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In 2014, the Research Council of Norway (RCN) launched its strategic initiative for biotechnology research called “Digital Life – Convergence for Innovation”. The Centre for Digital Life Norway (DLN) was created in 2015 as a national virtual centre for biotech research and innovation. At the time of writing the centre consisted of a national networking project, 17 directly funded research projects and 18 associated research projects, as well as a research school and a strategic innovation project. In 2021 the national centre has begun its second period, with more partners and an even clearer mandate to change the Norwegian biotech sector, by way of – metaphorically expressed – being a flagship and acting as a lighthouse. In the original vision, the flagship and lighthouse character of the Digital Life initiative was above all meant to rely on the development of a new style of knowledge production, characterised by the concepts of “integration”, “interdisciplinarity”, “convergence” and “transdisciplinarity”. Indeed, throughout the processes of policy development, planning and funding – as well as during the operational phase of DLN - the notion of transdisciplinarity has been emphasised: DLN research and DLN activities in general should be, or at least strive towards becoming, transdisciplinary. While the original strategic policy document for Digital Life (RCN, 2014) never explicitly defined transdisciplinarity as such, it was implicitly defined as a mode of collaboration and interaction between research disciplines that was “something more” than interdisciplinarity, with higher ambitions and with an aim of tighter integration of different types of knowledge in order to solve societal challenges.

This working paper traces the trajectory of Syrian official documents across Syria and Germany in times of political upheaval, flight and integration. Documents issued by the Syrian state continue to be a fundamental element in the life of Syrians in Germany as they are still needed for certain mundane, yet crucial, purposes. Syrians are therefore forced to engage with Syrian state bureaucratic apparatuses at a distance. The journey of the papers across time and geographical borders unveils the highly political ambivalences and tensions embodied in Syrian paperwork in the context of German policies of asylum and integration. In Syria, the documents and their retrieval are embedded in the politics of security governing the Syrian citizenship regime. On arrival in Germany, the papers gain new meanings in their encounter with the German integration process and legal system rooted in the Rule of Law. At the same time, the papers' enmeshment with German bureaucracy reproduces (from a distance) the political dynamics between Syrians and the Syrian state in the past. Situated at a crossroads of the web of state(-s) power in and between Syrian and German bureaucracies, the papers re-integrate Syrians’ past into their present in Germany. By revealing this complex web of relationships, this working paper offers a reflection on the limits of studying the European context of integration and asylum 'fromwithin'.

Introduction: The concept of integration, although dating from the 1990s, has only recently appeared in French public health policy. It must be linked with “coordination”, which is the base of most French public policies applied to geriatrics since the 1960s. Herein, we report the French Society of Geriatrics and Gerontology working group’s findings according to three axes: definition of integration, objectives of this organisational approach and the means needed to achieve them. Discussion: Integration is a process that aims to overcome the fragmentation of services for vulnerable people. This process requires a multilevel approach, particularly concerning how to modify public policies and financing systems. Notably, all relevant levels need to develop shared processes, tools, resources, financing, interventions and action-reports on the latter. Integration must to be accompanied by a local dedicated professional (the “pilot”). Results of recent experiments showed that it is possible to implement integrative dynamics in France.

This thesis sought to analyse Norwegian Integration Act and policies and to examine whether it is multicultural or assimilatory in nature. This was done by studying the Integration Act, policies through white papers and other official documents as well as through parliamentary debates. Lastly, the thesis examined religious education by examining the subject called KRLE and how it is being taught through syllabus in schools in Oslo. This thesis examined both assimilation and multiculturalism and examine whether Norwegian policies are assimilatory in nature or multicultural, which might be the variable which gives this thesis some sort of value, as there is little research combining these in one thesis/article and that in the same context, the Norwegian in this context. It was argued that multiculturalism and assimilation are two philosophies or ideologies. Assimilation can be defined as a desired outcome for a society where members would be culturally indistinguishable from one another, which implies a process of becoming the same, an absorption of immigrants within the host society’s culture. Multiculturalism can be defined as a policy which supports cultural diversity and supports the right of minorities to preserve their cultural identities ensuring that they get access to the society, and which encompasses legal principles and commonly shared values dominant in the society. Multiculturalism and assimilation were operationalised in order to examine them through the empirical data, by applying certain instruments to each of them. In order to capture multicultural ideas, this thesis sought to apply the qualitative research design called ideational analysis. The objective of ideational analysis is to examine ideas from texts; hence it was argued that it was wise to apply this research design. The findings suggest that through some multicultural instruments find multiculturalism being applied, but overall, one could find that the integration law, the white papers and other official documents, parliamentary debates, and the religious education, are more inclined towards being assimilatory in nature. The three out of four hypotheses posed in the thesis seems to be correct, and thus one could argue that policies have a goal for assimilation. One could see multiculturalism being applied in practice as a way adapting to the society, but not as an official governmental goal. Coming to religious education, findings suggest that Christianity as a religion is being given emphasis at the expense of e.g., other religions and philosophies of life. This is done so, because of cultural heritage, as religion is regarded as an integral part of the culture.

Interdisciplinary inquiry hinges upon abductive arguments that integrate various kinds of information to identify explanations worthy of future study or use. Integrative abduction poses unique challenges, including different kinds of data, too many patterns, too many explanations, mistaken meanings across disciplinary lines, and cognitive, pragmatic, and social biases. Argumentation tools can help explicate and negotiate bias as interdisciplinary investigators sift and winnow candidate patterns and processes in search of the best explanation.

Paraguay's power system is based entirely on hydropower. It serves as the largest net electricity exporter in Latin America. Nonetheless, the country´s electricity consumption per capita is one of the lowest in the world and the transmission and distribution network has one of the highest losses in Latin America. This paper presents an electricity expansion investment outlook (2018–2040) for Paraguay using OSeMOSYS, analyzing three electricity demand scenarios under different electricity export prices to Brazil. The study identifies the least-cost power generation mix, future investments and the financial requirements to meet the needs of different demand scenarios. We find that Paraguay will need to invest in hydropower plants, by mainly expanding the capacity of Yacyreta to cover its electricity needs and sustain national electricity exports levels. In the High demand scenario, where the electricity demand could approximately double by 2040, the country's overall electricity exports decrease by 50% compared to the Reference scenario. Based on the different scenarios examined, the government spends approximately 18.3–31.2 billion USD on power plant investments for the period 2018–2040 to cover future electricity demand. The findings could be useful in supporting decision-making concerning socio-economic development pathways in the country. Supplementary Information The online version contains supplementary material available at 10.1007/s12667-020-00420-w.

