This article focuses on the narrow "strike zone" that plaintiffs must overcome in private securities actions instituted in the Fourth Circuit. Based on empirical data generated over a fourteen-year span, there emerges a clear finding that during that time period defendants were victorious in almost all cases, either on the merits of the case or due to procedural obstacles. The authors posit that this pattern of difficulty for plaintiffs arises, at least in part, from the Fourth Circuit's restrictive interpretation of various requisite elements of these causes of action, such as materiality and scienter, as well as the Fourth Circuit's approach to the pleading standards mandated by the PSLRA and the Federal Rules of Civil Procedure. The authors examine in detail some of the leading securities cases that establish Fourth Circuit precedent in these areas, as well as notable cases from the survey period, to illustrate the confines of the narrow "strike zone" available to plaintiffs to establish a meritorious claim.


As humans we constantly develop theories and methods in order to change and improve our way of working or to find better ways of conducting design work. This thesis is about this strive.The design process of particular interest in this thesis is system design, in the sense of design of computer applications. One major line of reasoning is that the rationality of design work underlying today's system design methods does not reflect the rationality in practice. If a design method is to be accepted by practitioners, it has to reflect a rationality related to the rationality familiar to the practitioners.A comparison is made between different kinds of design processes: the research process, the engineering process and the artistic process, in order to discuss the possibility of a generic design process. One conclusion is that there is no such thing as the "natural" or "given" design process.An outline of an ideal-oriented design theory is presented. The purpose is to make design practice understandable and to reveal the hidden rationale of design work. A rationale must be seen as the sum of at least three different forms of knowledge: reason, aesthetics and ethics, where aesthetics is the ability to judge (the aesthetical-practical form of knowledge). Today "reason" (in the sense of pure empirical-theoretical knowledge) is the dominant form of knowledge in system design methods, This leads to a view of design as problem solving and as "fixing a malfunctioning reality". The design process should instead be viewed as a creative way to design a new reality. In order to discuss this ideal-oriented theory, the concepts of vision, operative image, thought figure, design situation, and intuition are introduced.Some aspects of the design process emerge as particularly important. There is a shift of attention from problem oriented design to ideal oriented, from functionally oriented to aesthetically oriented, from depictive to creative. There is also a shift in the way we view designed artifacts. The artifact is to be seen as a social actor. The design process is a way to invent and establish the space of possible actions. To design is to create a social environment.As a result, the meaning of the concept "method" also changes. The purpose of a design method should be to develop the designers' design ability and to create readiness to act, not to guide the designers in a specific design situation. There is an elaborate discussion of what may constitute the design ability and of how a designer should a a and think in order to improve his design ability.The results of an interview study with twenty system designers are presented. The study shows that if we want to understand the hidden rationale of design practice, it is both meaningful and useful to view the system design practice as ideal-oriented design.The results of the interviews are formulated as a question: How would and could the methodology and practice of system design change if it were based on an ideal-oriented design theory? Some areas where further work and development ought to be done are presented.


SIR,-Mr. A. McWilliam (19 August, p. 489) gives a general report on the advantages of the quinquennial grant system of financing universities. It is often implied that this system might be used with advantage in the National Health Service. Comparatively few people, however, have first-hand experience of the application of both the annual and quinquennial systems. The fact that the two methods have existed for 19 years side by side in teaching hospitals and medical schools may be held to indicate that neither system is wholly satisfactory. In this period if one system had no disadvantage it would have displaced the other. What are the disadvantages of the quinquennial grant system ? I think there are none in an economy in which there is no monetary depreciation. The difficulties arise when there is inflation. Mr. McWilliam says, "The quinquennial block grant, without any supplementation except for proved increased costs (and by no means all of these), is both an incentive to economy and a firm basis for forward planning." The unfortunate fact is that, apart from academic salary increases and the rates on property paid to the local authority, there is no significant supplementation throughout the quinquennium. In any recent five-year period rises in wages and non-academic salaries, particularly of technicians, which have not been reimbursed, have severely hampered planned development. Most of the medical schools in London have ended up quinquennia with considerable deficits, which rightly have been carried over as a first charge on subsequent grants. The development of medical teaching and research is now so rapid and costs rise so unpredictably that five years is too long a period for medical schools or the University Grants Committee to make realistic financial forecasts of recurrent expenditure. The alternative need not be an annual grant, something in between may well be about right.I am, etc.,


Citizen science (CS) has been an increasingly utilized means by which scientists leverage members of the public to increase the amount of data collected and analyzed. However, the underrepresentation of individuals from certain socio-cultural groups can have consequences that can manifest in the scientific outcomes of those CS projects such as biases in the data. Additionally, this underrepresentation can potentially affect long-term viability and support of CS as a community of practice. CS programs that promote greater inclusivity would likely provide opportunities for communities to define, investigate, and address pressing issues in collaboration with professional scientists. In this paper we discuss a CS project that sought to include underrepresented communities in Baltimore, Maryland using Pandya's framework for inclusive CS. While the project met all of its scientific research goals, translating the CS for broader social outcomes in the community proved challenging. Here we highlight perspectives from local community members and research personnel about the barriers to CS engagement, challenges in translating scientific outcomes to social justice efforts, and opportunities to address these barriers in CS program development and design.


Concerning life insurance, penetration rate is one of the main goal of every developed insurance industry. In this sense systematic marketing is a significant component in strategic plan of insurance companies. To achieve the goal insurers need to group their client into different groups in which some common features are shared and people demonstrate a similar pattern. This paper utilizes K-means clustering as an unsupervised learning algorithm in order to divide customers into number of clusters. The clusters are constructed based on two independent variables namely; car and life insurance premiums. Then the descriptive statistics of other determining features are provided with which the most willing group in purchasing life insurance is presented.


Self-driving cars are soon to become a reality to the commercial market. A self-driving car does not have a human operator, which enables some interesting characteristics. The main benefits are considered to be:The number of accidents and traffic jams should be reduced.Enhanced comfort.Energy usage could be decreased while capacity could be increased.This study concerns the causes for improved energy efficiency. The reason for improved energy efficiency is mainly because of the variation in terms of acceleration, braking and distance holding are reduced. The vehicles are more intelligent and can work together as a unity. There are reasons to believe that self-driving cars will first operate in highway conditions. The study has therefore tried to estimate what the potential benefits could be in terms of energy usage and capacity when comparing two sets of traffic flows in such an environment. One set of traffic flow was symbolized by self-driving cars, and one set was composed by conventional vehicles. With the settings and conditions defining the simulations in this study one can expect positive effects in both in energy usage and capacity with a traffic flow symbolized by self-driving cars. When comparing the two sets, with an increasing traffic flow from non-congestion up to congestion, the results showed energy savings around 10 percent with self-driving cars.


Cognitive processes relies on language skills and one component of language is
semantics and semantics is thought to be the knowledge about the universe and thought to be
represented in tempero-parietal areas in brain and damage to this area results in semantics deficits
exhibited in form of naming deficits.In recent years, case studies of brain-injured patients have
demonstrated selective impairments in naming objects in specific categories and through specific
modalities. Although many studies have provided evidences of category specific and modality
specific naming impairments, such deficits are rarely reported in our clinical settings. The paper
attempts to highlight a case who did not reveal any apparent deficits in linguistic skills when
examined with Western Aphasia Battery (WAB) except minor difficulties in naming visually
presented objects. The errors seen in the present patient is in visual perceptual level and in semantic
processing level, and the errors are not homogenous. Visuo-verbal disconnection can be a type of
modality specific naming impairment which is seen in the present patient. It was proposed that the
inability to name the visually presented objects reflects a disconnection between the right
hemisphere's semantic system which supports performance of nonverbal semantic tasks and the left
hemisphere system which is required for naming. So the visual semantics and the verbal semantics
can be thought as partially specialized sub regions within a general frame work. As these subjects
have intact ability to name through other modalities, it is important to identify them by assessing their
ability to gesture the visually presented object.
The scientific literature is rich of various types of dissociations of linguistic knowledge such as
category specific and modality specific impairments. Furthermore, within the category specific
impairments, researchers have identified various dichotomies, affecting certain types of categories
and sparing the rest. There are many studies which discuss about the existence of modality specific
and the category specific impairment in naming. The existence of category specific and modality
specific naming deficits leads to the assumption that there is a multiple cognitive representation in the
brain and the assumption of unitary semantics in brain need to be questioned.


A gamma-ECS cDNA from Medicago truncatula was isolated using an Arabidopsis thaliana cDNA as probe. The analysis of the amino acid sequence deduced from this cDNA revealed 80% identity with the gamma-ECS from A. thaliana and Brassica juncea and suggested a plastidial localisation for the enzyme. Gamma-ECS activity and high level of GSH were detected in the gamma-ECS-deficient E. coli strain expressing a fusion protein containing the M. truncatula gamma-ECS protein. Southern blot analysis suggests that gamma-ECS is encoded by a small multigenic family in M. truncatula and shows that homologous genes are present in two other leguminous plants, Medicago sativa and Pisum sativum. Gamma-ECS gene expression was analysed by Northern blot in seedlings, plantlets and mature plants.


Real world datasets often contain entries with missing elements e.g. in a medical dataset, a patient is unlikely to have taken all possible diagnostic tests. Variational Autoencoders (VAEs) are popular generative models often used for unsupervised learning. Despite their widespread use it is unclear how best to apply VAEs to datasets with missing data. We develop a novel latent variable model of a corruption process which generates missing data, and derive a corresponding tractable evidence lower bound (ELBO). Our model is straightforward to implement, can handle both missing completely at random (MCAR) and missing not at random (MNAR) data, scales to high dimensional inputs and gives both the VAE encoder and decoder principled access to indicator variables for whether a data element is missing or not. On the MNIST and SVHN datasets we demonstrate improved marginal log-likelihood of observed data and better missing data imputation, compared to existing approaches.


