OBJECTIVE
To identify a causative mutation for dilated cardiomyopathy (DCM) in Doberman Pinschers by sequencing the coding regions of 10 cardiac genes known to be associated with familial DCM in humans.

ANIMALS
5 Doberman Pinschers with DCM and congestive heart failure and 5 control mixed-breed dogs that were euthanized or died.

PROCEDURES
RNA was extracted from frozen ventricular myocardial samples from each dog, and first-strand cDNA was synthesized via reverse transcription, followed by PCR amplification with gene-specific primers. Ten cardiac genes were analyzed: cardiac actin, α-actinin, α-tropomyosin, β-myosin heavy chain, metavinculin, muscle LIM protein, myosinbinding protein C, tafazzin, titin-cap (telethonin), and troponin T. Sequences for DCM-affected and control dogs and the published canine genome were compared.

RESULTS
None of the coding sequences yielded a common causative mutation among all Doberman Pinscher samples. However, 3 variants were identified in the α-actinin gene in the DCM-affected Doberman Pinschers. One of these variants, identified in 2 of the 5 Doberman Pinschers, resulted in an amino acid change in the rod-forming triple coiled-coil domain.

CONCLUSIONS AND CLINICAL RELEVANCE
Mutations in the coding regions of several genes associated with DCM in humans did not appear to consistently account for DCM in Doberman Pinschers. However, an α-actinin variant was detected in some Doberman Pinschers that may contribute to the development of DCM given its potential effect on the structure of this protein. Investigation of additional candidate gene coding and noncoding regions and further evaluation of the role of α-actinin in development of DCM in Doberman Pinschers are warranted.


Many problems in environmental and soil research require techniques that quantify the soil microenvironment. It has become increasingly apparent that we need novel micro-analytical techniques to compliment well established methods that study soils at macro-spatial scales. Despite tremendous progress in this field over the last decade, quantitative methods have developed within separate disciplines and operate at different spatial scales hampering their integration. Moreover, it means that opportunities to integrate these methods may be overlooked. In this paper we develop methods that enable integration of a 3-D non-invasive technique to characterise soil structure (X-ray CT) with a 2-D spectroscopic method that characterises the spatial distribution of chemical elements on surfaces (SEM-EDX). First we developed statistical software to locate the 2-D plane in which SEM-EDX analyses were performed within the 3-D volume. Then we demonstrate that selected compounds, including particulate sources of C and CaCO3, can be quantified with SEM-EDX and subsequently visualized within the 3-D soil environment. Finally, we demonstrated that when we characterized sequential slices with SEM-EDX we could use co-kriging methods to predict the 3-D spatial distribution of chemical elements. We discuss the possibilities and problems that need to be resolved to combine these methods.


This article presents our analysis of faculty open-ended written comments (n=156) on the topic of grade inflation. Our review of faculty comments reveals stark disagreement among the faculty on grade inflation. Further qualitative analyses reveal that faculty repeatedly point to three themes in their statements on grade inflation: university mission, mastery learning, and administrative policy. Interestingly, faculty use these themes both ways. That is, no matter the position that faculty take, faculty use these themes to explain and validate their own positions on grade inflation. We conclude that this reflects post modern society. "Was this survey ... necessary? You are attempting to prove there is grade inflation--why? Whom would you have control grades if not the individual instructor?" As this comment suggests, the subject of college grades and grade inflation is a sensitive topic among faculty. This very sensitivity, sometimes defensive and sometimes bordering on aggression, can explain why many are reluctant to study grade inflation (Levine, 1987; Mitchell, 1998). Though not a popular topic, we decided to study grade inflation at our University, a public open-admissions university, by surveying faculty. The majority of the faculty (53%, n=329) responded to our survey. The high response rate allowed us to examine faculty position on grade inflation on any number closed-ended dimensions. These survey results we report elsewhere (McSpirit, Kopacz, Jones and Chapman, 2000). What we report here, is what we believe to be our most interesting analyses, the results from our analyses of open-ended comments of faculty on grade inflation. In the space provided on our survey, nearly half (n=156) of surveyed faculty provided lengthy and varied statements on their own views on grade inflation. Some faculty wrote of their own grading philosophies. Others expressed their own feelings on whether rising grades posed a threat to institutional integrity and academic standards. Some others went on to identify what they perceived to be the cause of the problem and what should be done about it. Still others wrote that very little could be done about it because it was endemic to society: "It is a national problem. ...," and one that they tied to social and moral decline: "Lack of a work ethic, pride of achievement, [and] `do as little as I can to get by' attitude ..." But, not all faculty who expressed their views, expressed the view that grade inflation is a social or academic malignancy. Yet, both those who did and those who did not went on to explain the basis for their belief. Strangely enough, faculty often started from the same explanation to argue their distinct positions on grade inflation. In the following sections, we describe two common explanations which faculty, on both sides, use to argue their position on grade inflation. Specifically, we describe that the faculty target both the University mission statement and mastery learning approaches to justify why grade inflation is a problem or not a problem. Other than these two themes, we find that faculty are also reluctant to identify themselves as the cause for grade inflation. Many faculty are more likely to blame the administration or university policy for why grades might be unreasonably high rather than indict themselves. University Mission Statement The mission of the university provided one of the most interesting justifications for both those who believed in the existence of grade inflation and those for who did not. At the institution where we conducted the survey, a major part of the institutional mission is to provide a college opportunity for students from a rural, poor area of Appalachia. We must note that in spite of this mission and the validity of the following faculty statements, the university has a nationally recognized Honors program and many other academic and professional programs with national reputation. The University enrolls many well-prepared students, both in and out of the Honors program, who are willing and able to devote much time and effort to their academic studies. …


Research shows that African Americans and Hispanics experience longer delays in dementia diagnosis than do whites. This study focuses on the duration and direction of help-seeking pathways among individuals who had either very short (median: 1 year, 9 months) or very long (median: 9 years, 2 months) times-to-diagnosis. Participants reported the frequencies of events, actions, outcomes, and results around four key time points in the pathway: First Notice of a Problem, Recognition of a Pattern, First Doctor Visit, and Final Diagnosis. Using reported frequencies of events, actions, and outcomes around these events, we constructed the modal pathway or 'canonical narrative' and then used correspondence analysis of the data to model short and long pathways. Short pathways were dominated by stepwise movement toward diagnosis (84.5% of inertia or variance) and some ambivalence around symptom recognition (10%). Long pathways were marked by a shift away from movement toward diagnosis (44.5%) but toward the family's taking over key quotidian tasks (55.5%). We suggest that Hispanic and African American caregivers effectively provide a kind of 'scaffolding' for the patient, which may in fact be adaptive rather than dysfunctional. Thus, delayed diagnoses and non-diagnosis may reflect 'active' choices for dealing with the disease rather than avoidance of the problem.


Objectives: First-trimester levels of PAPP-A and free β-hCG are decreased in pregnancies conceived as a result of assisted reproduction, especially in-vitro fertilization (IVF). The aim of this study was to evaluate if sub-fertility, measured as increased timeto-pregnancy (TTP) in spontaneously conceived pregnancies, affects the levels of PAPP-A and free β-hCG. Methods: We included 13,935 singleton pregnant women, who attended the prenatal screening program between January 2005 and December 2010 and gave birth at Aarhus University Hospital, Denmark. TTP was evaluated through a questionnaire completed by the pregnant women in the first trimester. PAPP-A and free β-hCG were measured between gestational week 8+0 and 13+6. IVF pregnancies (n = 962) were used for comparison, and we excluded unintended pregnancies (n = 2.797) and pregnancies with no information about TTP (n = 460), which left 9,507 spontaneous pregnancies with information about TTP. Results: The median PAPP-A MoM was significantly lower in pregnant women with a TTP ≥ 24 months compared with the reference group with a TTP < 6 months (0.96 MoM vs. 1.06 MoM, P = 0.003). The levels were not as low as in IVF pregnancies (0.89 MoM). The median level of free β-hCG was also significantly lower in pregnancies with a TTP ≥ 24 months compared with pregnancies with a TTP < 6 months (1.04 MoM vs. 1.12 MoM, P = 0.03). TTP at 6–11 months and TTP at 12–23 months did not significantly affect levels of PAPP-A or free β-hCG. Conclusions: Increased time-to-pregnancy in spontaneously conceived pregnancies is associated with decreased levels of PAPP-A and free β-hCG measured in the first trimester, suggesting that some of the well-known decrease in IVF-pregnancies could be related to sub-fertility instead of the infertility treatment per se. OP23.06 Effects of method of conception and gestational age on first trimester biochemical markers


The influence of alloying elements, deliberate or otherwise, and material processing on the performance of aluminium during surface treatment and finishing are considered. Thus, with a significant focus on copper, but with consideration of other elemental additions, the behaviour of aluminium during growth of oxide at ambient temperature, etching or pickling, conversion coating and anodizing, essential processes for generation of fit-for-purpose products, is highlighted. Further, such processes generate, modify or transform the initially present air-formed alumina film. Consequently, with knowledge of the phenomena proceeding at the alloy/film and film/environment interfaces and those within anodic or other films, the possibility of controlling features of nanoscale dimensions for improved performance arises. For example, deliberate selection of alloying elements enables control of nanotextures formed at treated surfaces, and formation of compositionally and morphologically modified films as well as generation of nanoparticles with various functional properties.


This thesis project studies and compares two of the most commonly used electric driving methods of induction motors (IM). These methods, which have been used for three decayed are Field Orientation Control (FOC) and Direct Torque Control (DTC). Theoretical background for both methods is explained. Due to its simplicity of use, MATLAB/ SIMULINK is used to simulate the dynamic model of (IM) and applying both techniques on it. The comparative study of speed, torque, and flux is performed under two cases which are the normal operation and in the presence of voltage-sag and short interruption.