Practice has developed into a key concept in management research, including B2B marketing and purchasing studies. However, the adoption of the term in B2B marketing and purchasing is characterized by some difficulties. Research on B2B practices is growing, but seems marked by fragmentation, inconsistency, and lack of precision among others. Without conceptual consistency and integrity, B2B practice studies are at risk of becoming derailed, compromising the developments of future theory and practice within B2B. In this critical review paper, we therefore seek to create an overview of B2B practice research as perceived through a practice lens. Based on a review of 116 identified practice papers from key B2B journals, we map the topic areas where the practice concept has been applied for investigations, and we also investigate how well the applied practice conceptualization in these papers align with a recognized practice theory conceptualization. We find that the majority of B2B studies align poorly with the three elements of practice: managerial action, habitual behavior, and action-structure duality. Since many of the alignment issues in the review are caused by methodological problems, we propose a series of methodological tools that can provide a more accurate understanding of B2B practices in future research.

The paper describe the organisational discretion of health

Context: In 2006 the Labour Government in England published its long awaited White Paper on ‘community services’, following on from the 2005 Green Paper on the future of social care. The policy envisages an unprecedented shift of activity and resources from acute care to community settings, along with a much stronger focus on preventive care. Several mechanisms are to be put in place to ensure this shift takes place, most notably practice-based commissioning, payments-by-results and enhanced partnership working. Purpose: This article outlines the intended changes and assesses the extent to which they add up to a coherent strategy. Conclusion: It is argued that although there is widespread support for the overall vision, the strategy contains some difficult policy tensions that are common to other welfare systems. These will have to be addressed if the vision is to be a reality.

Purpose Despite many calls to strengthen connections between health systems and communities as a way to improve primary healthcare, little is known about how new collaborations can effectively alter service provision. The purpose of this paper is to explore how a health authority, municipal leaders and physicians worked together in the process of transforming primary healthcare. Design/methodology/approach A longitudinal qualitative case study was conducted to explore the processes of change at the regional level and within seven communities across Northern British Columbia (BC), Canada. Over three years, 239 interviews were conducted with physicians, municipal leaders, health authority clinicians and leaders and other health and social service providers. Interviews and contextual documents were analyzed and interpreted to articulate how ongoing transformation has occurred. Findings Four overall strategies with nine approaches were apparent. The strategies were partnering for innovation, keeping the focus on people in communities, taking advantage of opportunities for change and encouraging experimentation while managing risk. The strategies have bumped the existing system out of the status quo and are achieving transformation. Key components have been a commitment to a clear end-in-view, a focus on patients, families, and communities, and acting together over time. Originality/value This study illuminates how partnering for primary healthcare transformation is messy and complicated but can create a foundation for whole system change.

The ITHACA project aims to contribute to the rising research and policy interest on migrant transnationalism and its effects on countries of origin and destination as well as on migrants themselves (and their families). This concept paper sets out the research framework within which the ITHACA Project will develop. More specifically, in this paper we propose a working definition of integration and highlight the conditions of integration that may be relevant for migrants’ transnational mobility. We then discuss transnationalism and physical mobility as one type, perhaps the most basic, of transnational activity. We connect our definition of transnational mobility to the wider field of transnationalism studies today. We subsequently focus on the types of transfers that may be triggered through transnational mobility. In the concluding sections we present the project’s research design and the research questions to be explored. Funded by DG Home of the European Commission.

Introduction: Team-based care can improve integrated health services by increasing comprehensiveness and continuity of care in primary healthcare (PHC) settings. Collaborative models involving providers from different professions can help to achieve coordinated, high-quality person-centred care. In Canada, there has been variation in both the timing/pace of adoption and approach to interprofessional PHC (IPHC) policy. Provinces are at different stages in the development, implementation, and evaluation of team-based PHC models. This paper describes how different policies, contexts, and innovations across four Canadian provinces (British Columbia, Alberta, Ontario, Quebec) facilitate or limit integrated health services through IPHC teams. Methods: Systematic searches identified 100 policy documents across the four provinces. Analysis was informed by Walt and Gilson’s Policy Triangle (2008) and Suter et al.’s (2009) health system integration principles. Provincial policy case studies were constructed and used to complete a cross-case comparison. Results: Each province implemented variations of an IPHC based model. Five key components were found that influenced IPHC and integrated health services: patient-centred care; team structures; information systems; financial management; and performance measurement. Conclusion: Heterogeneity of the implementation of PHC teams across Canadian provinces provides an opportunity to learn and improve interprofessional care and integrated health services across jurisdictions.

Summary: Introduction: Neglected tropical diseases control programmes run separately. For settings with more than one endemic disease, combined mass drug administration (MDA) has potential practical advantages compared with separate programmes but needs confirmation of safety. We assessed the safety of combined MDA for multiple neglected tropical diseases using ivermectin, diethylcarbamazine, albendazole (IDA) and azithromycin (AZI). Methods: We conducted an open-label, cluster-randomized trial involving individuals living in 34 wards (smaller administrative division) in two study sites, Namatanai District and Lihir Island, Papua New Guinea. We randomly assigned wards to the combined treatment arm (which received a single dose of the triple combination IDA and a single dose of AZI at the same visit) or the control arm (which received IDA separately followed by AZI separately one week after). All participants underwent safety assessments one day after drug administration. Methodology for collecting the adverse events (AEs) was a general question (in Namatanai) and individual questions about specific AEs (in Lihir). The primary endpoint was the prevalence of AEs. Safety of combined treatment was taken to be non-inferior to that of IDA if the upper limit of the two-sided CI for the difference in rates was equal or lower than 5%. Findings: The study enrolled 15,656 participants. Of those enrolled, 7,281 (46.3%) received the combined regimen and 8,375 (53.3%) received standard treatment with IDA for lymphatic filariasis between Nov 1, 2018, and Apr 15, 2019. Of the individuals in the control group, 4,228 (50.5%) attended a second visit one week apart to receive AZI for yaws. In Namatanai, the proportion of AEs was similar in the combined group (0.8%) compared to the IDA group (1.3%, difference 0.5% [95CI -2.5% to 1.4%]) or the AZI group (3.6%, d -2.8% [95CI -8.6% to 2.8%]). In Lihir, the proportion of AEs was higher in the combined group (23.0%) compared to the IDA group (12.2%, d 10.8% [95% CI 1.5% to 20.2%]) or the AZI group (11.1%, d 11.9% [95% CI 2.7% to 21.1%]).We observed 21 (0.3%) grade-2 AEs in the combined treatment group, 33 (0.4%) in the IDA separately group, and 18 (0.2%) in the AZI separately group. No participants required treatment for any AE. We observed no deaths, serious AEs, or AEs of special interest. Interpretation: In the largest trial so far involving coadministration of regimens based on IDA and AZI, the combination was safe and feasible in a population of more than 15,000 people. Combined MDA based on these two regimens opens up new potential for the control of neglected tropical diseases in the Western Pacific region. Funding: International Trachoma Initiative, “la Caixa” Foundation, Kern Pharma.

