Scholarly collaboration is relatively well described quantitatively on the macro level thanks to the analyses of large bibliographic databases. At the same time, there are known limitations of the bibliometric approaches to studying collaboration in science. We argue that in orderto improve our understanding of social processes operating in science it is necessary to take a more in-depth look: (1) identify kinds of actors that are recognized as potential partners in collaboration, (2) what features of collaborative relations are considered crucial for en-gaged actors, (3) what kinds of structures of networks composed of collaboration relations actors are embedded in, and what factors influence these structures. With 30 individual in-depth interviews (IDI) with Polish scholars we gathered detailed information about individual collaborations that allowed us to analyze collaborative ties from individual perspective and map respondent-centered networks of collaboration. Scholars identify individuals as well as teams or institutions as collaborators. They also distinguish symmetric and asymmetric collaborations. Structures of respondent-centered collaboration networks are affected by (a) leadership strategies of team principals (especially whether teams are built around positions or individuals); (b) institutional location (by making establishing external collaborations easier for scientists from bigger institutions); (c) scientific degree and recent changes in financing of science (as young scientists receive more freedom from usual organizational hierarchies by receiving substantial grants).


Osteocytes, the most ubiquitous bone cell type, are responsible for bone maintenance and communication as well as mechanotransduction. Osteocytes reside in spaces within the bone matrix called lacunae, which are used as a proxy for the cells themselves in X-ray imaging. Previous studies have revealed that lacunar volume was reduced in females with increasing age, thus likely contributing to bone frailty and diseases such as osteoporosis. The implications of diseases caused by changes in the bone osteocyte lacunar-canalicular network are not yet fully understood. Since much of the past research revolved around gross bone morphology, this study investigated age and sex-related differences in the bone cellular network of the human species. Utilizing synchrotron radiation-based micro-Computed Tomography, male (n=12) and female (n=8) cortical bone specimen from the mid-diaphyses of the left femora were assessed for tissue volume (μm3), canal volume (μm3), canal surface (μm2), cortical porosity (%), canal surface to tissue volume (μm-1), canal diameter (μm), canal separation (μm), number of canals, and number of lacunae. These parameters were compared between age, sex, and the interaction between both factors. In regard to number of lacunae and their density, a statistically significant reduction was observed with age (p = 0.017) but not with sex or the interaction variable. Thus, lacunar density was reduced with age, but no significant differences between males and females were observed. Limitation in sample size prevented a more extensive result. As such, further investigation is encouraged to confirm the reduction of lacunar volume over the human lifespan.


Although smoking is an established causal factor for upper aero digestive tract cancer (UADTC), most of the evidence originates from the West. Thus, we analysed data from 455,409 subjects in the Asia Pacific Cohort Studies Collaboration. Over a median of around six years follow-up, 371 deaths from UADTC were observed. The hazard ratio (95% confidence interval) for current smokers, compared with those who had never smoked, was 2.36 (1.76 – 3.16), adjusted for age and alcohol drinking. Tobacco control policies are urgently required in Asia to prevent millions of deaths from UADTC that smoking will otherwise cause.


A 3D model coupled with the Volume of Fluid (VOF) method of water-air two-phase flow is applied, and the roughness of walls is considered. The water-air two-phase flow simulation of the covered culvert is carried out while Jinan section of first-phase in east line of south-to-north water diversion project is taken as a case. The flow field of inverted siphon is discussed. The flow of inlet and outlet transition sections is gentle; the velocity distribution is nonuniform and the pressure distribution shows layered on current cross section. The water depth along the channel is downward.


Gambling is an behavior which illegal us where this ready made matter of habit of society. Straightening of law cannot be executed and society nothing that perduli of gambling doing an injustice will that happened its environment.
This writing take formula of[is problem of 1. Factors any kind of causing the happening of gambling doing an injustice 2. Any kind of gambling impact to society and his environment 3. How straightening of law to gambling doing an injustice 4. Stages;Steps any kind of which must be done conducted so that to be straightening of law to gambling can be executed?
This writing use method approach of sosiologis yuridis. Source of used data cover the source of Primary data and of Sekunder. its Technique data collecting in the form of interview with responder coming from Society population of des colossal, moslem scholar, elite figure, and Colossal countryside head, later;then result of the research analysed descriptively qualitative.
Straightening of law to gambling doing an injustice of[is straightening of law still not yet walked is matching with the one which expected, its conclusion is straightening of uncommitted law of police with first baik.that is existence of Becking by police government officer to all Port gambling, both second is existence of collection of is expense of done/conducted by security money is police so that/ to be all gambler donot be arrested, third the existence of crime diskaritas, after arrested all gambler can be discharged and free because paying or redeeming a number of money to police government officer.
Its conclusion is the straightening of law to gambling do not be executed by because ugly police performance and lack of society sense of justice, straightening of law earn that is with Law enforcement or of law enforcement by officer of enforcer


The modification of OTO-contrasting method (O-osmium, T-thiocarbohydrazide, O-osmium) allowing one to stain the structures of biological tissue in the process of its fixation is presented. The modification consists of an intermittent treatment of tissues with osmium tetroxide and thiocarbohydrazide after the tissue prefixation. This results in the formation of osmium-thiocarbohydrazide copolymer in form of "osmium black" and high tissue contrast corresponding to the true osmiophilia. The use of this modification permits one to give up an additional slide contrasting with a lead citrate and uranyl acetate.


To provide the information that is necessary for making the proper use of kampo medicines, we have proposed the adequate methodology focused on the following issues: (i) kampo medicines emphasize the effects produced by the combination of herbal drugs rather than the individual effect of any single herb and (ii) Intestinal CYP3A has become a key factor for the bioavailability of orally administrated drugs. In the present study, we investigated both the in vivo and in vitro effects of Saireito and Hochuekkito (kampo formulas) on CYP3A activities. From our study, oral pre-treatment with Saireito or Hochuekkito did not affect the pharmacokinetics of nifedipine after intravenous administration to rats. When nifedipine was administered to rat intrajejunum, a significant decrease of AUC was showed by pre-treatment with both kampo formulas. Saireito pre-treatment led to 80% decrease in C max of nifedipine. Saireito caused significant increases in both protein expression and metabolic activity of CYP3A in intestinal microsome, whereas it had no effect on CYP3A in hepatic microsome. Our result also showed that this affect of Saireito can be gone by wash-out with 1 week. These findings demonstrated that Saireito may induce CYP3A activity of intestine but not of liver in rats. When resources for research are limited, well-designed scientific studies except clinical trials also have many advantages.


A number of papers have been published during 1991 in the area of congenital, hereditary and developmental spinal cord disorders, which discuss a wide range of rare spinal anomalies; there have, however, been no significant advances. The diagnosis of these disorders has been enhanced by the use of magnetic resonance imaging (MRI).


Neutral lipids—involved in many cellular processes—are stored as lipid droplets (LD), those mainly cytosolic (cLD) along with a small nuclear population (nLD). nLD could be involved in nuclear-lipid homeostasis serving as an endonuclear buffering system that would provide or incorporate lipids and proteins involved in signalling pathways as transcription factors and as enzymes of lipid metabolism and nuclear processes. Our aim was to determine if nLD constituted a dynamic domain. Oleic-acid (OA) added to rat hepatocytes or HepG2 cells in culture produced cellular-phenotypic LD modifications: increases in TAG, CE, C, and PL content and in cLD and nLD numbers and sizes. LD increments were reversed on exclusion of OA and were prevented by inhibition of acyl-CoA synthetase (with Triacsin C) and thus lipid biosynthesis. Under all conditions, nLD corresponded to a small population (2–10%) of total cellular LD. The anabolism triggered by OA, involving morphologic and size changes within the cLD and nLD populations, was reversed by a net balance of catabolism, upon eliminating OA. These catabolic processes included lipolysis and the mobilization of hydrolyzed FA from the LD to cytosolic-oxidation sites. These results would imply that nLD are actively involved in nuclear processes that include lipids. In conclusion, nLD are a dynamic nuclear domain since they are modified by OA through a reversible mechanism in combination with cLD; this process involves acyl-CoA-synthetase activity; ongoing TAG, CE, and PL biosynthesis. Thus, liver nLD and cLD are both dynamic cellular organelles.


The relationship between sleep disorders and neurodegeneration is complex and multi-faceted. Using over one million electronic health records (EHRs) from Wales, UK, and Finland, we mined biobank data to identify the relationships between sleep disorders and the subsequent manifestation of neurodegenerative diseases (NDDs) later in life. We then examined how these sleep disorders' severity impacts neurodegeneration risk. Additionally, we investigated how sleep attributed risk may compensate for the lack of genetic risk factors (i.e. a lower polygenic risk score) in NDD manifestation. We found that sleep disorders such as sleep apnea were associated with the risk of Alzheimer's disease (AD), amyotrophic lateral sclerosis, dementia, Parkinson's disease (PD), and vascular dementia in national scale biobanks, with hazard ratios (HRs) ranging from 1.31 for PD to 5.11 for dementia. These sleep disorders imparted significant risk up to 15 years before the onset of an NDD. Cumulative number of sleep disorders in the EHRs were associated with a higher risk of neurodegeneration for dementia and vascular dementia. Sleep related risk factors were independent of genetic risk for Alzheimer's and Parkinson's, potentially compensating for low genetic risk in overall disease etiology. There is a significant multiplicative interaction regarding the combined risk of sleep disorders and Parkinson's disease. Poor sleep hygiene and sleep apnea are relatively modifiable risk factors with several treatment options, including CPAP and surgery, that could potentially reduce the risk of neurodegeneration. This is particularly interesting in how sleep related risk factors are significantly and independently enriched in manifesting NDD patients with low levels of genetic risk factors for these diseases.


