With global environmental sustainability at the crossroads, approaches are needed to build an ecologically literate culture for collective societal navigation through the intricacies of swift environmental change. This paper demonstrates a transdisciplinary approach, grounded at the intersection between the arts and sciences, to increase awareness and understanding of the current biodiversity crisis. It focuses on one aspect of biodiversity, beta diversity, which examines how sets of animal and plant species differ between habitats. Theory and real examples of beta diversity of aquatic animal and plant species from dried-out ponds in Mediterranean Spain are presented in pixelized visuals. These visuals are artistic expression of and build the prior knowledge about beta diversity, which is scrutinized subsequently with statistical analyses to support the artistic approach with an objectively identified and numerically underpinned presentation of structure in the visuals. The choice to examine beta diversity in theory and reality first through art and then through science is deliberate. Combined, these aspects examine biodiversity through an eco-centric, rather than a species- and habitat centric view, incorporate elements of surprise (how can aquatic species in dry ecosystems survive), and reduce uncertainty . Together they can optimize a goal-directed learning process in the viewers necessary for making judgments, inducing affective reactions, and facilitating memory and decision making. The approach presented here provides an integral qualitative and quantitative model useful for a broader inductive-deductive education process towards finding sustainable solutions as our planet moves swiftly to a future without historical analogue. Combined art-sciences approaches, as the one presented here, are useful to facilitate citizens’ comprehension of the scientific and potential policy dimensions of environmental change, including biodiversity problems, especially because it is the general public that bears the costs of transformation and adaptation measures. With global environmental sustainability at the crossroads   in the form of results from often complex statistical and modeling approaches. However, many of the visualizations based on models  or output formats for numbers (graphs) only represent the results of a highly complex, deductive and artificial process. Abstraction and artificiality in scientific visualizations, while representing the order of nature and environmental change problems objectively, can also remove the viewer from context. Similar to the artistic approach, scientific visualizations of environmental problems can lead to a disconnect between peoples emotions to and experiences from nature  and turnover, which focuses on how the sets of species change across sites (exemplified by pest species above) Baselga . In theoThis paper aims at reconciling artistic and scientific approaches in an attempt to communicate biodiversity in general, and beta diversity in particular to the public. Using pixel art to visualize species and ecosystems in the form of simple geometric shapes, this paper will present the theoretical constructs (perfect nestedness and turnover) of beta diversity, and the beta diversity of real assemblages of animals and plants from dried-out pond ecosystems, in a semiarid environment where the impacts of climate change are substantial , which covers 12 227 ha. Despite historical degradation by agriculture practices, the area contains a unique wetland fauna and flora, highlighting the value of the remaining wetlands for regional biodiversity  follows the same approach. The resulting visuals take specific geometric shapes that make the scientific information tangible Figs. , 3. The ® Excel® for MAC v. 14.4.7. Each square in the matrices (pixel) was 1 × 1 cm and symbolized a species. The habitats are represented as columns. To better discern between habitats in the visuals blank columns were included. The real invertebrate examples contained 11 habitats/ponds (columns) and a total of 1875 pixels to represent the species across ponds in these visuals. The pond with the highest richness contained 21 species. The real macrophyte example contained less species  and only 10 habitats due to the lack of plant occurrence in one pond compared to the invertebrate example; therefore, its visual expression and data analysis is based on a smaller matrix (1012 pixels). The matrices of the perfect representation of nestedness and turnover were sized to fit the real example of invertebrates (1875 pixels); that is, there were 11 columns expressing hypothetical habitats and species richness as in the real example of invertebrates.Matrices for the visualization and statistical analyses of real examples and pure nestedness and turnover were constructed in MicrosoftTo inform the viewer about how nestedness and turnover are related in expressing beta diversity, I first examined how much these fractions explain numerically beta diversity in the visuals. The statistical approach is based on Baselga and Orme . It firsIn the next analysis I assessed the structure that is present in the geometric shapes of the visuals derived from each matrix . This analysis aimed at reducing uncertainty in the interpretation of the visuals through an objective identification of structure that can be expressed numerically in a simple way. I used a spatial modeling technique commonly applied in ecology : turnover, 0.80; macrophytes, 0.84] Table . Noise, The environmental challenges ahead are complex and multidimensional , and specific habitat (rainforests) protection  between adjacent ecosystems (columns) is arranged comprises one among multiple ways to demonstrate and communicate extinctions associated with beta diversity . Notwithstanding, the use of pixels and their purposeful arrangement in the visuals allows giving equal weight to species. This presentation achieves neutrality regarding the perceived socio-economic value of taxa by people. That is, by down-emphasizing value-laden connotations of animals and plants, thinking about biodiversity from an eco-centric rather than species-centered perspective can be spurred.Presenting turnover, another aspect of beta diversity, concomitantly to extinctions, further facilitates the presentation of beta diversity as an eco-centric concept. It essentially shows that other processes than only extinctions are relevant for envisioning and understanding biodiversity. The change of the sets of pixels between habitats in the visual of perfect turnover differs drastically from that of perfect nestedness, leading to the emergence of geometric shapes, a triangle (nestedness) and diagonal (turnover) respectively, that allows distinguishing both concepts instantaneously without the need of previous knowledge in the viewer. These distinct shapes provide a rapid means to demonstrate, communicate and let the viewer assimilate the multiple facets of biodiversity at large, and beta diversity in particular.raison d’être of scientific endeavor, which is considered important for engaging the public with learning and understanding of environmental problems  seems logic. However, in the perfect nestedness example the partitioning of the variance in equal fractions may be a priori a surprise for most viewers without knowledge in mathematical calculus. This element of surprise, achieved through a scientific approach, has great value in environmental communication because surprise and novelty stimulate learning and long-term memory formation (Lisman and Grace To further bolster the surprise effect the examples of plants and animal communities in ponds in a semiarid climate have been chosen on purpose. The impacts of climate change in dryland countries may be substantial (Alvarez-Cobelas et al. Since the costs of both prevention of and adaptation to environmental change, including biodiversity issues, must be borne by the general public, the comprehension of the scientific and policy issues by citizens is crucial to political decision making Kempton . This pa


Cohort studies and registries rely on massive amounts of personal medical data. Therefore, data protection and information security as well as ethical aspects gain in importance and need to be considered as early as possible during the establishment of a study. Resulting legal and ethical obligations require a precise implementation of appropriate technical and organisational measures for a Trusted Third Party.This paper defines and organises a consistent workflow-management to realize a Trusted Third Party. In particular, it focusses the technical implementation of a Trusted Third Party Dispatcher to provide basic functionalities  and measures required to meet study specific conditions of cohort studies and registries. Thereby several independent open source software modules developed and provided by the MOSAIC project are used. This technical concept offers the necessary flexibility and extensibility to address legal and ethical requirements of individual scenarios.The developed concept for a Trusted Third Party Dispatcher allows mapping single process steps as well as individual requirements and characteristics of particular studies to workflows, which in turn can be combined to model complex Trusted Third Party processes. The uniformity of this approach permits unrestricted re-combination of the available functionalities (depending on the applied software modules) for various research projects.The proposed approach for the technical implementation of an independent Trusted Third Party reduces the effort for scenario specific implementations as well as for maintenance. The applicability and the efficacy of the concept for a workflow-driven Trusted Third Party could be confirmed during the establishment of several nationwide studies . Epidemiological research in the context of cohort studies and registries becomes increasingly cooperative and often requires multi-site acquisition of extensive medical data. As a consequence research becomes more and more networked regarding communication, information exchange and cross-coordination between participating research institutions, laboratories and imaging facilities.For these reasons, legal aspects of data security and information protection significantly gain in importance. This concerns the written informed consent of potential participants, which is mandatory for acquiring medical data for research purposes from an ethical point of view. On the national level legal principles like data avoidance and frugality [§3a of the German Federal Data Protection Act ] as well as requirements for the separation of identifying data from further personal data (§40 BDSG) need to be accounted for. International legislation includes the “Convention for the Protection of Individuals with regard to Automatic Processing of Personal Data” (Council of Europe) , the “EUTechnology, Methods and Infrastructure for Networked Medical Research (TMF) provided a guideline [In Germany the uideline  