Fragmentation of processes and interventions plague the psychotherapies (Gilbert & Kirby, 2019). Part of the problem is that we have not agreed on a framework that could be the basis for integrating knowledge and the scientific enquiry of processes and interventions. This paper outlines an approach that brings together a variety of different disciplines in the service of consilience (Wilson, 1998, Consilience: The unity of knowledge, Vintage, New York, NY; Siegel, 2019). It presents the importance of an evolutionary framework for understanding the proclivities and dispositions for mental suffering and antisocial behaviour, and how they are choreographed in different sociodevelopmental contexts. Building on earlier models (Gilbert, 1989, Human nature and suffering, Routledge, London, UK; Gilbert, 1995, Clin. Psychol. Psychother., 2, 135; Gilbert, 1998, Br. J. Med. Psychol., 71, 353; Gilbert, 2016, Case formulation in cognitive behaviour therapy: The treatment of challenging cases, Wiley, Chichester, UK, pp. 50–89) the call is for an integrative, evolutionary, contextual, biopsychosocial approach to psychology and psychotherapy. Practitioner points Evolutionary functional analysis is part of an evolutionary, contextual, biopsychosocial approach to mental health that can serve as a scientific platform for the future developments of psychotherapy.Therapist skills and training will increasing need to focus on the multidimensional textures of mental states especially the context‐social‐body linkages.Therapies of the future will also focus more on the moral aspects of therapy and address the need to promote prosocial and ethical behaviour to self and others.

Objective To enhance the in vitro integration of self-assembled articular cartilage to native articular cartilage using chondroitinase ABC. Design To examine the hypothesis that chondroitinase ABC (C-ABC) integration treatment (C-ABCint) would enhance integration of neocartilage of different maturity levels, this study was conducted in 2 phases. In phase I, the impact on integration of 2 treatments, TCL (TGF-β1, C-ABC, and lysyl oxidase like 2) and C-ABCint, was examined via a 2-factor, full factorial design. In phase II, construct maturity (2 levels) and C-ABCint concentration (3 levels) were the factors in a full factorial design to determine whether the effective C-ABCint dose was dependent on neocartilage maturity level. Neocartilages formed or treated per the factors above were placed into native cartilage rings, cultured for 2 weeks, and, then, integration was studied histologically and mechanically. Prior to integration, in phase II, a set of treated constructs were also assayed to provide a baseline of properties. Results In phase I, C-ABCint and TCL treatments synergistically enhanced interface Young’s modulus by 6.2-fold ( P = 0.004) and increased interface tensile strength by 3.8-fold ( P = 0.02) compared with control. In phase II, the interaction of the factors C-ABCint and construct maturity was significant ( P = 0.0004), indicating that the effective C-ABCint dose to improve interface Young’s modulus is dependent on construct maturity. Construct mechanical properties were preserved regardless of C-ABCint dose. Conclusions Applying C-ABCint to neocartilage is an effective integration strategy with translational potential, provided its dose is calibrated appropriately based on implant maturity, that also preserves implant biomechanical properties.

This study examines the association between digital information technology (DIT) use and the utilization of transnational healthcare (THC) in older migrants, and investigates how this relationship depends on social integration or perceived discrimination in health services in the destination country. The data from a population-based study conducted in Finland in 2019, which targeted Russian-speaking residents aged 50 and above (n = 1082) nationwide, are analyzed. The analysis demonstrates that those who had a high level of DIT use were significantly more likely to use THC than those who had a low level of use. However, the findings do not show that the relationship depends on social integration or perceived discrimination. Older migrants can actively use transnational networks to address their health and well-being issues by using DIT and seeking healthcare abroad. Their health service use can be illustrated as an active process involving various geographical domains.

Background: An aging population is one of the key drivers reshaping health care systems. In China, the complex needs of its huge aging population require integration across the health and care sectors. Policies and progress: Over the past decade, the central government of China promulgated a series of policies to promote the establishment of aftercare facilities, specify approaches to integrate health and care service delivery at institutional and community levels, pilot long-term care insurance (LTCI) as a funding mechanism, and reform administrative structures in favor of integration. Progress has been made towards organizational and clinical integration of service delivery both at institutional and community levels. LTCI has been introduced as the financing mechanism covering long term care services. Discussions and Conclusions: The experiences of China in the integration of health and care could be summarized as a top-down approach in policy formulation and implementation, the significant employment of pilots and demonstrations, and the activation of market forces. However, China is still in the initial stage of integrating health and care and is faced with system-level challenges in its financing, management, and workforce, and faces technical challenges, such as a lack of tools, and standards. In the future, these issues need to be addressed.

Health sciences librarianship has historically benefited from avoiding critical conversations around the role of race in the profession, reflected through a select few number of articles on the topic. The purpose of this study was to add to this body of literature and apply a critical librarianship framework on the early scholarly record of health sciences librarianship and the legacy of integration within the Medical Library Association (MLA). Three Southern medical works and the integration views of Mary Louise Marshall, the longest-serving president of MLA from 1941 to 1946, were thematically and textually analyzed to redress the profession’s long-standing legacy with Whiteness and Black, Indigenous, and People of Color (BIPOC) representation. In reframing the historic past of MLA both through Marshall’s works and her views, the goal is to acknowledge ways in which the profession has impeded progress and present steps to remedy appropriate outreach for the future.

Increasingly, complexity science concepts are informing health care design and practice. The present paper describes the implementation of early complexity science principles in a Complex Care Program with the aim of strengthening the provision of integrated care. Grounded in cybernetic network theory, Stafford Beer’s Viable Systems Model [1] provided the guiding principles for the program’s redesign. The Viable Systems Model with its broadly applicable principles [1], is now the conceptual model of information management in the program. Beer’s framework has enabled a relatively small number of clinicians to coordinate care for a large cohort of patients with significant clinical complexity, and a multitude of providers, in the community setting.

This study contributes to our understanding of how the emergence of the COVID‐19 pandemic changes the global Banking Financial Services and Insurance (BFSI) landscape. Before the COVID‐19 pandemic, BFSIs corporate strategy was solely aligned to the quest for operational efficiency. However, during the ongoing COVID‐19 pandemic, global BFSIs are forced to adopt digital transformation in their operations due to a rise in transaction volumes. The ongoing COVID‐19 pandemic already triggers holistic innovations concerning the global BFSI's product, process, concept, trend, or idea. Thus, the BFSI cannot survive without efficient and innovative system software for global operations. The study plots the hype cycle to identify relevant technologies to deal with real‐world business problems. The hype cycle indicates that the need for advanced data integration is growing and COVID‐19 pandemic has already triggered it. The study argues that the incorporation of data integration might be challenging initially for BFSIs but eventually it may result in an efficient model to handle these types of pandemic or unexpected circumstances.

