Proof Of Concept Stage Research Articles

Father Involvement in Early Childhood Care: Insights From a MEL System in a Behavior Change Intervention Among Rural Indian Parents.

Introduction: Fathers' involvement in care and early initiation of cognitive development activities have a positive impact on a child's social-behavioral, cognitive-academic and emotional-psychological development. This research study, conducted in Tamil Nadu in south India (2017–19), employed a Cluster Randomized Trial to test the impact of techno-social innovations in improving the involvement of fathers in child-care on child development outcomes. Qualitative studies were used to inform the trial and provide insights into pathways of change.Objective: This paper discusses the design, implementation and results of the study through the monitoring, evaluation and learning (MEL) framework to provide an understanding of the perceptions among parents and service providers surrounding early child development, the adaptations and learnings through the intervention period, and changes that were brought about through the intervention.Methods: The study was at a Proof of Concept stage, and the primary learning objective was to keep the learning process going through the period of the study, as well as obtain evidence to inform future model development. The measurement for change process in the study occurred in three distinct yet interconnected stages. In the first stage, the program was planned, and the design was refined for both the implementation and evaluation of the project. The next stage was the actual implementation: with a learning loop during the execution of the main intervention. The third stage was intended to reflect on the adaptations and pathways to change through the project period and collate evidence for model refinement.Results and Discussion: The data collected from the formative research was used to design, develop and implement the intervention. Lessons in coordination with the government program not only brought policy visibility, access to secondary data, and enabled field research, but also provided access to a workforce with immense field knowledge and presence in the rural underserved population. In order to continuously inform the implementation process of the intervention, the feedback loops allowed for adaptions to be made at each stage. The findings provide insights for programming early childhood development interventions, especially interventions regarding improving father's involvement in child-care, and ways to leverage evidence in these interventions.

Operationalizing Design Thinking in Business Intelligence and Analytics Projects

ABSTRACTDesign Thinking has been applied successfully in many fields; however, in Information Systems research most early studies focus on applying the specific toolsets to developing product and system designs to solve strategic, managerial, and operational problems. There is little research on how Design Thinking can be embedded in the learning processes in design‐oriented IS research and enabled in the context of business intelligence (BI) and business analytics (BA). How can Design Thinking be embedded in the learning processes and enabled in the context of BI/BA projects in the classroom environment, especially in the proof of concept stage? A practical view on integrating the mindset and toolset of the Design Thinking approach and in the learning process as a case based in‐class experience is presented along with a guideline for coaching the Design Thinking team and the lessons learned from each stage of Design Thinking. The results of this study show that Design Thinking practices can be enlisted to help students frame their creations and that these practices have a valuable contribution as alternatives when designing curricula for teaching and learning.

ASIED: a Bayesian adaptive subgroup-identification enrichment design

ABSTRACT Developing targeted therapies based on patients’ baseline characteristics and genomic profiles such as biomarkers has gained growing interests in recent years. Depending on patients’ clinical characteristics, the expression of specific biomarkers or their combinations, different patient subgroups could respond differently to the same treatment. An ideal design, especially at the proof of concept stage, should search for such subgroups and make dynamic adaptation as the trial goes on. When no prior knowledge is available on whether the treatment works on the all-comer population or only works on the subgroup defined by one biomarker or several biomarkers, it is necessary to incorporate the adaptive estimation of the heterogeneous treatment effect to the decision-making at interim analyses. To address this problem, we propose an Adaptive Subgroup-Identification Enrichment Design, ASIED, to simultaneously search for predictive biomarkers, identify the subgroups with differential treatment effects, and modify study entry criteria at interim analyses when justified. More importantly, we construct robust quantitative decision-making rules for population enrichment when the interim outcomes are heterogeneous in the context of a multilevel target product profile, which defines the minimal and targeted levels of treatment effect. Through extensive simulations, the ASIED is demonstrated to achieve desirable operating characteristics and compare favorably against alternatives.