An objective of wheat (Triticum aestivum L.) breeding and seed purification programs is to develop uniform cultivars. However, lack of uniformity may occur due to outcrossing, mechanical mixtures, or aneuploidy. We were interested in the prevalence of aneuploidy resulting in tall off-types in semidwarf wheat cultivars. Rht1 and Rht2 are the most common height-reducing genes deployed, and reside on chromosomes 4B and 4D, respectively. In this study, tall off-types were selected from 11 cultivars representing Rht1 and Rht2 genotypes. The chromosomal constitution of the tall off-types were determined based on phenotypic and cytogenetic analysis of offspring. Six cultivars with Rht1 genotypes produced an average frequency of 0.15% monosomic 4B plants that averaged from 16 to 22% taller than the height of euploid plants. Five cultivars with Rht2 genotypes produced an average frequency of 0.06% monosomic 4D plants that averaged 12 to 18% taller than the height of euploid plants. Our results indicate that tall off-types resulting from monosomic 4B and 4D conditions occur in several semidwarf cultivars. However, the frequency and phenotypic effect are greater in semidwarf cultivars with Rhtl. Thus, use of Rht2 to cause semidwarf habit may help minimize the problem of tall off-types.


At the heart of this book is a belief that poetry matters, and that it enables us to enjoy and understand life. In this accessible guide, Andrew Hodgson equips the reader for the challenging and rewarding experience of unlocking poetry, considering the key questions about language, technique, feeling and subject matter which illuminate what a poem has to say. In a lucid and sympathetic manner, he considers a diverse range of poets writing in English to demonstrate how their work enlarges our perception of ourselves and our world. The process of independent research is modeled step-by-step, as the guide shows where to start, how to develop ideas, and how to draw conclusions. Providing guidance on how to plan, organise and write essays, close readings and commentaries, from initial annotation to final editing, this book will provide you with the confidence to discover and express your own personal response to poetry.


Recently, various kinds of planetary explorations have become more feasible, taking the advantage of low thrust propulsion means such as ion engines that have come into practical use. The field of space activity has now been expanded even to the rim of the outer solar system. In this context, the Japan Aerospace Exploration Agency (JAXA) has started investigating a Deep Space Port built at the L2 Lagrange point in the Sun-Earth system. For the purpose of making the deep space port practically useful, there is a need to establish a method to making spaceship depart and return from/to the port. This paper first discusses the escape maneuvers originating from the L2 point under the restricted three-body problem. Impulsive maneuvers from the L2 point are extensively studied here, and using the results, optimal low-thrust escape strategies are synthesized. Furthermore, this paper proposes the optimal escape and acceleration maneuvers schemes using Electric Delta-V Earth Gravity Assist (EDVEGA) technique


Methods for regular monitoring of care and services are needed for psychiatrists to act on, to refine practice. We developed a computer-based instrument to be used by staff working with schizophrenic patients. The instrument was tested in a group of patients randomly assigned to an integrated-care program. Data on time, place, direct/indirect contacts, and the main elements of the content of care were regularly recorded on a pocket computer and later transferred to a desktop computer for analysis. One-year data on 24 subjects are presented on three levels: individual, case load, and total patient population. Of the encounters 66% were individual patient contacts. Staff spent 59% of the time at patients' homes. A computer-aided system with built-in information on care delivery, program fidelity, and outcome can be the basis of decision-making on different health-management levels.


Local adaptation of the World Health Organisation (WHO) Farnham approach to managing pathogen risk in recreational waters was readily achieved given the extensive microbiological beach data for Sydney, and a clear understanding of applying the 'Annapolis Protocol' sanitary survey component to beach classification. Daily enterococci counts were predicted by rainfall (>10 mm in 24 h or >5 mm over 4-5 days), or by wind direction/speed, sunlight and tide during dry periods. Quantitative microbial risk assessment models (maximum risk exponential model for gastroenteritis and adenovirus exponential model for respiratory illness) fitted the United Kingdom epidemiological data and show potential for use. Flexibility in interpreting what is important for local conditions is essential, illustrated by replacing the general descriptions in the Farnham report with more ridged values for stormwater-impacted beaches. Hence, a user-friendly format for bather risk management, based on key environmental predictors of faecal pollution (such as rainfall, wind direction and tide) should largely replace the need for regular and costly microbiological testing; providing risk estimates in real time and allowing immediate control measures, such as signage or temporary beach closures. Ongoing testing resources should be directed to understanding the source(s) of faecal contamination, comparing enterococci/enteric virus survival under warm Australian conditions and spot checks for recalibration of environmental factors.


In the traditional designs of milling cutter, we cannot get the required accuracy of machining as there may be local deformation on the edges, even more the cutter can break down. Aiming at this situation, a finite-element model of straight pin milling cutter with helical tooth are built using Marc, a nonlinear finite-element analysis software, the different cutting forces of the milling cutter during the cutting process are analyzed and the cutting forces of the milling cutter at different parameters are studied. We get the stress, the strain and the temperature distribution of the milling cutter in different situation. Our work offer a theoretical basis of improving stress of the cutter, designing the structure of cutters reasonably and analyzing the cutter failure as well as a new method of analysis and calculation of the cutter life and strength.


Volume kinetics is a method used for analyzing and simulating the distribution and elimination of infusion fluids. Approximately 50 studies describe the disposition of 0.9% saline, acetated and lactated Ringer's solution, based on repeated measurements of the hemoglobin concentration and (sometimes) the urinary excretion. The slow distribution to the peripheral compartment results in a 50–75% larger plasma dilution during an infusion of crystalloid fluid than would be expected if distribution had been immediate. A drop in the arterial pressure during induction of anesthesia reduces the rate of distribution even further. The renal clearance of the infused fluid during surgery is only 10–20% when compared with that in conscious volunteers. Some of this temporary decrease can be attributed to the anesthesia and probably also to preoperative psychologic stress or dehydration. Crystalloid fluid might be allocated to "nonfunctional" fluid spaces in which it is unavailable for excretion. This amounts to approximately 20–25% during minor (thyroid) surgery.


Despite the growing acceptance of left ventricular assist device (LVAD) therapy to improve survival and quality of life in heart failure (HF) patients, uncertainties persist regarding the definition of a successful implant. We sought to define an innovative approach to assess success and subsequently compare preoperative variables affecting outcomes. From January 2007 to 2015, 278 patients underwent LVAD implantation. Median age at implant was 62 years and 81% patients were males. Indication for support was bridge-to-transplantation in 36% patients and the etiology of HF was ischemic in 49% patients. Based on clinically relevant and accepted standards, we defined successful LVAD implant as someone who was alive or transplanted at 2 years, had two or less readmissions in the first year, had no major adverse events in the first year, and had a New York Heart Association class of ≤ II at 6 months. Follow-up was obtained for a median of 1.7 years for a total of 605 patient-years-of-support. Based on our criteria, 81/278 (29%) patients were defined as having a successful implant. Univariate predictors of LVAD failure included destination therapy indication (hazard ratio [HR] = 2.11 [1.24, 3.58]), ischemic cardiomyopathy (HR = 1.73 [1.02, 2.94]), and a higher left ventricular ejection fraction (HR = 1.54 [1.07, 2.22]). After multivariable analysis, only destination therapy indication (HR = 2.2 [1.28, 3.78]) was found to be independently predictive of success failure. Despite an overall trend toward improved outcomes on device therapy, our criteria classified only one-third of patients as successful. Continued improvements in AE profiles, appropriate patient selection, and optimal time of implantation, together hold the key to improve outcomes after LVAD therapy.


Background: There is an emerging body of evidence that supports the potential clinical value of left ventricular (LV) intracavity blood flow kinetic energy (KE) assessment using four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR). The aim of this systematic review is to summarize studies evaluating LV intracavity blood flow KE quantification methods and its potential clinical significance. Methods: A systematic review search was carried out on Medline, Pubmed, EMBASE and CINAHL. Results: Of the 677 articles screened, 16 studies met eligibility. These included six (37%) studies on LV diastolic function, another six (37%) studies on heart failure or cardiomyopathies, three (19%) studies on ischemic heart disease or myocardial infarction and finally, one (6%) study on valvular heart disease, namely, mitral regurgitation. One of the main strengths identified by these studies is high reproducibility of LV blood flow KE hemodynamic assessment (mean coefficient of variability = 6 ±  2%) for the evaluation of LV diastolic function. Conclusions: The evidence gathered in this systematic review suggests that LV blood flow KE has great promise for LV hemodynamic assessment. Studies showed increased diagnostic confidence at no cost of additional time. Results were highly reproducible with low intraobserver variability.


The Solar Occultation in the Infrared (SOIR) channel mounted on top of the SPICAV instrument of the ESA's Venus Express mission has observed the atmosphere of Venus during more than eight years. This IR spectrometer (2.2-4.3 μm) with a high spectral resolution (0.12 cm-1) combined an echelle grating with an acousto-optic tunable filter for order selection. SOIR performed more than 1500 solar occultation measurements leading to about two millions spectra.
The Royal Belgian Institute for Space Aeronomy (BIRA-IASB) was in charge of SOIR's development and opera- tions as well as its data pipeline. BIRA-IASB carried out several studies on the composition of Venus mesosphere and lower thermosphere: carbon dioxide, carbon monoxide, hydrogen halide (HF, HCl, DF, DCl), sulfur dioxide, water (H2O, HDO) as well as sulphuric acid aerosols in the upper haze of Venus. Density and temperature profiles of the upper atmosphere of Venus (60 km to 170 km) at the terminator have been retrieved from SOIR's spectra using different assumptions, wherein the hydrostatic equilibrium and the local thermodynamical equilibrium in the radiative transfer calculations. These results allow us to produce an Atmospheric model of Venus called Venus Atmosphere from SOIR measurements at the Terminator (VAST). Data obtained by SOIR will also contribute to update the Venus International Reference Atmosphere (VIRA).
Recently, the treatment of the raw data to transmittance has been optimized, and a new dataset of spectra has been produced. All raw spectra (PSA level 2) as well as calibrated spectra (PSA level 3) have been delivered to ESA's Planetary Science Archive (PDSPSA). Consequently the re-analysis of all spectra has been undergone.
We will briefly present the improvements implemented in the data pipeline. We will also show a compilation of results obtained by the instrument considering the complete mission duration.