In the aftermath of the British referendum to leave the European Union and the European Commission's ‘White Paper on the Future of Europe’, it is not only time to take stock of the existing literature on differentiated integration, but also to rethink the perimeters of disintegration. We argue that phenomena such as Brexit embrace forms of differentiation which trigger the need for conceptualizing differentiated disintegration altogether. This article first sketches the path of the scholarly debate in a chronological way to grasp the breadth of existing literature. Second, it discusses differentiated disintegration as a potentially new area for research. Mapping several scenarios for future research, we propose that differentiated (dis)integration needs to be conceived as a negotiated, but profoundly path-dependent process, which is structurally locked-in, and deeply conditioned by pre-existing organizations and institutions of European integration.

Background Although the COVID-19 pandemic has significantly boosted the implementation of digital services worldwide, it has become increasingly important to understand how these solutions are integrated into professionals’ routine work. Professionals who are using the services are key influencers in the success of implementations. To ensure successful implementations, it is important to understand the multiprofessional perspective, especially because implementations are likely to increase even more. Objective The aim of this study is to examine health and social care professionals’ experiences of digital service implementations and to identify factors that support successful implementations and should be considered in the future to ensure that the services are integrated into professionals’ routine work. Methods A qualitative approach was used, in which 8 focus group interviews were conducted with 30 health and social care professionals from 4 different health centers in Finland. Data were analyzed using qualitative content analysis. The resulting categories were organized under the components of normalization process theory. Results Our results suggested 14 practices that should be considered when implementing new digital services into routine work. To get professionals to understand and make sense of the new service, (1) the communication related to the implementation should be comprehensive and continuous and (2) the implementation process should be consistent. (3) A justification for the service being implemented should also be given. The best way to engage the professionals with the service is (4) to give them opportunities to influence and (5) to make sure that they have a positive attitude toward the service. To enact the new service into professionals’ routine work, it is important that (6) the organization take a supportive approach by providing support from several easy and efficient sources. The professionals should also have (7) enough time to become familiar with the service, and they should have (8) enough know-how about the service. The training should be (9) targeted individually according to skills and work tasks, and (10) it should be diverse. The impact of the implementation on the professionals’ work should be evaluated. The service (11) should be easy to use, and (12) usage monitoring should happen. An opportunity (13) to give feedback on the service should also be offered. Moreover, (14) the service should support professionals’ work tasks. Conclusions We introduce 14 practices for organizations and service providers on how to ensure sustainable implementation of new digital services and the smooth integration into routine work. It is important to pay more attention to comprehensive and continuing communication. Organizations should conduct a competence assessment before training in order to ensure proper alignment. Follow-ups to the implementation process should be performed to guarantee sustainability of the service. Our findings from a forerunner country of digitalization can be useful for countries that are beginning their service digitalization or further developing their digital services.

В статье анализируются региональные и макрорегиональные аспекты современного положения Вьетнама, показаны его достижения в деле поступательной интеграции в международную систему на основе использования преимуществ регионализма, а также выявлены новые вызовы на данном пути. Автор подробно анализирует три типа балансирования, к которым активно прибегает Вьетнам: институциональное, внешнее и внутреннее балансирование, — и ставит возникшие в этой связи вопросы. Каковы пределы использования инструментов балансирования и хеджирования во внешней политике таких стран, как Вьетнам? Возможно ли участие Вьетнама в новых проектах минилатерализма типа Quad наряду с сохранением приверженности линии АСЕАН? Каковы пределы использования инструментов свободной торговли для обеспечения экономического роста страны без ущерба для национальных интересов и суверенитета? Достаточными ли возможностями обладает Вьетнам для реализации своих амбиций на субрегиональном, региональном и макрорегиональном уровнях?, The proposed paper aims at analyzing a number of features of Vietnam’s stance in regional and macro-regional dynamics, marking Vietnam’s achievements in its gradual integration in the international system utilizing the benefits of regionalism and revealing new challenges along this way. The author analyzes in detail three types of balancing that Vietnam actively resorts to: institutional, external and internal balancing, as well pose questions that have arisen in this regard. What are the limits of balancing and hedging in the foreign policy of such countries as Vietnam? Whither Vietnam is able to reconcile its participation in the new minilateral frameworks like Quad with its adherence to the ASEAN Way? What are the limits of trade liberalization instruments in ensuring the economic growth without losses for national interests and sovereignty? Does Vietnam has enough resources to put in practice its ambitions at subregional, regional and macro-regional levels?

The paper tries to shed some light on the problems of centralization and decentralization within an economic union and the federal member states. Integration and decentralization are not opposite policy strategies but both meaningful if the single public goods and services supplies are analyzed in more detail. Both strategies doubtlessly have advantages, which can be realized if the manifold possibilities are combined in an efficient approach of good governance. Best practice approaches in inter- or supra-national integration, fiscal federalism and taxation do exist and have to be successfully implemented. Obviously such a modern fiscal policy has to be accompanied by an appropriate monetary policy, which in an economic union has to be carried out by an independent central bank as one of the necessary countervailing powers in a democratic setting. A modern fiscal policy strategy efficiently controls budget deficits, which naturally have to be limited to finance reliable public investments. Such strategy has to be safeguarded through modern methods of budgeting and fiscal planning. Modern public management with a clear code of conduct for the government officials ensures corruption free administration.

Purpose Within public services there is a widely recognised role for workers who operate across organisational and professional boundaries. Much of this literature focusses on the organisational implications rather than on how boundary spanners engage with citizens. An increased number of public service roles require boundary spanning to support citizens with cross-cutting issues. The purpose of this paper is to explicate the emotional labour within the interactions that boundary spanners have with citizens, requiring adherence to display rules and building trust. Design/methodology/approach This is a conceptual paper which draws on illustrative examples to draw out the emotional labour within two types of boundary spanning: explicit and emergent. Findings Emotional labour theory offers a way to classify these interactions as requiring high, medium or low degrees of emotional labour. Boundary spanning theory contributes an understanding of how emotional labour is likely to be differently experienced depending on whether the boundary spanning is an explicit part of the job, or an emergent property. Originality/value Drawing on examples from public service work in a range of advanced democracies, the authors make a theoretical argument, suggesting that a more complete view of boundary spanning must account for individual-level affect and demands upon workers. Such a focus captures the “how” of the boundary spanning public encounter, and not just the institutional, political and organisational dimensions examined in most boundary spanning literatures.

It is demonstrated that using three-dimensional profile fitting of Bragg peaks increases the accuracy and resolution of neutron crystallographic data collected from proteins and reveals new features in nuclear density maps calculated from these data., Neutron crystallography is a powerful technique for directly visualizing the locations of H atoms in biological macromolecules. This information has provided key new insights into enzyme mechanisms, ligand binding and hydration. However, despite the importance of this information, the application of neutron crystallography in biology has been limited by the relatively low flux of available neutron beams and the large incoherent neutron scattering from hydrogen, both of which contribute to weak diffraction data with relatively low signal-to-background ratios. A method has been developed to fit weak data based on three-dimensional profile fitting of Bragg peaks in reciprocal space by an Ikeda–Carpenter function with a bivariate Gaussian. When applied to data collected from three different proteins, three-dimensional profile fitting yields intensities with higher correlation coefficients (CC1/2) at high resolutions, decreased R free factors, extended resolutions and improved nuclear density maps. Importantly, additional features are revealed in nuclear density maps that may provide additional scientific information. These results suggest that three-dimensional profile fitting will help to extend the capabilities of neutron macromolecular crystallography.