BACKGROUND: Estimates of the case-fatality rate (CFR) associated with coronavirus disease 2019 (COVID-19) vary widely in different population settings. We sought to estimate and compare the COVID-19 CFR in Canada and the United States while adjusting for 2 potential biases in crude CFR. METHODS: We used the daily incidence of confirmed COVID-19 cases and deaths in Canada and the US from Jan. 31 to Apr. 22, 2020. We applied a statistical method to minimize bias in the crude CFR by accounting for the survival interval as the lag time between disease onset and death, while considering reporting rates of COVID-19 cases less than 50% (95% confidence interval 10%–50%). RESULTS: Using data for confirmed cases in Canada, we estimated the crude CFR to be 4.9% on Apr. 22, 2020, and the adjusted CFR to be 5.5% (credible interval [CrI] 4.9%–6.4%). After we accounted for various reporting rates less than 50%, the adjusted CFR was estimated at 1.6% (CrI 0.7%–3.1%). The US crude CFR was estimated to be 5.4% on Apr. 20, 2020, with an adjusted CFR of 6.1% (CrI 5.4%–6.9%). With reporting rates of less than 50%, the adjusted CFR for the US was 1.78 (CrI 0.8%–3.6%). INTERPRETATION: Our estimates suggest that, if the reporting rate is less than 50%, the adjusted CFR of COVID-19 in Canada is likely to be less than 2%. The CFR estimates for the US were higher than those for Canada, but the adjusted CFR still remained below 2%. Quantification of case reporting can provide a more accurate measure of the virulence and disease burden of severe acute respiratory syndrome coronavirus 2.


College students today have the harrowing task of sifting through massive amounts of information that no longer fits into nice, neat categories. The role of the librarian has shifted along with the information landscape, from the role of information gatekeeper to information guide. As information has become more prolific and accessible, it is more important than ever to teach students how to evaluate the information they discover to determine whether it is appropriate and relevant for their information need. In a world filled with fake news and constructed realities, the idea that truth has value, let alone exists, can seem outdated or even hostile. However, Christ-followers believe that part of the revelatory process is discovering the truth. Christian librarians should instruct our students to use discernment to seek truth even when the world avoids it. Christian librarians can combine dedication to the librarian profession, passion for teaching, and immersion in Christian values to guide students in truth-seeking behavior.


This introductory-level text is ideal for a college-level course that covers the basic elements of food preparation, food service, and food science, and provides the information needed by students preparing for careers in one of the many related fields of the food industry. Highly researched and comprehensive in coverage, while also student focused and manageable for any quarter or semester course, UNDERSTANDING FOOD, SECOND EDITION thoroughly explores the science of food through core material on food selection and evaluation, food safety and food chemistry. The many aspects of food service are covered including meal planning, basic food preparation, equipment, food preservation and government regulations. The final sections of the text supply food preparation, classification, composition, selection, purchasing and food storage information for a range of traditional food items. A rich illustration and photo program and unique pedagogical features help to make the information easily understandable and interesting to students.


George Frideric Handel's eight Great Suites performed by Danny Driver (piano): Suite No 1 in A major HWV426; Suite No 2 in F major HWV427; Suite No 3 in D minor HWV428; Suite No 4 in E minor HWV429; Suite No 5 in E major HWV430;
Suite No 6 in F sharp minor HWV431; Suite No 7 in G minor HWV432; Suite No 8 in F minor HWV433; Suite in C minor 'Partita' HWV444; Suite in E minor HWV438; Chaconne in G major HWV435.

Danny Driver's recordings of CPE Bach's keyboard works have been much admired: praised by critics as deeply stylish and revelatory accounts of eighteenth-century works on a modern piano, with Driver's impeccable pianism constantly present. Now he turns to Handel's 'Eight Great Suites', largely written when the composer was resident in Cannons, near London.

The 'Great Suites' are an inspired, idiosyncratic amalgam of Gallic courtly dances, Italian vocal lyricism, Teutonic counterpoint and robust English tunefulness. Whereas Bach's keyboard suites follow broadly similar patterns, centred on the traditional French dance sequence of Allemande, Courante, Sarabande and Gigue, Handel's are unpredictable, with no two suites alike in the number and ordering of their movements. There are fugues, arias with variations, Italian-style sonata movements, even (in No 7) a Passacaglia. Compared with the elaborate finish of Bach's suites, Handel's often give the impression of written-down improvisations. In the fantasia-like Preludes, especially, Handel hints at his own genius as extemporiser, while leaving plenty to the performer's own imagination.


BACKGROUND AND OBJECTIVES: Reliable data on the persistence of the ex-pression of tumor antigens over time and consequent analyses of its impact on the clinical course of malignancies are crucial for their evaluation as clinical parameters and immunotherapeutic targets. This study represents the first longitudinal investiga-tion of Cancer-Testis (CT) antigen expression in Multiple Myeloma (MM) patients and its relevance for therapeutic, diagnostic, and predictive clinical use.
DESIGN AND METHODS: 330 bone marrow (BM) samples from 129 MM patients and 40 samples from healthy BM donors were screened for the expression of 4 CT antigens (MAGE-C1/CT7, MAGE-C2/CT10, MAGE-A3, and SSX-2) by conventional RT-PCR. Selected patient samples were analyzed by real-time PCR and Western Blot. Finally, statistical analyses of experimental and clinical data were carried out.
RESULTS: CT antigens were frequently and persistently expressed, indicating that down-regulation of these immunogenic targets does not represent a common tumor escape mechanism in patients with multiple myeloma. Strong correlations of CT anti-gen expression levels with the clinical course of myeloma patients as indicated by the number of bone marrow-residing plasma cells and peripheral paraprotein levels further suggest a potential role for CT antigens as independent tumor markers. Inte-restingly, antigen MAGE-C1/CT7 was found to represent an extraordinarily frequent coexpression partner, indicating a potential role as a gatekeeper gene. In addition, MAGE-C1/CT7 represented an indicator of early relapse and dramatically reduced survival in patients following allogeneic stem cell transplantation (alloSCT).
CONCLUSIONS: Analyzing a large number of patients with MM, this study estab-lished essential parameters endorsing the use of CT antigens as immunotherapeutic target structures and for the first time suggested the use of the mRNA expression of distinct CT antigens as diagnostic and predictive markers.


Background New oral anticoagulants (NOAC), such as apixaban, rivaroxaban and dabigatran, are indicated for stroke prevention in atrial fibrillation and acute thromboembolic events. Provision of treatment with NOAC is contingent on prior administrative approval according to district criteria in order to obtain the health service provider's discount. Before our project, there was no clear policy for submission of requests when starting treatment with NOAC during hospitalisation. Many patients discharged from our hospital with a prescription for NOAC without the administrative approval chose not to purchase the drug at full price and to turn to the family physician to request administrative approval. As a result, a gap in medical treatment may occur which puts the patient at risk that may have negative consequences on their health state. Purpose To establish a process and implement a workflow for requesting administrative approval when starting NOAC treatment during hospitalisation. Material and methods Mapping the desired process for requesting administrative approval for new treatment with NOAC for patients members of Clalit Health Services (CHS), the largest health maintenance organisation (HMO) in Israel. Meir Medical Centre belongs to Clalit HMO. Creating a request form for the administrative approval. Presenting the process in the internal wards. Implementing the process and conducting a pilot in internal wards while monitoring sending requests and receiving administrative approval for the treatment. Results Before starting our project, we collected data regarding request submission when starting treatment with NOAC. We found that of 42 patients (members of Calit HMO) who started a new treatment, only 1 (2.4%) approval request was sent during hospitalisation. Preliminary data at the end of a month of a pilot in 3 internal wards showed that treatment with NOAC was started for 32 patients. 22 (68.7%) were members of Clalit HMO. For 14 (63.6%), a request form for the administrative approval was sent while they were still hospitalised. Conclusion By establishing a process for requesting administrative approval for new treatment with NOAC during hospitalisation, we improved patient safety and ensured continuity of treatment with these important drugs during transition from the hospital to the community setting. References and/or acknowledgements Acknowledgement for internal ward's staff. No conflict of interest


Background: Bone morphogenetic proteins require proteolytic processing to generate the mature ligand. Results: The BMPs Gbb and Scw have three cleavage sites, and BMP7 has one, which are differentially required to produce the functional ligand. Conclusion: Gbb, Scw, and BMP7 have distinct processing requirements despite being closely related. Significance: Rapid evolution of cleavage sites is a general mechanism for fine-tuning BMP ligand activity to function. Bone morphogenetic proteins (BMPs) are synthesized as proproteins that undergo proteolytic processing by furin/subtilisin proprotein convertases to release the active ligand. Here we study processing of BMP5/6/7/8 proteins, including the Drosophila orthologs Glass Bottom Boat (Gbb) and Screw (Scw) and human BMP7. Gbb and Scw have three functional furin/subtilisin proprotein convertase cleavage sites; two between the prodomain and ligand domain, which we call the Main and Shadow sites, and one within the prodomain, which we call the Pro site. In Gbb each site can be cleaved independently, although efficient cleavage at the Shadow site requires cleavage at the Main site, and remarkably, none of the sites is essential for Gbb function. Rather, Gbb must be processed at either the Pro or Main site to produce a functional ligand. Like Gbb, the Pro and Main sites in Scw can be cleaved independently, but cleavage at the Shadow site is dependent on cleavage at the Main site. However, both Pro and Main sites are essential for Scw function. Thus, Gbb and Scw have different processing requirements. The BMP7 ligand rescues gbb mutants in Drosophila, but full-length BMP7 cannot, showing that functional differences in the prodomain limit the BMP7 activity in flies. Furthermore, unlike Gbb, cleavage-resistant BMP7, although non-functional in rescue assays, activates the downstream signaling cascade and thus retains some functionality. Our data show that cleavage requirements evolve rapidly, supporting the notion that changes in post-translational processing are used to create functional diversity between BMPs within and between species.


