bluuebunny/crossref_metadata_2025 huggingface dataset:
PP125 Evidence-based Policy Making – Bottom-Up Heuristic Engagement Process
Authors: Trindade Evelinda , Buehler Anna Maria , Petramale Clarice , D'Albuquerque Luiz Augusto Carneiro , Uip David , Pozzo Lorena
Published: January 2018

INTRODUCTION:

Solid organ and hematopoietic cell transplantation are some of the more expensive procedures universally paid by the public Brazilian Unified Healthcare System (SUS). Transplanted patients depend on maintenance immunosuppression to prevent death or graft loss. A bottom-up heuristic process proposed new immunosuppression drugs for incorporation into the SUS.

METHODS:

Systematic evidence synthesis and Brazilian transplantation registries base-cases, Kaplan-Myer survival and economic assessments were presented in specialized national congresses with open public Delphi sessions to build professional Clinical and Therapeutic Protocols (PCDT) by consensus. Five consensus transplantation PCDTs with a SUS perspective budget impact and sensitivity analysis were submitted to the Health Ministry SUS Technology Incorporation National Commission (CONITEC) plenary for a decision. PCDTs were publicized in CONITEC Internet and Diário Oficial da União, an, official periodic publication, as well as undergoing widespread dissemination through mailings for Public Consultation. Public contributions were added to PCDTs to support Health Ministry policy making.

RESULTS:

The São Paulo State Health Secretariat coordinated the synthesis and economic assessments made by 115 experienced transplantation specialists and health technology evaluators over ten years. Heart, lung, liver, pancreas and hematopoietic cells transplantation PCDTs (with tacrolimus, sirolimus and everolimus alternative immunosuppression) can significantly prevent 27.8 percent, 28.1 percent, 7.2 percent, 11.1 percent and 4.3 percent graft loss or graft versus host disease and death, respectively, for refractory transplantees rescue during the first year post-transplantation, saving healthcare resources. Ten-year follow-up data demonstrated partial benefits were sustained. Analysis demonstrated +USD689,655.17, +USD501,567.40, -USD377,802.51, +USD221.289,42 and +USD50.734,08 budget impact, respectively, resulting in an overall USD1,085,443.55 for 2,146 transplantees. The 5 PCDTs were favorably voted by CONITEC plenary members, 155 public contributions were added by patients and stakeholders, and the Brazilian Health Ministry decided to adopt the SUS reimbursement listing.

CONCLUSIONS:

Democratic participation gave PCDTs real-world basis adjustments, SUS innovation and improved compliance.
PP130 Nudging In Public Health: Accountability For Practical Wisdom
Authors: Stanak Michal
Published: January 2018

INTRODUCTION:

Nudging is the application of behavioural sciences aimed at influencing behaviour in a non-prescriptive way. It is a tool of public health decision makers to produce health gain. Just like decisions in the field of Health Technology Assessment (HTA), nudging decisions are inevitably value laden. The current European Network for HTA (EUnetHTA) approach to evaluate ethical aspects encompasses mainly utilitarian and principlistic approaches. The aim of this project is to incorporate the virtue ethics approach in public health decision-making processes based on the example of nudging.

METHODS:

The narrative analysis of nudging is based on a systematic literature search conducted from 28 October to 13 November 2015 in the following databases: Medline via Ovid, Embase, and TRIP Database. A total of sixty-two articles were listed as relevant as a result of searches and, in addition, twenty-five more articles were found through hand searching.

RESULTS:

Regardless of the potential issues related to nudging (manipulation or coercion), nudging is considered cost-effective and inevitable because of the malleability of human psychology for example, alcoholic drinks served in smaller glasses nudge people to drink less alcohol.