proposinuideline . Followiuideline . MoreoveIt is of importance that the employees of a TTP (the data trustee) do not depend on the institutions which are providing or processing the research data. In particular the employees need to be independent in terms of their contracts, incomes, duties, work hours and other operational aspects from all scientists of the project that they support. This can be realized either in a separate legal organisation or on a contract level. According to TMF guidelines  and legaAlong these guidelines an independent TTP was established at the Institute for Community Medicine at the University Medicine Greifswald to exclusively handle participant identifying data, which have been separated from all further informative variables including metadata. The TTP centrally provides the necessary data protection functionalities and measures for various studies and registries. Figure This paper focusses the technical implementation of a TTP. The goal is to define and organise a consistent workflow-management within the TTP. Allowing to increase reusability for individual TTP scenarios, the workflow approach shall reduce the effort for implementation and maintenance.The spectrum of tasks of a data trustee includes the management of identities, informed consents and the generation of pseudonyms. Additionally, the data trustee supports the matching of personal data from population registries and further external data sources.identity management is required to manage participants and assigned participant identities. It includes probabilistic matching algorithms for an efficient and fault-tolerant record-linkage. Furthermore, it comprehends the provision and management of appropriate pseudonyms for each set of identities. Especially in prospective cohort studies and registries compiling variations in the identifying data of a participant , e.g. different spelling in a participant’s name, need to be stored.An management of informed consents includes the provision of patient information documents, the consent itself and a monitoring of various types of revocations. For digital processing informed consent documents are depicted as modular examinable policies and modules and are combined with additional data like electronic signatures, dates and organisational information. This modular informed consent allows for verifiable as well as contemporary statements, whether for example the processing of a participant’s data, the secondary use of collected data or the specimen-collection is legitimate or not.To ensure compliance to the principles of informational self-determination , the paradministration of pseudonyms within the TTP is a key functionality when medical scientific data needs to be processed and permanently stored. In order to provide scientific data for research projects and secondary use, the data has to be pseudonymised secondarily or be anonymised. In some cases an anonymisation is not applicable. Follow-up investigations, the communication of incidental findings or the linkage of secondary data require the pseudonymisation to be reversible in order to retrieve the corresponding participants for further contact.The efficient generation and HO 1937/2-1)) has developed a set of practical tools to address data protection challenges and to provide support for the implementation of a data management in epidemiologic research projects. These free software tools  facilitate the principles of “privacy by design” [For the implementation of the independent TTP several open source software modules are used. Following the basic concepts and processes described by the TMF , the MOSE-PIX (Enterprise Patient Identifier Cross Referencing) [gPAS (generic Pseudonym Administration Service) [gICS (generic Informed Consent Service) [The rencing)  allows arencing) . The comService)  adopts sService)  completeService) . ModularThe simultaneous use of the MOSAIC software modules E-PIX, gICS and gPAS allows implementing basic requirements of an independent TTP. The administration of participant identities, informed consents and pseudonyms can be performed using graphical web interfaces. However, due to their modular design there is no direct communication among these components. In order to realize more complex workflows, a manual intervention of the data trustee is necessary in many tasks. For example, if a new participant is recruited, it is necessary to assign a unique identifier based on his IDAT (identity management), to pseudonymise this unique identifier (pseudonym administration) and to return the generated pseudonym in order to start capturing the medical data within the study site.Most widely automating the communication between the software-modules E-PIX, gPAS and gICS through well-defined workflows reduces the number of necessary manual interventions of the data trustee. Only a small number of crucial decisions remains, where a human interaction cannot be replaced .TTP Dispatcher represents the conceptual continuation of a request dispatcher, which was introduced in the GANI_MED project. [The required communication between the previously described TTP services depends on the workflow of a specific cohort or registry and, hence, individual characteristics may differ from the typical scenario. In order to flexibly orchestrate the particular TTP services and to coordinate the corresponding communication between the services, a dispatcher has been developed. The project. .TTP service modules gPAS, gICS and E-PIX via corresponding Service Adapters. The service adapter connects the TTP Dispatcher with the respective module. This approach enhances the interoperability of the TTP implementation and reduces the technical effort to add further software modules if necessary. Moreover, using service adapters facilitates and standardises the dispatcher-internal handling of the utilized service functionalities. The Configuration Manager administrates project-specific and dispatcher-specific configurations in a separate database. This includes workflows, roles and rights as well as a set of individual parameters . The External Interface allows connections to selected functionalities for external use in order to integrate the TTP Dispatcher in external applications. It can be accessed using the representational state transfer protocol (REST) or web-forms. The external interface and concept is oriented towards an existing identity management solution . The spIn terms of a TTP, a workflow technically describes a sequence of  processes and operations, starting with an input and ending with a defined outcome. Workflows are being used to control and process the necessary calls to the connected software modules E-PIX, gPAS and gICS. They are distinguished into groups. Basic workflows represent common tasks of a data trustee and are of relevance in most project scenarios, e.g. checking if a participant already exists in the management system or generating pseudonyms for a list of participant identifiers. Project-specific workflows describe all necessary individual processes and operations beyond, for example all required steps to automatically generate a pseudonym when a new participant is created in a study site based on his IDAT and a valid informed consent. The separation of basic and project-specific workflows allows a consistent approach for several implementations of the TTP Dispatcher. This architecture hereby supports portability to other research projects, reduces maintenances and improves the sustainability of a TTP implementation.The technical description of each workflow is performed using Apache Camel . Based oThe starting point of a workflow defines the origin of an object or message (“from”). Combined with several processing steps , simple criteria-based conditions and a target point (“to”) a workflow is specified. The necessary information  is passed directly between the individual workflow steps. The TTP Dispatcher comes with a basic set of predefined workflows  by reusing and combining predefined workflows. Thus the individual character of cohort studies and registries can be depicted straightforward. Moreover, study specific processes are most widely automatable and manual intervention of the data trustee could be essentially reduced.The components and workflows of a TTP vary according to their specific context. For example, the Central Clinical Cancer Registry in Mecklenburg-Western Pomerania  does notImplementing a TTP on a basis of tools without uniform interfaces and with varying technical standards, demands an advanced IT knowledge and requires massive implementation efforts. That is why using the MOSAIC modules , 10, 11 Following the described approach for the technical implementation of a Trusted Third Party supports compliance with project-specific legal data protection requirements in cohort studies and registries. But in order to exhaustively fulfil security, data protection, ethical and legal requirements , additioThe aim of the described TTP Dispatcher approach has a significant difference to existing IT platforms supporting clinical research, such as EHR4CR . The proThe concept of the TTP Dispatcher has already seen successful implementation in the German Centre for Cardiovascular Research (DZHK)  and the During the recruitment of participants for cohort studies and registries particularly the acquisition, processing and storage of personal health data necessitate both compliance with ethical standards and stringent policies for data protection. For Germany, the resulting requirements for data management are compiled comprehensively in the guideline provided by the TMF . ConformThis paper demonstrates how generic software modules developed and provided by the MOSAIC project , 10, 11 The proposed approach for the technical implementation of a TTP facilitates the necessary flexibility, portability and reusability for application in cohort studies and registries. This is achieved by mapping the individual requirements and characteristics of a particular study to pre-defined workflows. Reusability additionally benefits from the encapsulation of module logic and a uniform interface for all modules avoiding study specific modifications of individual modules or functionalities. The generic software modules connected with the workflow approach presented in this paper can easily be adopted to accommodate national and international requirements in terms of informed consent, identity management, pseudonymisation, data linkage and data transfer.However, specification of a uniform interface for essential functionalities and parameters accounting for established standards and methods within the scientific community must still be considered time-consuming and labour-intensive. Future work will focus on further facilitating the establishment of an independent TTP, including workflow visualization, a generic module configuration independent from the deployed services, a graphical configuration tool for the configuration of the dispatcher and an extended central role-and-rights-management.