Abstract During the last decades, the living conditions for young people with disabilities have changed dramatically in Sweden, as well as in other parts of the Western world. The boundaries between what is considered normal as opposed to different have become less clear as a result of these changes. This has been followed by new problems regarding integration and changing patterns of marginalization. The aim of this study was to gain a deeper understanding of the ways in which young adults' social identity is shaped by their dual belongings: to the category of individuals with disabilities as well as to mainstream society. In- depth interviews were carried out with 15 young adults with mental disabilities and mild intellectual disabilities occasionally combined with various forms of social problems. The analysis focused on the ways in which the young adults related to what they describe as normal and different as well as their strategies for navigating between them. The data was subsequently divided into three categories: Pragmatic Navigators, Critical Challengers, and Misunderstood Rebels, which reflect the ways in which the respondents describe themselves and the perspective they have developed to manage their existence.


From the silent era through the 1950s, the U.S. Department of Agriculture was the preeminent government filmmaking organization. In the United States, USDA films were shown in movie theaters, public and private schools at all educational levels, churches, libraries and even in open fields. For many Americans in the early 1900s, the USDA films were the first motion pictures they watched. And yet USDA documentaries have received little serious scholarly attention. The lack of serious study is especially concerning since the films chronicle over half a century of American farm life and agricultural work and, in so doing, also chronicle the social, cultural, and political changes in the United States at a crucial time in its development into a global superpower. Focusing specifically on four key films, Winn explicates the representation of African Americans in these films within the socio-political context of their times. The book provides a clearer understanding of how politics and filmmaking converged to promote a governmentally sanctioned view of racism in the U.S. in the early 20th century.


For any two observables on a full tribe we can always construct a two–dimensional observable. In this case the crucial role is played by pointwise multiplication of the functions of tribe. Riean and Mundici, studied semisimple MV–algebras enriched by an additional product operation. The abstract product operation on MV–algebra is relating with the natural pointwise multiplication of functions. The sequential product on effect algebras defined by Gudder and Geechie, is based on the similar idea as above. In this paper the meet function as a generalization of the product is defined and the properties of D–posets with meet function are presented.


This study provides an insight into the role and functions of a remote Indigenous radio station that broadcasts to five communities in the Northern Peninsula Area (NPA) of Cape York, Queensland. It evaluates the activities of NPA Radio in the context of previous research that investigates how community-based media forms empower and inform specific sectors of society. Using field research, the study reveals five key themes relating to the role of NPA Radio in the communities of Seisia, New Mapoon, Bamaga, Umagico and Injinoo. These can briefly be described as providing information and community news; maintaining and sharing culture; connecting the communities of the NPA; connecting individuals and key services; and fostering a sense of belonging and ownership.


We investigate the kinematics and ionization structure of the broad emission line region of the gravitationally lensed quasar QSO2237+0305 (the Einstein cross) using differential microlensing in the high- and low-ionization broad emission lines. We combine visible and near-infrared spectra of the four images of the lensed quasar and detect a large-amplitude microlensing effect distorting the high-ionization CIV and low-ionization H α line profiles in image A. While microlensing only magnifies the red wing of the Balmer line, it symmetrically magnifies the wings of the CIV emission line. Given that the same microlensing pattern magnifies both the high- and low-ionization broad emission line regions, these dissimilar distortions of the line profiles suggest that the high- and low-ionization regions are governed by different kinematics. Since this quasar is likely viewed at intermediate inclination, we argue that the differential magnification of the blue and red wings of H α favors a flattened, virialized, low-ionization region whereas the symmetric microlensing effect measured in CIV can be reproduced by an emission line formed in a polar wind, without the need of fine-tuned caustic configurations.


The article highlights the worldwide dissemination of precision agriculture scientific researches published from the period of 1996–2018, data gathered in the Scopus citation database, using the science mapping method. The findings show that there is a constant rise in the number of publications in precision agriculture. The USA is not only leading in the adoption of precision agriculture technologies but also in the publication of papers, accompanied by China placed in second place. The most frequent keywords highlighted the main topics authors concentrated on more, and the national affiliation of most cited papers was the USA. The main prominence and contributions of the results present scientific research trends in precision agriculture in the last two decades, and demonstrate the main countries, authors and organizations who have contributed, and were more productive in this area.


Introduction: Biosimulation models might play a crucial role to train interventional procedures especially acute endbronchial bleedings.The simulation of an repeated emergency situation enables the bronchoscopist and his team to act professionally. Background: Until now the available models couldn9t reproduce this key aspect in interventional bronchoscopy in a satisfactory way. Methods: We developed a new biosimulation model with 2 transparent covers and a free moving diaphragm.The control unit with an vacuum pump allows full expansion of the pig training lung.A flexible bedded connector adds the trachea of the head to the pig lung.This allows a training in rigid bronchoscopy on an expanded pig lung.We inserted flexible tubes into the bronchial tree to simulate different bleeding situations with artificial blood. The realistic effect was increased by sutured "endobronchial tumors". Results: At an interventional training course in November 2010 organized by the Austrian Society of Pneumology the system allowed the participants to train various kinds of interventions.The feedback given by all the 16 trainees showed a convincing and realistic effect to train interventional procedures.Furthermore the possibility of managing the bleeding situations could be trained. Conclusions: This model might be helpful to develop algorithms for all interventional procedures especially connected to the handling of bleedings.


The sympathetic nervous system is markedly activated in most patients with congestive heart failure, but it is not clear whether such activity is clinically beneficial (and should be enhanced) or detrimental (and should be blocked). Some insights into this question can be gained by reviewing the results of clinical trials with β-adrenergic agonists and antagonists. Long-term treatment with agents that stimulate the β-receptor (prenalterol and pirbuterol) has not proved to be useful in the treatment of chronic heart failure; moreover, prolonged treatment with β -receptor -agonists (dobutamine and pirbuterol) may adversely affect survival. Most of the studies with β -agonists, however, have employed agents that interact nonselectively and with a high degree of intrinsic activity with both β1 and β2-receptors. It is possible that the problems that have been encountered with the use of β -agonists could be minimized by agents that are more selective and have less intrinsic activity. Yet, such agents may actually function as β-adrenergic antagonists (rather than agonists) in states of heightened sympathetic activity. Indeed, sustained therapy with drugs that attenuate the effects of the sympathetic nervous system (by blocking tyrosine hydroxylase or β-adrenergic receptors) may produce hemodynamic and clinical improvement and may reduce long-term mortality in chronic heart failure. Although β-adrenergic blockade carries important risks, these might be minimized by the use of drugs that spare myocardial and vascular β2-receptors or possess some intrinsic agonist activity. These observations suggest that the sympathetic nervous system exerts both beneficial and detrimental actions in chronic heart failure, and these roles modify the safety and efficacy of drugs that are designed to enhance or interfere with the system.


PURPOSE
To unravel the regulatory network underlying nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) -mediated lymphomagenesis of anaplastic large-cell lymphoma (ALCL) and to discover diagnostic genomic classifiers for the recognition of patients with ALK-positive and ALK-negative ALCL among T-cell non-Hodgkin's lymphoma (T-NHL).

PATIENTS AND METHODS
The transcriptome of NPM-ALK-positive ALCL cell lines was characterized by silencing the expression of ALK or STAT3, a major effector of ALK oncogenic activity. Gene expression profiling (GEP) was performed in a series of systemic primary T-NHL (n = 70), including a set of ALK-positive and ALK-negative ALCL (n = 36). Genomic classifiers for ALK-positive and ALK-negative ALCL were generated by prediction analyses and validated by quantitative reverse-transcriptase polymerase chain reaction and/or immunohistochemistry.

RESULTS
In ALCL cell lines, two thirds of ALK-regulated genes were concordantly dependent on STAT3 expression. GEP of systemic primary T-NHL significantly clustered ALK-positive ALCL samples in a separate subgroup, underscoring the relevance of in vitro ALK/STAT3 signatures. A set of genomic classifiers for ALK-positive ALCL and for ALCL were identified by prediction analyses. These gene clusters were instrumental for the distinction of ALK-negative ALCL from peripheral T-cell lymphomas not otherwise specified (PTCLs-NOS) and angioimmunoblastic lymphomas.

CONCLUSION
We proved that experimentally controlled GEP in ALCL cell lines represents a powerful tool to identify meaningful signaling networks for the recognition of systemic primary T-NHL. The identification of a molecular signature specific for ALCL suggests that these T-NHLs may represent a unique entity discernible from other PTCLs, and that a restricted number of genes can be instrumental for clinical stratification and, possibly, therapy of T-NHL.


Entrepreneurship is all over the world emerging as gainful employment and a means of helping women to improving their economic and social status while asserting themselves in the business world. This paper examined the influence of socio-cultural factors on growth of women owned micro and small enterprises (MSEs) in rural areas of Kitui County. Growth of micro and small enterprise means increase in sales, profits, employees, production and service lines. The study used descriptive survey as the research design involving a target population of 390 women owned micro and small entrepreneurs drawn from manufacturing, agriculture, commerce and services sectors in Kitui County. Proportionate stratified sampling was used to form a sample of 194 women entrepreneurs. Simple random sampling was applied on the sample to select the respondents from each sector. Questionnaires and observation guide were used to collect data which was analysed using descriptive and inferential statistics. The results suggested that socio-cultural factors positively influenced the growth of women- owned MSEs. The study recommended for the government continuously review laws pertaining to women's land ownership and inheritance rights, efforts to be made to educate both women and men on their respective rights while ensuring full implementation of the new constitution to empower women and be able to change their roles. Special programmes to train, capacity build and mentor women particularly in entrepreneurship should be put in place to change women mind set to make women- owned enterprises more competitive while the government should continuously work towards providing conducive business environment.


Public confidence in policing has received much attention in recent years, but few studies outside of the United States have examined the sociological and social-psychological processes that underpin trust and support. This study, conducted in a rural English location, finds that trust and confidence in the police are shaped not by sentiments about risk and crime, but by evaluations of the values and morals that underpin community life. Furthermore, to garner public confidence, the police must be seen first to typify group morals and values and second to treat the public with dignity and fairness. All these findings are consistent with the perspective that people are Durkheimian in their attitudes towards crime, policing and punishment-a perspective developed here in this paper.