No policy intervention, nudging or HTA, is value neutral and hence it requires an ethical evaluation. It takes traits of character, virtues, to discern which principle to apply in what circumstances and phronesis, practical wisdom, is the key virtue of a decision maker. Phronesis is not a moral judgement deduced from principles, but it is context specific, bottom-up, action orientated, and framed through dialogues. It focuses on the agent, the decision maker, who, via the use public scrutiny, should be held accountable for phronetic decisions made.

CONCLUSIONS:

Nudging is a cost-effective tool that can improve the populations health in a non-prescriptive way. Transparent reporting open to public scrutiny is necessary for the sake of evaluating whether the decisions made were phronetic for it takes traits of character, virtues, to decide between competing moral principles.
PP135 Stakeholder Involvement In A Health Technology Assessment Of Hyperhidrosis
Authors: Wade Ros , Rice Stephen , Moloney Eoin , Stoniute Julija , Layton Alison , Levell Nick , Stansby Gerard , Jones-Diette Julie , Llewellyn Alexis , Wright Kath , Craig Dawn , Woolacott Nerys
Published: January 2018

INTRODUCTION:

Hyperhidrosis is characterized by uncontrollable excessive sweating, which occurs at rest, regardless of temperature. Symptoms can significantly affect quality of life. There is substantial variation in the secondary care treatment of hyperhidrosis and uncertainty regarding optimal patient management. The objective of the Health Technology Assessment (HTA) was to review the evidence and establish the expected value of undertaking additional research into effective interventions for the management of primary hyperhidrosis in secondary care. Capturing the perspectives of patients and clinicians treating hyperhidrosis was an important part of the research.

METHODS:

The assessment included a systematic review and economic model, including value of information analysis. Patients, dermatologists, a vascular surgeon and a specialist nurse (who set up the UK Hyperhidrosis Support Group) provided advice at various stages, including at an end-of-project workshop, to help interpret results and prioritize research recommendations.

RESULTS:

Patient and clinician advisors were unsurprised by the finding that there is evidence of a large effect of botulinum toxin injections on axillary hyperhidrosis symptoms in the short to medium term; there was consensus amongst patients and clinicians that botulinum toxin injections were very effective. The advisors agreed that a trial of botulinum toxin injections (plus anesthetic) versus iontophoresis for palmar hyperhidrosis would be useful. Patients and clinicians were happy with the sequence of treatments identified as being cost effective for axillary hyperhidrosis: iontophoresis, botulinum toxin injections, anticholinergic medication, curettage, endoscopic thoracic sympathectomy. All patients agreed that the Hyperhidrosis Quality of Life index (HidroQoL©) tool was superior to other commonly used tools for assessing quality of life in hyperhidrosis.

CONCLUSIONS:

Patients and clinicians considered the key findings of the systematic review and economic analyses to be appropriate. Advisors advocated a trial of botulinum toxin injections (plus anaesthetic) versus iontophoresis for palmar hyperhidrosis. Patients preferred the HydroQoL® tool over other commonly used quality of life tools in hyperhidrosis research.
PP149 Assessment Of New Medical Devices With Administrative Databases
Authors: Callea Giuditta , Cavallo Maria Caterina , Tarricone Rosanna
Published: January 2018

INTRODUCTION:

Administrative data (for example, hospital discharge databases, HDDs) can be used as a real world source of clinical and economic evidence for assessing new medical devices (MDs), provided that their use can be identified in the data. In absence of updated classification systems for procedures and diagnoses, which allow to identify the use of new technologies in the data, traceability can still be achieved thanks to authorities coding guidelines (that is, indication on how to combine the existing codes for procedures and/or diagnoses when new technologies are used).

In 2009 Italy adopted version 2007 of the International Classification System of Diseases (ICD-9-CM) and version 24 of Diagnosis Related Groups (DRGs), which are still in use. The aim of this work was to investigate the capacity of the classification system currently used in Italy, which is at high risk of obsolescence, to identify innovative MDs.

METHODS:

To achieve our goal, we performed a systematic search of all the national and regional coding guidelines published from 2009 (that is, the year of introduction of the new classification systems) to 2015. We extracted from each document the list of technologies for which the Ministry of Health and/or the Regional Authorities provided with coding indications.