Geothermal potential of Sedimentary Basins, especially of the Swiss Molasse Basin

Sedimentary basins usually have significant geothermal potential. Deep aquifers are key components. The factors, conditions, and processes that define and control the potential are: processes during basin formation like sedimentation, karstification, fracturing; rock porosity, permeability/fluid content; depth/temperature; hydrogeology; production sustainability. They are demonstrated on selected examples: USA basins, Paris Basin, Molasse Basin. Of the latter, the French, German and Austrian parts are treated first and then the Swiss Molasse Basin (SMB) in more detail.The various efforts undertaken to assess and quantify the SMB potential are described, example maps presented. The realizations of the SMB potential so far are really modest: of 10 deep drilling projects performed in various locations to date only one is successful, two are a partial success. The official Swiss energy strategy EN2050 includes electricity supply in the future; this assigns 4.4 TWh to geothermal sources in 2050. This would be delivered from geothermal power plants, foreseen are 250 MWe installed capacity from hydrothermal reservoirs and another 250 MWe from petrothermal (EGS) sources. Only the SMB could host hydrothermal resources; the current data don’t make much hope. In principle, EGS plants could take heat (and convert it to electricity) from below the SMB. The EGS technology itself has great potential but it is still in the proof of concept stage. Intensive R&D is ongoing in several countries, however, very substantial funding will be needed to answer the many questions still open.

Time stability of carbon nanotube gas sensors

In this communication, we report on the long-term stability of a carbon nanotube (CNT) thin-film based NH3 gas sensor. These sensors were fabricated with a reproducible, large-scale, low-cost spray deposition process and are examined in terms of NH3 sensitivity and long-term stability. The devices are measured directly after fabrication; 1-year and 4-years post fabrication while being stored in ambient conditions without further encapsulation. The retainment of up to 96% of response demonstrates the stability of such CNT-based devices. Hence, it solves a critical issue for stepping beyond the proof of concept stage. Not only can CNT-based gas sensors be utilized for years, but such sensors also do not require any special recalibration over the years.

A Bayesian paradigm for decision-making in proof-of-concept trials

ABSTRACTDecision-making is central to every phase of drug development, and especially at the proof of concept stage where risk and evidence must be weighed carefully, often in the presence of significant uncertainty. The decision to proceed or not to large expensive Phase 3 trials has significant implications to both patients and sponsors alike. Recent experience has shown that Phase 3 failure rates remain high. We present a flexible Bayesian quantitative decision-making paradigm that evaluates evidence relative to achieving a multilevel target product profile. A framework for operating characteristics is provided that allows the drug developer to design a proof–of-concept trial in light of its ability to support decision-making rather than merely achieve statistical significance. Operating characteristics are shown to be superior to traditional p-value-based methods. In addition, discussion related to sample size considerations, application to interim futility analysis and incorporation of prior historical information is evaluated.

Evolving Concepts in Phases I and II Drug Development for Crohn's Disease.

The highest attrition rates during drug development programmes occur at the proof of concept stage. Given the large number of molecules under development for Crohn's disease, a need exists to improve the efficiency of early drug development by fast-tracking promising agents and terminating ineffective ones. Multiple opportunities are available to achieve these goals, including the use of more responsive outcome measures, and the incorporation of sophisticated pharmacokinetic modelling and/or highly specific pharmacodynamic markers into exposure-based dosing regimens and novel trial designs. In this article we review these strategies and propose an integrated paradigm of early drug development in Crohn's disease.

Proteomics goes forensic: Detection and mapping of blood signatures in fingermarks.

A bottom up in situ proteomic method has been developed enabling the mapping of multiple blood signatures on the intact ridges of blood fingermarks by Matrix Assisted Laser Desorption Mass Spectrometry Imaging (MALDI-MSI). This method, at a proof of concept stage, builds upon recently published work demonstrating the opportunity to profile and identify multiple blood signatures in bloodstains via a bottom up proteomic approach. The present protocol addresses the limitation of the previously developed profiling method with respect to destructivity; destructivity should be avoided for evidence such as blood fingermarks, where the ridge detail must be preserved in order to provide the associative link between the biometric information and the events of bloodshed. Using a blood mark reference model, trypsin concentration and spraying conditions have been optimised within the technical constraints of the depositor eventually employed; the application of MALDI-MSI and Ion Mobility MS have enabled the detection, confirmation and visualisation of blood signatures directly onto the ridge pattern. These results are to be considered a first insight into a method eventually informing investigations (and judicial debates) of violent crimes in which the reliable and non-destructive detection and mapping of blood in fingermarks is paramount to reconstruct the events of bloodshed.