The food industry is one of the most suitable sectors for solar process heat applications. Concentrating solar power (CSP) systems generate steam using mirrors or lenses to concentrate a large area of sunlight onto a receiver. In this study, how a CSP system connected hybrid to the boiler system can be utilized to produce more sustainable peach puree concentrate (PPC) have been examined. The amount of steam required for PPC production was calculated using the measurements rendered in a real fruit juice concentrate plant and the data obtained from them. A parabolic trough-type CSP system of 1 MWth was designed, which is placed in the area of the plant, and it was determined that the steam quantity obtained during the production period is able to meet how much of the current consumption. Also, it has been shown how much CO2eq emission reduction will be achieved by using CSP. Practical Applications Concentrated fruit juice production is one of the thermal energy intense food processes. Therefore, utilization of renewable energy sources for process heat is very important. We designed a CSP system in this study with using production data from a real fruit juice factory. This CSP system is naturally applicable to both fruit juice and all food industry using steam at similar temperatures and pressures. Fossil fuels are one of the main responsible for global warming. For this reason, the use of solar thermal systems is promising to ensure sustainability in food production and reduce the environmental impacts of the product.

Yet another paper about integration?.

Dyslexia has been associated with a problem in visual–audio integration mechanisms. Here, we investigate for the first time the contribution of unisensory cues on multisensory audio and visual integration in 32 dyslexic children by modelling results using the Bayesian approach. Non‐linguistic stimuli were used. Children performed a temporal task: they had to report whether the middle of three stimuli was closer in time to the first one or to the last one presented. Children with dyslexia, compared with typical children, exhibited poorer unimodal thresholds, requiring greater temporal distance between items for correct judgements, while multisensory thresholds were well predicted by the Bayesian model. This result suggests that the multisensory deficit in dyslexia is due to impaired audio and visual inputs rather than impaired multisensory processing per se. We also observed that poorer temporal skills correlated with lower reading skills in dyslexic children, suggesting that this temporal capability can be linked to reading abilities., Multisensory audio visual processing in dyslexia is due to impaired audio and visual inputs rather than impaired multisensory processing per se.

Flowers have been hypothesized to contain either modules of attraction and reproduction, functional modules (pollination‐effecting parts) or developmental modules (organ‐specific). Do pollination specialization and syndromes influence floral modularity? In order to test these hypotheses and answer this question, we focused on the genus Erica: we gathered 3D data from flowers of 19 species with diverse syndromes via computed tomography, and for the first time tested the above‐mentioned hypotheses via 3D geometric morphometrics. To provide an evolutionary framework for our results, we tested the evolutionary mode of floral shape, size and integration under the syndromes regime, and – for the first time – reconstructed the high‐dimensional floral shape of their most recent common ancestor. We demonstrate that the modularity of the 3D shape of generalist flowers depends on development and that of specialists is linked to function: modules of pollen deposition and receipt in bird syndrome, and access‐restriction to the floral reward in long‐proboscid fly syndrome. Only size and shape principal component 1 showed multiple‐optima selection, suggesting that they were co‐opted during evolution to adapt flowers to novel pollinators. Whole floral shape followed an Ornstein–Uhlenbeck (selection‐driven) evolutionary model, and differentiated relatively late. Flower shape modularity thus crucially depends on pollinator specialization and syndrome., New Phytologist, 226 (1), ISSN:0028-646X, ISSN:1469-8137

Background The PRogramme for Improving Mental Health carE (PRIME) evaluated the process and outcomes of the implementation of a mental healthcare plan (MHCP) in Chitwan, Nepal. Aims To describe the process of implementation, the barriers and facilitating factors, and to evaluate the process indicators of the MHCP. Method A case study design that combined qualitative and quantitative methods based on a programme theory of change (ToC) was used and included: (a) district-, community- and health-facility profiles; (b) monthly implementation logs; (c) pre- and post-training evaluation; (d) out-patient clinical data and (e) qualitative interviews with patients and caregivers. Results The MHCP was able to achieve most of the indicators outlined by the ToC. Of the total 32 indicators, 21 (66%) were fully achieved, 10 (31%) partially achieved and 1 (3%) were not achieved at all. The proportion of primary care patients that received mental health services increased by 1200% over the 3-year implementation period. Major barriers included frequent transfer of trained health workers, lack of confidential space for consultation, no mental health supervision in the existing system, and stigma. Involvement of Ministry of Health, procurement of new psychotropic medicines through PRIME, motivation of health workers and the development of a new supervision system were key facilitating factors. Conclusions Effective implementation of mental health services in primary care settings require interventions to increase demand for services and to ensure there is clinical supervision for health workers, private rooms for consultations, a separate cadre of psychosocial workers and a regular supply of psychotropic medicines.

Refugees are at an increased risk of mental health problems and low subjective well-being. Living circumstances in the host country are thought to play a vital role in shaping these health outcomes, which, in turn, are prerequisites for successful integration. Using data from a representative survey of 4325 adult refugees who arrived in Germany between 2013 and 2016, we investigated how different living conditions, especially those subject to integration policies, are associated with psychological distress and life satisfaction using linear regression models. Our findings show that an uncertain legal status, separation from family, and living in refugee housing facilities are related to higher levels of distress and decreased life satisfaction. Being employed, contact to members of the host society, and better host country language skills, by contrast, are related to reduced distress and higher levels of life satisfaction. These associations should inform decision making in a highly contested policy area. Electronic supplementary material The online version of this article (10.1007/s10903-019-00968-5) contains supplementary material, which is available to authorized users.

Background. Integration of mental health services into nonspecialist settings is expanding in low and middle income countries (LMICs). Among many factors required for success, such programs require reliable administration of mental health screening tools. While several tools have been validated in carefully conducted research studies, few studies have assessed how reliably nonspecialist clinicians administer these tools to low-literacy LMIC populations in routine care. Methods. Ninety-seven patients accessing human immunodeficiency virus primary care in Malawi who completed Patient Health Questionnaire (PHQ)-9 depression screening with their clinician then completed a second PHQ-9 with a trained research assistant (RA) blinded to the first result. Results. Compared to clinicians, RAs identified more patients with any depressive symptoms (PHQ-9 score ⩾5: 38% v. 32%), moderate/severe symptoms (PHQ-9 ⩾ 10: 14% v. 6%), any suicidality (14% v. 4%), and active suicidality (3% v. 2%). Across these indicators, clinician and RA ratings had strong overall agreement (81–97%) but low corrected Kappa agreement (31–59%). Treating RA results as the reference standard of a carefully supervised research administration of the PHQ-9, clinician administration had high specificity (90–99%) but low sensitivity (23–68%) for these indicators. Conclusions. In routine care in LMICs, clinicians may administer validated mental health screening tools with varying quality. To ensure quality, integration programs must incorporate appropriate and ongoing training, support, supervision, and monitoring.