The four essays within this study investigate a series of issues recently emerged in monetary theory and policy. While the common theme is the empirical evaluation of the effects of structural change and institutional reforms, the perspective from which I study this problem markedly varies across the chapters. The first two chapters of the thesis are more closely related. In the first chapter, I derive and estimate interest rate reaction functions for the G-3 economies and four inflation-targeting countries, to assess whether policy behaviour in these economies has significantly changed in recent years. Contrary to a commonly stated view, some interesting differences emerge amongst the policy rules followed by the central banks in the G-3 economies. Furthermore, the adoption of inflation targets and the move to greater central bank independence in the second group of countries do not seem to have significantly altered the way in which monetary authorities react to final policy objectives. In the second chapter, I apply the same econometric methodology to an optimal interest rate rule derived for four former ERM -now EMU- countries. The existence of the exchange rate constraint permits to draw, inter alia, some empirically testable hypotheses about the effects of fiscal policy credibility on interest rate determination. My findings show that some of the economies faced, on their road to EMU, remarkable costs in achieving nominal convergence with Germany, mainly due to the presence of concerns on the sustainability of their fiscal stances. The third chapter conducts an empirical investigation on the leading indicator properties of broad monetary aggregates for future inflation in the euro area. Using aggregate data for the area, I first test for Granger non-causality of M3 on prices, and then estimate a series of forecasting equations for inflation. My findings suggest that the information content of monetary aggregates, but also of the term spread and the output gap, is helpful for forecasting the behaviour of future inflation in the area. To this purpose, however, the joint use of information obtained from monetary models as the one adopted in this exercise, and from other, more "structural" models of the euro area, appears a superior forecasting strategy. Finally, chapter four adopts a time-varying VAR perspective to obtain a tentative attribution of observed fluctuations of the bilateral real exchange rates between the USA, the UK and Italy, to shocks in relative productivity levels and the fiscal position. A Kalman filter approach is employed to assess the changing contributions of each of these variables, and of shocks to the monetary stance, to the behaviour of real exchange rates over the last 130 years. While confirming the relevance of fiscal shocks in triggering observed deviations of the exchange rate from PPP, the study finds little evidence in favour of persistent productivity effects on the real exchange rate. Moreover, the exchange rate regime in place plays a substantial role in determining how shocks are transmitted to the real exchange rate.


While a great deal of research has been done on identity development around awareness of racism and heterosexism, little has been conducted on understanding how Jews come to make sense of the impact of anti-Semitism (anti-Jewish oppression) on their lives. This article, based on my qualitative dissertation (MacDonald-Dennis, 2005) that explores the unique racial, ethnic, and ethnoreligious positionality of Jewish undergraduates, examines the developmental processes that Jewish undergraduates go through as they begin to understand and, hopefully, overcome anti-Semitism. I discuss the Jewish ethno-religious target development model that arose from the results of the study. Implications for social justice education are offered.


Mitogen-activated protein kinase (MAPK) cascades play important roles in the stress response in both plants and microorganisms. The mycorrhizal symbiosis established between arbuscular mycorrhizal fungi (AMF) and plants can enhance plant drought tolerance, which might be closely related to the fungal MAPK response and the molecular dialogue between fungal and soybean MAPK cascades. To verify the above hypothesis, germinal Glomus intraradices (syn. Rhizophagus irregularis) spores and potted experiments were conducted. The results showed that AMF GiMAPKs with high homology with MAPKs from Saccharomyces cerevisiae had different gene expression patterns under different conditions (nitrogen starvation, abscisic acid treatment, and drought). Drought stress upregulated the levels of fungi and soybean MAPK transcripts in mycorrhizal soybean roots, indicating the possibility of a molecular dialogue between the two symbiotic sides of symbiosis and suggesting that they might cooperate to regulate the mycorrhizal soybean drought-stress response. Meanwhile, the changes in hydrogen peroxide, soluble sugar, and proline levels in mycorrhizal soybean as well as in the accelerated exchange of carbon and nitrogen in the symbionts were contributable to drought adaptation of the host plants. Thus, it can be preliminarily inferred that the interactions of MAPK signals on both sides, symbiotic fungus and plant, might regulate the response of symbiosis and, thus, improve the resistance of mycorrhizal soybean to drought stress.


Our last chapter focused on managing stakeholders with a particular emphasis on relationships and the achievement of priorities. It also highlighted a common situation where an individual stakeholder may have their own stakeholders that they need to keep engaged and involved. In this chapter we shift our focus to supply chains: networks that connect multiple suppliers and customers through complex webs of relationships. The relationships often involve chains of suppliers (and therefore chains of customers) that need to be managed and engaged.


This paper is the executive summary of the portfolio of the author toward the award of
Engineering Doctorate of the Warwick University. The title of the portfolio is the same as the
title of this paper, which serves as a tool to integrate the works of the author in the whole
portfolio. There are ten other papers in the portfolio besides this one.
The development and implementation of the author's model of Strategic Change Management
(SCM) in a power supply manufacturing company in Hong Kong leading to Agility (AG) is
presented in the paper. SCM developed by the author is a comprehensive and practical model
that a company can use to improve various aspects of its business. The author has demonstrated
this in the areas of Total Quality Management and IS09000 implementation, technology
innovation, supply chain management, renovation of information systems, etc. Three mini
research projects are included in the portfolio, including the development of a What-if prototype
to tackle a common problem in manufacturing resources planning, the design of power supply
products for mass customization, and an empirical study on the factor structures and correlations
of employee job satisfaction (SAT), organisation excellence (EX) and agility (AG).
The SCM model starts with creating the culture for change, which the author sees as the role for
the top management of the organisation. The author presents his experience to create such
culture when he was parachuted into his organisation as the chief executive. The second step of
SCM is analysing the system. A comprehensive qualitative analysis of the economical, social
and cultural environment of the company as well as the market forces is given. The step that
follows is the implementation of changes, which is a cycle of setting priority, organising,
performance measurement, rewarding winners and reinforcement. Practical approaches to tackle
the changes in various stages of the cycle are presented.
SCM has helped in transforming the company toward agility, and the stage of agility is named
Agility Chain by the author. The result of such transformation is also evaluated from the angles
of operations performance, financial performance, stock price appreciation, and the change in
market perception. The empirical study of employees perception on SAT, EX and AG indicates
strong correlations among the three factor structures, and also indicates that the company is
moving toward agility under the author's strategic change management.


New South Wales, like most of Australia, has achieved significant reductions in the road toll over the last twenty years. These improvements have been particularly strongest for the most at-risk groups such as young drivers. There have also been improvements in fatal crash rates, though smaller in magnitude, for other age groups. However, in recent years the fatal crash involvement rates for middle-aged and older drivers, the largest group of drivers numerically, has either levelled off or worsened. This paper investigates the characteristics of middle-aged drivers involved in fatal crashes. (a) For the covering entry of this conference, please see ITRD abstract no. E210298.


An integrated injection logic inverter has been realised in GaAs/GaAlAs material using ion implantation and Zn diffusion. Si ions have been implanted to merge the current source with the switching transistor, whereas the Be implantation provides the base contact. The shallow p+-emitter of the pnp current source has been fabricated by Zn diffusion. Instead of a lateral pnp transistor, which is typical in I2L technology, a vertical arrangement has been used. This type of transistor shows a better current efficiency and can be fabricated with a better uniformity in terms of base width. First results of an I2L inverter with a vertical pnp transistor are shown.


Liberal democracy is under challenge on a global scale. The global financial crisis has accelerated and aggravated the crisis of liberal democracy in the global North. The paper examines the prospects for liberal democracy in the global South and argues that the prospects are mixed. The rise of China and the durability of its highly successful model of authoritarian capitalism poses a central challenge in a rapidly shifting global order where democratic capitalism in the North no longer generates the same level of enthusiasm as in the past. The paper examines alternative and competing models of capitalism and democracy in the global South and evaluates the credentials of democratic BRICS and nearBRICS as serious pro-democracy actors. Whilst the trend is towards less social inclusion in the North and greater social inclusion in the South, persistently high rates of inequality pose severe problems for the future of liberal democracy both in the global North and the global South.


International intellectual property (IP) protection is at the heart of controversies over the impact of economic interests on social or environmental concerns. Some see IP rights as unduly encroaching upon human rights and societal interests, others argue for stronger enforcement and additional exclusivity to incentivize new innovations and creations. Underlying these debates is the perception that international IP treaties set out minimum standards of protection - which presumably allow for additional protection with only the sky being the limit. This article challenges this view and explores the idea of maximum standards or ceilings within the existing body of international IP law. It looks at the relation between IP treaties and subsequent agreements or national laws which offer stronger protection. In particular, within the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), an important qualification may serve as a door opener for ceilings: While additional IP protection may not go beyond mandatory limits within TRIPS, the qualification not to "contravene" TRIPS is unlikely to safeguard TRIPS flexibilities against TRIPS-plus norms. The article further identifies and examines the rationales for maximum standards in international IP protection as: (1) Legal security and predictability about the boundaries of protection; (2) the global protection of users' rights; and (3) the free movement of goods, services and information. Examples of mandatory limits in the existing IP treaties and in ongoing initiatives can implement these. However, most of the relevant treaty norms are optional. The article concludes with some observations on the need for more comprehensive and precise maximum standards.


Six years ago, at the start of 1988, the prospect for
 democracy in South Asia did not appear very promising. The military
 rulers both in Pakistan and Bangladesh had managed to cloak their
 regimes in civilian attire and appeared well entrenched even if their
 quest for legitimacy had evaded them. In Nepal and Bhutan the hereditary
 monarchs showed no signs of conceding to the demands for popular
 participation despite the simmering political discontent in both
 countries. The democratic traditions of Sri Lanka had proved
 sufficiently resilient for the formal representative institutions to
 endure but the continued civil strife and violence had virtually reduced
 effective popular participation into a farce. Likewise in India, whilst
 the ghost of Indira Gandhi's authoritarian rule during the emergency in
 1975-77 had been exorcised by subsequent renewals of popular mandate,
 the democratic institutions and popular accountability had probably
 suffered irreversible damages and it was not uncommon amongst political
 analysts to speak of the 'ungovernability' of the country.