Towards Efficient Collaborative Digital Pathology: A Pioneer Initiative Of The FlexMIm Project

Introduction/ Background The development of digital resources for pathologists is a long process before truly validated algorithms can be used in daily practice. Aims In addition to developing new tools for helping Whole Slide Image (WSI) analysis by pathologists, the cooperative research project FlexMIm aims at setting up a shared platform allowing further technological improvements to be tested and evaluated online by a community of pathologists. Methods The FlexMIm consortium includes 27 pathology laboratories in the Paris area (coordinated by Assistance Publique-Hopitaux de Paris), research laboratories from University Pierre et Marie Curie (UPMC Univ Paris 06) and University Paris Diderot, as well as 3 companies: TRIBVN, PERTIMM and Orange (project coordinator). Based on a cloud architecture, the project embeds a dedicated WSI database and visualisation support. Groups of partners developed dedicated algorithms. These algorithms have been tested separately, then integrated into the online platform. A large test and validation protocol, involving operational versions of these algorithms, is on-going among the 27 pathology laboratories participating to this project. Results One algorithm was built for blur detection in WSI in order to improve the quality of the workflow. Other quantitative algorithms were built for immunohistochemical counts such as Ki67, for mitosis detection from H&E (Hematoxylin – Eosin) stained WSI and for supporting the detection of Regions of Interest (ROI) for dysplasia screening in inflammatory bowel diseases (IBD). A series of algorithms (as gland detections in IBD) are at the proof of concept stage. Dedicated semantics and research engine are included in the platform, supporting the ROI collaborative annotations in WSI. The ontology used is generated by an operational contextual graph produced and validated for IBD diagnosis, consolidated by a semantic template linked to the annotations of IBD WSI. Another collaborative tool on the platform allows the online implementation of ontologies, with creation and edition of concepts. A full IBD diagnostic ontology is already available and a prostate cancer diagnostic ontology is underway. A major point of this platform is that all participating pathologists can finally evaluate online all the resources developed during the project. Anonymised WSI uploaded by each pathologist can be annotated by all other pathologists. These WSI can then be analysed by all the algorithms and tools available in the platform. Pathologists can eventually fill evaluation forms that are analyzed by the project steering committee. Beside online resources, another goal of FlexMIm was to implement tools for faster WSI communication through networks especially in low bandwidth environments. The pathologists used a test bed in order to evaluate several compression algorithms on several visualisation devices (laptop, tablets), eventually leading to a “smart transportation” algorithm that can be activated in case of non-optimal network. Within 3 years, FlexMIm partners have thus built a platform which now integrates a whole set of algorithms to foster digital pathology adoption by a large cluster of Pathology laboratories.

Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review.

Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.

Development of a Multi-Centre Clinical Trial Data Archiving and Analysis Platform for Functional Imaging

Purpose: To provide clinicians & researchers participating in multi-centre clinical trials with a central repository for large volume dynamic imaging data as well as a set of tools for providing end-to-end testing and image analysis standards of practice. Methods: There are three main pieces to the data archiving and analysis system; the PACS server, the data analysis computer(s) and the high-speed networks that connect them. Each clinical trial is anonymized using a customizable anonymizer and is stored on a PACS only accessible by AE title access control. The remote analysis station consists of a single virtual machine per trial running on a powerful PC supporting multiple simultaneous instances. Imaging data management and analysis is performed within ClearCanvas Workstation® using custom designed plug-ins for kinetic modelling (The DCE-Tool®), quality assurance (The DCE-QA Tool) and RECIST. Results: A framework has been set up currently serving seven clinical trials spanning five hospitals with three more trials to be added over the next six months. After initial rapid image transfer (+ 2 MB/s), all data analysis is done server side making it robust and rapid. This has provided the ability to perform computationally expensive operations such as voxel-wise kinetic modelling on very large data archives (+20 GB/50k images/patient) remotely with minimal end-user hardware. Conclusions: This system is currently in its proof of concept stage but has been used successfully to send and analyze data from remote hospitals. Next steps will involve scaling up the system with a more powerful PACS and multiple high powered analysis machines as well as adding real-time review capabilities.