Background Electronic medical records (EMRs) are integrated information sources generated by health care professionals (HCPs) from various health care information systems. EMRs play crucial roles in improving the quality of care and medical decision-making and in facilitating cross-hospital health information exchange. Although many hospitals have invested considerable resources and efforts to develop EMRs for several years, the factors affecting the long-term success of EMRs, particularly in the EMR infusion stage, remain unclear. Objective The aim of this study was to investigate the effects of technology, user, and task characteristics on EMR infusion to determine the factors that largely affect EMR infusion. In addition, we examined the effect of EMR infusion on individual HCP performance. Methods A questionnaire survey was used to collect data from HCPs with >6 months experience in using EMRs in a Taiwanese teaching hospital. A total of 316 questionnaires were distributed and 211 complete copies were returned, yielding a valid response rate of 66.8%. The collected data were further analyzed using WarpPLS 5.0. Results EMR infusion (R2=0.771) was mainly affected by user habits (β=.411), portability (β=.217), personal innovativeness (β=.198), technostress (β=.169), and time criticality (β=.168), and individual performance (R2=0.541) was affected by EMR infusion (β=.735). This finding indicated that user (habit, personal innovativeness, and technostress), technology (portability), and task (mobility and time criticality) characteristics have major effects on EMR infusion. Furthermore, the results indicated that EMR infusion positively affects individual performance. Conclusions The factors identified in this study can extend information systems infusion theory and provide useful insights for the further improvement of EMR development in hospitals and by the government, specifically in its infusion stage. In addition, the developed instrument can be used as an assessment tool to identify the key factors for EMR infusion, and to evaluate the extent of EMR infusion and the individual performance of hospitals that have implemented EMR systems. Moreover, the results can help governments to understand the urgent needs of hospitals in implementing EMR systems, provide sufficient resources and support to improve the incentives of EMR development, and develop adequate EMR policies for the meaningful use of electronic health records among hospitals and clinics.

We propose a complete-search algorithm for solving a class of non-convex, possibly infinite-dimensional, optimization problems to global optimality. We assume that the optimization variables are in a bounded subset of a Hilbert space, and we determine worst-case run-time bounds for the algorithm under certain regularity conditions of the cost functional and the constraint set. Because these run-time bounds are independent of the number of optimization variables and, in particular, are valid for optimization problems with infinitely many optimization variables, we prove that the algorithm converges to an \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\varepsilon $$\end{document}ε-suboptimal global solution within finite run-time for any given termination tolerance \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\varepsilon > 0$$\end{document}ε>0. Finally, we illustrate these results for a problem of calculus of variations.

Background: A pilot study to identify if the delivery of teaching session to medical students would have the potential to enhance communication and a culture of integration between primary and social care, ultimately improving interprofessional relationships between primary and social care. Health and social care integration is a topic of great debate in the developed world and the focus of the upcoming Green Paper by the Secretary of State for Health and Social Care in the NHS. There is much uncertainty to how this should be done and is hindered by the various current barriers. The literature identifies that collaborative cultures encourage effective interprofessional relationships and that communication is vital to integration of primary and social care and should be established early in medical training. Materials and Method: The General Medical Council’s Outcomes for Graduates and Imperial College School of Medicine curriculum were reviewed out to identify outcomes relating to inter-professional relationships between primary and social care. The relevant year group was surveyed to identify if the learning objective was delivered. In order to determine if delivery of a teaching session on nurturing interprofessional relationships between primary and social care would be effective, it was delivered to early clinical years to measure benefits as a pilot study. This was devised of case-based scenarios derived from learning objectives developed with experienced health care professionals. A survey was administered before and after the teaching session to determine if the students felt they had improved with respect to the learning objectives. Results: The initial survey identified the majority of students found the learning objectives were not delivered. The teaching session found a statistically significant improvement in confidence to nurture interprofessional relationships between primary and social care. Conclusion: Effective interprofessional relationships between primary and social care, improving communication and collaborative cultures, can be effectively taught in medical school, to improve integration of primary and social care.

BackgroundWe describe the introduction, use, and evaluation of an automation and integration pharmacy development program in a private facility in Saudi Arabia. The project was specifically undertaken to increase throughput, reduce medication dispensing error rates, improve patient satisfaction, and free up pharmacists’ time to allow for increased face-to-face consultations with patients.ObjectiveWe forecasted growth of our outpatient service at 25% per annum over 5- and 10-year horizons and set out to prepare our outpatient pharmacy service to meet this demand. Initial project goals were set as a 50% reduction in the average patient wait time, a 15% increase in patient satisfaction regarding pharmacy wait time and pharmacy services, a 25% increase in pharmacist productivity, and zero dispensing errors. This was expected to be achieved within 10 months of go-live. Realignment of pharmacist activity toward counseling and medication review with patients was a secondary goal, along with the rapid development of a reputation in the served community for patient-centered care.MethodsPreimplementation data for patient wait time for dispensing of prescribed medications as a specific measure of patient satisfaction was gathered as part of wider ongoing data collection in this field. Pharmacist activity and productivity in terms of patient interaction time were gathered. Reported and discovered dispensing errors per 1000 prescriptions were also aggregated. All preimplementation data was gathered over an 11-month period.ResultsFrom go-live, data were gathered on the above metrics in 1-month increments. At the 10-month point, there had been a 53% reduction in the average wait time, a 20% increase in patient satisfaction regarding pharmacy wait time, with a 22% increase in overall patient satisfaction regarding pharmacy services, and a 33% increase in pharmacist productivity. A zero dispensing error rate was reported.ConclusionsThe robotic pharmacy solution studied was highly effective, but a robust upstream supply chain is vital to ensure stock levels, particularly when automated filling is planned. The automation solution must also be seamlessly and completely integrated into the facility’s software systems for appointments, medication records, and prescription generation in order to garner its full benefits. Overall patient satisfaction with pharmacy services is strongly influenced by wait time and follow-up studies are required to identify how to use this positive effect and make optimal use of freed-up pharmacist time. The extra time spent by pharmacists with patients and the opportunity for complete overview of the patient’s medication history, which full integration provides, may allow us to address challenging issues such as medication nonadherence. Reduced wait times may also allow for smaller prescription fill volumes, and more frequent outpatient department visits, allowing patients to have increased contact time with pharmacists.