Abstract- Technical implementation unit of the language (UPT Bahasa) is not just a place to study about language or TOEFL, but it should also be able to educate and nurture the student's character, in addition to providing knowledge to them. In interaction, staff and students must be active and goodness. Each staff must comprehend themselves about the best characteristics which will they show to the students in UPT Bahasa. Student's character is the priority to staff's attention because the good students in a good character will build the nation's character. The aims of this article are (1) To find out the student's character in UPT Bahasa Staff's surveillance and (2) To know what characteristic is needed to be good character student. This study used descriptive qualitative method to explore a variety of data.


Subcontractors are commonly involved in several quotation processes and new requests for quotation are continuously received from clients. To be able to respond with feasible design solutions at competitive price, new ways of working has to be adopted, especially when it comes to quotation preparation. High levels of accuracy of the preliminary design solutions and the cost estimations generated in the quotation process are a necessity. The purpose of this work is to investigate, explore, and develop a computerized method to support quotation preparation. The main objectives are to reveal concepts and principles to support application system development and evaluate the applicability of automated quotation preparation. The results are based on experiences from a case study at a sub-supplier to the car industry. In the case study, a design automation system for quotation preparation of seat heaters was developed. The system supports the pursuit of a valid design solution and the best solution in the individual case enabling the company to respond quickly with a competitive price when receiving a new request. In this paper, principles and concepts supporting system development are introduced and the system's applicability as a means in quotation preparation explored.


The knowledge of the interactions between leguminous tree and crops is of great importance to manage agroforests systems. This work evaluates the effect of leaves and roots aqueous extract of leucaena ( Leucaena leucocephala ) and pigeon pea( Cajanus cajan ) in of cowpea seeds germination and the possibility of the humic substances revert these inhibitory effects. In this sense were carried two experiments, in the first the treatments appear the aqueous extract of leaves and roots of leucaena and pigeon pea at 0, 2, 4, 6, 8 and 10% (v/v); in the second appear the root aqueous extract of guandu e leucaena in 5%(v/v) dosage, with humic substances at 0, 10, 20, 30 and 40% (v/v) concentrations. The aqueous extracts of leguminous leaves and roots caused reductions in the cowpea germination, being this, more dramatic when root extracts were applied. There was a quadratic effect of doses of leucena leaves and root aqueous extracts on the cowpea seeds germination The application of soil extracts containing humic substances in dosages of 20 and 30% reversed the inhibitory effect on the germination of cowpea caused by the pigeon pea root extracts, but not reversed the allelopathic effects caused by the leucaena roots aqueous extract (5% v/v).


In this article, the strategy followed by an automobile company for detecting the root causes of groan complaints related to rear drum brakes in commercial vehicles is presented using data collected from the sold troubled vehicles and from new vehicles from the production line, as well as the drum-brake test rig at the laboratory. Drum brake groan is often very intense and can cause large numbers of customer complaints. During a groan noise event, vehicle structure and suspension components are excited by the brake system and result in a violent event that can be heard and felt during brake application. This paper condenses experimental studies on a low frequency drum brake groan problem that has caused high warranty costs. First, the environmental conditions causing the groan were identified and the groan was reproduced. Vehicle tests were performed both at the factory and in traffic. To conclude the planned study, TVA (Total Value Analysis) and FMEA (Failure Mode and Effects Analysis) methods were used effectively. A strategy to determine the root causes was planned and implemented systematically to eliminate the secondary and tertiary effects of brake groan problems. In order to ge to the root causes, vibration and groan measurements were executed and interpreted according to TVA and FMEA charts. The sensitivity of the lining material of the brake shoes to different environmental conditions was investigated. Finally, the groan mechanism of the drum brake system is discussed and the solution to the low frequency drum brake groan problem is evaluated in detail.


Among noninvasive functional brain imaging techniques, 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET) has a comparative advantage in detecting active brain regions in freely locomoting animals. We developed an [18F]FDG‐PET protocol that visualizes active brain regions that respond preferentially to citrate‐induced multiple behaviors in freely locomoting rats. In addition, c‐Fos immunohistochemistry, an activity‐dependent mapping, was performed to examine whether the areas detected by PET correspond to regions with c‐Fos‐immunopositive neurons. Citrate (0.1 M) was intraorally applied to detect activated brain regions responding to gustation and the rejection behaviors including gaping and tongue protrusion, which would potently activate the limbic system. PET images during citrate stimulation were subtracted from those obtained during free locomotion or during application of distilled water. Citrate increased FDG signals in multiple gustation‐related regions: the nucleus accumbens (core and shell), the ventromedial nucleus of the thalamus, the basolateral and central nuclei of the amygdala, the hypothalamus, and the insular cortex. In addition, the ventrolateral striatum and the cingulate and entorhinal cortices, which have received less attention in the field of gustatory studies, also showed an increase in FDG signals. As expected, c‐Fos‐immunopositive cells were also found in these regions, suggesting that increased FDG signals induced by intraoral citrate injection are likely to reflect neural activity in these regions. Our [18F]FDG‐PET protocol reveals the contributions of multiple brain regions responding to aversive taste in freely locomoting rats, and this approach may aid in the identification of unknown neural networks especially relating to the limbic information processing. © 2013 Wiley Periodicals, Inc.


BACKGROUND
Low vitamin C status may increase the risk of mortality from cancer and cardiovascular disease.

OBJECTIVE
The objective was to test whether an association existed between serum ascorbate concentrations and mortality and whether the association was modified by cigarette smoking status or sex.

DESIGN
Serum ascorbate concentrations were measured in adults as part of the second National Health and Nutrition Examination Survey (1976-1980). Vital status was ascertained 12-16 y later.

RESULTS
The relative risk (RR) of death, adjusted for potential confounders, was estimated by using Cox proportional hazards models. Men in the lowest (<28.4 micromol/L) compared with the highest (>/=73.8 micromol/L) serum ascorbate quartile had a 57% higher risk of dying from any cause (RR: 1.57; 95% CI: 1.21, 2.03) and a 62% higher risk of dying from cancer (RR: 1.62; 95% CI: 1.01, 2.59). In contrast, there was no increased risk among men in the middle 2 quartiles for these outcomes and no increased risk of cardiovascular disease mortality in any quartile. There was no association between serum ascorbate quartile and mortality among women. These findings were consistent when analyses were limited to nonsmokers or further to adults who never smoked, suggesting that the observed relations were not due to cigarette smoking.

CONCLUSIONS
These data suggest that men with low serum ascorbate concentrations may have an increased risk of mortality, probably because of an increased risk of dying from cancer. In contrast, serum ascorbate concentrations were not related to mortality among women.


"Electronic record data for research: REDCap on FHIR" presentation delivered by Peter MacIsaac at the pre-HIC Conference IHE Workshop, Novotel Sydney, 29-Jul-2018.Describing REDCap as a research data collection tool, and the development of methods for integrating REDCap with EHR tools (e.g. Epic) in order to standardise the extraction of EHR data for research use.


People agree that reading is essential skill to get any knowledge in order to get the success of life either academically or socially. Reading needs to be embedded and nurtured because it is not a born skill. Still, the fact shows that EFL students in Indonesian context have not established good habits in reading English, as also experienced by EFL students in IAIN Tulungagung who are also categorized as reluctant readers due to their lack of vocabulary knowledge and number. Many studies on Extensive Reading (ER) indicate its positive impact on nurturing good habits of EFL reading in English. Accordingly implementing Extensive Reading Program to help them build love of reading is necessary. This article is then intended to dig up their responses on the implementation of ER program to the establishment of their love of reading. This research objective was achieved by distributing Reading Log during implementing Guided Extensive Reading Program (GERPro), distributing Questionnaire, and conducting interview to those involved in this ER program. The result of this research reveals that the EFL students joining this ER program claim that for those who do not establish good habits in reading English, ER proved to be able to embed their awareness of love of reading in English, and for those who already built reading love in their mother tongue-Indonesian language, their reading love in both Indonesian language and English gets increased. In addition, this GERPro contributes to the establishment of EFL students' love of online reading. In short, this research result can be pedagogically implemented by EFL teachers who would like to help their students nurturing good reading habits in English. However, for those who are moody, this GERPro does not work well. Consequently, the next researcher needs to conduct a research on how to work with moody EFL students so that their reading habits can be well established.


Abstract In recent years, a small insect was discovered predating seeds of Crocanthemum canadense (Canada Frostweed or Rockrose), which is an endangered plant with small, localized populations in Nova Scotia. This insect targets primarily chasmogamous flowers (insect-pollinated, open flowers) but not cleistogamous flowers (self-pollinated, closed) of Canada Frostweed. This behavior is of concern because a decrease in the number of seeds produced by outcrossing could cause a decrease in genetic variance within populations at affected sites (e.g., Canadian Forces Base Greenwood, NS). We extracted DNA from larvae collected from chasmogamous flowers and used the mitochondrial cytochrome oxidase subunit I (COI) gene to barcode the DNA. Results from queries showed a 91% match to Mompha (Lepidoptera: Momphidae) species on GenBank, indicating that this insect was a member of the genus Mompha, but that this particular species was not in the database. To further characterize this lepidopteran, we collected and incubated chasmogamous flowers to rear the larvae to adulthood. We identified the reared adults as Mompha capella, a species of Momphidae not previously documented in the Maritime provinces, Canada.