Helium, hydrogen, nitrogen, oxygen, methane, and carbon dioxide were used for gas permeation rate measurements. Vapor transport properties were studied for the aliphatic hydrocarbon (hexane), aromatic compound (toluene), alcohol (ethanol), as well as water for the representative samples. The mechanical properties and homogeneity of samples was checked by stress-strain tests. The addition of virgin CNTs and CFs improve mechanical properties. Gas permeability of EOC lies between that of the more permeable PDMS and the less permeable semi-crystalline polyethylene and polypropylene. Organic vapors are more permeable than permanent gases in the composite membranes, with toluene and hexane permeabilities being about two orders of magnitude higher than permanent gas permeability. The results of the carbon-filled membranes offer perspectives for application in gas/vapor separation with improved mechanical resistance.Gas and vapor transport properties were studied in mixed matrix membranes containing elastomeric ethylene-octene copolymer (EOC or poly(ethylene- Storage and handling of gasoline, and also refueling of cars, involve an outflow of gasoline vapors into the atmosphere . Refueli-energy savings;-environmental friendliness;-easy handling;-continuous process;-compact design and small footprint.In contrast, membrane separation constitutes a safer and more advanced method, and membrane separations for VOCs removal are characterized by a high efficiency. The main advantages offered by membrane processes are ,4:-enerThe investment costs of membrane units are higher than in the case of conventional separation methods; hence, the process has to be optimized with respect to membrane area and required quality of purification .Among polymer membranes used for VOCs separations , those bIn flat sheet configuration, membranes are usually subjected to compression forces. These forces may become significant in high-pressure applications, such as in membranes for gas separation or for reverse osmosis. In the case of inhomogeneous porous supports, such compression forces will be translated into a tensile force in the dense skin. Therefore, knowledge of the material’s tensile properties is important. The latter is particularly relevant in the case of hollow fiber membranes, in which the internal pressure is translated immediately into a tensile force on the membrane wall .The appropriate selection of polymer can guarantee sufficient chemical resistance of the final membrane for permeation of gases or vapors. In this context, polyolefines can be considered as potential candidates for membrane applications. The relatively low material cost of polyolefins  is also In order to overcome the limitation of both polymeric and inorganic membranes, Mixed Matrix Membranes (MMMs), consisting of a dispersion of filler particles within a polymeric matrix, have been widely investigated to overcome the upper-bound trade-off limit of the polymeric membranes as well as the main drawbacks, such as brittleness and lack of reproducibility associated with inorganic membranes . Thus, tCarbon fillers, such as carbon nanotubes (CNTs) and carbon fibers (CFs), are very interesting materials for nanocomposites preparation with a high reinforcing potential, already exploited in different applications . CNTs or CFs are often added to polymeric matrixes for mechanical reinforcement, and also for an increase of their electrical and thermal conductivity . AlternaThe merit of all above mentioned properties depend substantially on the state of filler dispersion in the polymeric matrix. A blending of fillers into polymer matrices in polymer melt is often used for composite fabrication. Carbon-based materials, such as CNTs or CFs, are generally incompatible with polymers, leading to filler agglomeration in polymer matrices rather than individualization of the filler particles. To enhance the dispersion state of filler, high-energy methods, such ultrasound treatment of the filler dispersed in the polymer solution, are usually used. Better results are achieved by the precipitation of the polymer from solution using a non-solvent  to preveIn some cases, CNTs and CFs have been reported to improve the transport properties in dense rubbery membranes  or in gl−3, melt flow index was 1.02 dg min−1 (at 190 °C/2.16 kg), and melting temperature Tm ~ 50 °C .The time lag method  was applThe present membrane preparation protocol by melt-pressing of a pre-formed dispersion was used as the conventional solution casting and solvent evaporation method is known to cause often aggregation of the nano-fillers during the evaporation step. By making a solution and quickly coagulating this in a non-solvent, it was found that such aggregation can be avoided for the CNTs and the CFs. In this light, EOC has the advantage over polyethylene and polypropylene of a good solubility in toluene at room temperature. The conditions of the melt pressing are chosen such that the porous structure formed during phase inversion was eliminated, producing completely dense films. The high viscosity in this molten phase guarantees that no aggregation of the fillers takes place during this step. The mutual affinity between the ox-CNTs is, however, so strong that there is already some aggregation in the original solution and, consequently, also in the final films. Silicone coating was needed in this case to fix the resulting pinhole defects before the permeability measurements.It is widely known that ultrasound may damage polymers, especially in solution ,37. ThisSEM observations on representative samples of the fillers and the membranes are given in Emod) in an approximately quadratic way.The effect of the different fillers on the elastic modulus of the membranes is plotted in The Young’s modulus increasing with the fillers addition is expected mechanical improvement. The strongest effect is observed for the carbon fibers, especially at high concentration. The quadratic correlation characterizes the filler-filler interactions giving a second order reinforcing effect . This trRm), and the elongation at break (εmax) of the untreated CFs and CNTs show a maximum. The untreated CFs and CNTs have a similar effect and both fillers increase Rm at low filler concentration (2%–10%). At higher loading the tensile strength of the CNT reinforced membrane remains twice as high as that of neat EOC and the CF filled membranes, which return to the value of EOC. The elongation at break (εmax) shows a maximum in the same concentration range. It then decreases to the value of EOC for the CNTs and remains slightly higher for the CFs-reinforced membranes. In contrast, the oxidized CNTs reduce the tensile strength and the maximum deformation for all compositions due to a poor dispersion and to defect formation in the films  are given in K represents the Young’s modulus at a deformation rate of 1 mm·min−1 (5% min−1) and increases rapidly with the filler content in a similar fashion as seen in n tends to decrease slightly with increasing filler content wheThe applicability of the Maxwell model is interesting because ideally it applies to systems containing low concentrations of spherical fillers. In all cases, the gas transport behavior of the CF-filled membranes is practically identical to that of the CNT-filled membranes. Therefore, only the latter will be described in more detail. The MMM permselectivities were close to that of the neat EOC, suggesting that the copolymer adhered well to the CNTs or CFs and that the corresponding MMMs are defect free. This is further supported by the same order of gas permeability for both neat EOC and filler/EOC composites, with only a modest change in the absolute permeability.2 is so much higher than that of the other gases that the membranes are nevertheless CO2 selective. This is a typical characteristic of rubbery membranes.The diffusion coefficients, determined by the time lag method, and the indirectly calculated solubility coefficients are plotted in Vapor permeation tests were carried out with representative alkanes (hexane), aromatics (toluene) and alcohols (ethanol) on all membranes. A more extensive series of vapors was used with both the neat EOC membranes and EOC + 10% CNTs. The vapor permeability  is three2 but higher than that of the other permanent gases , while both the tensile strength and the maximum deformation present a maximum near the filler content of 10%.Thus, the carbon fillers enhance the mechanical resistance of the membranes, maintaining or even improving their transport properties. If this behavior is maintained under operating conditions, as may be expected, the presence of carbon fillers will counteract the effect of plasticization of the membranes by vapor sorption, which often compromises the performance of conventional membrane systems. Therefore, the reported membranes are potentially suitable candidates for vapor removal from permanent gas streams.


To determine the effectiveness of built environment interventions in managing behavioural and psychological symptoms of dementia (BPSD) among residents in long-term care settings.Systematic review of literature published from 1995–2013. Studies were included if they: were randomized controlled trials, quasi-experimental trials, or comparative cohort studies; were in long-term or specialized dementia care; included residents with dementia and BPSD; and examined effectiveness of a built environment intervention on frequency and/or severity of BPSD. Quality of included studies was assessed using the Downs and Black Checklist. Study design, patient population, intervention, and outcomes were extracted and narratively synthesized.Five low to moderate quality studies were included. Three categories of interventions were identified: change/redesign of existing physical space, addition of physical objects to environment, and type of living environment. One of the two studies that examined change/redesign of physical spaces reported improvements in BPSD. The addition of physical objects to an existing environment (n = 1) resulted in no difference in BPSD between treatment and control groups. The two studies that examined relocation to a novel living environment reported decreased or no difference in the severity and/or frequency of BPSD post-intervention. No studies reported worsening of BPSD following a built environment intervention.The range of built environment interventions is broad, as is the complex and multi-dimensional nature of BPSD. There is inconclusive evidence to suggest a built environment intervention which is clinically superior in long-term care settings. Further high-quality methodological and experimental studies are required to demonstrate the feasibility and effectiveness of such interventions. Alzheimer's disease and related dementias are chronic, progressive disorders that result in the impairment of cognitive functions, including memory, orientation, comprehension, and executive function Commonly described as a heterogeneous set of complex symptoms manifesting as