Traditional medicine is widespread in Ghana, with 80% of Ghanaians relying on its methods for primary health care. This paper argues that integrating traditional and biomedical health systems expands the reach and improves outcomes of community health care. Moving beyond literature, it stresses the importance of trust-relationships between healers and biomedical staff. Insights are based on qualitative research conducted in Ghana’s Northern Region (2013–2014). Five challenges to integration emerged out of the data: a lack of understanding of traditional medicine, discrimination, high turnover of biomedical staff, declining interest in healing as a profession, and equipment scarcity. Besides challenges, opportunities for integration exist, including the extensive infrastructure of traditional medicine, openness to collaboration, and grassroots initiatives. Contemplating challenges and opportunities this paper provides recommendations for integration, including: identify/select healers, promote best practices, institute appropriate forms of appreciation/recognition of healers, provide aid and equipment, use communication campaigns to promote integration and steer attitudinal change towards healers among biomedical staff. Most crucial, we argue successful implementation of these recommendations depends on a concerted investment in relationships between healers and biomedical staff.

Graph theory analysis on resting state electroencephalographic rhythms disclosed topological properties of cerebral network. In Alzheimer's disease (AD) patients, this approach showed mixed results. Granger causality matrices were used as input to the graph theory allowing to estimate the strength and the direction of information transfer between electrode pairs. The number of edges (degree), the number of inward edges (in-degree), of outgoing edges (out-degree) were statistically compared among healthy controls, patients with mild cognitive impairment due to AD (AD-MCI) and AD patients with mild dementia (ADD) to evaluate if degree abnormality could involve low and/or high degree vertices, the so called hubs, in both prodromal and over dementia stage. Clustering coefficient and local efficiency were evaluated as measures of network segregation, path length and global efficiency as measures of integration, the assortativity coefficient as a measure of resilience. Degree, in-degree and out-degree values were lower in AD-MCI and ADD than the control group for non-hubs and hubs vertices. The number of edges was preserved for frontal electrodes, where patients' groups showed an additional hub in F3. Clustering coefficient was lower in ADD compared with AD-MCI in the right occipital electrode, and it was positively correlated with mini mental state examination. Local and global efficiency values were lower in patients' than control groups. Our results show that the topology of the network is altered in AD patients also in its prodromal stage, begins with the reduction of the number of edges and the loss of the local and global efficiency.

This is one of the few studies that explores preferences of and experiences with integrated sexual and reproductive health (SRH)-HIV care among users of mainstream family planning and postnatal care services who are women living with HIV (WLWH). This paper reports on the quantitative data from 179 clients attending public sector clinics and from 30 qualitative in-depth interviews with WLHIV in Kenya. Quantitative data show that integration is happening for the vast majority of these clients at their last HIV visit. However, qualitative data show that very often the care received by WLWH is fragmented as providers do not offer multiple same-day appointments for FP and ARV refills. Our study has shown factors that could either prevent or enable receipt of integrated SRH and HIV care for WLWH. To address these factors, management systems need to be able to support providers to make flexible decisions and facilitate better coordination and communication across clinics within facilities.

First class transport is fundamental for a healthy society and a thriving economy. By providing a high degree of mobility for ideas, people and goods, it enables innovation to flourish, businesses to serve wide markets and citizens to travel easily for work and for pleasure. This leads to job creation; regional, national and European Union (EU) economic development; better social cohesion and a better quality of life. This is why transport is one of the seven ‘Societal Challenges’ on which Europe's Horizon 2020 research programme is focusing in 2014–2020. Much is being done to improve transport in Europe in specific topics, including in technology, in networks and in financing. Yet Europe is failing to capture the full benefits of these investments. As the European Commission's 2011 Transport White Paper recognises, today's European transport system remains fragmented, inefficient and inadequate. Analysis of the root causes of this poor performance shows that, while technology barriers are significant, policy issues dominate. The authors examine the arguments for a more connected approach and report on progress towards achieving such an approach. This sees European transport as one system and optimises it as such. This contrasts with the present situation of many fragments, individually good but poorly related. This connected approach will lead to better overall transport provision and better results for the resources invested. However, transport involves many stakeholders, who tend to focus on their own specific modes and issues. Truly effective transport will only develop if all stakeholders work together. We consider new initiatives to bring together all relevant actors at EU, national and regional levels to tackle the problems described above. These would, for example: (i) bring a stronger systems-level perspective to research and development efforts; (ii) coordinate investments in demonstrators and pilots; (iii) identify and fast-track changes necessary in regulations and standards; and (iv) mobilise demand, in particular through better coordinated public procurement. Such an approach will build on existing initiatives, at modal, sectoral and administrative levels, and unlock the full value creation potential of existing investment programmes.

The pulp and paper industry (PPI) is a business that produce large amounts of residues annually. Besides bark, large quantities of sludge are produced from the various parts of the industrial process. The sludge that comes from the biological wastewater purification process is denoted biosludge and is known as a particularly problematic waste product. It is of interest to reduce the amount of sludge from the PPI or to find new ways of handling the produced sludge. The common way to treat the PPI sludge is by incineration in the site’s bark boiler. The material is however difficult to dewater and often does more harm than good in the boilers. Different technologies to try and dewater the sludge further have been investigated previously, one that has recently been noted is hydrothermal treatment. The technology described in this thesis work is called hydrothermal carbonization (HTC) which uses water as a reaction media to turn the sludge into a coal-like material called hydrochar. The hydrochar has a higher heating value than the initial sludge and is more hydrophobic which makes it easier to dewater. This Master’s thesis describes the process technologies of the HTC process and presents some of the recent work done within the area. The properties of different residues from the PPI are presented before the integration of an HTC process on the biorefinery site in Domsjö, Sweden is discussed using previously published articles. A survey concerning sludge from industries within a 500 km range of the Domsjö biorefinery site is made to investigate whether residual streams similar to the ones at the Domsjö site are available in the vicinity. The results show that an HTC process demands energy in the form of steam and/or electricity. A previously made pinch and total site analysis show that the most accessible steam at the Domsjö biorefinery site, that most appliances and process steps uses, is at 7 bars. There are also steam levels of 20 and 32 bar in the area, which is within the range an HTC plant requires. The HTC process water demands further treatment which puts an extra stress on the already existing water purification process. The Domsjö biorefinery site produces 6000 tonnes of biosludge per year. Several HTC companies produce units that normally treat 20000-50000 tonnes of sludge per year, which indicates that additional sludge could be added to reach full capacity. The survey shows that there are similar materials available in the surroundings. It is concluded that further investigations concerning the sludge materials must be made before real implementation consequences can be calculated.