Though often proclaimed a woman s writer, Margaret Drabble is ultimately concerned with larger philosophical and psychological issues the most important being the question of the human will. Moran sees Drabble s fiction as being focused more on the problems which confront both men and women, of living in the bewildering contemporary world. It is a world of IRA terrorism, aborted fetuses, and suicide, but it is also a world of homecoming parties, homebaked bread, and waterfalls. It is a world where in spite of the fact that a human being is a tiny, powerless speck in a turbulent, menacing universe, there are redeeming qualities to the position. There is both beauty and humor in the condition of being human. Drabble s novels hold up for our admiration people who perceive these qualities of life in spite of its prevailing gloom. For Drabble, the psychological and physical connections of family provide both spiritual and psychological solace. Although the family curtails individual freedom, by influencing one s character and imposing familial responsibilities, it is ultimately a bulwark against life s turbulence and uncertainties. "


The authors treat esotropia by simultaneous horizontal and cyclo-vertical surgery. Horizontal surgery consists of recession of both medial rectus muscles and cyclo-vertical surgery of desagittalization of the oblique muscles combined, if necessary, with a weakening of a vertical rectus muscles. Techniques and indications of this surgery are discussed and analysis made of the results of 785 cases treated with 960 operations. According to this analysis the surgical indications are adapted to this procedure.


A new composite material of ultrafine Ag/PW11O39-doped AgCl nanoparticles (NPs) encapsulated in a metal–organic framework (NH2-MIL-101(Al)) was prepared by an incipient wetness impregnation method together with photo-reduction under UV irradiation. The as-prepared composite material (abbr. Ag/POM-AgCl@NH2-MIL-101(Al)) was characterized by XRD, EDX, SEM, XPS, FT-IR and diffuse reflectance spectroscopy (DRS). By virtue of the coordination interaction between the polyoxometalate (POM) unit and Ag+ ion in the K6[α-AgPW11O39] precursor and the confined cavity of NH2-MIL-101(Al), the fast reaction between Ag+ and Cl− ions was depressed and the over agglomeration of crystalline AgCl was limited. When the partial Ag+ ions were reduced into Ag0 metal in the AgCl NPs under UV irradiation, the resultant ultrafine Ag/POM-AgCl nanoparticles (NPs) possess an average particle size of 3.2 nm in diameter, representing one of the currently smallest Ag/AgCl composite NPs. The catalytic activity of this material was evaluated by the catalytic reduction of 4-nitrophenol and photocatalytic degradation of Rhodamine B (RhB) under visible light irradiation. Compared with its counterparts (Ag/AgCl NPs@NH2-MIL-101(Al)), the introduction of POM units into the Ag/AgCl composite NPs significantly improved the photocatalytic activity for degradation of RhB under visible light irradiation. A relevant photocatalytic mechanism was proposed.


Vorperian's pulsewidth modulation (PWM) switch model consists of a PWM transformer and a nonlinear resistor. The recognition that any of the three transformer terminals can serve as the common terminal leads to two alternate PWM transformer models and the corresponding two alternate PWM switch models. For a given PWM dc-dc converter, one of the three PWM switch models is more "natural" for graphic-oriented analysis/design, e.g., it allows the idealized converter to be analyzed by inspection. Furthermore, all three PWM transformers may be used to graphically manipulate the converter circuit to a form that can be analyzed by inspection. The alternate forms of the PWM transformers and the PWM switch models are effective as graphic-oriented teaching and learning tools for PWM converters. This is demonstrated using examples based on the boost converter and the Cuk converter.


Case–control studies of childhood cancer and foetal exposure to diagnostic x-rays suggest that doses as small as 10 mSv increase the risk of cancer to a detectable extent. A comparison of the risk coefficient derived from the largest such study with that obtained from the Japanese atomic bomb survivors irradiated in utero (average dose, ∼ 300 mGy) shows that, once all sources of uncertainty are taken into account, these risk estimates are not incompatible. The absence of a discernible variation in the risk per unit dose over this dose range is consistent with a linear dose–response. However, uncertainties are such that definitive conclusions on the shape of the dose–response at low doses cannot be drawn from this epidemiological evidence alone. Nonetheless, the evidence does suggest that the risk is not zero at doses of the order of 10 mSv.


The Agrobacterium tumefaciens Ti plasmid virulence (vir) region contains at least six transcriptional units required for the efficient transfer of T-DNA to the plant genome (virA, B, C, D, E, and G). We have reported that two proteins encoded by the 5'portion of the virD operon are required for a site-specific endonuclease activity that nicks the direct repeats which flank the T-DNA. We have presented the nucleotide sequence for this portion of the operon. The nucleotide sequence of the remainder of the virD operon essential for virulence has now been determined. Two additional open reading frames encode proteins of 21.3 and 75.8 kilodaltons (kd). Translational fusions between virD2, virD3, and virD4 proteins and trpE produced fusion proteins of the size predicted from the nucleotide sequence data. We have used antisera directed against the trpE-virD2 fusion protein to detect both native virD2 protein and a virD2-lacZ fusion protein in crude extracts from Agrobacterium.


The presence of herbicide-resistant Lolium rigidum in Mediterranean (Spanish) citrus orchards
was reported in 2005 and it poses a serious threat to crop management. The main objective
of this research was to investigate which components could be responsible for the persistence
of annual ryegrass populations in Mediterranean mandarin and orange orchards. This is the first
study regarding L. rigidum populations in Mediterranean citrus orchards. Surveys were con-
ducted in 55 commercial citrus orchards in eastern Spain in 2013 by interviewing technicians
who were working in cooperatives about crop management. The level of infestation by
L. rigidum and the presence of harvester ants (Messor barbarus) then were estimated in the same
orchards. The variables were subjected to a two-dimensional analysis and both univariate and
multivariate logistic regression models were fitted for each of the three L. rigidum density levels
that had been established. The multivariate models showed the significant factors that were
associated with various L. rigidum densities: (i) at a low density, the herbicides that were
applied, the number of applications in 2013 and the type of irrigation (flood or drip); (ii) at a
medium density, the presence of harvester ants; and (iii) at a high density, the herbicides that
were applied in 2013. The results indicated that drip irrigation and one application of
glyphosate mixed with other herbicides (or herbicides other than glyphosate) were associated
with a lower L. rigidum density. The alternative management options that are presented here
should help farmers to reduce weed problems in Mediterranean citrus orchards. Future
research is required to better understand the presence of herbicide-resistant populations, as
well as the possible beneficial presence of granivorous ant species.


This paper proposes a structure and two strategies for hybridization of a RAT (Ram Air Turbine) with supercapacitor storage. The structure consists in coupling a High Voltage DC (HVDC) source (RAT) with a low voltage storage device through a specific topology of bidirectional DC-DC static converter. The energy management strategies consists in entrusting the storage with the "high frequency" harmonics of the load power while the RAT only produces the average power: the RAT sizing and its mass can then be reduced. Lab test bench architecture, control strategy, topology of the converter and experimental results are presented in this paper.


Purpose: Transgender individuals experience barriers accessing primary care. In Ontario, primary care is delivered through a variety of delivery models. Literature supports team delivery of primary care for transgender individuals, yet little is known about care delivery in Ontario and the role of primary care teams. We intend to explore how primary care for transgender individuals is delivered within the different primary care models in Ontario and the roles primary care team members enact in care delivery, barriers, enablers, and clinical competence of practitioners in delivering transgender care. Methods: Case study methodology was used to compare transgender care across three Ontario primary care models. Key informants identified cases known to provide transgender care for case selection. Qualitative interviews were conducted. Documentary evidence and field notes were collected. Results: Practitioners clearly articulated their role and activities they were responsible for in providing care, however, they tended to work independently. In cases with an interdisciplinary team there was limited collaboration. Nurse practitioners, physicians, and counselors contributed most to the delivery of care. Key challenges included lack of service coordination within organizations, and the need for practitioner education. Continuing educational sessions, guidelines, and mentorship aided capacity building. Conclusions: Providing primary care to transgender individuals is within the scope of practice for primary care practitioners and can be part of routine care delivered in different models of care. Primary care team collaboration can be strengthened by regular team meetings. Professional training needs to include transgender education and continuing education opportunities need development.


A spirituality discourse in substance abuse treatment offers useful unconventional constructs in treatment services to ethnic minority groups with substance use disorder (SUDs). It is important to locate spirituality within culture, place, and history in order to understand the spiritual needs of persons from minority groups with SUDs. There are many studies that merit a spiritual approach in treatment for ethnic minority groups with SUDs. However, spirituality is a broad concept that means different things to different people. Therefore, such an unconventional approach should be approached critically and cautiously. This chapter looks at the utilisation of an integrated eclectic approach with a focus on inclusion of spirituality in treatment services from a biopsychosocial-spiritual perspective. Tapping into the spiritual needs and the meaning that people ascribe to spirituality and religion (S&R) in treatment services is often more valued than conventional secular treatment services. Also, the client's spirituality is generally overlooked by professionals offering such services simply because it is so controversial. This chapter proposes an integrated eclectic methodology calling for a biopsychosocial-spiritual perspective to address the needs and well-being of ethnic minority groups with SUDs as a com-prehensive person-centred and holistic approach, utilising mindfulness techniques.


Industrial policy programs are frequently used by governments to stimulate economic activity in particular sectors of the economy. This study explores how an industrial policy program can affect the creation and evolution of an industry and, ultimately, the long-term performance of firms. We examine the history of the Brazilian bioethanol industry, focusing on the industrial policy program implemented by the Brazilian government in the 1970s to develop the industry. We put together a novel data set containing detailed information about the history of bioethanol producers. Our findings show that plants founded during the industrial policy program tend to be, in the long run, more productive than those founded before the program was in place. Based on additional analyses and complementary fieldwork, we infer that the wave of acquisitions that occurred after the end of the industrial policy program had an important effect on the performance of the plants founded when the program was in place. Industrial policy, especially in conjunction with a competitive post-industrial policy business landscape, can succeed in nurturing competitive firms.