agitation, disinhibition, physical and/or verbal aggression, anxiety, depression and delusions, BPSD requires a multifaceted approach to achieve successful management Previous studies examining modifications to the built environment have drawn from a number of design principles and frameworks for dementia care homes and suggest that purposeful design of one's surroundings may play an active role in promoting a sense of well-being and improved functionality Despite the recent advances in the breadth and depth of built environment interventions, their effectiveness in managing BPSD specifically within LTC settings remains unclear. The objective of this systematic review is to determine the effectiveness of built environment interventions, in comparison to usual care or no intervention, on the frequency and/or severity of BPSD among residents in LTC.A systematic review was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses , quasi-experimental trials, or prospective comparative cohort studies, were set in a long-term care (LTC) facility or a unit or facility specializing in dementia care, included residents with dementia diagnosed with behavioural and psychological symptoms in dementia (BPSD), involved an environmental intervention specific to the physical or built structure of the living environment  and reported outcomes related to the clinical efficacy of built environment interventions on BPSD were selected . ReferenData from the included studies was extracted in duplicate using a standard data extraction form. Any discrepancy was resolved through discussion and consensus. Data related to study design, publication date, country, number of participants, dementia diagnosis, healthcare setting, procedure or intervention information, outcome measures and relevant results reported by each study were extracted and narratively synthesized. Specifically, reported outcome measures included decreases in frequency and/or severity of responsive behaviours or episodes of BPSD. Heterogeneity in reported outcomes and/or summary measures precluded pooling of data for meta-analysis.Each included study was assessed for quality using the Downs and Black Checklist The literature search identified 258 unique abstracts. Previous high-quality systematic reviews were hand-searched for articles that met the inclusion criteria and 1 relevant article was identified. Two-hundred and twenty-three citations were excluded in the abstract review and 36 were assessed in full-text. Thirty-one articles were excluded following full-text review  and ultimately, five studies were included in the final analysis .The included studies were of low to moderate quality. Using the Downs and Black Checklist, the included studies scored between 14 All 5 included studies were non-randomized comparative cohort studies published between 1992 and 2010. Four of the included studies were pre- and post-intervention design. The control group from the remaining study was sampled from two separate LTC facilities compared to those in the intervention group Three general categories of intervention were identified: a change or redesign of existing physical structures or spaces within the environment et al. (1992) the basic intervention of unlocking doors to the common courtyard of a specialized care facility reportedly led to decreased agitation amongst residents with dementia compared to the control conditions when the doors were locked Two of the included studies examined the impact of changing or redesigning the existing physical structures or spaces within the living environment on the behaviours of study participants et al. (2004) measured the level of affect in participating residents with dementia during time spent in the control living room setting compared in two multisensory environments added to the LTC facility: a Snoezelen room and a landscaped garden One study examined the impact of adding new physical objects or features to an existing component of the built environment. Specifically, Cox et al. (2004), of 185 residents with dementia, the quality of life, which included measures of responsive behaviours such as agitation, socially appropriate behaviour, social withdrawal and interest in the environment, were compared between participants in traditional LTC facilities (control group) and in a purpose-built specialized dementia care facility Two studies examined the impact of several responsive or agitated behaviours following a complete relocation in living environment. Relocation of a small sample of 16 residents from a traditional care unit to a specialized dementia care unit in a single LTC facility resulted in decreased agitation amongst participants, specifically in verbally aggressive behaviour, 6-months post-intervention Five relevant studies were identified in the present systematic review of built environment interventions for the management of BPSD in LTC. The included studies were all designed as comparative cohort studies, had relatively small sample sizes, and were of low to moderate quality. With no standardized system to classify interventions to the built environment Manipulations to the built environment and other non-pharmaceutical approaches have been widely discussed as first-line therapies to managing BPSD in institutionalized seniors The variability in manipulations to the built environment observed amongst studies demonstrates great creative capacity with regards to these interventions. However, with the limited number of included studies, the small numbers of participants, and given that most of the included studies were from single sites it is difficult to predict the feasibility for large-scale implementation of such interventions at the health system level. Inadequate reporting of the required resources and costs across studies also precluded inferences of the most cost-effective of interventions; though it is apparent that some are likely to be more costly and burdensome relative to others. For example, relocating an entire building of LTC residents to a new purposively designed LTC facility requires substantially different resources compared to the unlocking of doors in an existing building. Thus, decisions to undertake a given built environment intervention must balance the specific needs of the residents and care-givers/staff as well as the appropriateness of the intervention, with the inherent cost and resource limitations of the facility or health system.et al. (2003) examined broader categories of environmental interventions beyond the physical construct of one's living space  and similarly noted variability in intervention protocols, sample sizes, quality of evidence and extent of outcome data reported The findings of this present study are consistent with those reported by previous systematic reviews. The systematic review conducted by Gitlin There are several limitations to the synthesis of the evidence in this review. By focussing specifically on interventions to the physical or built structure of the living environment for residents with BPSD in LTC or specialized dementia care units or facilities, other interventions applied to the built environments of an individual's own home, temporary or transition housing, seniors' daycare facilities, or acute care facilities were excluded from this review. Interventions that involved manipulations experienced by the residents within the environment, but without any physical or structural manipulation to the environment (e.g. music therapy) were also excluded. Most studies also had short-term follow-up periods (no longer than a few months post-intervention), rendering it difficult to determine whether results can be sustained or generalized over the long-term. Lastly, as mentioned, heterogeneity within intervention categories and insufficiency in reported outcome data, as well as the overall low quality of the included studies precluded meta-analyses.The complex and multi-dimensional nature of BPSD requires a multifaceted management approach S1 ChecklistPRISMA 2009 Checklist.(DOC)Click here for additional data file.S1 AppendixSearch Strategies for the Literature Search (1995–June 2013).(DOCX)Click here for additional data file.S2 AppendixInclusion and Exclusion Criteria for the Systematic Review.(DOCX)Click here for additional data file.


Endo-perio lesions might be interdependent because of the vascular and anatomic connections between the pulp and the periodontium.The aim of this study is to emphasise that primary endodontic lesion heals after a proper instrumentation, disinfection and sealing of the endodontic space.The primary endodontic lesion with a secondary periodontal involvement first requires an endodontic therapy and, in the second stage, a periodontal therapy. The prognosis is good, with an adequate root canal treatment; it depends on the severity of the periodontal disease, appropriate healing time and the response to the treatment.A correct diagnosis is sometimes difficult; an accurate identification of the etiologic factors is important for an adequate treatment.Primary perio-endo lesion may heal after a proper disinfection and sealing of the endodontic system, the one-year follow-up radiograph showing bonny repair. Invasive periodontal procedures should be avoided at that moment.The microorganisms and by-products from the infected root canal may cross accessory and furcal canals and determine sinus tract and loss of attachment. In both clinical cases presented in this article, successful healing was obtained after a proper disinfection and sealing of the endodontic system. The treatment results should be evaluated after two or three months and only then, should the periodontal treatment be considered. Prognosis depends on the severity of the periodontal involvement, periodontal treatment and patient response [10].The size of the periapical lesion in an isolated endodontic disease does not affect the clinical outcome . Therefore, a primary endodontic lesion draining from the attachment apparatus should be initially treated by an endodontic therapy [10]. Periradicular lesions may initially expand horizontally through cancellous bone and then proceed vertically [8].The differential diagnosis is difficult when a sinus tract, originating from the endodontic lesion may drain along the periodontal ligament, giving the appearance of periodontal disease [1. Because the endodontic pathogens and their byproducts may affect the integrity of the periodontium, they have to be eliminated during root canal treatment.2. The placement of calcium hydroxide paste is indicated, because of its antibacterial, proteolytic and anti-inflammatory proprieties, it might inhibit resorption and periodontal contamination, before the periodontal treatment is initiated.3. If proper endodontic treatment is performed, sinus tract extending to the gingival sulcus or furcation area can heal.4. Usually, the endodontic treatment alone is not sufficient for healing the combined lesion and a proper periodontal treatment is needed to influence the secondary periodontal disease.