The efficacy of copper bactericides for control of Xanthomonas campestris pv. vesicatoria in eastern Oklahoma tomato fields was evaluated. Copper bactericides did not provide adequate control, and copper-resistant (Cur) strains of the pathogen were isolated. The Cur genes in these strains were located on a large indigenous plasmid designated pXV10A. The host range of pXV10A was investigated; this plasmid was efficiently transferred into 8 of 11 X. campestris pathovars. However, the transfer of pXV10A to other phytopathogenic genera was not detected. DNA hybridization experiments were performed to characterize the Cur genes on pXV10A. A probe containing subcloned Cur genes from X. campestris pv. vesicatoria E3C5 hybridized to pXV10A; however, a subclone containing Cur genes from P. syringae pv. tomato PT23 failed to hybridize to pXV10A. Further DNA hybridization experiments were performed to compare pXV10A with pXvCu plasmids, a heterogenous group of Cur plasmids present in strains of X. campestris pv. vesicatoria from Florida. These studies indicated that the Cur genes on pXV10A and pXvCu plasmids share nucleotide sequence homology and may have a common origin. Further experiments showed that these plasmids are distinctly different because pXV10A did not contain sequences homologous to IS476, an insertion sequence present on pXvCu plasmids.


We have searched for the violation of baryon number B and lepton number L in the (B-L)-conserving modes tau- -> anti-Lambda0 pi- and tau- -> anti-Lambda0 K- as well as the (B-L)-violating modes tau- -> Lambda0 pi- and tau- -> Lambda0 K- using 237 inv. fb of data collected with the BABAR detector at the PEP-II asymmetric-energy e+e- storage ring. We do not observe any signal and determine preliminary upper limits on the branching fractions B(tau- -> anti-Lambda0 pi-) Lambda0 pi-) anti-Lambda0 K-) Lambda0 K-) < 15 x 10^-8 at 90% confidence level.


A special specimen was created cutting a rectangular notched area from the surrounding of the upper left corner of a wide body aircraft door. Then a fatigue traction load was applied in order to induce an MSD crack initiation and propagation. An innovative DBEM (Dual Boundary Element Method) modelling approach was devised, capable of explicitly modelling the different test article layers with their rivet connections even in a 2d approach. The rivets that are close to the propagating crack are coupled with the corresponding holes by non linear contact conditions, and the accuracy improvements are assessed in comparison with a previous linear analysis, in which traction and displacements continuity conditions on the hole-rivet interface had been imposed. The importance of such influence on the simulation precision need to be assessed due to the strong impact that a non linear analysis produces on computational times. For such a complex problem (three different panels, made of different materials, each one with a variable thickness and connected by numerous rivets), experimental crack propagation data were available for the numerical-experimental comparison. With such non linear approach, a significant improvement on the growth rate correlation is obtained, that justify the increased computational effort.


Purpose The Accreditation Council for Graduate Medical Education (ACGME) states that "residents should participate in scholarly activity." However, there is little guidance for effectively integrating scholarly activity into residency. This study was conducted to understand how pediatric residency programs meet ACGME requirements and to identify characteristics of successful programs. Method The authors conducted an online cross-sectional survey of all pediatric residency program directors in October 2012, assessing program characteristics, resident participation in scholarly activity, program infrastructure, barriers, and outcomes. Multivariate logistic regression was used to identify characteristics of programs in the top quartile for resident scholarly activity participation. Results The response rate was 52.8% (105/199 programs). Seventy-seven (78.6%) programs required scholarly activity, although definitions were variable. When including only original research, systematic reviews or meta-analyses, and case reports or series with references, resident participation averaged 56% (range 0%–100%). Characteristics associated with high-participation programs included a scholarly activity requirement (odds ratio [OR] = 5.5, 95% confidence interval [CI] = 1.03–30.0); program director belief that all residents should present work regionally or nationally (OR = 4.7, 95% CI = 1.5–15.1); and mentorship by >25% of faculty (OR = 3.6, CI = 1.2–11.4). Only 47.1% (41) of program directors were satisfied with resident participation, and only 30.7% (27) were satisfied with the quality of research training provided. Conclusions The findings suggest that resident scholarly activity experience is highly variable and suboptimal. Identifying characteristics of successful programs can improve the resident research training experience.


Persistent hunger, widespread undernourishment and frequent famine affect the food security situations. The major objective of this research is to evaluate rural households' food security using resilience indicators. Households were classified into three wealth groups as poor ( 3250kcal). The classification produces reasonable comparisons based on measures of asset ownership and characteristics. Results indicate that the daily average kcal per day per AE for the poor is 1183.949kcal and for the rich is 4561.767 kcal. Sanitation facility of the poor is 25% less than that of the rich. The underlying factors to household food security system to sustain, seven components of resilience were taken into account to measure households' capability to absorb the negative effects of unpredictable shocks. Each building block was separately estimated using different multivariate techniques, which becomes covariates in estimation of resilience index. Except access to public services, which is negatively correlated with other variables, all are positively correlated to resilience. This can be imagined given that weak APS increases when households become poorer. In the second factor, APS becomes positive, which shows that it is a positive characteristic of resilience. Adaptive capacity is positive in the first factor and negative in the second factor. It shows the likely that when a household becomes poor, put the poor in difficulty to acquire resources that they did not have before. The third factor triggers hidden information of the resilience blocks. From all the building blocks under the third factor, stability and adaptive capacity are positive, which likely tells common story in terms of food security situations.


Introduction Afatinib is a first-line treatment option for patients with an advanced nonsmall cell lung cancer (NSCLC) expressing an epidermal growth factor receptor (EGFR) activating mutation. This study aimed to evaluate the association between early adverse events induced by afatinib and overall survival (OS) and progression free survival (PFS) in patients with advanced NSCLC. Methods The study was a pooled post hoc analysis of the randomized trials LUX-Lung 3 and LUX-Lung 6 which evaluated afatinib versus pemetrexed-cisplatin or gemcitabine-cisplatin, respectively. Cox proportional hazard analysis was used to assess the impact of adverse events occurring within the first 28 days of afatinib therapy on the PFS and OS outcomes in treatment-naïve advanced NSCLC patients harbouring an EGFR activating mutation. Results There were 468 patients who initiated first-line afatinib therapy within LUX-Lung 3 and LUX-Lung 6. A significant association between early rash and improved OS (hazard ratio (HR 95% CI); grade 1 = 0.74 [0.56–0.97]; grade 2+ = 0.64 [0.46–0.89]) (P = 0.018) was observed, although no significant association with PFS was present (P = 0.732). A significant association was identified between early diarrhoea and improved PFS (grade 1 = 0.83 [0.62–1.12]; grade 2+ = 0.62 [0.44–0.88]) (P = 0. 015), although no significant association with OS was present (P = 0.605). No associations between early stomatitis or paronychia and OS or PFS were identified. Conclusion Rash occurring early after the initiation of afatinib was significantly associated with improved OS, an indicator that rash may be a surrogate of patients likely to achieve long-term survival. Consideration of using rash as a dose adjustment target may be warranted for future prospective trials aiming to optimise outcomes with afatinib therapy.


AIMS
Prediction models for outcomes in atrial fibrillation (AF) are used to guide treatment. While regression models have been the analytic standard for prediction modelling, machine learning (ML) has been promoted as a potentially superior methodology. We compared the performance of ML and regression models in predicting outcomes in AF patients.

METHODS AND RESULTS
The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) and Global Anticoagulant Registry in the FIELD (GARFIELD-AF) are population-based registries that include 74 792 AF patients. Models were generated from potential predictors using stepwise logistic regression (STEP), random forests (RF), gradient boosting (GB), and two neural networks (NNs). Discriminatory power was highest for death [STEP area under the curve (AUC) = 0.80 in ORBIT-AF, 0.75 in GARFIELD-AF] and lowest for stroke in all models (STEP AUC = 0.67 in ORBIT-AF, 0.66 in GARFIELD-AF). The discriminatory power of the ML models was similar or lower than the STEP models for most outcomes. The GB model had a higher AUC than STEP for death in GARFIELD-AF (0.76 vs. 0.75), but only nominally, and both performed similarly in ORBIT-AF. The multilayer NN had the lowest discriminatory power for all outcomes. The calibration of the STEP modelswere more aligned with the observed events for all outcomes. In the cross-registry models, the discriminatory power of the ML models was similar or lower than the STEP for most cases.

CONCLUSION
When developed from two large, community-based AF registries, ML techniques did not improve prediction modelling of death, major bleeding, or stroke.


To effectively realize the optimal operation target of paperless production, real time production and integration in manufacturing process for workshop manufacturing system, this paper puts forward an equipment integration-based workshop e-Manufacturing execution mode, and analyzes the basic elements for the operation mode. Furthermore, some of the key issues which are important to support the operation mode are described in detail, including system integration technologies, equipment integration-based real time data collection and information interaction technologies. Finally, the operation mode is applied in a NC workshop of an automobile part manufacturing enterprise in Chongqing, and its feasibility is demonstrated.


This article investigates the role of European Union Cohesion Policy in the development of European identity, drawing on an original and representative survey in 17 regions across 12 member states. We advance a theoretical model which distinguishes cognitive, instrumental and communicative drivers of identity formation. Contrary to existing scholarship, we find that EU Cohesion Policy does contribute to European identity. Citizens that perceive benefits for themselves and for their region's development from EU Cohesion Policy are more likely to develop a European identity. We also find that awareness of the EU Cohesion Fund and exposure to publicity on EU funded projects is positively correlated with European identity. However, while Cohesion Policy contributes to citizens' self-categorization as European, it does not associate with their emotional attachment to Europe. The study has important implications for understanding European identity formation and communicating the benefits and role of the EU in regional policy.