Multi-unit sustained vibration loading platform for biological tissues: Design, validation and experimentation

The relationships between mechanical inputs and resulting biological tissue structure, composition, and metabolism are critical to detailing the nuances of tissue mechanobiology in both healthy and injured tissues. Developing a model system to test the mechanobiology of tissues ex-vivo is a complex task, as controlling chemical and mechanical boundary layers in-vitro are difficult to replicate. A novel multi-unit vibration loading platform for intervertebral discs was designed and validated with both independent electronic data and experimental loading of 6 bovine intervertebral discs (IVDs) and an equal number of unloaded controls. Sustained vibration was applied using closed-loop positional control of pushrods within four independent bioreactors with circulating phosphate buffered saline. The bioreactors were designed to be modular with removable components allowing for easy cleaning and replacement. The loading regime was chosen to maximize target mRNA expression as reported in previous research. Aggrecan, decorin, and versican mRNA all reported statistically significant increases above control levels. Biglycan, collagen type I and II showed no significant difference from the control group. Further study is required to determine the resulting effect of increased mRNA expressions on long-term disc health. However these results indicate that this research is past the proof of concept stage, supporting future studies of mechanobiology utilizing this new device. The next stage in developing this novel loading platform should consider modifying the tissue grips to explore the effects of different directional loading on different gene expression, and also loading different types of tissues.

Targeting αvβ3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides

The outstanding physio-pathological role played by integrin receptors in living subjects motivates the enormous interest shown by scientists worldwide for this topic. More than twenty years of research has spanned across the structural and functional elucidation of these proteins and over their antagonism-based biomedical applications. The proof-of concept stage, aimed at identifying potent inhibitors, covered a decade of studies, and paved the way for a more advanced era of research where these antagonist molecules were thrown into the deep end of applicative studies. This review intends to summarize the major efforts conducted thus far and focuses on the design, synthesis and biomedical applications of cyclic RGD-containing alpha(v)beta(3) integrin antagonists, in both their small and macromolecular formats. In particular, Chapters 1 and 2 offer a comprehensive outlook on the rational basis for the design of integrin inhibitors, Chapter 3 chronicles the biological and medical applications of monofunctional RGD integrin ligands both in their monomeric and multimeric asset, and Chapter 4 illustrates the potential of RGD-based multifunctional systems in molecular medicine.

Synthetic neoglycopolymer-recombinant human collagen hybrids as biomimetic crosslinking agents in corneal tissue engineering

Saturated neoglycopolymers, prepared via tandem ROMP-hydrogenation (ROMP = ring-opening metathesis polymerization) of carbohydrate-functionalized norbornenes, are investigated as novel collagen crosslinking agents in corneal tissue engineering. The neoglycopolymers were incorporated into recombinant human collagen type III (RHC III) as collagen crosslinking agents and glycosaminoglycan (GAG) mimics. The purely synthetic nature of these composites is designed to reduce susceptibility to immunological and allergic reactions, and to circumvent the transmission of animal infectious diseases. The collagen-neoglycopolymer biomaterials exhibit higher stability to collagenase-induced biodegradation than the control materials, composites of RHC III crosslinked using EDC/NHS (EDC = 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide; NHS = N-hydroxysuccinimide). Even at this proof of concept stage, the thermal stability, enzymatic resistance, and permeability of the neoglycopolymer hydrogels are comparable or superior to those of these fully optimized control materials, which have successfully been tested clinically. Tensile strength is adequate for transplantation, but lower than that of the optimized control materials.

Coupled FEMDEM/Fluids for coastal engineers with special reference to armour stability and breakage

Sea-level rise and increased storminess present huge challenges to coastal engineers worldwide. The seaward slope of many breakwaters and shoreline defence structures consists of thousands of interlocking units of concrete or rock making up a massive granular defence against wave attack. The units are placed freely to form an armour layer which is intended to both dissipate wave energy and remain structurally stable. Design guidance on the mass and shape of these units is based on empirical equations derived from Froude scale physical model tests. The two main failure modes for concrete armour layers are displacement (hydraulic instability) and breakage (structural instability) which are strongly coupled. Breakage mechanisms cannot all be faithfully reproduced under scaled physical models. Fundamental understanding of the forces governing such wave-structure interaction remains poor and unit breakages continue to baffle the designers of concrete armour units. This paper illustrates a range of DEM and FEMDEM methods being developed to model the granular solid skeleton of freely packed brittle units. Such discrete element methods are increasingly being used by engineers for solids modelling. They are especially powerful when coupled with a CFD model which can resolve ocean wave dynamics. The aim is to describe a framework for coupled modelling technologies applicable to coastal engineering problems. Preliminary simulation test cases, still at proof of concept stage, but based on a wealth of validation studies are presented. Thus, we report a snap-shot of progress towards a future where designers combine multi-physics numerical technology with knowledge from scaled physical models for a better understanding of wave energy turbulence, block movement, and internal stresses within armour units.