RESULTS:

Our results show that only a few recent technological innovations can be identified in the Italian HDDs. This reduces the possibility for decision makers to measure new technologies outcomes and costs in the real world clinical practice.

CONCLUSIONS:

The traceability of new MDs' can support Heath Technology Assessment (HTA). Indeed, HTA programs should use real world evidence to re-assess MDs 2–3 years after their introduction in clinical practice. The use of routinely collected data, such as HDD, would allow to measure new technologies' “real” effectiveness in “real” world, on “real” patients in “real” hospitals to complement the evidence from Randomized Controlled Trials.
VP02 Are Journal Editors A Barrier To Publication Of Real World Evidence?
Authors: Oehrlein Elisabeth , Graff Jennifer , Perfetto Eleanor , Mullins C. Daniel , Dubois Robert , Anyanwu Chinenye , Onukwugha Ebere
Published: January 2018

INTRODUCTION:

Health technology assessment (HTA) bodies often rely heavily upon evidence from peer-review publications to inform their recommendations. Since journal editors attitudes likely influence the types of study designs that are accepted through the peer-review process and on to publication, journal editors serve as gatekeepers to translation of evidence, including real word evidence (RWE), into practice. Given past skepticism of RWE study designs, journal editors perceptions of and possible biases toward RWE are important to understand as they may impact dissemination and, therefore, uptake of research findings. The objective of this study was to examine current views of journal editors regarding the: (i) value of RWE studies and (ii) challenges editors face in managing, reviewing, and publishing RWE manuscripts.

METHODS:

Journal editors representing general medicine (GM), specialty medicine (SM), health policy/services research (HSR) were invited to participate in a telephone interview, a survey, and an in-person, roundtable discussion.

RESULTS:

In total, seventy-nine journals were approached, resulting in: 15 interviews (GM = 2; SM = 5; HSR = 8), 17 survey responses (GM = 2; SM = 6; HSR = 9) and 8 roundtable participants. RWE was viewed favorably by interviewed editors (n = 15). Characteristics of high-quality RWE manuscripts included: research question novelty/relevance, rigorous methodology, alignment of data with question, and the extent data-source advantages are optimized. Similar manuscript review processes and challenges were voiced for RWE and other study designs. HSR editors were more likely than SM or GM editors to participate, potentially indicating these researchers are more comfortable or interested in RWE. A possible study limitation was that editors favorable toward RWE may have been more likley to participate.

CONCLUSIONS:

Peer-review journal editors appear to have favorable views regarding RWE studies and can be accelerators to dissemination of RWE findings. However, they do report that studies and processes could be improved. One suggested improvement included a checklist for editors to speed rejections and improve communications with authors.
VP67 The Value Of The European Network For Health Technology Assessment (EUnetHTA) Outputs For National Health Technology Assessment: The French Experience
Authors: Guzina Irena , Meyer François
Published: January 2018

INTRODUCTION:

The French National Authority for Health (HAS) has participated in the work of the European Network for Health Technology Assessment (EUnetHTA) since its creation in 2006. HAS has been an active partner in most EUnetHTA activities, and the lead partner of specific work packages.

METHODS:

This report presents a summary of the main contribution of HAS to the two latest EUnetHTA projects (Joint Action (JA) 1 and Joint Action 2 (JA2)), their impact on national production, and Health Technology Assessment (HTA) doers feedback as to the opportunities and challenges of participating to the network and using its outputs.

RESULTS:

In JA 1 and JA 2 projects, HAS has: coordinated activities related to Early Dialogues and Additional Evidence Generation; coordinated the development of nine JA1 methodological guidelines for rapid relative effectiveness assessment (REA) of pharmaceuticals; participated in the production of two JA2 methodological guidelines; participated in the production of one JA1 and seven JA2 rapid REA reports, and two JA2 full HTAs.