Planning involves the generation of a network of actions that achieves a desired goal given an initial state of the world. There has been significant progress in the analysis of planning algorithms, particularly in partialorder and in hierarchical task network (HTN) planning (Kambhampati 95; Erol et al. 94). In this abstract we propose a more general framework in which planning is seen as a graph rewriting process. This approach subsumes previous work and offers new opportunities for efficient planning.


Chemotactic cytokines or chemokines form a family of proinflammatory proteins that are functionally linked to various classes of proteases, including matrix metalloproteinases (MMPs). Both families of molecules are key players in the migration of inflammatory cells in autoimmune diseases and in invasive cancers. For example, the chemokine interleukin-8 acts as a fast secretagogue of gelatinase B in granulocytes and is increased in the synovial fluid of arthritis patients and may locally recruit and activate neutrophils. The latter are the most abundant inflammatory cell type in the joints of patients with rheumatoid arthritis. In the case of the inflamed joint, the contribution of matrix remodeling enzymes in the breakdown of cartilage and bone is trivial. Gelatinase B (MMP-9) was documented in autoimmune diseases and cancer by immunohistochemistry with the use of monoclonal antibodies. Studies in rheumatoid arthritis and multiple sclerosis led us to postulate the "Remnant Epitopes Generate Autoimmunity" or REGA model for autoimmunity. This model is based on the pathophysiological role of three major classes of molecules involved in aspecific primary immune defense mechanisms: the cytokines, the chemokines and the proteases. The REGA model has proven to be useful for the development of disease treatment strategies. Particular cytokines are disease-limiting and may thus be used for the treatment of autoimmune disorders. Cytokines and chemokines that induce enzymes promote disease and may be antagonized. Along this line of research, we have recently identified natural and biosynthetic chemokine antagonists. Some of these have shown potent antiviral activity against human immunodeficiency virus. It is expected that these might also become useful in the treatment of autoimmune diseases and invasive cancers. A similar effect may be expected by the antagonization of damaging proteases or with the use of recombinant or synthetic enzyme inhibitors.


Context: Tangled commits are changes to software that address multiple concerns at once. For researchers interested in bugs, tangled commits mean that they actually study not only bugs, but also other concerns irrelevant for the study of bugs.
Objective: We want to improve our understanding of the prevalence of tangling and the types of changes that are tangled within bug fixing commits.
Methods: We use a crowd sourcing approach for manual labeling to validate which changes contribute to bug fixes for each line in bug fixing commits. Each line is labeled by four participants. If at least three participants agree on the same label, we have consensus.
Results: We estimate that between 17\% and 32\% of all changes in bug fixing commits modify the source code to fix the underlying problem. However, when we only consider changes to the production code files this ratio increases to 66\% to 87\%. We find that about 11\% of lines are hard to label leading to active disagreements between participants. Due to confirmed tangling and the uncertainty in our data, we estimate that 3\% to 47\% of data is noisy without manual untangling, depending on the use case.
Conclusion: Tangled commits have a high prevalence in bug fixes and can lead to a large amount of noise in the data. Prior research indicates that this noise may alter results. As researchers, we should be skeptics and assume that unvalidated data is likely very noisy, until proven otherwise.


Abstract The article presented here is rooted in our doctoral research in Ethnology and Social History developed in the lagoon of Venice in 2010-2013. It is a research based on the methodology of ethnographic field research, in parallel with the bibliographic and archive research. The fieldwork was conducted between March 2010 and August 2012 with 21 informants, fishermen aged 20 to 90 years. In this article we analyze how the formation of a new food taste is a process that can be defined "cultural". We can meet an example in the history of mussel-farming on the island of Pellestrina, an island of fishermen in the southern lagoon of Venice, where the exploitation of this mollusk as food and economic resource appears rather late in history. Our research enabled us to find some frequent allusions to the alleged toxicity of this mollusk, called in Venice peòcio, that is to say "louse", and once considered inedible. What mechanisms have transformed today the mussels into an appreciated and great demanded food, into "traditional food"?


In situ heart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf available scaffolds are used to induce endogenous heart valve restoration. Such scaffolds are designed to recruit endogenous cells in vivo, which subsequently resorb polymer and produce and remodel new valvular tissue in situ. Recently, preclinical studies using electrospun supramolecular elastomeric valvular grafts have shown that this approach enables in situ regeneration of pulmonary valves with long-term functionality in vivo. However, the evolution and mechanisms of inflammation, polymer absorption and tissue regeneration are largely unknown, and adverse valve remodeling and intra- and inter-valvular variability have been reported. Therefore, the goal of the present study was to gain a mechanistic understanding of the in vivo regenerative processes by combining routine histology and immunohistochemistry, using a comprehensive sheep-specific antibody panel, with Raman microspectroscopy for the spatiotemporal analysis of in situ tissue-engineered pulmonary valves with follow-up to 24 months from a previous preclinical study in sheep. The analyses revealed a strong spatial heterogeneity in the influx of inflammatory cells, graft resorption, and foreign body giant cells. Collagen maturation occurred predominantly between 6 and 12 months after implantation, which was accompanied by a progressive switch to a more quiescent phenotype of infiltrating cells with properties of valvular interstitial cells. Variability among specimens in the extent of tissue remodeling was observed for follow-up times after 6 months. Taken together, these findings advance the understanding of key events and mechanisms in material-driven in situ heart valve tissue engineering.


Tourism in the Hudson Bay region of central northern Canada generally is associated with non-consumptive forms of nature-based activities (such as polar bear viewing). However, the region has experienced variable growth in the cruise sector in recent years. This paper examines patterns of cruise activity in all subregions of the Hudson Bay region during three cruise seasons (2006, 2008, and 2009) and mainly reveals a pattern of decline. Since the prevalence of sea ice is an important part of visitor experiences of polar cruises, we examine sea ice change and occurrence of icebergs in the Hudson Bay region. Our sea ice analysis suggests that the length of the navigable shipping season is increasing in this region, which may facilitate both earlier and later shipping. But in terms of cruise traffic, we suggest that the demise of ice coverage signals a possible decline in cruise activity in most of the Hudson Bay region because ice-supported wildlife may shift north with the diminishing ice regime. Given the possible environmental and socio-cultural implications of changing cruise activity patterns in the Arctic and the absence of broad-scale monitoring and surveillance of the industry, use of these available data sources is vital to building a clearer picture.


PURPOSE
To evaluate the importance of the presence of 3T3 fibroblasts for establishing limbal epithelial cultures from cell suspension obtained from corneo-scleral rims (CSR).

METHODS
Corneo-scleral rims from different donors (n=6) had their posterior stroma and endothelium stripped away. Each corneo-scleral rim was divided into three equal segments that were set up in tissue culture in three different conditions: one of the segments was placed with the epithelial side up on the bottom of a 6-well culture plate (Group A). The other two fragments were trypsinized and the obtained cell suspension was cultured with (Group B) or without (Group C) irradiaded 3T3 cells. The cells were cultured in supplemental hormonal epithelial medium (SHEM), the epithelial migration and clone formation in groups A, B and C were evaluated with phase contrast microscopy and rodamine B staining.

RESULTS
Epithelial cell growth was observed in 4/6 rims (Group A). All epithelial cell suspensions that were cultured with 3T3 cells (Group B) formed clones. No adhesion or true clone formation (holo- or meroclones) was observed in the cell suspensions that were cultivated without 3T3 (Group C) (p=0.009).

CONCLUSIONS
Epithelial cell suspension obtained from corneo-scleral rims in this model needs to be cultivated with 3T3 cells in order to form clones and establish limbal epithelial cell colonies with the potential to be used for ocular surface reconstruction.


PURPOSE
TikTok, the fastest growing social media application worldwide, has been infrequently studied in medicine. We analyzed the top radiology-related posts on TikTok in order to describe opportunities for radiology engagement.

MATERIALS AND METHODS
We retrieved the top 300 posts meeting the search criteria "radiology." User- and post-related data were categorized based on a prespecified coding system. Descriptive statistics were reported. Kruskal-Wallis H and Mann-Whitney U tests were performed to assess for differences in followers, plays, likes, and comments among posts and users.

RESULTS
284 working posts were broadcast by 187 unique users with median 119 followers (interquartile range [IQR]: 31-1,206) and 20 posts (IQR: 7-49). Most (81%, 151/187) were nonphysician radiology personnel, while only 5% (9/187) were radiologists. Posts by radiologists had more plays than those by nonphysician radiology personnel (median 3643 vs 1282, P = 0.001). The 284 posts had median 1520 plays (IQR 429-4374), 60 likes (IQR 18-272), and 2 comments (IQR 0-9). Most posts were work-related (184/284, 65%), followed by clinical (68/284, 24%), personal (30/284, 11%), or promotional (2/284, 1%). However, posts by radiologists were mostly clinical (65%, 31/48) and represented a large majority of posted imaging cases (29/33, 88%). Posts about COVID-19 represented 38% (107/284) of the study sample and 48% (93/193) of posts after the first U.S. COVID-19 case COVID-19 posts had significantly more comments (3 vs. 2, P = 0.034) and more likes approaching significance (89 vs 51, P = 0.134) than non-COVID-19 posts.

CONCLUSIONS
Though radiologists represent a minority of TikTok users their post represent the majority of this platform's clinical content. This presents an important opportunity for radiologists to utilize TikTok for contemporary, unique content creation and engagement with nonphysician radiology personnel.