The uses of humic substances and organic residues for soil mulching have been more common during last years. This way, an experiment was carried out to evaluate the fruit quality and yield of guava cv. Paluma as a function of humic substances and organic soil mulching in Brazil. The experiment was performed from January 2012 to June 2013 (first trial) and from July to November 2013 (second trial) using a randomized blocks with treatments distributed in a factorial arrangement (5 × 2 × 2) of five humic substances doses (0, 10, 20, 30 and 40 mL of Humitec plant -1 ), two organic mulching use (with and without organic mulching) and two consecutive harvests, with four replications of two plants each. Humic substances enhance fruit production more efficiently in guava plants grown without soil mulching. Guava fruit production increases from the first to the second harvest. Fruit quality for titratable acidity, soluble solids, vitamin C and soluble solids/titratable acidity ratio is adequate independently of soil mulching use. Humic substances improve fruit quality of guava cv. Paluma. Under soil and climate conditions, and considering the first two production cycles of guava, it is possible to recommend about 20 mL L -1 of humic substances for production of high quality guava fruits. Key words: Humic acids, post-harvest, Psidium guajava.


We present a general equilibrium model of the global oil market, in which the oil price, oil production, and consumption, are jointly determined as outcomes of the optimizing decisions of oil importers and oil exporters. On the supply side the oil market is modelled as a dominant firm – Saudi Aramco – with competitive fringe. We establish that a dominant firm may exist as long as it enjoys a cost advantage over the fringe. We provide an expression for the optimal markup and compute the spare capacity maintained by such a firm. The model produces plausible dynamics in response to oil supply and oil demand shocks. In particular, it reproduces successfully the jump in oil output of Saudi Aramco following the output collapse of Iraq and Kuwait during the first Gulf War, explaining it as the profit-maximizing response of the dominant firm. Oil taxes and subsidies affect the oil price and welfare through their effect on the trade-off between oil production efficiency and oil market competition.


4H-SiC substrate wafers with epi-layers were observed using monochromatic synchrotron X-ray topography in grazing incidence geometries, to investigate the defects in the epi-layer. Misfit dislocations with b=+1/3[11 2 0] caused by the difference in lattice parameter between the epi-layer and the substrate were observed. The misfit dislocations are located near the interface as edge dislocations, and appear at the top surface as screw dislocations on basal planes. It was observed that more than half of them were introduced from the growing epi-layer surface. The misfit dislocations and some screw dislocations with b=+1/3[11 2 0] are observed to remain as basal plane dislocations at the surface, while other basal plane dislocations were converted to threading edge dislocations in the epi-layer.


Results of the statistical analysis of the electrical breakdown time delay for neon-filled tube at 6.5 mbar with and without /spl gamma/ and ultraviolet (UV) irradiation are presented in this paper. Experimental distributions of the breakdown time delay are established on the basis of 1000 successive and independent measurements for different exposition dose rates of /spl gamma/-irradiation, and UV illumination with known spectrum. Obtained experimental density distributions are modeled with convolution-based model, proposing two independent random variables with exponential and Gaussian distribution, respectively. The tendency of the breakdown time delay distribution to change shape from the exponential-like to the Gaussian-like is found by increasing the exposition rate of the /spl gamma/ irradiation. In addition, the characteristic strong reduction of the time delay is identified in the tube under the UV illumination.


The late Professor Havlicek's Econometrics notes are often cited. But until now they have been very difficult to obtain. Here, you have the complete notes as published in Fall 1976 and in Fall 1980. They are identical in content. However, neither PDF reproduction is perfect. If there is a passage that seems difficult to read in one version, then please try the other!


Shell suture obliteration (ankylosis) was exceptionally frequent in the earliest turtles, in contrast to post-Triassic taxa. Since modern turtles grow mostly along sutures, early ankylosis in Triassic taxa is intriguing. The Triassic turtle Proterochersis porebensis Szczygielski & Sulej, 2016 is known from numerous specimens, allowing observation of shell microstructure changes during ontogeny. Shell ankylosis occurred seemingly randomly in individuals of variable size, including small and morphologically juvenile, and completely obscured the initial bony composition. We propose that this phenomenon in the Triassic turtles can be an effect of early evolutionary stages of shell histogenesis and physiological mechanisms still used in shell regeneration in modern species. We also describe some parallels between the unusual peripheral microstructure of another Triassic turtle, Waluchelys cavitesta Sterli, Martínez, Cerda & Apaldetti, 2020, and Proterochersis porebensis. Microstructural changes imply that Proterochersis porebensis could change habitat during ontogeny, small individuals appearing more aquatic and larger more terrestrial.


The objective of the paper was to measure deformations of the skidding road which were caused by single, double and triple crossings of caterpillar harvester Mht 8002HV.The measurements were carried out on the skidding road with a transverse slope (4.5o) to the axis of the road, and longitudinal (2.6o) to the axis of the skidding road. The measurements were carried out with the use of a device for remote imaging of the land surface. The device operates by moving Leica Disto Plus laser rangefinder over the tested surface with the use of the coordinate system controlled by a computer (CNS control). Based on the results, it was reported that three crossing of a harvester caused slight deformations of the skidding road, and slight transverse declination of the skidding road caused loading of the caterpillar and resulted in its 70% loading with the total weight of the machine in the centre of the caterpillar. Despite irregular loading of caterpillars, theoretically average unit pressure on soil caused by more loaded caterpillar did not exceed 70 kPa. Whereas, average depth of the rut, which was measured, after three crossings of the harvester was 4,8 cm and for the less loaded caterpillar it was 3,6 cm. Three crossing of the machine uncovered the root systems of trees and considerable relocations of the ground fragments.


To detect the clinical diagnostic criteria for non-invasive diagnosis of erosive gastritis in children with juvenile arthritis have been studied the 92 children aged 9 to 16 years (mean age-13,9 ± 2,3 years) with verified diagnosis of juvenile arthritis, of whom 10 had erosive gastritis (group 1) and 82 without erosions (group 2). A comparison of the groups on 23 grounds by analysis of contingency tables and the subsequent discriminant analysis, has developed a new non-invasive method for determining the erosive lesions of the mucous membrane of the stomach in children with juvenile arthritis, including a score of history, complaints and the results of laboratory studies the level of the G-17, pepsinogen I, pepsinogen II, and the ratio of pepsinogen I to pepsinogen II, the presence of autoantibodies to the H+, K+/ATPase of the parietal cells of the stomach, the test for occult blood "Colon View Hb and Hb/Hp". Developed a diagnostic table, including 11 features with scores each. The total score 27 or higher allows a high degree of probability to determine the erosive lesions of the gastric mucosa in children with juvenile arthritis.


Purpose – This research evaluates (1) work situations prompting participants to recall memories of a wilderness-based leadership training program, (2) the content of suchmemories, and (3) the leadership attitudes and behaviors inspired by those memories. Design/methodology/approach – A qualitative content analysis of semi-structured interviews was performedwith 36 leaders who had participated in a wilderness leadership transformation program in the past (on average six years before). Findings –The findings suggest that, at moments with emotional pressure and psychological stress, episodic memories of wilderness experiences have a positive influence on actual leadership style. Memories involved moments of solitude, a deep connection with nature, and peer-to-peer counseling. The interviewees regularly relived their emotion-ladenwilderness experiences, acquiring direction and guidance. Simultaneously, episodic memories of nature immersion promoted an enduring transformation of their leadership styles. Research limitations/implications –The findings cannot be blindly generalized as referring to all leaders. The leaders in this study are a subset of leaders who are inclined towards personal growth and leadership development. It is challenging to motivate leaders unkeen on changing to achieve better leadership. Practical implications – This study indicates that the inclusion of emotional concepts to address the root causes of learning among leaders might be the most promising way to innovate leadership development. Originality/value – The present study makes a novel contribution to relevant literature by examining leadership transformation through episodic remembrance of leaders' experiences in nature.


The aim of this study was to explore the lived experience of palliative nursing care for different generations of a migrant family in the New Zealand context. Methodology used was an intrinsic case study. The twin threads of the family's region and their immigration experience influenced their experiences and their ways of coping in the four domains of family relationships, the support they received from their community, their ability to communicate, and their relationship with palliative care services. Palliative care was by a family approach with strong community support and empowered by culturally safe and appropriate nursing practice. This study explored the underpinnings of culturally safe palliative nursing care.


1Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University, College of Medicine, Seoul, South Korea; 2QST Hospital, National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan; 3Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan Background: The aim of this study was to investigate whether carbon-ion beam irradiation in combination with 5-fluorouracil (5-FU) is superior to carbon-ion beam irradiation alone in targeting colorectal cancer stem-like cells (CSCs). Materials and Methods: Human colorectal cancer (CRC) cells, HCT116 and HT29, were treated with carbon-ion beam irradiation alone or in combination with 5-FU. Cell viability assay, colony and spheroid formation assay, apoptotic assay, and quantitative real-time PCR analysis of apoptosisand autophagy-related gene expression were performed. Results: Carbon-ion beam irradiation dose-dependently decreased CRC cell viability and showed significantly enhanced cell killing effect when combined with 5-FU. Carbon-ion beam irradiation in combination with 5-FU significantly increased the percentage of apoptotic cells. The expression of some apoptotic and autophagy-related genes such as Bax, Bcl2, Beclin1 and ATG7 was significantly induced by carbon-ion beam irradiation alone and was further enhanced when the beam was combined with 5-FU. The spheroid forming capacity of CD133+ cell subpopulations was significantly inhibited by carbon-ion beam in combination with 5-FU. Histopathologically, the combination of carbon-ion beam irradiation and 5-FU destroyed more xenograft tumor cells, and resulted in increased necrosis, cavitation, and fibrosis, compared to carbon-ion beam irradiation alone. Conclusion: In conclusion, carbon-ion beam treatment combined with 5-FU has the potential to kill CRC cells including CSCs by inducing increased apoptosis and autophagy.