With great vigour and from the vantage point of long experience of writing and teaching Jewish history, Moshe Rosman treats the key questions that postmodernism raises for the writing of Jewish history.What is the relationship between Jewish culture and history and those of the non-Jews among whom Jews live? Can we-in the light of postmodernist thought-speak of a continuous, coherent Jewish People, with a distinct culture and history? What in fact is Jewish cultural history, and how can it be written? How does gender transform the Jewish historical narrative? How does Jewish history fit into the multicultural paradigm? Has Jewish history entered a postmodern phase? How can Jewish history utilize the methodologies of other disciplines to accomplish its task? All these are questions that Jewish historians need to think about if their work is to be taken seriously by mainstream historians and intellectuals, or indeed by educated Jews interested in understanding their own cultural and historical past. While engaging with the questions raised by postmodernists, the author adopts a critical stance towards their work. His basic claim is that it is possible to incorporate, judiciously, postmodern innovations into historical scholarship that is still based on documentary research and critical analysis. The resulting endeavor might be termed 'a reformed positivism'. Rosman presents a concentrated, coherent, cogent argument as to what considerations must be brought to bear on the writing of Jewish history today. By highlighting in one book the issues raised by postmodernism, How Jewish is Jewish History? provides those in the field with a foundation from which to discuss how it should be practiced in light of this generation's challenges. It is a valuable resource for students of Jewish history and historiography and a handy tool for scholars who must confront the issues aired here in their own more narrowly focused scholarly works.


Activated carbon (AC) has been widely used as catalyst for oxygen reduction reaction (ORR) in air-cathode microbial fuel cells (MFCs). Here we demonstrate a new method to improve the AC air-cathode by blending it with reduced graphene oxide (rGO). rGO sheets are first deposited on Ni foam and AC is then brushed onto it with controlled mass loading. rGO sheets not only improve the electrical conductivity of AC, but also provide a large number of ORR areas. Rotating ring disk electrode measurements reveal that the number of transferred electrons at rGO-AC cathode is 3.5, indicating the four-electron pathway is the dominant process. Significantly, the MFC with rGO-AC cathode delivers a maximum power density of 2.25 ± 0.05 W/m^2, which is substantially higher than that of plain AC cathode (1.35 ± 0.07 W/m^2) and those for other air-cathode MFCs using AC as ORR catalyst under the same mass loading.


Multiple overtracing strokes are common drawing behaviors in freehand sketching; that is, additional strokes are often drawn repeatedly over the existing ones to add more details. This paper proposes a method based on stroke-tolerance zones to group multiple overtraced strokes which are drawn to express a 2D primitive, aiming to convert online freehand sketches into 2D line drawings, which is a base for further 3D reconstruction. Firstly, after the user inputs a new stroke, a tolerance zone around the stroke is constructed by reference to its polygonal approximation points obtained from the stroke preprocessing. Then, the input strokes are divided into stroke groups, each representing a primitive through the stroke grouping process based on the overtraced ratio of two strokes. At last, each stroke group is fitted into one or more 2D geometric primitives including line segments, polylines, ellipses, and arcs. The proposed method groups two strokes together based on their screen-space proximity directly instead of classifying and fitting them firstly, so that it can group strokes of arbitrary shapes. A sketch-recognition prototype system has been implemented to test the effectiveness of the proposed method. The results showed that the proposed method could support online multiple overtracing freehand sketching with no limitation on drawing sequence, but it only deals with strokes with relatively high overtraced ratio.


BACKGROUND
World Health Organization guidelines for prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) recommend administration of zidovudine and single-dose nevirapine (NVP) for HIV-1-infected women who are not receiving treatment for their own health or if complex regimens are not available. This study assessed antiretroviral resistance patterns among HIV-infected women and infants receiving single-dose NVP in Thailand, where the predominant circulating HIV-1 strains are CRF01_AE recombinants and where the minority are subtype B.

METHODS
Venous blood samples were obtained from (1) HIV-infected women who received zidovudine from 34 weeks' gestation and single-dose NVP plus oral zidovudine during labor and (2) HIV-infected infants who received single-dose NVP after birth plus zidovudine for 4 weeks after delivery. HIV-1 drug resistance testing was performed using the TruGene assay (Bayer HealthCare).

RESULTS
Most mothers and infants were infected with CRF01_AE. NVP resistance was detected in 34 (18%) of 190 women and 2 (20%) of 10 infants. There was a significantly higher proportion of NVP mutations in women with delivery viral loads of >50,000 copies/mL (adjusted odds ratio, 8.5; 95% confidence interval, 2.2-32.8, P = .002 for linear trend) and in those with subtype B rather than CRF01_AE infections (38% vs. 16%; adjusted odds ratio, 3.6; 95% confidence interval, 1.1-11.8; P = .038).

CONCLUSIONS
The lower frequency of NVP mutations among mothers infected with subtype CRF01_AE, compared with mothers infected with subtype B, suggests that individuals infected with subtype CRF01_AE may be less susceptible to the induction of NVP resistance than are individuals infected with subtype B.


The I4U consortium was established to facilitate a joint entry to NIST speaker recognition evaluations (SRE). The latest edition of such joint submission was in SRE 2018, in which the I4U submission was among the best-performing systems. SRE'18 also marks the 10-year anniversary of I4U consortium into NIST SRE series of evaluation. The primary objective of the current paper is to summarize the results and lessons learned based on the twelve subsystems and their fusion submitted to SRE'18. It is also our intention to present a shared view on the advancements, progresses, and major paradigm shifts that we have witnessed as an SRE participant in the past decade from SRE'08 to SRE'18. In this regard, we have seen, among others , a paradigm shift from supervector representation to deep speaker embedding, and a switch of research challenge from channel compensation to domain adaptation.


The effects of oleuropeoside were studied on the electromechanical properties of isolated guinea-pig atria. In spontaneously beating right atria, ole-uropeoside decreased the amplitude of contractions (IC50 = 1.3 0.2 x 104M), slightly decreased atrial rate, and lengthened sinus node recovery time. Ole-uropeoside also inhibited peak contractile force in electrically driven left atria incubated in normal (IC50 = 1.5 0.5 x 1W4M) and in 27mM K Tyrode solution (IC50 = 1.7 0.4 x 104M). These negative inotropic effects were not accompanied by significant changes in the characteristics of action potentials recorded in atria incubated in either normal or depolarizing solutions. These results indicate that oleuropeoside produced an electromechanical uncoupling that cannot be attributed to an inhibitory effect on Ca2 entry through L-type channels. Therefore, the negative inotropic effect may reflect an action of oleuropeoside perhaps at an intracellular level.


Background: Organs transplantation is the only treatment for end-stage organ failure. However, the disparity between organs availability and the number of patients in the waiting lists is widening globally, especially in Iraq for many reasons. This study aims to assess the level of attitudes and perceptions among Iraqi young adults towards organs donation and transplantation as the first study to be conducted in Iraq for such purpose. Methods: This observational study was conducted among 912 Iraqi young adults through a structured questionnaire which was disseminated among social media platforms. Participants consented before filling the questionnaire and their responses were analyzed to test the hypothesis of the study. Results: Most of the participants were females, Muslims and in their undergraduate level. Overall, 84.2% of the participants were willing to donate their organs after death and (97.9%) of them actually agreed to sign for organs donation. Most of those who were not willing to donate have no idea whether their religion approves it or not. There was no statistically significant difference in willingness to donate between different socioeconomic classes or residency areas. Conclusions: Most of the participants are convinced with donating their organs after death and are willing to sign for organ donation programs, advocating for initiating an official governmental transplant agency with multiple local committees distributed among health directorates all over the country managing it. The hesitancy to donate organs was attributed mostly to religious and associated with lack of knowledge issues, thus education might be the key to positive attitudes. Significance for public health Organs donation and transplantations are crucial for end stage organ failure patients. Assessing the attitudes and perceptions of the population especially of young adults will help to create a throughout vision on the future of this socially conflicting issue. These attitudes will reflect back to affect the population as a whole. Putting these findings out as the first study ever conducted in Iraq on such topic will definitely help the policy makers to observe the need for an action by providing yet another scientific and accurate justification to work actively on the project of organs donation for the sake of general Iraqi people.


Pipelines perform a critical function in the petroleum business by transporting hydrocarbon commodities between oil fields, refineries, and consumer markets. We formulate an optimization problem for determining the optimal pumping modes and flow configuration for liquid pipeline operations. Based on requested flow rates and commodity prices submitted by users of the pipeline system, the system manager can solve an optimization problem to determine flow rates allocated to all customers, flows on each pipeline section, and pumps station operating settings in order to maximize economic value provided by a pipeline while adhering to limitations of pump machinery and the physics of fluid flow. In particular, the optimal solution will maximize the economic benefit for the pipeline transport network users and utilization of system capacity while also minimizing the energy expended in operation. This problem is nonconvex, and solutions are only guaranteed to be locally optimal. In this study we pose a mathematical optimization formulation with minimal modeling that captures the basic phenomena involved, and an algorithm based on general-purpose interior point optimization is proposed for efficient solution. We demonstrate our approach on a realistic case study based on a pipeline system in the United States.