This paper introduces the concept of intangible assets in sequential supply chains and the importance of their appropriability in the organizational decision of firms. We focus on the quality of intellectual property rights (IPR) institutions, which on top of the hold-up problem between a supplier and the final producer entails an additional risk of imitation as technology may leak to competing producers in the market. The level of IPR enforcement in the location of a supplier can therefore play a crucial role in determining the decision of a final good producer whether to outsource or integrate a particular stage of production. The analysis is performed with Antràs and Chor (2013) in the background, where the position of the input along the supply chain, i.e. its upstreamness, and the degree of sequential complementarity of stage-specific inputs influence the organizational strategy of firms through the incentive structure of supplier investments. Our findings show that introducing intangible assets in sequential supply chain may have the opposite effect of contractibility on outsourcing decision, where only tangible property rights are considered. We argue therefore that the risk of imitation is a relevant feature that needs to be accounted for in the incomplete contract literature. Our theoretical predictions are validated on Slovenian firm-level data.

Histone deacetylase inhibitors (HDACi) have been shown to render HPV-carrying cells susceptible to intrinsic and extrinsic apoptotic signals. As such, these epigenetic drugs have entered clinical trials in the effort to treat cervical cancer. Here, we studied the effect of common HDACi, with an emphasis on Trichostatin A (TSA), on the transcriptional activity of the HPV-16 Long Control Region (LCR) in order to better understand the impact of these agents in the context of the HPV life cycle and infection. HDACi strongly induced transcription of the firefly luciferase reporter gene under the control of the HPV-16 LCR in a variety of cell lines. In the HaCaT keratinocyte cell line undergoing differentiation induced by TSA, we observed a reduction in LCR-controlled transcription. Three major AP-1 binding sites in the HPV-16 LCR are involved in the regulation by TSA. However, whatever the status of differentiation of the HaCaT cells, TSA induced integration of extra-chromosomal transfected DNA into the cellular genome. Although these data suggest caution using HDACi in the treatment of HR HPV infection, further in vivo studies are necessary to better assess the risk., SCOPUS: ar.j, info:eu-repo/semantics/published

// Yanan Pang 1, * , Weixing Guo 2, * , Jiaqi Wang 1, * , Guixia Xu 1 , Kai Cheng 1 , Guangwen Cao 3 , Mengchao Wu 2 , Shuqun Cheng 2 , Shanrong Liu 1 1 Changhai Hospital, Second Military Medical University, Shanghai, China 2 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China 3 Department of Epidemiology, Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Shanrong Liu, e-mail: liushanrong@hotmail.com Shuqun Cheng, e-mail: chengshuqun@aliyun.com Keywords: HBV-HCC, CGH, integration, biomarker Received: July 31, 2015 Accepted: January 01, 2016 Published: January 12, 2016 ABSTRACT Integration of hepatitis B virus (HBV) DNA into the human liver cell genome is believed to promote HBV-related carcinogenesis. This study aimed to quantify the integration of HBV DNA into the leukocyte genome in hepatocellular carcinoma (HCC) patients in order to identify potential biomarkers for HBV-related diseases. Whole-genome comparative genomic hybridization (CGH) chip array analyses were performed to screen gene copy number variations (CNV) in the leukocyte genome, and the results were confirmed by quantitative polymerase chain reaction (qPCR). The commonly detected regions included chromosome arms 19p, 5q, 1q and 15p, where 200 copy number gain events and 270 copy number loss events were noted. In particular, gains were observed in 5q35.3 (OR4F3) and 19p13.3 (OR4F17) in 90% of the samples. Successful homologous recombination of OR4F3 and the HBV P gene was demonstrated, and the amplification at 5q35.3 is potentially associated with the integration of HBV P gene into natural killer cells isolated from peripheral blood mononuclear cells (PBMCs). Receiver operating characteristic (ROC) curve analysis indicated that the combination of OR4F3 and OR4F17 a novel potential biomarker of HBV-related diseases.

The connection between science and mathematics is undeniable but also a complex phenomenon. The present study aimed to examine types of questions in science exam papers in 7 th grade “force and motion” unit and the consistency between questions and objectives in this unit. The study also aimed to determine if there are questions related to mathematics. If yes, which mathematics subjects they are related with. Document analysis was used for data collection. 19 exam papers prepared by different science teachers were collected and examined. Findings revealed that science teachers mainly used multiple choice questions and their questions included mathematical knowledge.

Objectives In children, there is often lack of sufficient information concerning the pharmacokinetics (PK) and pharmacodynamics (PD) of a study drug to support dose selection and effective evaluation of efficacy in a randomised clinical trial (RCT). Therefore, one should consider the relevance of relatively small PKPD studies, which can provide the appropriate data to optimise the design of an RCT. Methods Based on the experience of experts collaborating in the EU-funded Global Research in Paediatrics consortium, we aimed to inform clinician-scientists working with children on the design of investigator-initiated PKPD studies. Key findings The importance of the identification of an optimal dose for the paediatric population is explained, followed by the differences and similarities of dose-ranging and efficacy studies. The input of clinical pharmacologists with modelling expertise is essential for an efficient dose-finding study. Conclusions The emergence of new laboratory techniques and statistical tools allows for the collection and analysis of sparse and unbalanced data, enabling the implementation of (observational) PKPD studies in the paediatric clinic. Understanding of the principles and methods discussed in this study is essential to improve the quality of paediatric PKPD investigations, and to prevent the conduct of paediatric RCTs that fail because of inadequate dosing.

Vector delivery is still a bottleneck for gene therapy. To overcome some disadvantages of adenoviral and retroviral vectors, we developed a hybrid vector. This hybrid vector, AdLTR-luc, was created by adding two elements from Moloney murine leukemia virus (MoMLV) flanking the luciferase cDNA into an E1/E3-deleted, replication deficient serotype 5 adenovirus vector (Zheng et al., Nature Biotechnol, 2000), and demonstrated that the MoMLV element upstream of the luciferase cDNA was broken during the integration event. The purpose of the current study was to determine if the MoMLV element downstream of the luciferase cDNA was also broken when integration occurred. We used the same A5 cell clones (#10 and 11) from the earlier the paper along with restriction endonuclease digestions, plus Southern hybridization, and PCR. Southern hybridization indicated that the luciferase cDNA was intact in the cloned cells. Results from Xho I and Sal I digestions showed that integration occurred in cloned cells. Southern hybridizations after Nco I digestion suggested that there was a break in both MoMLV elements, upstream and downstream of the luciferase cDNA. After DNA digestion with Not I, hybridization analyses indicated that the MoMLV upstream element was broken during integration. Digestion of genomic DNA with either Xba I/Kpn I, Bam HI/Sac I, or Bam HI/Nco I demonstrated that the MoMLV downstream element was also broken during integration. A PCR assay was unable to amplify the junctional region between the downstream MoMLV element and the adenoviral E2B gene, consistent with a break in that element. Although AdLTR-luc integration is atypical (Zheng et al., Nature Biotechnol, 2000), the present results suggest that both MoMLV elements have important roles in this event.