Background The UK Department of Health (DH) published national guidance in end of life care for the first time (DH 2008/2009), highlighting the Liverpool Care Pathway for the Dying Patient (LCP) as a best practice model of care in the last hours or days of life. After an extensive 2 year consultation process, resulting in important amendments around more explicit goals on hydration, nutrition and skin integrity, communication and guidance for diagnosing dying, the current LCP (Version 12) was published in 2009. The Marie Curie Palliative Care Institute Liverpool, in collaboration with the Royal College of Physicians, has undertaken round 3 of the National Care of the Dying Audit Hospitals (NCDAH). The NCDAH allows submission of data against 2 elements – organisational (all NHS Trusts) and clinical (LCP) elements of care delivery in the last hours or days of life. Data driven Key Performance Indicators (KPI) were developed for organisational and clinical elements of the audit. The NCDAH Round 3 has been included in the 'Quality Accounts' list of national audits promoted by the DH in 2011-2012, and is the first round to measure care delivery against outcomes on LCP V12. Aim Present findings of the NCDAH Round 3: • Organisational elements of care delivery and KPI's • Clinical Outcomes: against core elements of care (LCP V12) • National implications for policy. Method Retrospective audit cycle: organisational and clinical elements of care in the last hours or days of life in hospitals in England. Findings 131 NHS Trusts have submitted organisational data, and 178 individual hospitals have submitted outcome data from 7058 patients whose care was supported by the LCP. Participation has increased by 13% from round 2. Conclusion Results will be discussed with national implications for policy, education and training, and key recommendations for improvements into the future.


This study analyzes the ownership-performance relationship in large-scale farms using extensive survey and farm accountancy data from Czech agriculture. Controlling for ownership endogeneity, no significant influence of ownership on financial performance was found. However, ownership concentration and managerial ownership positively effect labor productivity. Farm group analysis detects highly heterogeneous ownership form combinations and suggests that ownership endogeneity stems from mutual sources with economic performance. The results imply that one of these sources is management quality and its ownership transformation strategies. They further disclose that ownership structure and agency problems are more of a concern in larger farms.


The treatment of IBD has evolved significantly over the past 15 years. Historically, steroids and immunosuppressive drugs, such as methotrexate (MTX), azathioprine (AZA) and 6-mercaptopurine (6-MP) had been the mainstay of therapy. When infliximab (IFX) was approved for the treatment of Crohn's disease, it began the era of trying to understand how best to optimise our available treatment options. Initially, antitumour necrosis factor (anti-TNF) agents were used after immunosuppressives failed. Then, evidence showed that using AZA together with IFX early in the disease course was more effective than the typical sequential treatment algorithm.1 With the addition of newer anti-TNF drugs and development of different treatment regimens,2–5 there are still significant questions related to the most effective therapeutic strategy. Perhaps the most controversial of these questions is when to use anti-TNF monotherapy versus combination therapy with 6-MP, AZA or MTX.

When considering patients with rheumatoid arthritis, where anti-TNF therapy also has a demonstrated efficacy, it is clear from randomised controlled trials (RCT) that the use of combination therapy improves clinical outcomes.6 Although it is logical that a similar benefit should exist in IBD, the evidence base upon which to make decisions is less robust, leading to patient and provider concerns regarding the balance between efficacy and toxicity. Providers have two sources of data to rely upon when addressing this concern with IBD patients, RCTs and observational data. RCTs are more rigorous, generally have better patient follow-up, and more often include prospective measurement of study end-points using well-accepted and often validated outcome measures. For this reason, RCTs result in a relatively robust assessment of key outcome measures such as clinical response, remission and mucosal healing. Although the data from RCTs may not directly translate to the 'real world',7 whatever generalisability is lost due to the application of strict inclusion …


The Reference Centre for Intestinal Spirochaetal Infections, located in the School of Veterinary Studies at Murdoch University, was established in 1990. Since that time the Centre has received financial support from the Pig Research and Development Corporation to fulfil two broad aims. Firstly, it acts as a specialised laboratory that has the capacity to isolate, identify and type intestinal spirochaetes as a direct supporting service to the Australian Pig Industry, acting through Pig Veterinarians and Regional Veterinary Diagnostic Laboratories. Initially work focused on Serpulina hyodysenteriae, the agent of swine dysentery, but more recently has increased to include the new species Serpulina pilosicoli, the agent of porcine intestinal spirochaetosis. The availability of this service assists with diagnosis, and ultimately control of these economically important infections. Intestinal spirochaetes are fastidious, and the Centre supplies the specialised facilities and expertise needed to work with them. Results from the laboratory are collated to give an ongoing and comparative overview of the diseases and their associated organisms in Australia. This is an important monitoring role. The laboratory now houses a large and unique collection of intestinal spirochaetes, representing an important resource nationally and internationally.

The second major aim of the Centre, and that requiring most time and resources, is to conduct research on improved methods for diagnosis, typing and control of porcine intestinal spirochaetal infections. The results of this work are fed back to improve the efficiency of the diagnostic laboratory, to improve understanding of the epidemiology of the infections, and to increase options for control. An important byproduct of this work has been the training of a group of outstanding postgraduate students, who will undoubtedly continue to make considerable contributions to research in the longer term.

In the spirit of the AVA Conference where this paper is presented - "Challenging the boundaries" - in the rest of this article I will outline areas where work from the Reference Centre has done just that. Two major new paradigms have been established by our work: these relate to the use of diet to control swine dysentery, and the role of intestinal spirochaetes other than S. hyodysenteriae in the aetology of disease in pigs. The development of polymerase chain reaction (PCR) protocols at the Centre, and improved methods for typing S. hyodysenteriae and S. pilosicoli isolates will also be summarised because of their potential importance and relevance to Australian Pig Veterinarians dealing with diseases caused by intestinal spirochaetes.


With the development of market economy, the diversified marketing models and personalized consumer demand make the obsolete traditional sale of tobacco products unable to adapt to the modern market environment increasingly. This paper analyzes and summarizes systematically the theory on customer satisfaction, customer value of both domestic and international, and then it introduce the concept of the satisfaction index. Based on this concept, a customer value driver of the weighted satisfaction index model is built. This thesis builds an EPIS analysis model of 'Extend—Preserve—Improve—Solve', which relays on the degree of importance and satisfaction index. In this model, the index can be counted. Empirical research on Henan tobacco market has been done and countermeasures to enhance the customer value of Henan tobacco retailers have also been proposed


Training is the task of guiding a cognitive radio engine through the process of learning a desired system's behavior and capabilities. The training speed and expected performance during this task are of paramount importance to the system's operation, especially when the system is facing new conditions. In this paper, we provide a thorough examination of cognitive engine training, and we analytically estimate the number of trials needed to conclusively find the best-performing communication method in a list of methods sorted by their possible throughput. We show that, even if only a fraction of the methods meet the minimum packet success rate requirement, near maximal performance can be reached quickly. Furthermore, we propose the Robust Training Algorithm (RoTA) for applications in which stable performance during training is of utmost importance. We show that the RoTA can facilitate training while maintaining a minimum performance level, albeit at the expense of training speed. Finally, we test four key training techniques (ε-greedy; Boltzmann exploration; the Gittins index strategy; and the RoTA) and we identify and explain the three main factors that affect performance during training: the domain knowledge of the problem, the number of methods with acceptable performance, and the exploration rate.


BACKGROUND AND OBJECTIVES: Orofacial pain is the pain felt in the oral cavity and the face, with a multifactorial etiology, being a representative of the temporomandibular dysfunction. Among the various possibilities for treatment are acupuncture and the dry needling. The objective of this study was to compare the effectiveness of these two therapies in the cases of myogenic temporomandibular dysfunction. CONTENTS: A review of articles relating to the topic was conducted on the LILACS, Medline, Scielo and Pubmed database, cross-referencing the following descriptors: "acupuncture" OR "electroacupuncture" OR "dry needling" AND "orofacial pain syndrome" OR "orofacial pain" OR "temporomandibular dysfunction" OR "temporomandibular disorders", myofascial temporomandibular dysfunction or trigger points in last the 16 years. Clinical trials, systematic reviews, metanalysis, case studies involving human beings were included. The selected languages were English and Portuguese. Twenty-one articles were found that were carefully evaluated and tabulated. The present study identified that both acupuncture and dry needling were significantly important in the resolution of the signs and symptoms of the myogenous temporomandibular dysfunction, with adequate effectiveness. CONCLUSION: It can be pointed out that dry needling seems to be more effective in the resolution of local pain on the myofascial trigger points than just using of acupuncture points at a distance. Acupuncture demonstrated positive influences in the general health quality and pain of patients with myofascial temporomandibular dysfunction. Therefore, the therapy of choice will depend on the professional's assessment of the clinical conditions of the patient and the therapeutic goals to be achieved.


Photoelectron circular dichroism (PECD) is experimentally investigated with chiral specimens with varying amounts of enantiomeric excess (ee). As a prototype, we measure and analyze the photoelectron angular distribution from randomly oriented fenchone molecules in the gas phase that result from ionization with circularly polarized femtosecond laser pulses. The quantification of these measurements shows a linear dependence with respect to the ee values. In addition, differences in the ee values (denoted as detection limit) of below one percent can be distinguished for nearly enantiopure samples, as well as for almost racemates. In combination with the use of a reference, the assignment of absolute ee values is possible. The present measurement time is a few minutes, but this could be reduced. This table-top laser-based approach should facilitate widespread implementation in chiral analysis.