Ram-air wings form an ever increasing market of soft fabric, air inflated wings. They are primairily used in air sports such as parachuting, paragliding and kiting. Ram-air kites may also be used for electric power generation by letting the kite pull a cable from a drum that is connected to a generator. An example if this principle is the Laddermill concept. But since ram-air wings are flexible by nature they will deform and depart from their intended design shape when they are loaded by aerodynamic forces. These deformations generally affect the performance of the wings adversely. Kites with a higher lift-to-drag ratio on the Laddermill could mean a direct increase of the energy produced per square meter of kite. Besides this benefit for the Laddermill there is a huge, world-wide market of parachuting, paragliding and kiting that can benefit from more research and a better understanding of the deformation and aerodynamic performance of ram-air wings. The goals of this thesis are to be able to point out where a ram-air kite departs from the intended design shape, to investigate how well the kite performs, to understand how the deformations affect the airflow and to make suggestions for possible improvements of the design. Since little has been published about these subjects this report will most of all form a basis for further research. This report presents a method to analyse the shape and the aerodynamics of a ram-air kite. The kite is tested in the windtunnel. Its 3D shape is captured using two techniques: photogrammetry and laser scanning. Using the geometry data the structural deformation of the wing is dissected. With computational fluid dynamics the aerodynamics of the deformed shape is analyzed. An extra result of this study is the comparison of photogrammetry and laser scanning in terms of their suitability to capture the 3D shape of the ram-air kite. A number of interesting deformations and flow features were found on the ram-air wing: - Theoretically the bumps (ballooning) and grooves on a ram-air wing hinder the spanwise flow on a 3-dimensional wing, but in practise this effect is only visible on small parts of the upper surface. - The pull of the suspension lines on the under surface and the internal construction of the wing make the upper surface of the wing deform. This results in a decrease of the upper surface curvature, especially near the nose. This curvature decrease causes a loss of lift of at least 5%. - Because the flat, 2-dimensional fabric is inflated into a 3-dimensional shape the fabric wrinkles. The wrinkles continue from the top and bottom surface into the ribs that internally connect and support the top and bottom surface. On average these wrinkles shorten the ribs in chordwise direction by 3.5%. This decreases the surface area of the wing and it makes the ribs effectively thicker. Many more details became visible with the thorough analysis of the wing's shape. The conclusion is that the performance of the ram-air wing can be improved by changing these details. The photogrammetry measuring technique gave better results than laser scanning and is very suitable tool to make these details visible. It allows a designer to identify where the real flying shape deviates from the design shape. This can help kite designers and designers of other ram-air wings to reverse-


The Escape Room phenomena began in Japan in 2007. The premise of an Escape Room is that 'players' are locked inside a room and, in order to escape, they must solve a range of puzzles, riddles, and open mechanisms and locks inside a given timeframe. While the educational affordances of an escape room have been and continue to be explored (see for example Brown, Darby & Coronel, 2019) the grandeur and physical complexities required to set up an escape room mean than it is not a sustainable option for the average classroom teacher or smaller tertiary courses.
The Escape Game, however, is played on a smaller scale with portable (often mostly printable) resources with players aiming to either break into something (a toolbox for example) by solving riddles, puzzles and opening locks within a given timeframe. The logistical ease of set up and iterability mean that the escape game format is becoming increasingly popular across all sectors of education—from young primary school learners to tertiary tauira (see for example Yachin, & Barak, 2019).
A successful example of the escape game movement in education is Breakout EDU (see for example Detwiler, Jacobson, & O'Brien, 2018). In addition to being a platform that provides resources to create your own and use other educator-made physical breakout games, Breakout EDU also provide members with a digital escape game creator and online repository. It was the Breakout EDU digital game format that was used as the mediating artefact in this case study.
A digital escape game, Mathematical Medley, was created for educators undertaking a postgraduate mathematics education course. The game was embedded into the course's learning management system and activated at a certain time point for tauira to complete in groups or individually (as they chose). The purpose  of the study was to explore how a digital escape game might promote the learning of mathematical content (subject knowledge); and how a digital escape game might enable the use and development of key competencies and mathematical processes. An overview of the escape game, purpose, findings and implications of using the mediating artefact will be shared during the presentation of this case study.


Textbook style problems including detailed solutions introducing pharmaceutical topics at the level of an introductory chemical engineering course have been created. The problems illustrate and teach subjects which students would learn if they were to pursue a career in pharmaceutical engineering, including the unique terminology of the field, common unit operations, calculations per taining to drug manufacturing, and some of the specific concerns of the industry such as regulations and testing. Over seventy problems have been created; selected problems have been administered to students and their impact evaluated. Students demonstrated significant gains in knowledge of pharmaceutical engineering topics.


By interrupting the integrity of the systemic and renal renin-angiotensin system, angiotensin-converting enzyme inhibitors have been shown, experimentally, to preferentially reduce postglomerular capillary arteriolar resistance, to reduce glomerular capillary pressure, and to increase the ultrafiltration coefficient. Under normal physiological conditions, angiotensin-converting enzyme inhibitors have little effect on glomerular filtration rate; however, they increase effective renal plasma flow at renal perfusion pressures within the normal autoregulatory range and renal vascular resistance is decreased. In contrast, calcium antagonists have been shown, experimentally, to preferentially reduce preglomerular capillary arteriolar resistance. Their effects on angiotensin II and postglomerular capillary arteriolar resistance (hence, glomerular capillary pressure and the ultrafiltration coefficient) are controversial. Under normal physiological conditions, calcium antagonists increase both glomerular filtration rate and effective renal plasma flow at renal perfusion pressures within the normal autoregulatory range and renal vascular resistance is decreased. In patients with essential hypertension, studies have demonstrated that angiotensin-converting enzyme inhibitors (as predicted) sustain glomerular filtration rate, increase effective renal plasma flow, and decrease renal vascular resistance. However, essential hypertensive patients with impaired glomerular filtration rate may demonstrate marked improvement in both glomerular filtration rate and effective renal plasma flow. Calcium antagonists (as predicted) may increase both glomerular filtration rate and effective renal plasma flow (at high renal perfusion pressures) and may decrease renal vascular resistance. Calcium antagonists may also improve both glomerular filtration rate and effective renal plasma flow in patients with impaired glomerular filtration rate. Long-term clinical trials comparing the renal effects of angiotensin-converting enzyme inhibitors with those of calcium antagonists in essential hypertensive patients have not been reported. It remains to be determined if the potentially different effects of these two classes of antihypertensive drugs on the renal microcirculation do or do not translate into different renal protective advantages to patients at risk for the development and/or progression of hypertensive nephrosclerosis.


This study examined possible selective impairment of endothelial dysfunction in the peripheral vascular bed in patients with chronic heart failure in the absence of confounding factors influencing endothelial function (i.e. hypertension, hypercholesterolaemia and diabetes mellitus). Several recent studies have suggested that endothelium-dependent peripheral vasodilation is impaired but endothelium-independent vasodilation is preserved in patients with chronic heart failure. However, a classical paper has demonstrated that sodium nitrite-mediated calf blood flow is clearly depressed in patients with valvular heart disease and cardiomyopathy. We examined forearm blood flow changes mediated by acetylcholine and nitroprusside in patients with valvular heart disease (n = 55) or congenital heart disease (n=13), and a comparison was made with healthy volunteers (n = 21). The blood flow changes mediated by acetylcholine and nitroprusside were significantly impaired in both patient groups (P<001). When blood flow responses were collected from all patients, two types of vasodilatory capacity were found to have decreased significantly with increasing clinical severity of heart failure (New York Heart Association functional class; P<001). This suggests that the peripheral vasodilatory responses mediated by endothelium-dependent and endothelium-independent vasodilators are significantly impaired in patients with symptomatic chronic heart failure due to non-ischaemic heart disease. (Eur Heart J 1996; 17: 1875-1881)


Recent research has shown that inserting a gene for the protein component of telomerase into senescent human cells reextends their telomeres to lengths typical of young cells, and the cells then display all the other identifiable characteristics of young, healthy cells. This advance not only suggests that telomeres are the central timing mechanism for cellular aging, but also demonstrates that such a mechanism can be reset, extending the replicative life span of such cells and resulting in markers of gene expression typical of "younger" (ie, early passage) cells without the hallmarks of malignant transformation. It is now possible to explore the fundamental cellular mechanisms underlying human aging, clarifying the role played by replicative senescence. By implication, we may soon be able to determine the extent to which the major causes of death and disability in aging populations in developed countries-cancer, atherosclerosis, osteoarthritis, macular degeneration, and Alzheimer dementia--are attributable to such fundamental mechanisms. If they are amenable to prevention or treatment by alteration of cellular senescence, the clinical implications have few historic precedents.


Objective: Robotic surgery is a new technique with the benefits of a 3-dimensional view, the ability to use multidegree-of-freedom forceps, the elimination of physiological tremors, and a stable camera view. The aim of this study was to evaluate the feasibility and short-term outcomes of robotic surgery for gastric cancer, compared with conventional laparoscopic surgery. Methods: A literature search was performed for comparative studies reporting perioperative outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG). The methodological quality of the selected studies was assessed. The data were analyzed using Stata (Version 13.0) software. Results: Eleven studies of 3503 patients totally were included for meta-analysis. Compared with LG, RG indicated potentially favorable outcomes in terms of blood loss [weighted mean difference (WMD)=−36.50; 95% confidence interval (CI), −61.39 to −11.61], and time to oral intake (WMD=−0.28; 95% CI, −0.46 to −0.09). But RG suggested longer operative time (WMD=53.48; 95% CI, 38.84-68.12). There were no differences in terms of postoperative flatus, length of hospital stay, postoperative complications, and lymph nodes harvested (P>0.05). Conclusions: RG for the treatment of gastric cancer is a feasible and safe procedure in the hand of experienced laparoscopic surgeons. But the long-term outcomes between the 2 techniques need to be further examined.


Objective
This study was to investigate the effect of caloric restriction on the plasticity of visual cortex in adult monocular deprivation (MD) amblyopic mice, as well as to promote the treatment of amblyopia, and to explore the possible molecular mechanism of this benefical effect.

Methods
Fifty healthy newborn Kunming mice of clean grade were randomly divided into 3 groups using a random number table method: normal control group (n=14), MD+ ad libitum group (n=18) and MD+ caloric restriction group (n=18). A mouse model of adult MD amblyopia was established, and caloric restriction intervention and ad libitum were performed on MD+ caloric restriction group and MD+ ad libitum group, respectively.The visual acuity and flash visual evoked potential (F-VEP) of each group were detected.The synaptic structure of visual cortex neurons was observed by transmission electron microscope, and the expression of phosphorylated AMP-activated protein kinase-α (p-AMPKα) and silent information regulator 1 (SIRT1) in visual cortex were detected by Western blot.The animal feeding and use was in accordance with the standards set by the ARVO.