The national uptake of EUnetHTA outputs included entire adoptation of one REA report and adaptation of another. EUnetHTA templates and methodological guidelines have been taken into account when updating or developing national ones. Thanks to the network, HAS HTA doers could exchange on ongoing assessments with European colleagues, have enhanced their methodological know-how and enlarged their professional network.

As for the challenges encountered, it turned out that the re-use of EUnetHTA reports for a technology of interest to HAS was not always possible, mainly due to discordances in deadlines or assessment questions between EUnetHTA and national productions.

CONCLUSIONS:

HAS has actively participated in different EUnetHTA projects since the network's creation. This collaboration has enabled HAS HTA doers, among others, to optimize national assessments and enhance their methodological know-how.
VP76 European Collaboration In Health Technology Assessment – Experiences And Possible Benefits
Authors: Mayer Julia , Ettinger Sabine , Nachtnebel Anna
Published: January 2018

INTRODUCTION:

Consistently high-quality health care is expected throughout Europe while concurrently, financial resources of member states are decreasing. National Health Technology Assessment (HTA) institutes are informing evidence-based reimbursement decisions in the national context, leading to redundancies in HTA production and tying up limited resources. Since 2006, the European Union project, the European Network for HTA (EUnetHTA) is aiming at enhancing the efficient use of HTA resources and facilitating transnational collaboration. Our aim is to present previous experience in joint assessment of medical devices. Furthermore, possible benefits of European collaboration for stakeholders will be discussed.

METHODS:

Processes and challenges of the completed EUnetHTA Joint Action (JA) 2 are summarized and discussed. Benefits, aims and opportunities of the ongoing EUnetHTA JA 3 are described.

RESULTS:

Six rapid assessments of medical devices, focusing on the assessment of effectiveness and safety, were published during EUnetHTA JA 2. Challenges in European medical device assessment encompass the choice of topics, the time point of assessments and the lack of European standards for systematic patient involvement. Characteristics of medical devices, like learning curves, call for monitoring them throughout their lifecycle.

The benefit of European collaboration for stakeholders is manifold: uncertainty with regard to actual added value of a technology is minimized through Early Dialogues; harmonized and transparent assessment processes increase the quality of reports; work division among HTA organizations allows a resource-efficient assessment of a bigger amount of technologies; patient involvement ensures consideration of patient relevant endpoints.

The importance of cross-border collaboration in HTA is shown in the continuation of the EUnetHTA project, which aims to sustainably strengthen international collaboration even after expiration of EU-funding.

CONCLUSIONS:

European collaboration in medical device assessment can ensure cross-border health care and efficient cooperation of national health systems. The focus should be set on a wide implementation of jointly established methods and quality standards. The European collaboration can lead to a concrete benefit for various stakeholders.
VP83 How To Identify Technologies Eligible For Health Technology Assessment: A Bottom-Up Approach
Authors: Maltoni Susanna , Camerlingo Maria Domenica , Negro Antonella , Palestini Luigi , Ragazzi Giovanni , Trimaglio Fabio
Published: January 2018

INTRODUCTION:

Governance of health technologies in Emilia-Romagna region, Italy, includes a local and a regional level. Medical devices (MDs) are requested by clinicians to hospital committees that may carry out an evaluation at local level or ask for a regional evaluation using Health Technology Assessment (HTA) methodology. Until the past year, committees weren't provided with a clear pathway to identify technologies for regional HTA evaluation. The aim of this study was to describe a bottom-up, shared approach to produce a tool with elements to be considered when judging if a technology is eligible for regional HTA or not.

METHODS:

To identify elements, we adopted a qualitative approach and the methodology of focus group (1,2) which consisted in starting from health professionals experience to build a shared knowledge. Two panels of stakeholders were convened, the first one comprising regional decision-makers deciding whether to reimburse and introduce a MD in Regional Health System; the second panel comprised regional clinicians that use, test and ask for MDs. Panels were asked to capture possible elements of MDs that should be considered for identifying the most promising and interesting ones for a regional HTA.