The General Baptist Missionary Society of England began its work at Cuttack, a provincial town on the east coast of India, in 1822. It engaged suitable adult native converts as itinerant preachers. It encouraged them to maintain journals and describe their everyday life in rich detail. This paper offers a reading of three crucial concerns of the everyday life these journals construct: time, interiority, and public good. Constituted by simultaneously pursued dialogues with English and Oriya discursive traditions, these notions and attendant practices helped the formation of a small Christian middleclass that nurtured a new understanding of being human. The paper concludes by arguing in favor of local cultures of selfhood: a history of the particular discursive negotiations undertaken by the Oriya preachers accomplishes a fuller understanding of colonial modernity at Cuttack.


ABSTRACT This study aims to identify the mechanisms through which land tenure governance affects the technical efficiency of grain production in an integrated framework and to examine the impacts of the public governance, village self-governance, and relational governance of land tenure on the technical efficiency of contracted land and rented-in land. Farm-level survey data collected from Liaoning, Jiangxi, and Jiangsu provinces covering the years of 2014 and 2015 is used for the empirical analysis. The findings indicate that (i) public governance associated with land certification significantly increases the technical efficiency of grain production; (ii) village self-governance and administrative land reallocations can serve as substitutes for the land rental market in optimizing the distribution of land resources and improving technical efficiency; and (iii) compared to multi-year transfer contracts, both annual and open-ended transfer contracts have negative impacts on technical efficiency.


The paper addresses the problem of fragmentation of the communities involved in the design of digital media for education. It draws on the experience gained at the Educational Technology Lab in the design of Logo-based microworlds with three different platforms respectively based on component computing, 3D game engines and 3D navigation with a GIS. In this paper I use the term half-baked to describe a microworld which is explicitly designed to engage its users with changing it as the main aspect of their activity. I discuss this kind of microworld as a tool for integrated design involving people with diverse expertise and/or roles to communicate. These kinds of microworlds implicitly exist within the community, but they can be explicitly designed mediated and put to use in the role of facilitators for integrated design and development to enable a growing communication amongst researchers, technicians, teachers and students. A template for presenting microworlds which was constructed through the experience with four such integrated communities is used to describe for each respective case the design principles, the affordances, the histories of development and the variety of emergent microworlds.


Ovarian cancer has a very poor prognosis. Symptoms develop late in the disease and therefore it is usually diagnosed in an advanced stage. Attempts to detect the disease at an earlier stage have not been successful thus far. Therefore, optimal treatment seems to be the most efficient means at the moment to fight this 'silent killer'. Prior studies consistently found that specialized gynaecologists, or gynaecological oncologists, performed adequate surgery significantly more often than general gynaecologists and survival was better after treatment in specialized hospitals. In the Netherlands about 1100 patients are diagnosed with ovarian cancer annually. Treatment of ovarian cancer patients takes place in almost all of the about 100 Dutch hospitals. Less than 40% of the ovarian cancer patients are treated by gynaecological oncologists. The question is whether the present Dutch system suffices to provide optimal care to ovarian cancer patients. We investigated this question in a cohort of 8621 Dutch ovarian cancer patients diagnosed between 1996 and 2003. All Dutch hospitals were classified according to specialization level (general, semi-specialized or specialized). About 40% of the patients had been treated in general hospitals, 41% in semi-specialized hospitals and 19% in specialized hospitals. Relative 5-year survival was 39%. Survival of patients older than 50 years with an early stage disease was longer after treatment in semi-specialized and specialized hospitals than in general hospitals. There was only a modest effect of hospital-specialization on the survival of patients with advanced ovarian cancer. Treatment outcomes were investigated in more detail in a sample of 1077 patients. Only 24% of the patients with early stage disease who received surgery by a general gynaecologist had been adequately staged, compared to about 60% of the patients operated by semi-specialized and specialized gynaecologists. Less than half of the patients with advanced disease received optimal debulking and specialization of the gynaecologists had little impact on the outcomes. However, gynaecologists performing more than 12 ovarian cancer surgeries per year (high-volume gynaecologists) achieved optimal debulking 3 times more often than gynaecologists operating 6 or less ovarian cancer surgeries annually. In addition, patients treated in specialized hospitals and by high-volume gynaecologists survived longer. We found no association between hospital type and the outcomes of first-line chemotherapy. However, overall survival was better in hospitals with 2 or more medical oncologists and in hospitals where 7 or more ovarian cancer patients were treated annually. This indicates that there might be an effect of the hospital type on the efficacy of second-line chemotherapy. Finally, the cost-effectiveness of treatment in general, semi-specialized and specialized hospitals was compared and the effect of improved treatment in specialized settings was investigated. With the present surgical results, treatment in semi-specialized hospitals was most cost-effective. However, if the percentages of adequately staged and optimally debulked patients were equal to the percentages described in literature, ovarian cancer care in specialized hospitals would also be a cost-effective strategy. These results imply that there is room for improvement of the Dutch treatment outcomes by increasing the level of specialization and concentrating ovarian cancer care.


Blood group antigens (BGAs) can act as functional molecules but also can evoke autoantibodies and alloantibodies, causing autoimmune hemolytic anemia, hemolytic disease of the newborn and hemolytic transfusion reactions. In Section I, Dr. Marilyn Telen discusses physiologic and pathologic functions of RBC BGA-bearing molecules. She reviews some associations of BGAs with RBC membrane integrity and hemolytic anemia; association of BGAs with enzymatic and transport functions; and adhesion molecules expressed by RBCs, especially with reference to their pathophysiological role in sickle cell disease. In Section II, Dr. Lawrence Petz discusses the problems of providing blood for patients who have RBC autoantibodies. He provides an algorithm for excluding the presence of "hidden" alloantibodies, when all units appear to be incompatible due to the autoantibody. He emphasizes that clinicians should be aware of these approaches and not accept "the least incompatible unit." In Section III, Dr. George Garratty describes two processes, in development, that produce RBCs that result in RBCs that can be described as "universal" donor or "stealth" RBCs. The first process involves changing group A, B, or AB RBCs into group O RBCs by removing the immunospecific sugars responsible for A and B specificity by using specific enzymes. The second process involves covering all BGAs on the RBC surface using polyethylene glycol (PEG). Results of in vitro and in vivo studies on these modified RBCs are discussed.


Conventional color imaging requires absorptive color-filter arrays, which exhibit low light transmission. Here, we replace the absorptive color-filter array with a transparent diffractive-filter array (DFA) and apply computational optics techniques to enable color imaging with a sensitivity that is enhanced by a factor as high as 3.12. The DFA diffracts incident light onto a conventional monochrome sensor array to create intensity distributions that are wavelength dependent. By first calibrating these wavelength-dependent intensity distributions and then applying computational techniques, we demonstrate single-shot hyperspectral imaging and absorption-free color imaging.


In the sonata practice of the mid-eighteenth century, composers frequently asserted the minor dominant prior to the major dominant in the second part of the exposition. Beethoven dramatized this technique in two senses: first, he used it after it had largely fallen out of fashion, thus affording it considerable dramatic impact (e.g., Piano Sonatas Ops. 2, no. 2, and no. 3); second, he graduated from using the "wrong" mode to the more radical technique of using the "wrong" key. For instance, for the secondary key of the Piano Sonatas Ops. 31, no. 1, and 53 ("Waldstein"), he substitutes the major mediant for the dominant. These and similar cases result in the deferred arrival of the tonic in the secondary theme of the recapitulation. Consequently, when the tonic belatedly arrives, the listener is more cognizant of it. In this way Beethoven brings the resolution of large-scale tonal dissonance to the fore. I suggest that such a tactic is metamusical—that Beethoven was in a sense writing music about music, about the relationship between a particular piece and the tonal and formal conventions it relies on and also problematizes. After presenting a number of such metamusical instances, this article traces the stages by which Beethoven "progressed" from the mid-eighteenth-century approach to sonata expositions to his more radical one; it then offers a typology of key-problematizing techniques. It concludes by briefly considering the extent to which these procedures can be squared with Schenkerian theory and its ideal of structural hearing.


Background Remote Aboriginal communities in Australia have substantially higher rates of chlamydia (CT), gonorrhoea (NG) and trichomoniasis (TV) diagnosis compared with non-Indigenous people, despite many years of programme and policy aimed at reducing disparity. Methods 'STRIVE' is a stepped wedge cluster randomised controlled trial, underway in 68 remote Aboriginal communities. The primary objective is to assess if a sexual health quality improvement programme within primary care clinics improves STI management and in turn reduces STI prevalence. Data is extracted from both patient management systems and from laboratories. To evaluate the impact of the trial, the largest STI prevalence study in Aboriginal people has been undertaken twice. Results In the first year of the trial, testing rates have improved overall by 27% at 21 sites and by 50% or more at 11 sites. In 2011, baseline prevalences for CT and NG (n = 2483) and TV (n = 1848) among 16–34 year olds were 9%, 7% and 13% respectively. Highest prevalences were reported among 16–19 year olds for CT 13% (95% CI; 10.8–16.4), NG, 12% (95% CI; 9.7–15.1) and TV, 17%(95% CI; 13.7–21.1). There were 17,848 STI tests conducted in 2010 and among females aged 16–34; 33.3% had ≥ 1 STI (highest in 16–19 year olds: 48.9%) and 21.3% of males had ≥ 1 STI (highest in 16–19 year olds:33.4%). The most frequent co-infection was CT and NG which was found in 3.4% of females (highest in 16–19 year olds: 8.6%) and 3.9% of males (highest in 16–19 year olds:10.1%). Discussion STRIVE has provided information not previously available in regard to a comprehensive epidemiological picture of STI morbidity and health service responses in remote Aboriginal communities and highlights work required especially among young people. The results of STRIVE may be of relevance to other areas globally with STI endemic rates.