Results
The weight of mice in MD+ caloric restriction group increased from the beginning of the first week, and was significantly lower than that in the MD+ ad libitum group (P<0.05). Compared with the MD+ ad libitum group, the visual acuity was restored, the latency was shortened, and the amplitude of F-VEP was increased in the deprived eyes of MD+ caloric restriction group (all at P<0.05). Transmission electron microscope observation showed that the width of synaptic gap of visual cortical neurons was significantly narrower, and the thickness of postsynaptic density was significantly thicker in MD+ caloric restriction group than that in the MD+ ad libitum group (both at P<0.05); compared with the normal control group, the synaptic gap was widened and the postsynaptic density was significantly thicker than that in the MD+ ad libitum group (both at P<0.05). Western blot showed that the expression of p-AMPKα in visual cortex in the normal control group, MD+ caloric restriction group and MD+ ad libitum group was 0.89±0.03, 0.94±0.02 and 0.74±0.02, and the expression of SIRT1 was 0.97±0.11, 0.95±0.14 and 0.58±0.13, respectively, showing significant differences among the three groups (F=14.57, P=0.00; F=23.91, P=0.00), the expressions of p-AMPKα and SIRT1 in visual cortex were increased in MD+ caloric restriction group than those in MD+ ad libitum group (both at P<0.05).

Conclusions
Caloric restriction can restore the ultrastructure of synapses and improve the visual cortical plasticity in adult MD mice, so that help to improve visual function.Its mechanism may be related to the activation of AMPK-SIRT1 pathway.

Key words:
Caloric restriction; Adult mice; Monocular deprivation; Visual cortical; Plasticity


The paper discusses the risks in the bank and the associated operational problems. A simplified map of the different types of operational risks is presented. Additionally, the reasons causing risks for a bank are examined. GAP analysis is outlined as a key key instrument for analyzing the potential risks to liquidity and some important recommendations are made regarding the calculations of the remnants of client funds. Main conclusions focus on the construction of variants of different scenarios of the bank's liquidity circumstances and the determination of the vulnerability of the bank to the parameters for the "crisis".


This paper reviews the NTIRE 2020 challenge on video quality mapping (VQM), which addresses the issues of quality mapping from source video domain to target video domain. The challenge includes both a supervised track (track 1) and a weakly-supervised track (track 2) for two benchmark datasets. In particular, track 1 offers a new Internet video benchmark, requiring algorithms to learn the map from more compressed videos to less compressed videos in a supervised training manner. In track 2, algorithms are required to learn the quality mapping from one device to another when their quality varies substantially and weakly- aligned video pairs are available. For track 1, in total 7 teams competed in the final test phase, demonstrating novel and effective solutions to the problem. For track 2, some existing methods are evaluated, showing promising solutions to the weakly-supervised video quality mapping problem.


AIM
To compare the expression of VEGF-A and desmoplastic reaction of colorectal cancer between the young aged and old aged patients excluding the stage of tumor.

METHODS
Our study was a retrospective study on VEGF-A expression and desmoplastic reaction in pathology anatomy specimens of patients with colorectal cancer at young age (less than 40 years of age) and older age (more than equal 60 years of age). The samples had been taken since 2001 until 2008 and the sample size for each group was 42 samples for young age and 36 samples for older age subjects. To carry out the examination of VEGF expression, our study utilized the immunohistochemistry method. In addition, desmoplastic reaction as a preliminary study was evaluated by using routine HE staining. To recognize the difference of VEGF-A expression and the degree of desmoplastic reaction in young aged and older aged patients with colorectal cancer, a Chi-Square test was performed. The statistics was considered as significant when p value <0.05.

RESULTS
Forty-two patients were at younger age (< or =40 years) and 36 patients were at older age (> or =60 years), with characteristics of them 37 males and 41 females. Tumor grading was performed based on WHO criteria. Ten subjects with high-grade tumor and 32 subjects with low-grade in the young age group; while in the older age group, there were 9 subjects with high-grade tumor and 27 subjects with low grade tumor. In young age, there was twice greater likelihood to have pronounced desmoplastic reaction compared to the older age (OR = 2.1).

CONCLUSION
The VEGF-A expression in younger and older age was nearly the same; however, there was significant difference of desmoplastic reaction in younger aged patients compared to the older aged. There was also comparable correlation between strong positive VEGF-A expression and strong desmoplastic reaction in young patients with colorectal cancer.


Abstract Background and purpose Chest wall toxicity is observed after stereotactic body radiation therapy (SBRT) for peripherally located lung tumors. We utilize machine learning algorithms to identify toxicity predictors to develop dose–volume constraints. Materials and methods Twenty‐five patient, tumor, and dosimetric features were recorded for 197 consecutive patients with Stage I NSCLC treated with SBRT, 11 of whom (5.6%) developed CTCAEv4 grade ≥2 chest wall pain. Decision tree modeling was used to determine chest wall syndrome (CWS) thresholds for individual features. Significant features were determined using independent multivariate methods. These methods incorporate out‐of‐bag estimation using Random forests (RF) and bootstrapping (100 iterations) using decision trees. Results Univariate analysis identified rib dose to 1 cc < 4000 cGy (P = 0.01), chest wall dose to 30 cc < 1900 cGy (P = 0.035), rib Dmax < 5100 cGy (P = 0.05) and lung dose to 1000 cc < 70 cGy (P = 0.039) to be statistically significant thresholds for avoiding CWS. Subsequent multivariate analysis confirmed the importance of rib dose to 1 cc, chest wall dose to 30 cc, and rib Dmax. Using learning‐curve experiments, the dataset proved to be self‐consistent and provides a realistic model for CWS analysis. Conclusions Using machine learning algorithms in this first of its kind study, we identify robust features and cutoffs predictive for the rare clinical event of CWS. Additional data in planned subsequent multicenter studies will help increase the accuracy of multivariate analysis.


The sandy lower supratidal zone, called "Westplate," of Mellum Island (southern North Sea) is colonized by epipsammic cyanobacteria. The microbes form habitats of different stages of development adjacent to each other (biofilms: initial stages; mats: mature stages). Whereas biofilms do not contribute much to cohesion of sedimentary grains, mats significantly stabilize the supratidal surface, which leads to local conservation of a former physically shaped surface relief at microbially overgrown sites. In fall, the Westplate is covered by variously orientated ripple marks, termed "multidirected ripple marks." Field measurements and investigations on the epipsammon revealed that ripple marks of similar orientations were covered by microbial assemblages of similar stages of development. The results permit the following interpretation. The sediments of the Westplate are reworked by high-water spring tide flood currents, the directions of which are frequently changed by strong winds. Because the water depth of the flood current is very shallow, some parts of the uneven sedimentary surface are more affected by hydrodynamic stress than others. At sites of calmer hydrodynamic conditions, predominantly filamentous cyanobacteria settle in time, forming mats. Constant physical reworking of slightly deeper parts of the supratidal surface, however, only permits the development of less-sediment –stabilizing biofilms composed mainly of coccoid cyanobacteria. After the supratidal area drains, the deeper parts are also colonized by mat-constructing cyanobacteria, and the ripple marks become consolidated by the organic layer. Repetition of these interactive processes of physical reworking and microbial colonization is documented by the patchy ripple structure of the supratidal surface.


Barbara Cassani set up the no-frills airline GO for British Airways. She was a rare breed. A female airline chief executive who believed in doing things differently. Her European low-cost operation was launched in May 1998 with GBP25 million backing and within three years she took it into profit. Riding high, she led a management buy-out from BA, supported by the venture capitalist outfit 3i. They paid GBP110 million for the airline. Yet, less than a year later the venture capital group - battered by a falling stock market - had a chance to cash in their chips. GO was sold to arch-rival easyJet for an astonishing GBP374 million. At at time when the airline industry is of great interest to the public as well as being in flux, this fast-paced read gives a fascinating insight into how to create a successful company with limited resources in such a short space of time. THE GO STORY is filled with real characters overcoming the odds to achieve great things and shows the remarkable vision and talent of the author, Barbara Cassani.


We investigate the development of a general-purpose framework for mechanized reasoning about the meta-theory of programming languages. In order to provide a standard, uniform account of a programming language, we propose to define it as a logic in a logical framework, using the same mechanisms for definition, reasoning, and automation that are available to other logics. Then, in order to reason about the language's meta-theory, we use reflection to inject the programming language into (usually richer and more expressive) meta-theory.One of the key features of our approach is that structure of the language is preserved when it is reflected, including variables, meta-variables, and binding structure. This allows the structure of proofs to be preserved as well, and there is a one-to-one map from proof steps in the original programming logic to proof steps in the reflected logic. The act of reflecting a language is automated; all definitions, theorems, and proofs are preserved by the transformation and all the key lemmas (such as proof and structural induction) are automatically derived.The principal representation used by the reflected logic is higher-order abstract syntax (HOAS). However, reasoning about terms in HOAS can be awkward in some cases, especially for variables. For this reason, we define a computationally equivalent variable-free de Bruijn representation that is interchangeable with the HOAS in all contexts. The de Bruijn representation inherits the properties of substitution and alpha-equality from the logical framework, and it is not complicated by administrative issues like variable renumbering.We further develop the concepts and principles of proofs, provability, and structural and proof induction. This work is fully implemented in the MetaPRL theorem prover. We illustrate with an application to F<: as defined in the POPLmark challenge.