Sargodha district is one of the least studied regions of Pakistan regarding its ethnobotanical values. This paper is the first report related to the documentation and conservation status of the tree species in the Sargodha district, and their folk ethnobotanical uses. An interview base survey was conducted in the study area in2010-2013. The ethnobotanical data revealed the use of 100 tree species (6 gymnosperms, 94 angiosperms) belonging to 77 genera (6 gymnosperms, 71 angiosperms) and 39 families (4 gymnosperms, 35 angiosperms), with the Fabaceae ranking first with 19 tree species, followed by the Moraceae (12 species). Tree species like Aegle marmelos,Butea monosperma, Diospyrus malabarica, Gmelina arborea, Kigeliaafricana, Manilkara hexandra, Manilkara zapota, Mimusops elengi,Nyctanthes arbor-tristis, Putranjiva roxburghii, Terminalia arjuna and Terminalia bellerica are not only unique in their medicinal value butalso interesting because of their unusual occurrence here. Thevetia peruviana, Cassia fistula, Celtis australis, Delonix regia, Diospyrus malabarica, Grevillea robusta, Haplophragma adenophylum, Jacaranda mimosifolia, Lagerstroemia speciosa, Plumeria rubra, Pterospermum acerifolium, Roystonea regia, Taxodium distichum and Tectona grandis are included among the worth looking ornamental tree species. Capparisdecidua, Dalbergia sissoo, Tamarix aphylla, Tamarix dioica, Prosopis cinerariaand Ziziphus mauritiana are the most commonly used timber species. Other common ethnobotanical utilization of these trees includeseither sheltering or fuel or agricultural uses. Lack of awareness about the potential uses of these species, and particularly ignorance of the concerned authorities, have led to a decline in the population of this precious tree flora. Documentation of this tree flora, and associated indigenous knowledge, can be used as a basis for developing management plans for conservation and sustainable use of this florain the study area. A well-organized management is critical to restore and conserve this endangered natural resource in the District Sargodha,Pakistan. The immense medicinal and timber value of thesetree species make it necessary to promote their conservation to simultaneously alleviate the poverty and improve the socio-economicstatus of the study area.


Playing Hide and Seek Targeted cancer therapies have shown promising results in patients, but few of these drugs provide long-term benefits because tumor cells rapidly develop drug resistance. Nathanson et al. (p. 72, published online 5 December) show that glioblastoma cells can become resistant to erlotinib, an epidermal growth factor receptor (EGFR)–targeted drug, by eliminating extrachromosomal copies of the mutant EGFR gene. After a period of drug withdrawal, the mutant EGFR gene reappears on extrachromosomal DNA and the tumor cells become resensitized. The discovery that cancer cells can evade drug therapy by this "hide and seek" mechanism may help to optimize the dosing schedule of erlotinib in glioblastoma patients. Tumor cells become resistant to targeted therapies by eliminating the gene encoding the drug target from extrachromosomal DNA. Intratumoral heterogeneity contributes to cancer drug resistance, but the underlying mechanisms are not understood. Single-cell analyses of patient-derived models and clinical samples from glioblastoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) demonstrate that tumor cells reversibly up-regulate or suppress mutant EGFR expression, conferring distinct cellular phenotypes to reach an optimal equilibrium for growth. Resistance to EGFR TKIs is shown to occur by elimination of mutant EGFR from extrachromosomal DNA. After drug withdrawal, reemergence of clonal EGFR mutations on extrachromosomal DNA follows. These results indicate a highly specific, dynamic, and adaptive route by which cancers can evade therapies that target oncogenes maintained on extrachromosomal DNA.


Ontogenetic changes in mouth and gut during larval developmental stage of
Malaysian river catfish, Mystus nemurus were studied for 21 days to facilitate and
determine the suitable feed and feed particle size for the growing larvae. The eggs
began to hatch at day 2 after fertilization (DAF) and most of the larvae hatched
within 2-4 DAF. The larval mouth was opened at the end of the first day after
hatching (DAR) and the commencement of exogenous feeding was began on the 4
DAH after the movement of jaws. The barbels began to appear on the upper jaw
and lower jaw on 3 DAR, and two small barbels appeared around olfactory pits by
5 DAR. Free neuromasts were observed under the lower jaw on 7 DAR and
around the olfactory pits, the eyes, and upper operculum by the 9 DAH. Strong
(Ma = 5.5108 TL + 47.16, R2 = 0.9302 at 45° opening and Ma = 10.138 TL + 87.141, R2 = 0.9302 at 90° opening) relationships were found to exist between
mouth size and total length of fish.
The morphological and histological development of the gut in M nemurus
larvae was observed using a profile projector and a light microscope. During the
yolk absorption period, the gut was a simple, straight, undifferentiated tube
throughout its length. By 4-5 DAR, the gut differentiated to the oesophagus,
stomach, and intestine. At the first feeding, the larval gut was functional, but was
structurally and functionally less complex than that of adults. By the 13 DAH, four
developed tissue layers (mucosa, submucosa, muscularis and serosa) were
observed in the larval gut which are the characteristics of the gut of an adult
vertebrate.


This thesis explores the links between gender relations and violence against girls in and around schools in Mozambique. A participatory approach to research was used to explore young girls' and boys' experiences of gender violence in homes, schools and streets. This
involved interviews, focus group discussions and observation with a range of institutional actors: parents, family members, teachers, 'sugar daddies' and young people. The study is framed as an ethnographic case study and investigates how gender and power relations are
constructed through experience, interaction with others and through what girls and boys observe and acquire in different sites of learning including school, church, family and community, and the media.
Drawing on the theoretical concepts of agency, power relations and subjectivities within gender and social analysis (Butler, 1990; Foucault, 1978; 1982; McNay, 2000; 2003), I explore how gender as a cultural construct is acquired by participants in structured and unstructured learning contexts. The concept of 'situated learning' (Lave and Wenger, 1991) is drawn upon to examine the validity of formal, non-formal and informal processes of learning
through which young people learn about gender relations and sexuality in this community in Mozambique. Conceptualisation of learning as a continuum from informal to formal suggests that learning is a lifelong activity shaped by people, context and culture, and that knowledge which involves local knowledge and contextual practice experience, is acquired through 'communities of practice' (Lave and Wenger, 1991).
In terms of the role of the school, the thesis shows how school shapes gender relations through unequal teacher-student power relations, everyday practices and structures that can result in violent acts. The thesis also explores how initiation rites involving young people in groups and individually not only contribute to conveying gender stereotypes but also provide insights into the ways in which such traditions are being mediated and transformed. Drawing young people's voices into the debate, the thesis describes how girls and boys rely on unstructured, informal means of learning through the media and everyday life experience. It suggests that young people absorb knowledge and construct gender identities through
different learning processes that might implicitly and/or explicitly lead to gender violence.


Pulsed-field gel electrophoresis of the genomic DNA of penicillin-resistant strains of Streptococcus pneumoniae was carried out. Eleven clinical strains of serogroup 9 from different French towns and Paris hospitals were tested. The restriction enzymes Apal and Smal were used to digest intact chromosomes, and the fragments were resolved by field-inversion gel electrophoresis (FIGE). Five strains were similar using Apal and Smal. Four others were closely related when using Apal, and five others were closely related when using Smal. These results suggest that 10 of these strains are genetically related and have a clonal origin. The profile of the eleventh strain was completely different. Thus, in a given serotype the spreading of penicillin resistance can result from both clonal and independent events. Five strains had similar FIGE profiles to strains first isolated in Spain, suggesting that a resistant strain had spread from Spain to France.


Introduction: In spite of improvements in treatment of mantle cell lymphoma (MCL) over the last 10-15 years, this is still considered an incurable lymphoma entity, and the majority of patients eventually relapse. Ibrutinib is an active agent in R/R MCL, but with a limited duration of response. For patients refractory to this agent, there are few treatment options. Other active agents in R/R MCL are venetoclax, and the combination of lenalidomide and rituximab (R2). In this multi-centre open-label phase Ib-II trial, we evaluated safety and efficacy of this triplet combination in R/R MCL; previously exposed to ibrutinib and ibrutinib naive. Another objective of this trial was to test the feasibility of stopping treatment in patients achieving molecular remission. The objective of the phase Ib portion of the trial was to establish the recommended phase 2 dose (RP2D) of venetoclax and lenalidomide.
 Methods: Main eligibility criteria: patients with MCL, relapsing after or refractory to at least one rituximab-containing chemotherapy regimen, WHO PS 0-3, and measurable disease. The primary endpoint was overall response rate (ORR) at 6 months. Minimal residual disease (MRD) monitoring by patient specific RQ-PCR was performed every 3 months during follow-up, according to EuroMRD criteria.
 Treatment schedule (cycle length 28 days): Cohort A: Lenalidomide 15 mg p o daily, days 1-21, Venetoclax 400 mg p o days 1-28 (after ramp-up). Cohort B: Lenalidomide 20 mg p o daily, days 1-21, Venetoclax 400 mg p o days 1-28 (after ramp-up). Cohort C: Lenalidomide 20 mg p o daily, days 1-21, Venetoclax 800 mg p o days 1-28 (after ramp-up). Cohort Y: Lenalidomide 15 mg p o daily, days 1-21, Venetoclax 600 mg p o days 1-28 (after ramp-up). In all cohorts: Rituximab 375 mg/m2 i v day 1 in cycle 1, then 1400 mg s c (or 375 mg/m2i v) days 8, 15 and 22 in cycle 1, then day 1 in cycles 3, 5, 7, 9 and 11. The phase 1 portion of the study followed a sequential dose escalation, '3 + 3' design. The MTD was defined as the highest dose studied for which the incidence of DLT was less than two out of six subjects during the first 8 weeks of treatment. For both the phase I and II part of the trial, when MRD-negative in blood, treatment continue for another 3 months, when a new evaluation of MRD in blood and bone marrow is performed. If MRD negativity is confirmed, treatment is stopped and the patient will be followed with MRD and CT. Patients without molecular marker are followed by PET-CT.
 Results: Three patients each in Cohorts A, B and C were enrolled from 31-MAY-2018, at 5 centres in Sweden and Norway. No patient in Cohorts A+B experienced any DLT, but in Cohort C, 2/3 patients had grade 3-4 infection (DLT). A fourth cohort, named Y, was started, intermediate between B and C, without DLT, and the RP2D was established as Venetoclax 600 mg, and Lenalidomide 15 mg. Since then, an additional 8 pts have been recruited in the phase 2 portion (total 21). The median age is 71 years. Patients had received a median of 2 previous regimens (range: 1-7), and 3 had progressed after ibrutinib. Hematological toxicity was the most frequent AE, with 19/20 pts with G3-4 neutropenia, requiring G-CSF support, and 6/20 pts with G3-4 thrombocytopenia. Three events of G3-4 infection were recorded. Single patients each reported G-3-4 rash, renal failure, atrial flutter or melaena. No event of tumor lysis syndrome was reported. With a median follow up time of 5 months, 16 patients were evaluable for efficacy as of June 30, 2020. ORR is 56% with 5 CR and 4 PR. Median duration of response and PFS have not been reached. 4 pts (20%) have stopped treatment in CR and molecular remission, 6 are on treatment, 2 pts have undergone allo-SCT in remission, 1 pt stopped treatment due to toxicity, and 8 have progressed, out which 4 have died. One of two evaluable patients previously treated with ibrutinib responded with a PR. Of the 6 patients evaluable for MRD at 6 months, 6/6 patients have achieved molecular remission in blood and 5/6 in bone marrow.
 Conclusions: At a target dose of venetoclax of 600 mg, and lenalidomide 15 mg, this combination is tolerable and shows efficacy in R/R MCL, although associated with a high degree of neutropenia. Interestingly, a response adapted treatment strategy, by stopping treatment in molecular remission, appears to be feasible, although follow-up is still short.
 Figure