PRISMA guidelines have been developed to improve the reporting of systematic reviews (SRs). Other reporting guidelines and techniques to assess methodological quality of SRs have been developed. We aimed to assess the frequency of the use of reporting and other guidelines in SRs to assess whether PRISMA is being used inappropriately as a substitute for other relevant guidelines.Web of Knowledge was searched to identify articles citing the PRISMA guidelines over a 12-month period. The use of reporting guidelines (including PRISMA and MOOSE) and tools for assessing methodological quality (including QUADAS) was assessed. Factors associated with appropriate use of guidelines including review type, field of publication and involvement of a methodologist were investigated.Over the 12-month period, 701 SRs were identified. MOOSE guidelines were cited in just 17% of epidemiologic reviews; QUADAS or QUADAS-2 was referred to in just 40% of diagnostic SRs. In the multivariable analysis, medical field of publication and methodologist involvement  were significant predictors of appropriate use of guidelines. Inclusion of a meta-analysis resulted in 73% higher odds of appropriate usage of systematic review guidelines .Usage of SR reporting guidelines and tools for assessment of methodological quality other than PRISMA may be under-utilized with negative implications both for the reporting and methodological quality of systematic reviews. Systematic reviews (SRs) are “prepared using a systematic approach to minimizing biases and random errors which is documented in a materials and methods section” A plethora of reporting and methodological guidelines have been developed to assist in the reporting and conduct of all aspects of research, including SRs Inadequate reporting risks shrouding the conduct of systematic reviews impairing potential judgements in relation to the emphasis that should be placed upon their results and conclusions. It is, therefore, important that these guidelines are considered and applied where necessary to optimise both the conduct and reporting of all types of SR. The aims of the present research were to assess the frequency of correct use of appropriate guidelines in SRs and to highlight factors associated with inappropriate use or omission of relevant guidelines.st to December 31st 2012, using the Web of Knowledge database (http://apps.webofknowledge.com) by one of the authors (PSF). The first step consisted of a search for PRISMA publications on the PRISMA website (http://prisma-statement.org). The ‘Create citation report’ tool on the Web of Knowledge database was accessed to identify articles citing one of these six PRISMA guideline articles. SRs only were to be included in the research with other article types including narrative reviews, meta-epidemiologic studies, letters, editorials and other studies excluded from the analysis.Articles citing the PRISMA guidelines were searched from January 1Two researchers (PSF and DK) screened the titles and abstracts of all retrieved references. Electronic versions of potentially eligible reviews were retrieved and analyzed by the authors to assess eligibility. Review articles without a specific methodology section were excluded. Two reviewers independently extracted data from eligible reviews using piloted forms. Calibration was initially undertaken on 10 articles and disagreements were resolved through consensus or by discussion with a third reviewer (NP).Data were obtained on the type of systematic review, medical field of publication, number of authors, involvement of a methodologist or statistician in the paper, specific PRISMA article cited, reason for the citation, and whether meta-analysis was undertaken. The involvement of a methodologist was gauged from affiliations or qualifications reported and information in the review methodology section.Descriptive statistics were performed to categorize the number of SRs identified within each medical field and to relate reporting to the remaining study characteristics. Pearson chi-squared test and Fisher’s exact test were used to determine the association between appropriate PRISMA citation and trial characteristics including medical specialty, number of authors, methodologist involvement, specific PRISMA statement article cited, reason for citation, type of SR, and implementation of meta-analysis or otherwise. Univariable and multivariable logistic regression modeling was used to determine the association between appropriate PRISMA statement citation and predictor variables including medical field of research, number of authors, methodologist involvement, cited article and whether meta-analysis was undertaken. The adequacy of the model was assessed using the Hosmer-Lemeshow test. The level of statistical significance for all tests was pre-specified at 0.05. All statistical analyses were conducted with statistical software .et al., (2009) published in PLoS Medicine. The guideline most frequently omitted within the subset of SRs citing only PRISMA 3 in isolation.Seven hundred and one SRs were identified pertaining to 10 medical fields , Table 1In the univariable analysis , medicalThe requirement for high quality systematic reviews of healthcare interventions, epidemiological data and diagnostic information is clear as the emphasis on evidence-based decision-making continues. A corollary of this situation is for more complete and transparent reporting of the design and conduct of a SR, allowing stakeholders to reach informed decisions based on the validity of the findings. The PRISMA guidelines While there is significant overlap between MOOSE Meta-analyses of diagnostic tests have become increasingly prominent in medicine and will potentially have an increasing role in healthcare as decision makers consult the evidence before implementing new diagnostic technologies. It is important that such analyses provide reliable results; this is contingent upon both the quality of conduct and the clarity of reporting. As with over review types, diagnostic systematic reviews are susceptible to shortcomings pertaining to conduct and reporting Disentanglement of the conduct of SRs from reporting is more complex than is the case with primary studies, as significant overlap exists between the two. Nevertheless, PRISMA guidelines The over-reliance on PRISMA guidelines Potential limitations of this study included the relatively short time period assessed; however, a large number of eligible studies from diverse areas of medicine were included. Nevertheless, temporal changes in reporting characteristics will not be identified. In addition, given that the focus of the research was to assess the usage of PRISMA guidelines specifically, it is likely that epidemiologic and diagnostic reviews that cite more specific guidelines in isolation, without referring to PRISMA, exist.There is evidence that significant awareness of PRISMA guidelines exist. However, usage of other accepted reporting guidelines and tools for assessment of methodological quality have less prominence and may be under-utilized with negative connotations on both reporting and methodological quality of systematic reviews.


The unique component of the cerebral circulation is the so called blood–brain barrier (BBB). The anatomical structures of the BBB consist of the cerebral vascular endothelial cells, the surrounding pericytes, the basal lamina and the perivascular astrocytes. These form the so-called neurovascular unit . NotablyOn the contrary, the BBB has a considerable passive permeability to free water, as opposed to electrolytes and other solutes. An acute drop in plasma osmolality, therefore, results in an acute increase in brain water content . The neuThe complex regulation of cerebral volume in response to changes in osmolality is of central interest in the context of fluid therapy in patients with intact or disrupted BBBs. The physical composition of resuscitation fluids is of special relevance in this regard . Key detAn iso-osmotic crystalloid fluid  equally distributes to the intravascular and the interstitial space , becauseIn an ideal model of the vasculature, iso-oncotic colloid solutions remain in the intravascular space, since the endothelial barrier is not permeable to colloidal compounds ,12. In cIn summary, changes in plasma osmolality may be deleterious in patients with brain injury. Resuscitation fluids should therefore be isotonic in terms of osmolality (not osmolarity). Physicians should be familiar with the osmolality of the resuscitation fluids they use.BBB: Blood–brain barrier; SAFE: Saline and albumin fluid evaluation.The authors declare that they have no competing interests.


We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills.Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net.Database URL:http://rged.wall-eva.net Kidney diseases are among the major public health burdens globally and associated with increased risk of cardiovascular morbidity and mortality, resulting in poor prognosis , 2. The DNA microarray technology aims at simultaneous measurements of the expression of thousands of genes in one single experiment. Over the past few years, this technology allowed better understanding of the complex and heterogeneous molecular characteristics of renal tissues and helped to make individualized therapeutic strategies in kidney diseases . RecentlHere we present Renal Gene Expression Database (RGED), a database of gene expression profiles generated from high-throughput DNA expression profiling experiments in kidney diseases research. The database is provided with an integrated web-based utility, which made the data easily accessible to the kidney disease research community. User can investigate the expression profile of a certain gene in kidney diseases and analyse the correlations between two genes of interests . As the closely correlated genes are suggested to share a similar regulatory pathway, this feature of the database might provide potential research proposals on the mechanisms of kidney diseases.We searched NCBI Gene Expression Omnibus (GEO) database  for genehttp://rged.wall-eva.net. The web application is written in PHP and Javascript. The database runs a MySQL engine (innoDB) on an Ngnix Server (http://nginx.org/). When requested by the client web browser, the R package, ggplot2  and REACTOME .The main purpose of RGED is to help researchers to search gene expression profiles across various kidney disease states. The design of the web interface for the database enabled users search across the database easily without need of computer expertise. The home page of the website provides two ways to query the database: one is to search the gene of interest by inputting keyword, the other one is to browse the data sets by disease classification. Users can also simply click on the tags of some popular genes to start a quick search.P-value. By clicking on the gene symbol, more details about the gene expression profiles in the kidney diseases will be returned  is a potentially useful database of genes including data from various kidney diseases  and the national Key Technology R&D Program (No.2011BAI10B08). Funding for open access charge: 800 GBP.This work was supported by Conflict of interest. None declared.