RESULTS:

The two panels (seventeen regional clinicians and twenty-two decision makers, respectively) had two operative meetings and worked in parallel. At the end of the second meeting, a draft of the tool with elements identified by both groups was built. Panels were asked to test the draft on few medical devices and identify possible tool's criticalities limiting transferability. Tool resulted user-friendly and complete, requiring no changes. The final version, approved by two panels convened together during the last meeting, reports thirty-two distinct items referred to five domains (that is, potential: innovativeness, clinical, economic, and organizational impact, environmental factors). Each item must be valued on a Likert scale. The tool will be applied on every MD requested by regional clinicians and before implementation it will be tested during a 6-month pilot phase beginning March 2017.

CONCLUSIONS:

The process was plain and feedback from stakeholders has been positive. The tool is expected to increase transparency and homogeneity in identifying technologies eligible for regional HTA.
VP89 Assessing mHealth: Proposal Of A New Framework
Authors: Puig Elisa Puigdomenech , Gómez Santiago , Carrión Carme , Almazan Cari , Espallargues Mireia
Published: January 2018

INTRODUCTION:

The use of health apps is rapidly increasing. They intend to promote health or to treat diseases; in some cases, substituting medical duties. No specific frameworks to assess mHealth solutions in a broad scope and in a comprehensive way have been identified. We aim to propose a framework for mHealth assessment.

METHODS:

The framework development was based on:

•

Literature review to identify existing assessment models including the evaluation of health effects

•

Exploratory analysis with experts and user group discussions

•

Definition of the assessment model, following the domains of health technology assessment.

RESULTS:

Existing frameworks are mainly focused on certification criteria. Professionals and users agreed on the need to undertake mHealth assessments as to better inform user decisions. Assessments should be sensible to continuous changes of these technologies and be undertaken by independent organizations.

The proposed framework offers a step-by-step process by which any mHealth solution can be categorized and analyzed, according to: (i) Risk classification matrix: combining intervention type and patient type, (ii) Users: patients, professionals, informal caregivers individually or all of these together and (iii) Integration: stand-alone, fully integrated.

The model has four evaluation domains: technical maturity, risks, benefits and resources needed, including the commonly accepted evaluation perspectives: technical, contents, clinical/health, user perspective, organizational and socio-economic. Sub-domains are defined as: end-user, organization, healthcare system and community (society as a whole). Aspects to be assessed are selected according to the purpose of the evaluation (intended use / intended impact) and vary depending on the type of the mHealth solution: product or service.

CONCLUSIONS:

The mHealth assessment process is needed and should be: (i) continuous/iterative, providing timely conclusions and recommendations for improvement, (ii) inclusive/collaborative, involving all stakeholders,and (iii) constantly adapting to standards. The proposed framework is intended to support informed decisions when developing, integrating, selecting, recommending, or adopting mHealth solutions.
VP108 Environmental Sustainability In Hospitals Health Technology Assessment - A Survey
Authors: Tal Orna , Tal Shy-Lee , Azenkot Asaf , Mazuz Maya , Tzur Shirley
Published: January 2018

INTRODUCTION:

In the age of limited resources, hospital managers confront the need to strictly balance resource allocation at their disposal between drugs, wages, purchases and operation costs. This entails an endless search for creative pathways to efficiently merge the trends to preserve the environment.

A “green” hospital is an entity that is planned, built and operated so as to minimize the ‘ecological footprint’: for example, saving energy by utilizing natural light; recycling water, paper or waste; and using insulation and soundproofing (1).

‘Evidence-based environmental design’, a new approach to advanced building techniques, is gaining momentum worldwide. It synergizes with additional trends: promoting quality, improving potential utility, raising the accountability of hospital workers and involving the public and patients in overcoming health system dilemmas.