This randomized study compared the number of leukaphereses required to collect an optimal target yield of 5 x 10(6) CD34(+) peripheral blood progenitor cells/kg, using either stem cell factor (SCF) at 20 micrograms/kg/d in combination with Filgrastim at 10 micrograms/kg/d or Filgrastim alone at 10 micrograms/kg/d, from 203 patients with high-risk stage II, III, or IV breast cancer. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield of CD34(+) cells had been reached or a maximum of 5 leukaphereses performed. By day 5 of leukapheresis, 63% of the patients treated with SCF plus Filgrastim (n = 100) compared with 47% of those receiving Filgrastim alone (n = 103) reached the CD34(+) cell target yield. There was a clinically and statistically significant reduction (P <.05) in the number of leukaphereses required to reach the target yield for the patients receiving SCF plus Filgrastim (median, 4 leukaphereses) compared with patients receiving Filgrastim alone (median, 6 or more leukapherses; ie, <50% of patients reached the target in 5 leukaphereses). All patients receiving SCF were premedicated with antihistamines, albuterol, and pseudoephedrine. Treatment was safe, generally well tolerated, and not associated with life-threatening or fatal toxicity. In conclusion, SCF plus Filgrastim is a more effective peripheral blood progenitor cell (PBPC)-mobilization regimen than Filgrastim alone. In addition to the potential for reduced leukapheresis-related morbidity and costs, SCF offers additional options for obtaining cells for further graft manipulation.


Abstract The rate of return (ROR) on R&D in the South African Sugar Industry is estimated from a Ridge Regression of a production function of time series data for the period 1925 to 2001. The Industry has kept records on R&D expenditure, yields, rainfall and related factors over a 75-year period. Sugar cane yield was measured in tons sucrose to account for quality improvement. In this function, R&D expenditure lagged three years was significant (t = 6.5) in explaining increased sucrose production per ha. Other highly significant variables in this model were rainfall (t = 5.2) and real cost of production (t = 8.4). A dummy interaction with R&D was significant (t = 2.9) implying a greater impact for R&D technology during the period 1959 to 1975 than either before or after this period. The standardised regression model indicated that the R&D variable was one of the most important variables in explaining yield. Using the elasticity of production estimate for the R&D variable of the un-standardised model, a Benefit/Cost ratio for this variable of 1.41 was estimated, if benefit of millers is excluded and 1.59, if the gain to millers is included. In the latter estimates, the exports realisation price of sugar was used as the appropriate shadow price. A real internal rate of return was estimated at 17%. A unique feature of the South African Sugar Industry is that research is privately funded by the industry, which implies that the distortionary impact of taxes need not be accounted for, as is the case with public funded research.


Ad-Hoc wireless networks are self-organizing multi-hop wireless networks. Ad-Hoc networks can quickly and inexpensively be set up as needed Therefore, they are highly applicable in many fields such as emergency deployments and community networking. Mobile ad hoc networks have some challenges like the design of an efficient routing protocol. The multipath routing protocol with load balancing provides a solution for the congestion network and increases its capacity. To consider that the use of multiple paths simultaneously for transmission data allows to improve the network performance, we propose a protocol LB-AOMDV (Load Balancing-AOMDV), a solution to achieve better load balancing mechanism. In this paper, we also apply the Ant Colony optimization technique to the routing problem, after that we apply a extension of ACO that is ranked based ACO approach. We refer to the new modified protocol as the LB-AOMDV Rank Based Ant Colony Optimization algorithm .The main goal in the design of the protocol will be reduce the routing overhead, response time, end-to-end delay and increase the performance.


We report an odderon Regge trajectory emerging from a field theoretical Coulomb gauge QCD model for the odd signature J(PC) (P = C = -1) glueball states. The trajectory intercept is clearly smaller than the Pomeron and even the omega trajectory's intercept which provides an explanation for the nonobservation of the odderon in high energy scattering data. To further support this result we compare to glueball lattice data and also perform calculations with an alternative model based upon an exact Hamiltonian diagonalization for three constituent gluons.


were withdrawn and management arrangements reverted to status quo ante. Since the ASTMS declared its dispute with the board, the board has been trying to process the dispute. Now, two years later, this dispute has still not been heard, and the board's 1981 decision on management has therefore still not been implemented. We are satisfied that the successive delays preventing implementation of the disputes procedure have not been caused by the board. Certainly the BMA is concerned about the situation in Fife, for this has serious implications for patient care. And we must be clear that the only important issue in this matter is patient care, for the interpretation of the results of the tests in the laboratories can be applied in the wards only by doctors. May I suggest to Mr Craig that it is not only the government and doctors who believe that in the interests of patient care laboratory departments must be headed by medical consultants or scientists of equivalent standing, but also the public, who rely on these laboratories. DEREK BUCHANAN Scottish Secretary BMA Scottish Office, Edinburgh EH3 7QP


AIM
To describe the patient characteristics, management and cardiovascular sequelae of Kawasaki disease (KD) in patients taking part in a multidisciplinary follow-up in the Emma Children's Hospital during the period January 1999-June 2010.

DESIGN
Retrospective, observational study.

METHODS
We included 392 patients who were diagnosed with complete or incomplete KD. Clinical and outpatient statuses were used to collect clinical data.

RESULTS
The median age at onset of the disease was 3.2 years (range: 0.1-16.4). The male-to-female ratio was 1.6 : 1. Complete KD was diagnosed in 83.9% of patients. Patients with incomplete KD were younger than those with complete KD: 2.2 versus 3.4 years (both SD: 3.0; p < 0.01). 357 patients (91.1%) were treated with intravenous immunoglobulins; 65 patients (16.6%) received a second intravenous dose. Coronary artery aneurysms were diagnosed in 83 patients (21.2%). Male gender, age < 1 year, incomplete presentation and late start of treatment (> 10 days after start of fever) were shown to be independent risk factors for developing aneurysms. These abnormalities normalized in 50 of the 83 patients. 2 patients died of the disease within a year. 5 patients underwent coronary artery bypass grafting during the follow-up period.

CONCLUSION
Kawasaki disease is a rare form of vasculitis seen in children, in which aneurysms of the coronary artery can develop. Clinicians should be alert to the possibility of KD in cases of persistent inexplicable fever, especially in young children, even in the absence of complete clinical disease. A timely start to treatment reduces the risk of developing coronary artery aneurysms.


: Wind energy is one of the clean renewable energy. However, the low frequency (20-200HZ) noise generated from the wind turbine blades, which bothers the residents, becomes the major problem to be developed. It is useful for predicting the aerodynamic noise by flow field and pressure distribution analysis on the wind turbine blades. Therefore, the main objective of this study is to use different turbulence models to analyse the flow field and pressure distributions of the wing blades. Three-dimensional Computation Fluid Dynamics (CFD) simulation of the flow field was used to calculate the flow phenomena for the National Renewable Energy Laboratory (NREL) Phase VI horizontal axis wind turbine rotor. Two different flow cases with different wind speeds were investigated: 7m/s with 72rpm and 15m/s with 72rpm. Four kinds of RANS-based turbulence models, Standard k-ε, Realizable k-ε, SST k-ω, and v2f, were used to predict and analyse the results in the present work. The results show that the predictions on pressure distributions with SST k-ω and v2f turbulence models have good agreements with experimental data.


Author(s): D'Alessio, Joseph Anthony | Advisor(s): Tjian, Robert | Abstract: The exquisite structural and functional complexity of the mammalian body requires the exactingly precise spatial and temporal regulation of gene expression. The most critically regulated step of which is the transcription of DNA to RNA by the elaborate interplay of sequence-specific activators and repressors, chromatin modifiers, coactivators, the basal machinery and RNA polymerase II. Until recently, developmental stage and tissue-specific gene expression patterns were believed to be regulated primarily by the combinatorial actions of DNA binding activators and repressors, while the core machinery was held to be invariant. New evidence suggests that significant differences in coactivator and core promoter recognition complex composition between cell types and developmental time points may facilitate the global changes in gene expression programs necessary to confer functional diversity. Because of its critical role in vertebrate development and homeostasis, the role of coactivator and core promoter recognition complex switching in the developing liver was examined. This work shows that mouse liver progenitors or hepatoblasts contain significant levels of the canonical core promoter recognition complex TFIID, including the TATA binding protein and multiple associated factors or TAFs, and the canonical coactivator complex Mediator. These complexes and their constitutive proteins are significantly downregulated in adult hepatocytes. Furthermore, the promoters of several TFIID components become enriched for repressive chromatin marks in adult hepatocytes, and an in vitro model of liver development recapitulates the downregulation of these complexes observed in vivo. In contrast, expression of the TBP-related factor TRF3, the TAF7 paralogue TAF7l, and TAF13 is maintained or induced upon hepatic differentiation. Additionally, these proteins associate with high molecular weight complexes in vitro where they are enriched at hepatocyte-specific promoters, and their depletion attenuates hepatic gene induction. Together these observations support a model wherein liver development and the induction of hepatic gene expression requires the down regulation of TFIID and its replacement with one or more complexes likely containing TRF3, TAF7l and TAF13.


Dur ing the last week of January 1972, a severe outbreak of rust was seen in plantations of matchstock poplars (Populus deltoides Bartr. variet ies and clones) in the Wisemans Ferry district of New South Wales, about 40 miles no rth west of Sydney. The rust was identi fied as Melampsora medusae Thiirn. wh ich occurs on Populus spp . in North America, Europe and Japan . Abu ndant uredinia were present on infected trees, and severe leaf damage occurred. No rusts of poplar have been recorded previously in Australia or New Zealand. Since then, the disease has spread rapidly and has been recorded from as far away as Kempsey and Canberra. Further work is planned on the rust, whose aecial hosts are various conifers. Details of the or iginal outbreak and spread of the rust, and its identity, will be published elsewhere.