A new FTIR technique was developed for characterizing thin polymer films used in combinatorial materials science. Fourier transform infrared microspectroscopy mapping technique was used to determine the composition of polymer blend gradients. Composition gradients were made from poly(L-lactic acid) (PLLA) and poly (PDLLA) in the form of thin films (6 cm × 2 cm) deposited on IR reflective substrates. Three composition gradient films were prepared and characterized. The results demonstrate the reproducibility and feasibility of a new, high-throughput approach for preparing and characterizing polymer composition gradients. The combination of composition gradient film technology and automated nondestructive FTIR microspectroscopy makes it possible to rapidly and quantitatively characterize polymer composition gradients for use in combinatorial materials science. Polymer blending is designed to generate materials with optimized chemical, structural, mechanical, morphological and biological properties –4. PrepaPLLA and PDLLA are biodegradable polymers used in tissue engineering for medical applications. They are chemically identical but differ in their crystallinity  . Blends Mw = 300 000; Polysciences, Warrington, PA) and PDLLA  were prepared by dissolving the respective polymers in chloroform (1 % by mass fraction). Discrete composition films [ % by mass fraction] were prepared by mixing PLLA and PDLLA solutions in the appropriate ratios and then spreading the mixtures on low-emissivity (low-e) reflective glass slides  using a home-built flowcoater  and 3D plot, all obtained with the acquisition software} are shown in Figs. 5Figs. 5−1 to 1155 cm−1 region are shown in the middle panels of Figs. 5Figs. 5The results of the FTIR-RTM analyses of the three PLLA-PDLLA composition gradients {visual map, total absorbance map (1500 cmx-axis) and most of each film in the direction perpendicular to the gradient (y-axis) were mapped in order to get as much information as possible. The upper parts of each of the three composition gradient films were included in the maps to allow direct comparison between the films and to have reference markers on each map for easy and accurate location when the same films will be used with other techniques for additional characterization. Comparison between the visual maps shown in Figs. 5−1 to 1155 cm−1) maps show that the total absorbance of the films is proportional to film thickness as can be seen when the visual map and the absorbance map are compared for each of the gradients  is capable of qualitatively and quantitatively characterizing the chemical properties of optically thick polymer specimens . FTIR-RMin situ microscope FTIR reflection spectroscopy (MFTIRS) [in situ FTIR spectral library of CO adsorbed on different nanostructured Ru films and at various electrode potentials.Only a few reports describing the characterization of thin polymeric films with FTIR could be found in the literature. Transmission FTIR microscopy was used to determine the distribution of various transition-metal complexes embedded in thin pressed film fragments of polystyrene, poly(methyl methacrylate) and polystyrene-polyacrylonitrile copolymer, that were placed on KBr discs . FTIR mi(MFTIRS)  was usedAlthough there are no reports in the literature on characterizing PLLA or PDLLA with FTIR microspectroscopy, there are many studies using traditional FTIR spectroscopy. For example, a purified copolymer of PDLLA and polyethylene glycol (designed as drug delivery system) was dissolved in chloroform, coated on KBr tablets to form thin films and measured by an FTIR spectrophotometer . SolutioThe studies mentioned above are different from the system reported in this study in which composition gradients and discrete control blends  % by mass fraction were deposited directly on low-e reflective IR microscope substrates and characterized by FTIR-RTM. Further, the chemical composition along the gradients was determined by a calibration curve constructed from known discrete composition controls.Three composition gradients of PLLA and PDLLA blends were created on reflective substrates and were characterized with FTIR-RTM. The formation of the composition gradients was confirmed qualitatively by the FTIR ratio maps and quantitatively by processing the acquisition software maps in the processing software and determining the position-resolved composition values with the calibration curve. The results show that the gradients were present and the methods used to characterize them were consistent and reproducible from sample to sample.−1 peak and caused larger errors in the calculated peak ratios, resulting in artificial heterogeneity in the 100 % PDLLA and the 75 % PDLLA discrete film maps used for the calibration curve. The accuracy in the composition determination of the PDLLA-rich regions in the gradient films was also reduced because of the low intensity of the 1450 cm−1 peak in these thin regions. Efforts to prepare thicker gradient films are in progress.The technique reached its detection limits when extremely thin PDLLA-rich regions were measured. The absorptions of the atmospheric water interfered with the low intensity of the 1450 cmProcessing the FTIR maps with Method A allows for qualitative comparisons between various variables and maps, and manually processing individual representative spectra supplies a semi quantitative comparison. The use of the new high-throughput approach (Method B) however, improved the quantification of the results and saved enormous amounts of processing time. Additional efforts will be devoted to improving the integration of both software packages and to match the colors of the acquisition software maps to those acquired in the processing software.The non-destructive, non-contact nature of the FTIR-RTM enables further determination of additional properties on the same chemically-characterized specimens. An additional advantage of the current system is the capability to obtain parallel visual and IR maps with the same microscope, allowing the user to evaluate the thickness of the films.FTIR-RTM mapping was used here for the first time to map and determine the gradient composition of thin films of polymer blends flow coated on low emissive reflective glass slides. This resulted in reflection-transmission spectra enabling characterization of the full depth of the film and not just the surface, as was the case in several earlier studies with FTIR-RM –17. The


A study was made to identify the most effective protocol for reducing the risk of osteonecrosis of the jaws (ONJ) following tooth extraction in patients subjected to treatment with antiresorptive or antiangiogenic drugs.A MEDLINE and SCOPUS search (January 2003 - March 2015) was made with the purpose of conducting a systematic literature review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. All articles contributing information on tooth extractions in patients treated with oral or intravenous antiresorptive or antiangiogenic drugs were included.Only 13 of the 380 selected articles were finally included in the review: 11 and 5 of them offered data on patients treated with intravenous and oral bisphosphonates, respectively. No randomized controlled trials were found – all publications corresponding to case series or cohort studies. The prevalence of ONJ in the patients treated with intravenous and oral bisphosphonates was 6,9% (range 0-34.7%) and 0.47% (range 0-2.5%), respectively. The main preventive measures comprised local and systemic infection control.No conclusive scientific evidence is available to date on the efficacy of ONJ prevention protocols in patients treated with antiresorptive or antiangiogenic drugs subjected to tooth extraction.Key words:Bisphosphonates, angiogenesis inhibitors, antiresorptive drugs, extraction, osteonecrosis. Medication-related osteonecrosis of the jaws (ONJ) is defined as an area of exposed bone or bone that can be probed through an intra- or extraoral fistula in the maxillofacial region, persisting for over 8 weeks in patients receiving or who have received antiresorptive or antiangiogenic medication, and who have not undergone radiotherapy or present evidence of metastatic disease in the mentioned anatomical region . Once suA number of perioperative measures have been proposed for preventing this complication, including antiseptic rinses immediately before extraction and until healing of the socket , antibioIn view of the increasing number of patients receiving antiresorptive or antiangiogenic treatment, and the important morbidity associated to ONJ, we decided to conduct a systematic review with the purpose of identifying the most relevant protocols and best measures for preventing the development of ONJ secondary to tooth extraction.The present systematic review was carried out following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines . The PIC- Search strategyA systematic MEDLINE and SCOPUS database search (January 2003 - March 2015) was made to identify publications eligible for inclusion in the study, using a combination of MeSH terms and free text  as searc- Selection of studiesIn order to assess the eligibility of the studies, two reviewers  traced the titles and abstracts of the publications generated by the search strategy. The full-text articles were retrieved in the case of those studies that appeared to satisfy the screening criteria, and in the case of those which offered too little information in the title / abstract to firmly decide inclusion of the study or not. All articles contributing information on tooth extractions in patients treated with oral or intravenous antiresorptive or antiangiogenic drugs were included.The selected studies assessed the efficacy of a protocol for reducing the incidence of ONJ after tooth extraction, and were required to supply information on the type of antiresorptive or antiangiogenic treatment used, the administration route , the indication of treatment, a clear definition of the presence of ONJ, and the duration of follow-up (in months). The articles also were required to clearly specify the prevention protocol employed .Studies in patients under 18 years of age administered bisphosphonates (BPs) due to osteogenesis imperfecta were excluded, as were case series involving fewer than 10 patients, and animal studies. In the case of studies involving expansions of the same series of patients, only the most recent data were considered.The two reviewers independently assessed compliance with the inclusion and exclusion criteria. The reason for exclusion was recorded in the case of those articles that were eliminated in this phase.- Data extractionThe identified references were processed using the bibliographic management program Refworks (Proquest), and the data extracted from the articles were entered in a MS Excel spreadsheet. The studies were divided into three groups: (a) studies involving patients treated with intravenous BPs; (b) studies involving patients treated with oral BPs; and (c) studies involving patients treated with other antiresorptive or antiangiogenic drugs. The main variables analyzed in each study were: authors, date of publication, sample size, drug type, dose and administration route, indication and, number of extractions and their location (maxilla or mandible), the preventive protocol employed , and the appearance of ONJ.The article screening process is schematically shown in figure The studies involving subjects treated with intravenous BPs included a total of 634 patients, with a prevalence of ONJ of 6,9% (range 0-34.7%). In turn, the studies involving oral BPs included a total of 1261 patients, with a prevalence of ONJ of 0.47% (range 0-2.5%). The main preventive measures comprised local and systemic infection control .Although medication-related ONJ may manifest spontaneously, in up to 80% of all cases it is associated to tooth extractions or other surgical procedures involving bone exposure. In this study we therefore considered extraction as a potential risk factor for ONJ. Our findings show that few authors have systematically applied any of the prophylactic protocols proposed by the different international expert committees or scientific societies -9,13-20.- Bisphosphonates via the intravenous routeet al.  in patients receiving oral BPs have been the subject of debate . The conet al.  in turn There is no evidence that the interruption of oral BPs is able to eliminate the risk of ONJ. On the other hand, temporary suspension of the medication may have a negative impact in terms of bone resorption. It is therefore necessary to consider the risks of the dental procedure and discuss the possibility of suspending antiresorptive treatment with the prescribing physician . Furtheret al. (Regarding other prophylactic measures, Vescovi et al. , on usinNo conclusive scientific evidence is available to date on the efficacy of ONJ prevention protocols in patients subjected to tooth extraction and treated with antiresorptive or antiangiogenic drugs. In practical terms, and until future studies are able to define the ideal protocol, adoption of the preventive measures proposed by the international expert committees has weak scientific justification, but could afford some coverage from the medical-legal perspective.