Nobuo Uematsu is the original composer of the music and game sound in the Final Fantasy series. Known to be one of the most famous composers within this industry, his direction of sound in games has branched out vigorously in many directions since the first game of the series. Uematsu heavily influenced the direction of game sound history through his innovative works that make video game music stand up to par with even classical music, and through analysis, one may even find characteristics of classical composition styles in his works. His milestones were the very product of his own work, and left a big set of footprints for everyone else to follow within the game industry. Uematsu's compositions in game sound were so impactful to his audience that to this day, decades later, people still talk about the immense feeling of nostalgia from those sounds.


takes the best part of a year. This is little use to someone who needs to respond quickly to a domestic crisis, and if you become pregnant shortly after the closing date your application is unlikely to be sorted out before the baby is 10 months old and not within the limits of maternity leave. Secondly, the scheme is supposed to ensure that the .tandard of part timers is comparable with that of full timers. The ratio of full time to part time jobs is fixed and therefore works against those applying for jobs in specialties that attract a lot of women. It is ironic that obstetrics, paediatrics, and psychiatry are just the specialties in which Dr Begley and I believe the experience of being a mother can be so valuable. Thirdly, and perhaps most importantly, the scheme is specifically for doctors with domestic responsibilities, yet only a handful of men are using it. It is essential that the problem ofcombining family and work commitments is shared by both partners and is not seen as a women's problem. Many of us are married to doctors, and too often careers advice is aimed at how best to fit our careers around our husbands'. At present, childcare facilities are being cut rather than expanded and maternity leave arrangements are falling even further below the standards ofother north European countries. When I entered medical school in 1976 half of our year were women. Now, five years afer qualifying, many of us with domestic commitments are struggling. I urge all those who care about their children and their career to push for changes in the system. Can any of us be proud to belong to a profession where official advice for interviews is to conceal your pregnancy? PENELOPE CAMPLING


Maintaining a steady state of mucus barrier is an important potential target for polyphenol to exert its anticolitis activity. This study elucidates the pivotal role of polyphenol rosmaric acid (RA) in regulating the mucus barrier function and alleviating inflammation by identifying its gut microbiota-derived metabolites and evaluating its inhibitory effect on inflammasomes in colitis mice. Results demonstrated that RA treatment promoted the proliferation of goblet cells and restored the level of mucus secretion, especially Muc2. RA reshaped the microbiota of colitis mice, particularly the boost of core probiotics, such as p. Bacteroidaceae, f. Muribaculaceae, g. Muribaculaceae, g. Alistipes, and g. Clostridia_UCG-014. Nontargeted metabonomics and targeted metabonomics confirmed a significant increase in the bile acids and their metabolites (7-sulfocholic acid, stercobilin, chenodeoxycholic acid 3-sulfate, chenodeoxycholic acid sulfate, and ursodeoxycholic acid 3-sulfate), indole metabolites ((R)-2,3-dihydro-3,5-dihydroxy-2-oxo-3-indoleacetic acid, frovatriptan, 3-formyl-6-hydroxyindole, and brassicanal A), and short-chain fatty acids (SCFAs) (acetic acid, butyric acid, isobutyric acid, isovaleric acid, and valeric acid) that contributed to the strengthened mucus barrier function. In addition, being absorbed mainly in the lower digestive tract, RA inhibited the overexpression of inflammasomes (especially NLRP6) that occurred in colitis mice to promote the mucus secretion of goblet cells. These data confirmed that RA, as a promising candidate to enhance gut health, restored colonic mucus secretion in colitis mice by mediating the production of gut microbiota-derived metabolites and the overexpression of inflammasomes. The presented study provides scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols.


Many students in New Zealand are now of mature age, female, and mothers of dependent children (Allister et al. 2006). These students typically experience the challenge of sharing themselves between their children, partners, extended families and their fellow students, lecturers and studying. This research explored how a group of student-teachers who were also mothers experienced these dual roles and sought to document their beliefs, motivations, attitudes to these roles from the time they had entered teacher education. The following key themes emerged from the in-depth interviews with the women: strong motivation for wanting to become primary school teachers; the impact this decision had on the lives of their children, partners and extended families; the particular issues they faced as they tried to navigate the roles of mother and student-teacher; and the suggestions they had for continuing education and tertiary institutions to improve opportunities for other mothers wanting to study. This last theme is perhaps the most pertinent, as it offers implications for continuing education institutions wanting to attract and retain these students, who, as a group, represent a growing demographic trend in the student population.


A consensus genetic map for Pinus taeda (loblolly pine) was constructed by merging three previously published maps with a map from a pseudo-backcross between P. taeda and P. elliottii (slash pine). The consensus map positioned 4981 markers via genotyping of 1251 individuals from four pedigrees. It is the densest linkage map for a conifer to date. Average marker spacing was 0.48 centiMorgans and total map length was 2372 centiMorgans. Functional predictions for 4762 markers for expressed sequence tags were improved by alignment to full-length P. taeda transcripts. Alignments to the P. taeda genome mapped 4225 scaffold sequences onto linkage groups. The consensus genetic map was used to compare the extent of genome-wide linkage disequilibrium in an association population of distantly related P. taeda individuals (ADEPT2), a multiple-family pedigree used for genomic selection studies (CCLONES), and a full-sib quantitative trait locus mapping population (BC1). Weak linkage disequilibrium was observed in CCLONES and ADEPT2. Average squared correlations, R2, between genotypes at SNPs less than one centiMorgan apart was less than 0.05 in both populations and R2 did not decay substantially with genetic distance. By contrast, strong and extended linkage disequilibrium was observed among BC1 full-sibs where average R2 decayed from 0.8 to less than 0.1 over 53 centiMorgans. The consensus map and analysis of linkage disequilibrium establish a foundation for comparative association and quantitative trait locus mapping between genotype-phenotype discovery populations.


Household consumption and expenditure surveys are frequently conducted around the world and they usually include data on household food consumption, but their applicability to nutrition research is limited by their collection at the household level. Using data from Mongolia, this study evaluated four approaches for estimating diet from household surveys: direct inference from per-capita household consumption; disaggregation of household consumption using a statistical method and the "adult male equivalent" method, and direct prediction of dietary intake. Per-capita household consumption overestimated dietary energy in single- and multi-person households by factors of 2.63 and 1.89, respectively. Performance of disaggregation methods was variable across two household surveys analyzed, while the statistical method exhibited less bias in estimating intake densities (per 100 kcal) of most dietary components in both of the surveys. Increasingly complex prediction models explained 54% to 72% of in-sample variation in dietary energy, with consistent benefits incurred by inclusion of basic dietary measurements. In conclusion, in Mongolia and elsewhere, differences in how household and dietary measurements are recorded make their comparison challenging. Validity of disaggregation methods depends on household survey characteristics and the dietary components that are considered. Relatively precise prediction models of dietary intake can be achieved by integrating basic dietary assessment into household surveys.


The distribution of the precipitates on the grain boundaries in Fe-3%Si steel during secondary recrystallization annealing were studied using high-angle annular dark filed (HAADF) scanning transmission electron microscopy (STEM). Because HAADF image can show both grain boundaries and precipitates clearly, the change of precipitate distribution on grain boundaries can be quantitatively analyzed. It was observed that the total area of the precipitates on grain boundaries increased in the order of non-annealed, 600°C, and 900°C sample and the total area of precipitates on grain boundaries in the 1000 °C sample was much lower than that in the 900 °C sample. The compositions of the precipitates were also analyzed using X-ray energy-dispersive spectrometer (XEDS). The most precipitates were multi-phase ones, mainly composed of AlN and MnS. Our analysis results suggest that such a precipitate behavior is responsible for the abnormal grain growth of Fe-3%Si steel occurring under the temperature above 900 °C.


Neurogenin 3 (Ngn3), a proneural gene controlled by the Notch receptor, is implicated in the control of dendrite morphology and synaptic plasticity of cultured hippocampal neurons. Here we report the localization and subcellular distribution of Ngn3 in the hippocampus in vivo and in neuronal cultures. In situ hybridization showed Ngn3 mRNA expression in the pyramidal layer and dentate gyrus of adult mouse hippocampus. Immunohistochemistry studies revealed that Ngn3 localization is mostly cytoplasmic in the hippocampal eminence at embryonic day (E)17 and postnatal day (P)0. At P10 it is cytoplasmic in CA1–CA3 pyramidal neurons and nuclear in granule cells of the dentate gyrus. In the adult hippocampus Ngn3 is localized in the nucleus and cytoplasm of both pyramidal neurons and granule cells. During development of cultured hippocampal neurons, Ngn3 mRNA expression is higher at stages of neuronal polarization, as judged by reverse‐transcription polymerase chain reaction (RT‐PCR), and it is mostly cytoplasmic. The tracking of the subcellular localization of Ngn3 in neurons infected with a virus expressing myc‐Ngn3 suggests that the protein is quickly translocated to the cell nucleus after synthesis and then reexported to the cytoplasm. Treatment with leptomycinB, a potent and specific inhibitor of the exportin CRM1, induced its accumulation into the nucleus, suggesting that CRM1 mediates the nuclear export of Ngn3. These results suggest that Ngn3 may play a role in neuronal development by actions in the cytoplasm. J. Comp. Neurol. 518:1814–1824, 2010. © 2009 Wiley‐Liss, Inc.


This paper presents a new mathematical model for a hybrid flow shop scheduling problem with multiprocessor tasks in which sequence dependent set up times and preemption are considered. The objective is to minimize the weighted sum of makespan and maximum tardiness. Three meta-heuristic methods based on genetic algorithm (GA), imperialist competitive algorithm (ICA) and a hybrid approach of GA and ICA are proposed to solve the generated problems. The performances of algorithms are evaluated by computational time and Relative Percentage Deviation (RPD) factors. The results indicate that ICA solves the problems faster than other algorithms and the hybrid algorithm produced best solution based on RPD.


Turbulence, the ubiquitous and chaotic state of fluid motions, is characterized by strong and statistically non-trivial fluctuations of the velocity field, over a wide range of length- and time-scales, and it can be quantitatively described only in terms of statistical averages. Strong non-stationarities hinder the possibility to achieve statistical convergence, making it impossible to define the turbulence intensity and, in particular, its basic dimensionless estimator, the Reynolds number.
Here we show that by employing Deep Neural Networks (DNN) we can accurately estimate the Reynolds number within $15\%$ accuracy, from a statistical sample as small as two large-scale eddy-turnover times. In contrast, physics-based statistical estimators are limited by the rate of convergence of the central limit theorem, and provide, for the same statistical sample, an error at least $100$ times larger. Our findings open up new perspectives in the possibility to quantitatively define and, therefore, study highly non-stationary turbulent flows as ordinarily found in nature as well as in industrial processes.