The aim was to analyze the standpoints of professionals in health and architecture regarding environmental accountability, in comparison to public opinion, and enhance the dialogue between these three groups to create wise decision making toward improvements in the health system.

METHODS:

A structured questionnaire was prepared to examine environmental responsibility, focusing on hospital contours. The questionnaire was distributed among three groups to be completed anonymously: hospital employees (physicians and medical managers), professionals from the field of architecture and the general public. The distribution was via the internet and to the general public through a social network using the “snowball” mechanism.

RESULTS:

Distribution of the survey raised debates on the subject. We compared the views of 178 respondents (80 healthcare professionals, 47 from the field of architecture and 51 from the general public). Demographic and other criteria included age, gender, profession, priority setting, concepts of environmental responsibility and social values. Physicians prioritized economic factors as the main barrier (more than architects or the general public) and marked internal incentives as key factors. Environmental responsibility correlated with high quality of care and service among healthcare workers.

CONCLUSIONS:

Logistics and physical infrastructure interventions can enhance economic effectiveness. Moreso, they can initiate social and environmental responsibility and increase the level of confidentiality regarding the accountability of their managers towards quality-targeted work surroundings.
VP132 Cost Effectiveness Of A Predictive Risk Model In Primary Care
Authors: Snooks Helen , Porter Alison , Kingston Mark , Evans Bridie , Burge-Jones Deborah , Davies Jan , Hutchings Hayley , Watkins Alan , Whitman Shirley , Sewell Bernadette , Bailey-Jones Kerry , Dale Jeremy , Fitzsimmons Deborah , Harrison Jane , Heaven Martin , John Gareth , Lewis Leo , Philips Ceri , Williams Victoria , Warm Daniel , Russell Ian
Published: January 2018

INTRODUCTION:

Emergency admissions to hospital are a major financial burden on health services. In one area of the United Kingdom (UK), we evaluated a predictive risk stratification tool (PRISM) designed to support primary care practitioners to identify and manage patients at high risk of admission. We assessed the costs of implementing PRISM and its impact on health services costs. At the same time as the study, but independent of it, an incentive payment (‘QOF’) was introduced to encourage primary care practitioners to identify high risk patients and manage their care.

METHODS:

We conducted a randomized stepped wedge trial in thirty-two practices, with cluster-defined control and intervention phases, and participant-level anonymized linked outcomes. We analysed routine linked data on patient outcomes for 18 months (February 2013 – September 2014). We assigned standard unit costs in pound sterling to the resources utilized by each patient. Cost differences between the two study phases were used in conjunction with differences in the primary outcome (emergency admissions) to undertake a cost-effectiveness analysis.

RESULTS:

We included outcomes for 230,099 registered patients. We estimated a PRISM implementation cost of GBP0.12 per patient per year.

Costs of emergency department attendances, outpatient visits, emergency and elective admissions to hospital, and general practice activity were higher per patient per year in the intervention phase than control phase (adjusted δ = GBP76, 95 percent Confidence Interval, CI GBP46, GBP106), an effect that was consistent and generally increased with risk level.

CONCLUSIONS:

Despite low reported use of PRISM, it was associated with increased healthcare expenditure. This effect was unexpected and in the opposite direction to that intended. We cannot disentangle the effects of introducing the PRISM tool from those of imposing the QOF targets; however, since across the UK predictive risk stratification tools for emergency admissions have been introduced alongside incentives to focus on patients at risk, we believe that our findings are generalizable.
VP146 A Comparative Assessment Of 3D/2D Laparoscopic Display Systems
Authors: Andellini Martina , Faggiano Francesco , Sabusco Francesca , Derrico Pietro , Ritrovato Matteo
Published: January 2018

INTRODUCTION:

The purpose of the study was to gather evidence on safety and overall effectiveness of performing laparoscopic surgery by using 3D versus 2D display systems in a variety of pediatric surgical procedures in order to efficiently support the final investment decision on the video system to be acquired.