 Jerkeman: Abbvie: Research Funding; Roche: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Hutchings:Daiichi: Research Funding; Sankyo: Research Funding; Roche: Consultancy; Genmab: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; Roche: Honoraria; Genmab: Honoraria; Takeda: Honoraria; Takeda: Consultancy; Roche: Research Funding; Celgene: Research Funding; Genmab: Consultancy.


This symposium will assess the rationale, methods and initial outcomes of 'dual mentorship' in the setting of a history dissertation workshop staged at Loughborough University in spring 2015. Second-year undergraduates about to embark on writing their final-year dissertations (aka Honors theses) were provided with guidance from postgraduates trained in peerassisted learning techniques by educationalists and historians.
Dual mentorship therefore involves an inclusive form of
leadership, in which academics cede control of the classroom to postgraduates, who in turn share their research experiences with undergraduates in a collaborative manner.
Feedback from undergraduates demonstrated that the
workshop fulfilled its objectives of providing them with
intensive small-group teaching, honing their dissertation
proposals and increasing their confidence. By the end of the workshop, they felt better prepared to undertake the hardest intellectual challenge most of them will encounter in their educational career.
Moreover, the postgraduates recruited from seven institutions learnt as least as much from the workshop as the undergraduates. They received the relatively rare opportunity to share their expertise in research skills and to reflect on the fundamentals of research design while immersed in writing their own dissertations. The workshop asked them to devise sessions collectively while deciding individually how to deliver these, leading to instructive comparisons of teaching methods.
The mentorship of postgraduate students by academics within their own discipline is comparatively infrequent, since most pedagogical training takes place in cross-disciplinary settings and postgraduates are seldom observed for several hours of teaching. Recruiting postgraduates from different universities and a range of related fields also fostered new networks in the
often solitary work of dissertation research. The Loughborough scheme developed new communities of history practice (Lave and Wenger, 1991) involving PhD, undergraduate and academics.
The mutual benefits gained by undergraduates and
postgraduates suggest that workshops of this kind should be considered within curriculum design alongside other methods of dissertation preparation (Lavender, 2010) and that in the face of calls to diversify final-year projects (Healey et al., 2013)
'the standard 8000 to 12000-word dissertation remains a
valuable and viable exercise for all history students.
Following correspondence with Joanne Rae, the symposium
will be transmitted from Britain using WebEx video
conferencing. It will present different perspectives on 'dual mentorship' from four participants in the workshop: a history lecturer (Collins), an educationalist (Ingham), a history postgraduate (Carpenter) and an English postgraduate (Townend). These four views on the same workshop will allow us to consider its efficacy from those inside and outside the discipline of history, from a practicing teacher and a trainer of teaching, and from that of established academics and those beginning their academic careers.


Abstract
I suggest that many of the common psychoneuroses are behavioural reactions which arise in response to isolation of an individual from his group. This hypothesis is difficult to substantiate by statistical means and no attempt has been made to do so.

These behavioural reactions are of two types:

(1) Recognition-hunger reactions
These are reactions of diffidence, self-consciousness, tension states, "promotion" and "tired housewife" syndromes, where the individual is isolated because he undervalues himself in relation to his group.

(2) Status-protection reactions
These are reactions of resentment, jealousy, "chip-on-shoulder", compensation cases, and hypochondriasis where the individual is isolated because he overvalues himself in relation to the group.

The behavioural grid provides a model to illustrate this thesis. I think that great opportunities for friendship in our communities are likely to be of greater therapeutic value than psychotropic drugs—these opportunities are discussed.


Despite the impression that the federal statistical system has been starved for resources, the record over the last decade or so, judged by conventional deflation methods, has been one of rough stability. The quality of U.S. international data on commodity and service trade, direct investment, and export and import prices has improved, but there has been a serious deterioration in data on portfolio capital flows, stocks, and income. Where improvements have taken place, the main source has been computerization, both inside and outside the federal statistical system. The standard deflators for expenditures do not adequately take account of the decline in the cost of computing and therefore impart a downward bias to the estimates of input. Despite the gains in some areas, serious deficiencies remain for the increasingly important international sector. The improvements that have occurred have resulted mainly from Congressional and outside pressures, while successive administrations have shown little concern with the quality of the data they produce and presumably use for policy making.


How a cell maintains transcriptional fidelity across mitosis has remained an enduring mystery in biology. One challenge arises during mitosis when chromatin becomes condensed and transcription is shut off. How do the daughter cells re-establish the original transcription program? Here, we report that the TATA-binding protein (TBP), a key component of the core transcriptional machinery, remains bound globally to active promoters in ES cells during mitosis. Using live-cell single-molecule imaging, we observed that TBP mitotic binding is highly stable, with an average residence time of minutes. This stable binding is in stark contrast to typical TFs with residence times of seconds. To test the functional effect of mitotic TBP binding, we used a drug-inducible degron system and found that TBP promotes the association of RNA Polymerase II with mitotic chromosomes, and facilitates transcriptional reactivation following mitosis. These results suggest that the core transcriptional machinery maintains global transcriptional memory during mitosis.


Current hypotheses favour the concept that lowering oxidative stress can have a health benefit. Free radicals can be overproduced or the natural antioxidant system defenses weakened, first resulting in oxidative stress, and then leading to oxidative injury
and disease. Cardiovascular disease is one example of this process. This disorder continues to be the major cause of premature death worldwide. Oxidation of human low-density lipoproteins is considered an early step in the progression and eventual development of
atherosclerosis, one of the leading causes to cardiovascular dysfunction. Compelling support for the involvement of free radicals in disease development originates from epidemiological studies showing that an enhanced antioxidant status is associated with reduced risk of several diseases. Dietary nutraceuticals such as vitamins C, E and
polyphenolics and reduction of cardiovascular disease incidence are a notable example. This paper reviews the biology of ROS/RNS, their pathways through which they relate to the pathology of cardiovascular disease and discusses the putative roles that antioxidants, including phenolics, may play in controlling oxidative stress and reduce the incidence of cardiovascular disease. Keywords : Oxidative stress, cardiovascular disease, atherosclerosis, inflammation, cell signaling and transduction mechanisms, antioxidants, dietary phenolics. Internet Journal of Medical Update Vol. 1 (2) 2006: pp. 24-40


BACKGROUND
The phenotype of children with XXYY has predominantly been defined by comparison to other sex chromosome aneuploidies trisomies affecting male children; however, the intellectual ability of children with XXYY is lower than children with other sex chromosome aneuploidies trisomies. It is not known to what extent the phenotype identified to date is specific to XXYY, rather than a reflection of lower IQ. This study evaluates the mental health and behaviour of children with XXYY, in comparison to children with intellectual disabilities of heterogeneous genetic origin.

METHODS
Fifteen children with XXYY and 30 controls matched for age (4-14 years), sex and intellectual ability were ascertained from the IMAGINE ID study. IMAGINE ID participants have intellectual disabilities due to genetic anomalies confirmed by National Health Service Regional Genetic Centre laboratories. The mental health and behaviour of participants was examined with the Development and Well-being Assessment and the Strengths and Difficulties Questionnaire.

RESULTS
Children with XXYY experienced significantly more frequent and intense temper outbursts than the control group.

CONCLUSION
Our results suggest that temper outbursts may be specifically associated with the XXYY phenotype. These problems have a significant impact on the daily lives of boys with XXYY and their families. It is crucial to ensure that families are well supported to manage these difficulties.


The density functional version of symmetry-adapted perturbation theory, SAPT(DFT), is a computationally efficient method for calculating intermolecular interaction energies. We evaluate its accuracy by comparison with experimentally determined noble gas interaction potentials and sublimation enthalpies, most of which have not been previously calculated using this method. In order to compare the results with wavefunction methods, we also calculate these quantities using MP2 and, for noble gas dimers, using CCSD(T). For the crystal lattice energy calculations, we include corrections to the dispersion, electrostatic, and induction energies that account for the finite interaction distance cutoff and higher-order induction contributions. Overall, the energy values extrapolated to the complete basis set limit show that SAPT(DFT) achieves significantly better agreement with experiment than MP2.


