypothetical population show that there are areas with high unemployment rates, low school attendance and education levels, high levels of female headed household, and difficulties of access to educational and health facilities. Many households do not have toilet facilities, and obtain water from rivers, which could impact on the health of the communities. Migrant workers were investigated to see if these were likely to be migrants from neighbouring countries, or from other provinces. The numbers in the hypothetical population in these cases are small, so little can be concluded from this.


Many Natural Language Processing (NLP) techniques have been applied in the field of Question Answering (QA) for understanding natural language queries. Practical QA systems classify a natural language query into vertical domains, and determine whether it is similar to a question with known or latent answers. Current mobile personal assistant applications process queries, recognized from voice input or translated from cross-lingual queries. Theoretically speaking, all these problems rely on an intuitive notion of semantic distance. However, it is neither definable nor computable. Many studies attempt to approximate such a semantic distance in heuristic ways, for instance, distances based on synonym dictionaries. In this paper, we propose a unified algorithm to approximate the semantic distance by a well-defined information distance theory. The algorithm depends on a pre-constructed data structure semantic clusters, which is built from 35 million question-answer pairs automatically. From the semantic measurement of questions, we implement two practical NLP systems, including a question classifier and a translation corrector. Then a series of comparison experiments have been conducted on both implementations. Experimental results demonstrate that our distance based approach produces fewer errors in classification, compared with other academic works. Also, our translation correction system achieves significant improvements on the Google translation results.