Prior to the development of a disease, Preventive Medicine enables early detection of signs and symptoms of diseases; if logical measures are taken, an outbreak i.e the development of a disease may possibly be avoided. If the possibility of curing a disease is missed, only the treatment and relief of symptoms remains. The disease becomes incurable and chronic. Since the healing of serious illnesses is only effective as long as the patient is not yet seriously affected, the concept of healing should be redefined. Thus, the removal of a small tumor, the patient hasn't yet noticed, could be considered to fall into the category of preventive medicine  defined hierarchical table of the most common life-threatening causes of diseases. Physical exams - with the help of equipment - allow an assessment of a patient's condition at the time of the investigation.Sustainability, that is the period for which the test results are valid, can be estimated from the results of such studies and from the observation period of the study. Since there is no scientific advantages or post-closure plan for many diseases, routine follow-up examination are usually scheduled at set, agreed upon intervals, e.g. once a year.If a more accurate assessment of the disease risk in healthy patients is desired or the prognosis of a particular course of a known disease with known genetic factors favoring the disease is suspected, genetically predisposing factors should be checked. This is done by means of molecular genetic testing of possibly afflicted genes in the DNA of the patient. After creating an exact genetic fingerprint, worldwide comparisons of the genetic fingerprints among patients with the same or similar changes can be performed and conclusions can be drawn and predictions can be made.High quality laboratory equipment allows both targeted hotspot analysis (using the Sanger sequencing) as well as screening tests on several hundred genes (using the panel study of next-generation sequencing).For the screening tests, validated predisposing-genes are examined for the following disease groups:a.) Heart and vascular diseasesb.) Tumorsc.) Metabolic diseasesd.) Diseases of bones and connective tissuese.) Diseases of the sense organsf.) Neurodegenerative Diseasesg.) Organ and systemic diseasesh.) Blood diseasesThe use of molecular genetic studies is subject to strict guidelines that are laid down in the so-called Gene-Diagnosis-Law. For this reason, human genetic consultations are prescribed by a specialist in human genetics before performing predictive diagnostics on healthy patients. Human genetic counseling before proceeding with the diagnostic methods may be omitted if there is the suspicion of a genetically determined disease upon physical or other examinations.The overall concept includes subtle diagnostic methods in molecular medicine, particularly translational research techniques which have not yet become standard in the medical routine examinations. Therefore, we have coined the term "molecular prevention" for it.Blood tests UrinalysisPhysical Examination(Blood pressure measurement)(Skin inspection)Exercise stress test, sports medicine and performancePulmonary function testsResting ECGExercise ECG4-D echocardiographyCarotid duplexThyroid ultrasoundUpper abdominal ultrasoundExamination of the leg veins(Plethysmography)(Venous plethysmography)(Strain gauge plethysmography)Examination of the leg arteries(Pulse oscillography)Bone density measurementsEye examinations vision controlOcular pressurePhotograph of the fundusOcular coherence tomographyCapsule endoscopy of the entire gastrointestinal tractSleep apnea screeningHolter-monitorLong-term blood pressureLong-term glucose measurementCardiac MRI as a non-invasive coronary-diagnostic measureGenetic testing for disease genesDuration of basic checks: about 3.5 hours.For each patient, a wealth of research data is generated that allows the development of a personalized strategy. However, the analysis of data allows not only the determination of a precise medical treatment strategy, but also the precise definition of reasonable care intervals, the observance makes a continuous monitoring of disease development / progress possible. In addition, the data serves as a basis for life style consultation to avoid specific hazards for which the body of the individual patient holds inadequate compensation mechanisms. Personalized exercise and nutrition concepts help patients to remain healthy.


Survivors of sepsis report persistent problems that can last years after hospital discharge. The main aim of this study was to investigate long-term health-related quality of life in survivors of SIRS and sepsis compared with Welsh normative data, controlling for age, length of stay and pre-existing conditions. The second aim was to investigate any differences in long-term health-related quality of life specifically with the patients categorised into three groups: SIRS, uncomplicated sepsis, and severe sepsis/septic shock.A prospective study design was used in order to investigate all sepsis patients either presenting to the emergency department or admitted to the ICU of a regional trauma centre. A total of 106 patients were recruited and all patients were considered eligible as per the SIRS and sepsis criteria [P < 0.0001). Reductions in the physical components of health-related quality of life were more pronounced in severe sepsis/septic shock patients when compared with uncomplicated sepsis and SIRS patients.A total of 106 patients were included in the study. A mortality rate of 34% was recorded, leading to a final response rate of 72% by the end of the data collection period. Quality of life was significantly reduced in all patients when compared with local normative data (all This is the first observational study to specifically focus on the different groups of SIRS and sepsis patients to assess long-term quality of life. Local population norms were used for comparison, rather than wide geographical norms that fail to reflect the intricacies of a country's population. Significant reductions in quality of life were found in severe sepsis/septic shock patients compared with in uncomplicated sepsis and SIRS patients, when controlling for age, preexisting conditions, hospital and ICU length of stay.


This review aims to summarize the technique and clinical applications of CT perfusion (CTp) of head and neck cancer. The most common pathologic type (90%) of head and neck cancer is squamous cell carcinoma (HNSCC): its diagnostic workup relies on CT and MRI, as they provide an accurate staging for the disease by determining tumour volume, assessing its extension, and detecting of lymph node metastases. Compared with conventional CT and MRI, CTp allows for obtaining measures of tumour vascular physiology and functional behaviour, and it has been demonstrated to be a feasible and useful tool in predicting local outcomes in patients undergoing radiation therapy and chemotherapy and may help monitor both treatments. Head and neck cancers represent about 5% of all malignancies newly diagnosed each year. Squamous cell carcinoma is the most common histology, accounting for about 90% of these tumours. Head and neck squamous cell carcinomas (HNSCC) arise from the mucosa of the upper aerodigestive tract and are linked by common characteristics including a male-predominant presentation and a multifactorial etiopathogenesis. Historically tobacco and alcohol assumption are the most important risk factors while human papilloma virus (HPV) exposure is an emerging cause, particularly common in the oropharynx subsite and with a better clinical outcome .Most head and neck patients present in a locally advanced stage with a poor prognosis. In this setting various strategies have been tried to improve outcomes of the two main standard treatments (surgery and radiotherapy). Concomitant chemoradiation treatment has become the standard of care in the unresectable locally advanced disease and as organ preservation strategy . InductiGiven all these new therapeutic approaches, there remains the fact that a subset of patients obtain a major or complete response, especially from induction chemotherapy and target therapy, and we do not have predictive markers to anticipate this and to personalize the therapeutic strategy in order to improve outcomes or reduce toxicity.In the clinical practice cross-sectional imaging integrates endoscopic evaluation of HNSCC providing information about the local invasion of the tumour into the surrounding structures as well as the regional spread of the disease, as both have an impact on treatment and prognosis.The traditional evaluation of response to treatment is based on modification of tumour dimensions which is unidimensional for the universally recognized Response Evaluation Criteria in Solid Tumour (RECIST) .The assessment of tumour volume changes after treatment by CT may be used as an objective and reproducible technique for therapy monitoring, with good correlation with histology .Furthermore CT-determined tumor volume is a strong predictor of local and locoregional outcome of laryngeal carcinoma .However cross-sectional imaging techniques provide only morphologic assessment and do not tell us anything about the tumour biology.The knowledge about the cellularity or the perfusion of a tumour may help in the differentiation of the biological behaviour during and after treatment of lesions having the same histologic type .CT perfusion (CTp) has recently been used to obtain measures of tumour vascular physiology and hemodynamic. In contrast to the logarithmic relation between signal intensity and concentration of paramagnetic contrast medium of dynamic contrast enhancement MRI (DCE-MRI), the main advantage of CTp is the linear relationship between contrast concentration and attenuation in CT, which facilitates quantitative measurement of perfusion parameters . Also, CCTp is a theoretical tool able to quantify, through mathematical models and dedicated software, the “real” perfusion of tissues. The first technical requirement is the execution of repeated CT scans of the volume being analysed during and after intravenous administration of a fast bolus of iodinated contrast medium, to allow the study of the density variations over time . The denThe selection of the arterial input through the placement of a region of interest (ROI) on an artery allows obtaining a time-density curve of the artery, expressed in HU. This is then compared with the time-density curve of the tissue being analysed in order to distinguish between the quantity of contrast agent within the blood vessels (vascular compartment) and the quantity present in the interstitium (extra vascular/extra cellular compartment) .Some studies demonstrated that the use of internal carotid artery (ICA) or external carotid artery (ECA) ipsilateral or contralateral to the tumour as the arterial input has no significant effect on CTp calculation of HNSCC , 25. TawVarious kinetic models can be used to calculate the distribution of contrast agent in the different compartments through the estimation of the perfusion parameters. In some of these models the analysis is performed using the single-compartment or double-compartment method which respectively describes the vascular and extravascular compartments as single or separate compartments .The deconvolution method uses arterial and tissue time-density curves to calculate the impulse residue function (IRF), a theoretic