In situations where communication infrastructures are destroyed or do not exist at all, implementing a disruption/delay-tolerant network (DTN) may be the only choice. A special type of DTN, which is known as a pigeon network, utilizes controllable special-purpose vehicles called pigeons to convey messages among segregated nodes and gateways. This paper studies a basic scenario in a pigeon network, where the segregated nodes are in an area that is far from the gateway. Our focus is on the optimal scheduling problem that determines how long a pigeon should stay at each node so that the average delay of messages is minimized. Although this problem is related to the server vacation model, existing literature in this area mainly focuses on the performance evaluation of different scheduling schemes, whereas the study on the optimal scheduling schemes is rarely seen, particularly for bursty traffic. In search of the optimal scheduling scheme, we first introduce a peak-valley message generation model and investigate the optimal scheduling schemes for the peak phase and the valley phase, respectively. Based on the analytical result, we then propose a quasi-optimal dual-phase (QODP) scheme. We further design a robust phase identification scheme such that a pigeon is able to apply the locally optimal scheduling scheme at the corresponding phase. Simulation studies have demonstrated QODP's adaptability in facing different types of traffic and its significant performance improvement over the existing scheduling schemes.


Rotary swaging is an incremental cold forming process for rods and tubes. Infeed rotary swaging with structure in the reduction zone of the tools is investigated using a two dimensional finite element simulation. A few geometrical parameters are varied, for cosine and skew stairway shapes. The effective tool angle is kept constant. The influence is evaluated by the radial and axial process forces. Furthermore, the material flow is visualized by the neutral plane. The simulation results are quantitatively compared to each other to analyse the reaction force F A , which acts against the feeding force. Also, the results serve to find suitable geometries to be transferred to rotary swaging tools for practical application. It is shown that the shapes have a significant effect on the forces and the location of the neutral plane. Finally a first swaging tool is modified with an exemplary geometry for experimental investigations.


A typical unmanned and remotely operated vehicle is usually equipped with cameras which give insufficient information about the nearest environment and an operator has difficulties in driving such a vehicle in unknown environment. In this paper, we consider a problem of the vehicle nearest area map building based on additional devices. The vehicle is equipped with SICK LMS lasers, inclinometer and radars. Combining information from the devices allows to build a map which helps an operator to drive the vehicle more efficiently. We tested the system on a few military vehicles and the results show that our system really improves remotely driving.


We address two shortcomings of the common spatial patterns (CSP) algorithm for spatial filtering in the context of brain-computer interfaces (BCIs) based on electroencephalography/magnetoencephalography (EEG/MEG): First, the question of optimality of CSP in terms of the minimal achievable classification error remains unsolved. Second, CSP has been initially proposed for two-class paradigms. Extensions to multiclass paradigms have been suggested, but are based on heuristics. We address these shortcomings in the framework of information theoretic feature extraction (ITFE). We show that for two-class paradigms, CSP maximizes an approximation of mutual information of extracted EEG/MEG components and class labels. This establishes a link between CSP and the minimal classification error. For multiclass paradigms, we point out that CSP by joint approximate diagonalization (JAD) is equivalent to independent component analysis (ICA), and provide a method to choose those independent components (ICs) that approximately maximize mutual information of ICs and class labels. This eliminates the need for heuristics in multiclass CSP, and allows incorporating prior class probabilities. The proposed method is applied to the dataset IIIa of the third BCI competition, and is shown to increase the mean classification accuracy by 23.4% in comparison to multiclass CSP.


Laparoscopic surgery has transformed many procedures over the past three decades. Greater experience along advances in laparoscopic devices have augmented the number of laparoscopic liver resection (LLR). Today laparoscopic hepatectomy is a stablished technique worldwide with more than 9,000 cases reported so far (1). International consensus conferences in 2008 and 2014 established steps to safe implementation of this technique such as dual training in advanced minimally invasive surgery and liver surgery, showed short-term equivalence and suggested that laparoscopy should be the standard of care for minor liver resections and left-lateral sectionectomy (2,3).


Eggshell membrane is a natural biomaterial with macropores lattice and high surface area. The bio-sorption and decolorization of organic dye eosin B was investigated based on eggshell membrane. The effect of adsorption time, pH value and temperature of eggshell membrane on the decolorization of eosin B was studied. Time for adsorption to reach equilibrium is 100 min. Optimum pH value is 2.0 for the adsorption. And the amount of dye removed by egg shell membrane was increasing as temperature ascending. At room temperature and optimum conditions, 95% of eosin B could be removed and maximum adsorption of 40.9 mg/g had been achieved. The adsorption behavior of eggshell membrane towards eosin B fit well with Freundlich isotherm.


The diagnostic evaluation of acute chest pain has been augmented in recent years by advances in the sensitivity and precision of cardiac troponin assays, new biomarkers, improvements in imaging modalities, and release of new clinical decision algorithms. This progress has enabled physicians to diagnose or rule-out acute myocardial infarction earlier after the initial patient presentation, usually in emergency department settings, which may facilitate prompt initiation of evidence-based treatments, investigation of alternative diagnoses for chest pain, or discharge, and permit better utilization of healthcare resources. A non-trivial proportion of patients fall in an indeterminate category according to rule-out algorithms, and minimal evidence-based guidance exists for the optimal evaluation, monitoring, and treatment of these patients. The Cardiovascular Round Table of the ESC proposes approaches for the optimal application of early strategies in clinical practice to improve patient care following the review of recent advances in the early diagnosis of acute coronary syndrome. The following specific 'indeterminate' patient categories were considered: (i) patients with symptoms and high-sensitivity cardiac troponin <99th percentile; (ii) patients with symptoms and high-sensitivity troponin <99th percentile but above the limit of detection; (iii) patients with symptoms and high-sensitivity troponin >99th percentile but without dynamic change; and (iv) patients with symptoms and high-sensitivity troponin >99th percentile and dynamic change but without coronary plaque rupture/erosion/dissection. Definitive evidence is currently lacking to manage these patients whose early diagnosis is 'indeterminate' and these areas of uncertainty should be assigned a high priority for research.


Multiple models have been proposed to describe the epidemic spreading in the presence of interactions between two or more infectious diseases, but less is known about how dynamical aspects, such as time scales of diseases, affect the epidemic spreading. In this work, we evaluate the time shift produced in the number of people infected from one disease when interacting with another disease. Using a compartmental model, we produce different forms of relationship as competition, cooperation, and independence, assessing the effect of each one in the final result. We focus on the case of the unidirectional coupling between diseases, which enables us to study the impact of a perturbation to a driving disease on the driven one. We found that the prevalence of the driven disease is strongly affected if its time scale, defined by the time where the infection reaches the peak, is comparable to that of the driving disease. The secondary peak of the infection was observed under cooperative coupling if the time scale of the driving disease is much longer than that of the driven one.


We used field observations of freely foraging Aphytis aonidiae parasitoids in conjunction with results of laboratory studies of A. aonidiae and other Aphytis species to simulate lifetime patterns of behavior and reproduction. Field observations provided estimates of encounter rates with three classes of hosts, the mortality rate from predation on adult parasitoids, and host‐handling times for oviposition and host feeding by adult wasps. A series of physiological parameters, including the egg maturation rate and the value of host‐feeding meals, were estimated from previously published studies. Plasticity in parasitoid behavior was incorporated in two ways. For one set of simulations we used a behavioral rule derived empirically from observations of parasitoids made in the field, and for another we used a dynamic state‐variable model to generate a set of behavioral rules that maximize lifetime reproductive success. As was expected, the empirically derived rule led to better matches with field observations than did simulations using the output of the dynamic model. Projections of lifetime reproductive success in the field ranged between three and 37 eggs within the 95% confidence intervals of the mortality rate and host encounter rate and depending on which behavioral rule was used. Lifetime reproductive success from the simulation with central estimates of the mortality and host encounter rates that incorporated the empirical rule was 6.25 eggs. Using the empirical versus the theoretical rule in the simulations led to a 10%–30% decline in projections of lifetime reproductive success, depending on mortality and host encounter rates. Regardless of the behavioral rule, the simulations underscored the observation that the host encounter rate was greater than the egg maturation rate. The overall oviposition rate was sufficiently high to lead to daily episodes of temporary egg limitation during which parasitoids must mature an egg before being able to oviposit.


Abstract The discovery of a new genus and species of tyrannosauroid from the Demopolis Formation (middle Campanian) of Alabama increases the known diversity of the clade, although it does not elucidate the place of initial dispersal. This subadult tyrannosauroid is the most complete non-avian theropod collected and described from the Cretaceous of eastern North America. In contrast to tyrannosaurids, the new taxon possesses several plesiomorphic characters, including lacrimals that lack a distinct peaked cornual process, and a dorsoventrally shallow horizontal ramus of the maxilla. Autapomorphies include a wide jugal process of the ectopterygoid, a caudal pneumatic foramen of the palatine that pierces the rostral half of the vomeropterygoid process of the bone, an articular surface for the lacrimal on the palatine that is distally positioned on the dorsolateral process, and pedal unguals that have a distinct proximodorsal lip over the articular surface. Cladistic analysis indicates the new taxon is a basal tyrannosauroid and its presence in eastern North America suggests that the recent common ancestor of Tyrannosauridae probably evolved following the transgression of the Western Interior Seaway. Cladistic analysis indicates that Dryptosaurus aquilunguis is also a basal tyrannosauroid but is less derived than the new genus.


This thesis explores the inter-relationship between a narrative trajectory in Pauline studies, and an ecclesiological hermeneutical reading of Paul encompassing the writings of Stanley Hauerwas and the contemporary Methodist Church. I explore whether or not the idea of a narrative/ecclesiological hermeneutic might shed any light on a reading of 1 Corinthians as 'scripture' for the Church. The work involves a three-way dialogue between a Pauline text, the theology of Stanley Hauerwas and my own context as a Methodist Minister. I explore whether or not any or all of the 'voices' in the dialogue will bring fresh understanding in the hermeneutical process, add anything in interpretation or bring major critique to bear on any of the other 'voices' within that three-way dialogue. My work combines diverse approaches in new ways to investigate how scripture can be fruitfully appropriated in the contemporary Church. Building on the narrative approach to Paul I explore, through a series of Contextual Bible Studies, how 1 Corinthians can be read through the Hauerwasian lenses of vision and narrative. My conclusions are that Hauerwas's ecclesial perspective remains too distant from the particularities of specific church communities, and that their engagement with scripture is best enriched by a combination of historical-critical exegesis and Contextual Bible Study methods.