Computer screen photo-excited surface plasmon resonance imaging

Angle and spectra resolved surface plasmon resonance (SPR) images of gold and silver thin films with protein deposits is demonstrated using a regular computer screen as light source and a web camera as detector. The screen provides multiple-angle illumination, p-polarized light and controlled spectral radiances to excite surface plasmons in a Kretchmann configuration. A model of the SPR reflectances incorporating the particularities of the source and detector explain the observed signals and the generation of distinctive SPR landscapes is demonstrated. The sensitivity and resolution of the method, determined in air and solution, are 0.145 nm pixel −1, 0.523 nm, 5.13 × 10 −3 RIU degree −1 and 6.014 × 10 −4 RIU, respectively, encouraging results at this proof of concept stage and considering the ubiquity of the instrumentation.

Spray-On Special Effects Mendel Biotechnology Uses Chemical Genetics to Help Plants Cope with Stress

Ceres, Inc. (www.ceres.net), in Thousand Oaks, California, lacks the mythological lawn statues, but is named for the Roman goddess of agriculture. Since 2002, Ceres has been developing corn and soybeans for traits including enhanced yield, stress resistance, and more efficient nitrogen utilization as part of a $137 million license-based agreement with Monsanto. The privately held company engineers energy crops as well. Ceres is also using plants to produce clinically relevant compounds like taxol, artemesinin, and derivatives of opiates.“We are a functional genomics company, and we are engineering metabolic pathways in plants to produce plant-derived drugs more efficiently,” said Dr. Steven Bobzin, director of natural products chemistry. To do this, Ceres identifies the genes that encode biosynthetic enzymes in plants that produce the desired compounds and manipulates them. Ceres is specific in its focus. “We are not proposing to put pharmaceuticals in corn flakes,” Bobzin says, “we are producing small molecules in the biosynthetic pathway.”According to Bobzin, Ceres owes its progress to the advancement in genetic sequencing capacity. He cites the example of taxol, an expensive compound produced from yew. “We can increase the yield significantly…within the plant,” said Bobzin. According to Bobzin, the company has already identified some of the genes involved in the biosynthesis of taxol and is on the way to identifying the rest. Once completed, those genes will be transferred to another plant that will serve as a biosynthetic platform for production of large amounts of material in a more cost-effective way. Other genetically engineered candidates in the pipeline include opiate derivatives that will not cross the blood-brain barrier. Ceres does this by manipulating environmental conditions, as certain stresses improve yield. The company also uses transgenic approaches to express a targeted molecule in all tissues of the plant.But there is still much to discover. “There are going to be cases where these things don't work,” said Glenn Hicks, Ph.D., associate research plant cell biologist, who works in collaboration with Dr. Natasha Raikhel at the Center for Plant Cell Biology (CEPCEB) at the University of California, Riverside. “Evolution being what it is, there are going to be fundamental similarities between all plant species, but when it comes down to it, there are going to be some differences.” According to Hicks, while genes involved in the biosynthesis of specialized metabolites might not translate from Arabidopsis to maize, properties such as stress tolerance or photosynthesis are more fundamental and could equally apply to all plants.Companies like Mendel and Ceres can develop compounds to proof of concept stage, but will partner with a major agricultural company like Monsanto for the resources needed for commercialization, Hicks said, because proof of concept is a small percentage of the total costs of development and commercialization. “The agricultural industry went through this chemical boom in the 70s and 80s where everyone was interested in growth regulators and adding hormones to plants and enhancing yield,” said Hicks. “A lot of it turned out to be a bust.” According to Hicks, now, particularly as biotechnology advances are being implemented in agriculture, “the reality of some of the advances in genomics and automated chemistry is settling in, and although these approaches will not resolve all of our challenges, they are going to result in some great advances.”