BACKGROUND
Gastric stump cancer is often described as a tumor with a poor prognosis and low resectability rates.

OBJECTIVES
To compare the pathological characteristics of gastric stump cancer patients with those of patients with proximal gastric cancer.

METHODS
This retrospective study was based on the demographic and pathological data of patients diagnosed with gastric cancer and treated at Assaf Harofeh Medical Center during an 11 year period. The patients were divided into two groups: those undergoing proximal gastrectomy for proximal gastric cancer and those undergoing total gastrectomy for gastric stump cancer.

RESULTS
Patients with gastric stump cancer were predominantly male, older (P = 0.202, not significant), and had a lower T stage with less signet-ring type histology, fewer harvested and fewer involved lymph nodes (P = 0.03, statistically significant) and less vascular/lymphatic involvement than patients with proximal gastric cancer.

CONCLUSIONS
The lower incidence of involved lymph nodes and lymphovascular invasion in gastric stump cancer as compared to proximal gastric cancer in this study may imply that the prognosis of gastric stump cancer may be better than that of proximal gastric cancer. However, to verify this assumption a study comparing patient survival is required.


We present observations of the singly and doubly deuterated species of thioformaldehyde, HDCS and D2CS, toward the dark cloud Barnard 1. This is the first detection of D2CS in space and in dense, cold prestellar regions. Column densities obtained using rotational diagrams and a large velocity gradient model show an extremely high D enhancement in thioformaldehyde in Barnard 1. Although the column density of H2CS is smaller than that of H2CO, both species show similar D enhancements in their singly and doubly deuterated species. A chemical model—including multiply deuterated species—has been used in order to interpret the observations. Predicted rotational frequencies from laboratory data for HDCS and D2CS are significantly in error when compared to the observed frequencies in space. Consequently, we have derived new rotational constants for these two species and for H2CS and H2C34S using the observed frequencies in Barnard 1. The new rotational constants allow us to predict the rotational transitions of these species with the accuracy needed for the narrow line emerging from dark clouds. Rotational constants for HDCS and D2CS have been obtained from the observed transitions in the laboratory and in space.


Near Woodbridge, northwest of Toronto, Ontario, a 15 metre-high railroad cut and associated borrow pit, first excavated in 1962, exposed a multiple till sequence and intervening fossiliferous sediments. Work over the next 35 years revealed that Illinoian York Till, early Wisconsinan Sunnybrook Till, and late Wisconsinan Humber till, Halton Till, and Wildfield Till are interbedded with fossiliferous sediments equivalent to the Sangamonian Don Formation, early Wisconsinan Scarborough Formation (>50 ka BP), and middle Wisconsinan Thorncliffe Formation (45 ka BP). A complex periglacial record displays multistage fossil frost wedges, indicating intervals of severe climate in late Illinoian and early Wisconsinan time. Cored boreholes indicate deep gravel below and a till on Ordovician shale bedrock (Georgian Bay Formation). Vertebrates, molluscs, ostracodes, insects, and plants (diatoms, wood, seeds, pollen) indicate mostly cool conditions (boreal to tundra) for interstadial sediments. Interglacial conditions a...


Simulations are currently an essential tool to develop and test wireless sensor networks (WSNs) protocols and to analyze future WSNs applications performance. Researchers often simulate their proposals rather than deploying high-cost test-beds or develop complex mathematical analysis. However, simulation results rely on physical layer assumptions, which are not usually accurate enough to capture the real behavior of a WSN. Such an issue can lead to mistaken or questionable results. Besides, most of the envisioned applications for WSNs consider the nodes to be at the ground level. However, there is a lack of radio propagation characterization and validation by measurements with nodes at ground level for actual sensor hardware. In this paper, we propose to use a low-computational cost, two slope, log-normal path-loss near ground outdoor channel model at 868 MHz in WSN simulations. The model is validated by extensive real hardware measurements obtained in different scenarios. In addition, accurate model parameters are provided. This model is compared with the well-known one slope path-loss model. We demonstrate that the two slope log-normal model provides more accurate WSN simulations at almost the same computational cost as the single slope one. It is also shown that the radio propagation characterization heavily depends on the adjusted model parameters for a target deployment scenario: The model parameters have a considerable impact on the average number of neighbors and on the network connectivity.


Orthogonal frequency division multiplexing (OFDM) with a small number of subcarriers (≤ 64) is shown to be promising in the narrowband power line communication (PLC) when the peak-to-average power ratio is reduced to the CENELEC standards. Although many authors studied the performance of the OFDM systems under the impulsive noise, their considerations are mostly restricted to OFDM systems with a large number of subcarriers. In that case, discrete Fourier transform (DFT) spreads the impulsive noise in such a way that its distribution in the frequency domain can be approximated as Gaussian. If the number of subcarriers is small, these methods can be hardly used. We describe an iterative algorithm for correcting the impulsive noise erors for the OFDM transmission with a small number of subcarriers. Simulation results for a 16-OFDM-QPSK systems show that the influence of impulive noise can be essentially reduced.


Induction of CD8+ T cell immunity is a key characteristic of an effective vaccine. For safety reasons, human vaccination strategies largely use attenuated nonreplicating or weakly replicating poxvirus-based vectors, but these often elicit poor CD8+ T cell immunity and might not result in optimal protection. Recent studies have suggested that virulence is directly linked to immunogenicity, but the molecular mechanisms underlying optimal CD8+ T cell responses remain to be defined. Here, using natural and recombinant vaccinia virus (VACV) strains, we have shown in mice that VACV strains of differing virulence induce distinct levels of T cell memory because of the differential use of TNF receptor (TNFR) family costimulatory receptors. With strongly replicating (i.e., virulent) VACV, the TNFR family costimulatory receptors OX40 (also known as CD134) and CD27 were engaged and promoted the generation of high numbers of memory CD8+ T cells, which protected against a lethal virus challenge in the absence of other mechanisms, including antibody and help from CD4+ T cells. In contrast, weakly replicating (i.e., low-virulence) VACV strains were poor at eliciting protective CD8+ T cell memory, as only the Ig family costimulatory receptor CD28 was engaged, and not OX40 or CD27. Our results suggest that the virulence of a virus dictates costimulatory receptor usage to determine the level of protective CD8+ T cell immunity.


Objectives To describe the range of collaborative approaches to shared decision-making (SDM) observed in clinical encounters of patients with diabetes and their clinicians. Design A secondary analysis of videorecordings obtained in a randomised trial comparing usual diabetes primary care with or without using a within-encounter conversation SDM tool. Setting Using the purposeful SDM framework, we classified the forms of SDM observed in a random sample of 100 video-recorded clinical encounters of patients with type 2 diabetes in primary care. Main outcome measures We assessed the correlation between the extent to which each form of SDM was used and patient involvement (OPTION12-scale). Results We observed at least one instance of SDM in 86 of 100 encounters. In 31 (36%) of these 86 encounters, we found only one form of SDM, in 25 (29%) two forms, and in 30 (35%), we found ≥3 forms of SDM. In these encounters, 196 instances of SDM were identified, with weighing alternatives (n=64 of 196, 33%), negotiating conflicting desires (n=59, 30%) and problemsolving (n=70, 36%) being similarly prevalent and developing existential insight accounting for only 1% (n=3) of instances. Only the form of SDM focused on weighing alternatives was correlated with a higher OPTION12-score. More forms of SDM were used when medications were changed (2.4 SDM forms (SD 1.48) vs 1.8 (SD 1.46); p=0.050). Conclusions After considering forms of SDM beyond weighing alternatives, SDM was present in most encounters. Clinicians and patients often used different forms of SDM within the same encounter. Recognising a range of SDM forms that clinicians and patients use to respond to problematic situations, as demonstrated in this study, opens new lines of research, education and practice that may advance patient-centred, evidence-based care.


We report an investigation of humans' musical learning ability using a novel musical system. We designed an artificial musical system based on the Bohlen-Pierce scale, a scale very different from Western music. Melodies were composed from chord progressions in the new scale by applying the rules of a finite-state grammar. After exposing participants to sets of melodies, we conducted listening tests to assess learning, including recognition tests, generalization tests, and subjective preference ratings. In Experiment 1, participants were presented with 15 melodies 27 times each. Forced choice results showed that participants were able to recognize previously encountered melodies and generalize their knowledge to new melodies, suggesting internalization of the musical grammar. Preference ratings showed no differentiation among familiar, new, and ungrammatical melodies. In Experiment 2, participants were given 10 melodies 40 times each. Results showed superior recognition but unsuccessful generalization. Additionally, preference ratings were significantly higher for familiar melodies. Results from the two experiments suggest that humans can internalize the grammatical structure of a new musical system following exposure to a sufficiently large set size of melodies, but musical preference results from repeated exposure to a small number of items. This dissociation between grammar learning and preference will be further discussed.


There have been several substantial books on genetic resource conservation in recent years, mostly aimed at professional audiences. This one is aimed at a 'broader audience' of interested citizens, policy makers and others. The authors attempt this by going out into related fields such as crop evolution, plant breeding, tropical agricultural research systems, biotechnology and plant variety rights, as well as making a cautious venture into the murky political waters of the 1983 FAO Undertaking. Alas, the attempt has not been successful. The book is bland and the treatment superficial, even, on many details, just plain wrong. Sources cited are often secondary or even tertiary. The field is huge and the authors just haven't done enough homework. There is nothing here for the technician that isn't better covered elsewhere and the 'broader audience' would, I fear, have been better served by fewer and more critical facts and a less rosy glow. The book is attractively made and printed; it has some interesting half-tones but illdesigned diagrams. It is about an important subject and I am sorry that I cannot praise it.