tissue curve obtained assuming that the contrast agent is not diffusible and its concentration in the tissue is linearly dependent on the input arterial concentration when the blood flow is constant .Blood flow (BF), expressed in mL/min/100 g of tissue, is the flow rate of blood through the vasculature in tissue region. BF includes flow information from large vessels, arterioles, capillaries, and venules as well as arteriovenous shunts, which are more common in neoplastic tissue than in healthy tissue.Blood volume (BV), expressed in mL/100 g of tissue, represents the volume of blood that flows within vasculature in a tissue region.Mean transit time (MTT), expressed in seconds, represents the mean time the blood takes to pass through the microvasculature from the arterial to the venous end. MTT is inversely correlated to BF.Permeability-surface products (PS), expressed in mL/min/100 g of tissue, measure the product between the permeability and the total surface area of capillary endothelium in a unit mass of tissue . It is considered as a surrogate marker of immature leaky vessels which are more common in neoplastic tissue.Most papers published about CTp in the study of HNSCC used the deconvolution based software which generates the following perfusion parameters , 27.BloClinical interpretation of CTp is based on a qualitative analysis and a quantitative analysis. Qualitative analysis involves the analysis of the colour maps generated by the software for each perfusion parameter. Each pixel of the CT images is attributed a colour which represents the numerical value of perfusion parameter calculated for that pixel and the colour scale is chosen by the operator in order to maximize the differences between areas having different perfusion.Quantitative analysis involves the interpretation of numerical values of perfusion, which the software calculates for the area bounded by the ROI placed over the tumour representing the mean of the numerical values of each voxel included in the ROI .Similar to CTp studies of other tumour sites , PetraliOver the past decade several studies investigated the role of CTp both in monitoring and predicting short-term and long-term response to organ-preserving treatments in HNSCC, though different end points were considered: disease-free survival in some case  and tumoIn the clinical routine endoscopic examination integrated by biopsy and cross-sectional imaging represents the gold standard for therapy monitoring of HNSCC.Few studies  investigIn a small group of 9 patients treated with induction chemotherapy Gandhi et al.  found a Petralia et al.  confirmeP = 0.004), consistent with the findings of Hermans et al. [Serial fluctuations in perfusion parameters of HNSCC during a course or radiotherapy were prospectively evaluated by Truong et al. , by usins et al. . FurtherInterestingly Šurlan-Popovič et al. , in a sep 0,04) after 40 Gy which was more pronounced after 70 Gy  and a significant reduction of BV values after 40 Gy with a plateau after 70 Gy . MTT and PS values showed nonsignificant modifications.In particular responders presented a significant reduction of BF values , presumably due to a more extensive degree of hypoxia in low-perfused tumour and therefore characterized by low radiosensitivity  and BV (P < 0.004) CTp parameters showed a significant correlation with response to induction chemotherapy evaluated endoscopically.Similarly, in a study of 17 patients, Zima et al.  demonstrP ≤ 0.002) between responders and nonresponders with high BF, BV, and PS and low MTT correlated with a better tumour response, presumably reflecting better tumour oxygenation. The authors concluded their paper highlighting the role of CTp as a noninvasive, inexpensive, and widely accessible diagnostic tool, able to improve the choice of organ preservation treatment regimens in order to maximize the therapeutic efficacy [Bisdas et al.  confirmeefficacy .p  0,015) in nonresponder compared to responders to induction chemotherapy. They found a trend to correlation between baseline tumour BV and high tumor volume reduction assessed by CT [In the paper by Petralia et al.  only based by CT .max, BVmax, and BSmax were significantly different between patients with and without tumour recurrence (P < 0.04). Also, the authors underline the predictive value of PS and MTT. In particular they found a relative risk of recurrence about 14 time higher in patients with lower than the median BSmean values, which is apparently in contrast with the results of other studies demonstrating a significantly shorter disease-free survival in patients with high intratumoral microvessel density [Bisdas et al.  assessed density . Accordi density . On the  density .P ≤ 0.02).The same authors , in a laP = 0.01) and smaller recurrence-free survival (P = 0.03).Furthermore a simultaneous visual evaluation of the BF and the BV parametric maps showed that the presence of a mismatch (>30% of the examined lesion extent) between the colour-encoded maps correlates with shorter life expectance (This approach is based on the rational that a considerable mismatch, more evident in locally advanced tumours, may indicate a heterogeneous pattern of vascularisation, which may lead to a cascade that influences cellular phenotypes and presents with therapy resistance .All the preliminary results of previous studies show that elevated CT perfusion parameters are statistically correlated to a better response to radiotherapy and chemotherapy and prove that tissue oxygenation may also influence the spread of chemotherapy agents and a higher radiosensitivity.BV and BF have clearly emerged as the most significative CTp parameters as they may predict response to radiation therapy and chemotherapy and may help monitor both treatments.PS and MTT parameters are insufficiently predictive of the response compared with BV and BF: only one paper highlighted their achievable effectiveness .It must be also considered that published studies considered different end points and most of them correlated their findings with short-term follow-up.Large-scale studies examining the long-term predictive value of baseline CTp studies in patient treated both with neoadjuvant chemoradiation or chemoradiation with curative intent might help in tailoring the therapy regimen on individual basis. As an instance, the possibility to identify earlier a failed response to induction chemotherapy may help avoid this step during the therapeutic treatment plan.Therefore, a more standardized technique is hopeful in order to achieve reproducible and comparable method across different institutions.Future integrated applications with PET-CT findings or dual-energy CT may enable more understanding of the biologic behaviour of the tumour in vivo, making the CTp one of the potential cornerstone of biologic imaging of HNSCC.


Complications of patellar dislocation include osteochondral injury of the lateral femoral condyle and patella. Most cases of osteochondral injury occur in the anterior region, which is the non-weight-bearing portion of the lateral femoral condyle. We describe two patients with osteochondral injury of the weight-bearing surface of the lateral femoral condyle associated with lateral dislocation of the patella. The patients were 18- and 11-year-old females. Osteochondral injury occurred on the weight-bearing surface distal to the lateral femoral condyle. The presence of a free osteochondral fragment and osteochondral injury of the lateral femoral condyle was confirmed on MRI and reconstruction CT scan. Treatment consisted of osteochondral fragment fixation or microfracture, as well as patellar stabilization. Osteochondral injury was present in the weight-bearing portion of the lateral femoral condyle in both patients, suggesting that the injury was caused by friction between the patella and lateral femoral condyle when the patella was dislocated or reduced at about 90° flexion of the knee joint. These findings indicate that patellar dislocation may occur and osteochondral injury may extend to the weight-bearing portion of the femur even in deep flexion, when the patella is stabilized on the bones of the femoral groove. Many cases of patellar dislocation involve dislocation over the lateral femoral condyle. Serious complications may include osteochondral injury of the lateral femoral condyle and patella . The incAn 18-year-old woman fell during tennis practice and felt pain in her left knee joint. Initial examination showed patella ballottement and positivity on the apprehension test of the patella. Three of five Carter and Wilkinson scores were positive . Plain rAn 11-year-old girl fell while kicking a soccer ball and felt pain in her left knee joint. Initial examination showed patella ballottement and positivity on the apprehension test of the patella. Three Carter and Wilkinson scores were positive. Plain radiography of the knee joint showed avulsed bone between the condyles in the lateral view . EvaluatOsteochondral injury associated with lateral dislocation of the patella is caused in the lateral femoral condyle and patella by excess pressure of collision between the lateral femoral condyle and patella, induced by lateral traction of the patella with contraction of the quadriceps muscle in a knee valgus position. It is difficult to diagnose osteochondral injury by plain radiography alone. The incidence of osteochondral injury associated with patellar dislocation was estimated to be about 5% . AlthougThe patella starts to make contact with the trochlea at 20° flexion of the knee joint, with the contact point shifting toward the distal side of the femoral groove as flexion increases . The patBoth patients exhibited a predisposition towards patellar dislocation, with osteochondral injury occurring in the weight-bearing portion of the lateral femoral condyle upon patellar dislocation. Patellar dislocation may occur even in deep flexion, in which the patella is stabilized by bone, and osteochondral injury may extend to the weight-bearing portion of the femur.


The mode of delivery of trial information is a key determinant of recruitment to randomised controlled trials (RCTs), which can be modified in order to encourage patients to participate. This paper presents the development and initial validation of a simple six-step model to support recruitment.92 recruitment consultations with 60 new patients were recorded and analysed during a pilot RCT comparing surgical and non-surgical interventions for hip impingement. Recordings were analysed using techniques of thematic analysis and focused conversation analysis pioneered in previous studies. Analysis of recordings continued during the full-scale trial.The pilot study was successful, with 70% of patients approached across 9 centres agreeing to take part in the RCT, and the full-scale trial has achieved 75% recruitment in 19 centres. A simple six-step model providing a framework for good recruitment practice was developed at the pilot phase and then validated, and tested in the main trial. . The model enabled recruiters to explain the design and conduct of the RCT and provide reassuring information for patients in the context of consultations very different from routine practice.The six-step model provides a useful framework for recruitment to RCTs. It encourages the implementation of good RCT recruitment practice and provides strategies to support recruiters. The model requires further testing in a wide range of RCTs and clinical contexts.