Peritubular dentin (PTD) is a hypermineralized phase within the dentinal tubules in some vertebrate teeth as an interface between the intertubular dentin (ITD) and the cell processes. Our aim has been to understand the composition, structure and role of PTD as a mineralized tissue. We have utilized the technique of time of flight secondary ion mass spectrometry (TOF-SIMS) to map the distribution of positive and negative inorganic ions as well as organic components in the fully mineralized, intact PTD structure in bovine tooth cross-sections, and correlated these with scanning electron microscopy (SEM) in standard and backscatter modes. In recent work, we developed a procedure to freeze fracture the teeth and separate PTD from the less dense ITD by the use of aqueous sodium phosphotungstate step density gradients, after degrading the ITD collagen with NaOCl. Here, PTD-containing fragments were characterized by SEM and TOF-SIMS surface structure analysis. The TOF-SIMS data show that the isolated PTD does not contain collagen, but its surface is rich in glutamic acid-containing protein(s). The TOF-SIMS spectra also indicated that the intact PTD fragments contain phospholipids, and chemical analyses showed phosphatidylserine, phosphatidylinositol and phosphatidylcholine as the principal lipid components. In SEM sections, untreated PTD shows as a smooth collar around the tubule, but after digestion with ethylenediamine to remove all organic components, the porous nature of the mineral phase of small, thin platy apatite crystals becomes evident. Thus, the organic matrix of PTD appears to be a proteolipid-phospholipid complex.


The integration of digital voice with data in a common packet-switched network system offers a number of potential benefits, including reduced systems cost through sharing of switching and transmission resources, flexible internetworking among systems utilizing different transmission media, and enhanced services for users requiring access to both voice and data communications. Issues which it has been necessary to address in order to realize these benefits include reconstitution of speech from packets arriving at nonuniform intervals, maximization of packet speech multiplexing efficiency, and determination of the implementation requirements for terminals and switching in a large-scale packet voice/data system. A series of packet speech systems experiments to address these issues has been conducted under the sponsorship of the Defense Advanced Research Projects Agency (DARPA). In the initial experiments on the ARPANET, the basic feasibility of speech communication on a store-and-forward packet network was demonstrated. Techniques were developed for reconstitution of speech from packets, and protocols were developed for call setup and for speech transport. Later speech experiments utilizing the Atlantic packet satellite network (SATNET) led to the development of techniques for efficient voice conferencing in a broadcast environment, and for internetting speech between a store-and-forward net (ARPANEI) and a broadcast net (SATNET). Large-scale packet speech multiplexing experiments could not be carried out on ARPANET or SATNET where the network link capacities severely restrict the number of speech users that can be accommodated. However, experiments are currently being carried out using a wide-band satellite-based packet system designed to accommodate a sufficient number of simultaneous users to support realistic experiments in efficient statistical multiplexing. Key developments to date associated with the wide-band experiments have been 1) techniques for internetting via voice/data gateways from a variety of local access networks (packet cable, packet radio, and circuit-switched) to a long-haul broadcast satellite network and 2) compact implementations of packet voice terminals with full protocol and voice capabilities. Basic concepts and issues associated with packet speech systems are described. Requirements and techniques for speech processing, voice protocols, packetization and reconstitution, conferencing, and multiplexing are discussed in the context of a generic packet speech system configuration. Specific experimental configurations and key packet speech results on the ARPANET, SATNET, and wide-band system are reviewed.


Climate fluctuations and its effects on ecological processes are evident in most areas worldwide but whether such climatic effects are induced phenotypic plasticity or whether animals adapt to the new environment through micro-evolutionary processes is poorly known. In this study we have analyzed long-term data (22 years) on the relationship between climatic fluctuations and the adult survival of two distinct genetic morphs of the Common Guillemot (Uria aalge) breeding in a colony in the southern Barents Sea. In the North Atlantic, the Common Guillemot is a genetic color dimorphic species, with a non-bridled morph, with an entirely black or dark brown head, and a bridled morph having a white eye ring and auricular groove sloping back from the eye. Our results show that the two morphs responded differently to variation in the Barents Sea winter sea-surface temperature (SST). The survival rate of the bridled morph was negatively correlated to the winter SST in the Barents Sea, while that of the non-bridled morph was slightly positively correlated to the same parameter. Over the whole study period, SSTs fluctuated between warm and cold winters and the overall mean survival rates of the two morphs remained similar (96.2% and 95.9% for the bridled and non-bridled morph, respectively). This suggests a balanced selection and a stable dimorphism of the two morphs over this time period. The contrasting trends in the survival of the two morphs with respect to temperature suggest that further warming of the sea may induce directional changes and alter the frequency of the two morphs.


The arrival of 5G together with advances in artificial intelligence, machine learning, cloud computing, virtualization, and service orchestration have created a ubiquitous computing model at the network edge, enabling a host of new, AI driven edge computing applications. Although edge computing shares many characteristics of cloud computing, there are unique challenges for edge computing to meet the ever growing demands for scalability, security and multi-tenancy, especially in the upcoming 5G era. These challenges are discussed through two typical edge computing use cases: streaming video analytics and industrial IoT. A number of open research problems are discussed to call for help from the design automation community with the focus on new automation methodologies in building a cloud-native end-to-end edge computing platform.


Purpose - Motivated by the new European Union Directive 2014/95 on non-financial and diversity information, this paper aims to develop a future research agenda to conduct pragmatic, theory-oriented research into the Directive and corporate sustainability reporting. Design/methodology/approach - Drawing upon the relational dynamics between states, firms and society in regulating non-financial reporting (NFR), this essay frames and analyses the Directive and its grand theories, as unproven theories, by discussing its practical concerns and reviewing the academic literature. Findings - The Directive is an act of policy to legitimise NFR that encompasses two grand theories: improve the comparability of information and enhance corporate accountability. From a pluralist perspective, companies can rest assure that their compliance with the Directive will be perceived as socially desirable, proper and appropriate. However, some of the forces involved in translating the Directive into actionable policies operate contra to the Directive's goals and, instead, act as barriers to its grand theories. In addressing these barriers, a research agenda is proposed that both traces backward to re-examine the foundational theories of the past and looks forward to explore alternative possibilities for achieving these goals. Research limitations/implications - This paper provides researchers with a practical-driven and theory-oriented agenda for future research in light of the rising academic interest in the Directive. Practical implications - The barriers to the Directive's grand theories help policymakers and practitioners to understand the practical concerns about the implementation of the Directive and other mandatory NFR policies. Originality/value - This paper enriches the emerging debate on the Directive and highlights future possibilities for fruitful empirical research by developing a research agenda.


Introduction Poor tolerance of laxatives may be associated with inadequate bowel cleansing and reduced pathology detection. [1] Colonoscopy (CS), the gold standard, is uncomfortable, may require sedation and is not without risk. [2] CT colonography (CTC) is less invasive, requires less laxatives, but involves irradiation. Colon capsule endoscopy (CCE) is non-invasive, directly visualises the mucosa, but requires a more vigorous laxative regimen. [3] In this study, patient tolerance of each was compared. Method Split dose Kleenprep (4L) was used for CS and gastrografin (3 × 30 ml) and rectal insufflation for CTC. The regimen for CCE was either (STH) split dose Kleenprep (4L) plus two phosphosoda 'boosters' or (RFH) split dose Moviprep (2L) with phosphosoda/gastrografin 'boosters'. A bisacodyl suppository was used to promote capsule excretion if needed. Patients graded severity of laxative-related symptoms and recorded a Gloucester Comfort Score (GCS) for each procedure. They scored their overall experience (of bowel preparation and procedure combined) on a visual analogue scale (VAS 0–10: no-intolerable). Results CS was performed in 153 patients (86M, mn age 58.6±1.2). Prior failed CS, or refusal to have CS, occurred in 30.1% and 18.4%, respectively, of CTC patients (n=103; 36M, mn age 69.5±1.1), and 22.6% and 9.7% of CCE patients (n=31; 8M, mn age 42.9±3.6). CTC and CCE patients were predominantly female (p=0.003 cf. CS cohort, Kruskal Wallis). Moderate to severe laxative-related symptoms prior to CS, CTC and CCE (respectively) were nausea (12.4%, 2.9%, 29.1%; p<0.001), vomiting (2.6%, 3.9%, 8.7%; p=0.004), bloating (11.8%, 1.0%, 16.1%; p<0.001), pain (4.6%, 1.0% and 12.9%; p<0.001), headache (4.6%, 3.9% and 19.4%; p=0.019). GCS scores of moderate to severe discomfort occurred in 40.1%, 7.8% and 0% (p<0.001) and mean VAS scores for the overall experience were 4.9, 2.5 and 3.4 (p<0.001) respectively. Overall CS experience was worse than both CTC (p<0.001, Mann Whitney) and CCE (p=0.01) which yielded similar results. Conclusion Laxatives may cause distress and the less used, the better. However, procedural discomfort accounts for the overall poorer experience of CS patients compared to CTC and CCE, even though the latter cohorts contain more patients at risk of poorer tolerance (prior failed colonoscopy, refusal of colonoscopy and female predominance.[4] Investigation should be tailored according to the likely diagnoses and patient preference. References . Holt EW, et al., J Gastrointest Liver Dis 2014;23:135–40. . Standards of practice committee of the ASGE. Gastrointest Endosc 2011;74:745–752. . Spada C, et al., Gut 2015;64:272–281. . Ojidu H, McAlindon ME. Gut2016;65(1):A61. Disclosure of Interest None Declared


The section contains links to Aboriginal provincial associations, government programs and services related to the environment. It also contains links to environmental issues affecting Aboriginal people and to documents on natural resources management.