Evaluation of reaction variables in the dissolution of serpentine for mineral carbonation

The sequestration of CO 2 through the employment of magnesium silicates, olivine and serpentine, is beyond the proof of concept stage. Serpentine has been chosen as the feedstock mineral due to its abundance and availability. Although the reactivity of olivine is greater than that of serpentine, physical and chemical treatments have been shown to greatly increase the reactivity of serpentine. A sulfuric acid leaching stage has been shown to alleviate the rate limiting step of magnesium removal, thereby accelerating the overall carbonation process. Varying reaction conditions can significantly influence the results for the dissolution process with an extreme reaction environment providing desirable results. However, a more careful assessment of the reaction variables under milder conditions is needed for a better understanding of the reaction processes and potential pathways for high extraction yields under more modest conditions. Accordingly in this work, a statistical design of experiments was conducted to ascertain the effect of acid concentration, particle size and reaction time and temperature on the leaching of magnesium from serpentine using sulfuric acid. Results demonstrated that acid concentration provided primary control on the dissolution via the removal of water, which is closely correlated with the extraction of magnesium from serpentine. Particle comminution to a median size less than 163 μm remained an important consideration in increasing reactivity and liberating magnetite. Single variable experimentation demonstrated dissolution enhancements with increased reaction time and temperature. An increase in magnesium dissolution of 46% and 70%, over a baseline test, occurred for increased reaction time and temperature, respectively.

Alternative approaches to control—Quo vadit?

The increasing prevalence of anthelmintic resistance has provided a spur for research into ‘alternative/novel’ approaches to the control of helminthoses that are intended to reduce our reliance upon using chemoprophylaxis. The different approaches either target the parasite population in the host or on pasture, but the goal of all of them is to restrict host parasite contact to levels which minimise the impact of helminths on host welfare and/or performance. Infrapopulation regulation can be achieved through methods that enhance immunity such as optimised nutrition (immunonutrition), genetic selection and vaccination, or by an ‘anthelmintic’ route using bioactive forages, copper oxide wire particles, or use of targeted selective treatment strategies such as FAMACHA©, which reduce the selection pressure for the development of resistance by maintaining a population in refugia. Suprapopulation control can be achieved through grazing management, or by using predacious fungi such as Duddingtonia flagrans. All of these approaches have been developed beyond the proof of concept stage and some are capable of being employed currently. However, some still require knowledge transfer, or commercialisation before they can be tested and widely applied in the field. All of the different approaches present unique challenges to the researchers engaged in developing them, and in comparison to simple prescriptive anthelmintic treatments, their use appears complex and requires some expertise on behalf of the advisor and/or end user. At present, most of our data are derived from trials using single approaches, but it is apparent that we need to move towards integrating some of these technologies which again represents a further challenge to the extension/advisory services. Progress in establishing different approaches requires not only the funding to support their scientific development but also to support the development of computer based models which can be used to highlight deficiencies in our understanding of the control mechanisms and to identify impediments to their introduction. It is inevitable that some of the approaches currently under investigation will fail to become widely applied for a variety of reasons that are not solely financial. These include issues concerned with practicability/applicability, affordability/appropriateness, availability/deliverability and above all, the failure to provide a consistent, reliable effect when used under commercial farming conditions.

Branched Stent-Grafts for Endovascular Repair of Aortic and Iliac Aneurysms

Endovascular technique, which gains access through indirect transarterial routes and isolates the aneurysm without interrupting flow, has particular advantages in aneurysms of the aortic arch and thoracoabdominal aorta. Yet progress has been slow. The necessary branched stent-grafts face several unique technical challenges. The simplest, most versatile approach involves assembling a modular stent-graft in situ from multiple parts. Techniques vary according to the presence or absence of an overlap zone, or cuff. The first cases of this type, reported over 4 years ago, had axially oriented cuffs. Recent efforts have seen the intercomponent attachment site reduced to a ring of Nitinol around a simple fenestration, with various hybrids of cuffed and fenestrated technique in between. Other advances, such as better sheaths, better covered stents, and commercial manufacture (Cook, Australia), have helped to extend the use of branched stent-grafts to a wider range of users and a wider range of aneurysms. Although their future role remains unclear, all these devices have gone beyond the proof of concept stage, and some, such as the bifurcated component for the endovascular iliac reconstruction, are ready to become standard parts of the endovascular.