METHODS:

A new methodology, that is, Decision-oriented HTA (DoHTA) (1) was applied to assess the technology on clinical, technical, organizational, economic, social, ethical and safety domains. A decision-tree covering all the relevant assessment aspects of 3D systems has been derived and weighted following the Analytic Hierarchy Process. Afterwards, another pairwise comparison list was set up to compare both alternative technologies with respect to every lowest indicator.

RESULTS:

DoHTA results of the 3D system has mainly forecast its impact on clinical efficacy and productivity within the specific context of use. The 3D system is particularly suitable in reducing the mean error rate, thanks to the stereoscopic depth cues which are lost in 2D vision (2,3) From the technical perspective, the analyses have indicated the reduction in median instrument path length, an enhancement of median motion smoothness, and the decrease in grasper frequency with the 3D display. However, the comparative cost analysis has pointed out that the 3D procedure cost was higher that its comparator.

CONCLUSIONS:

The assessment of the 3D visual system seems to reasonably satisfy the criteria of feasibility, clinical effectiveness and safety. However, the adoption of the 3D display system in surgical practice could involve increased hospital costs, mainly because of the initial cost of the technology. Indeed, based on the appreciation of the results of DoHTA, especially taking into account the positive technical and clinical features, we conclude that the 3D system may be a good alternative to the 2D system.
VP197 Sustainable Production Of Rapid Health Technology Assessments And Clinical Guidelines
Authors: Macpherson Karen , Thompson Lorna , Myles Susan
Published: January 2018

INTRODUCTION:

With increasing resource pressures on health systems, rapid developments in innovative technologies and limited numbers of skilled assessors, there is a need to establish sustainable methods to provide advice on healthcare technologies for decision makers. The European Network for Health Technology Assessment (EUnetHTA) has been testing an approach of collaborative production of rapid Health Technology Assessments (HTAs) and adaptation of these locally. The Scottish Health Technologies Group (SHTG) participated in two collaborative and adaptation projects to test whether this could save time and resource, whilst providing a product as robust and relevant as if developed locally. Concurrently the Scottish Intercollegiate Guidelines Network (SIGN) has been exploring ways to develop clinical guidelines more efficiently, including the use of rapid HTAs to inform recommendations.

METHODS:

Having established the relevance of the topics to NHS Scotland, SHTG participated as peer reviewers for EUnetHTA reviews on mitral valve repair and mechanical thrombectomy. On completion, SHTG summarized their content to fit with the well-accepted rapid review report format used in Scotland. Content was supplemented with a review of economic evidence, currently not included in the European reports, local epidemiological information and recently published studies. The thrombectomy report and associated Advice Statement were used by a small expert group to update a SIGN clinical guideline recommendation.

RESULTS:

Providing advice through adaptation proved feasible and acceptable to stakeholders. Limited time was saved because of the supplementary work undertaken, and lessons have been learned about what should and should not be done in future .The guideline recommendation was updated and made available more quickly than similar previous updates.

CONCLUSIONS:

Further such collaborations and adaptations will be pursued as this appears to be a sustainable approach for the future. The process could be aided by EUnetHTA publishing forward work plans and also by the inclusion of economic information, with details of the decision-making context provided, to allow assessment of its relevance locally.
Leave EPA Now or Wait It Out? That’s the Question Staffers Face
Authors: Showstack Randy
Published: January 2018

In interviews, some former Environmental Protection Agency workers, most of whom left the agency in 2017, discuss their careers and efforts to help colleagues find jobs and to preserve EPA’s strengths.
Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures
Authors: Miranda André M. , Lasiecka Zofia M. , Xu Yimeng , Neufeld Jessi , Shahriar Sanjid , Simoes Sabrina , Chan Robin B. , Oliveira Tiago Gil , Small Scott A. , Di Paolo Gilbert
Published: January 2018

Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders.
Crystal structure of an assembly intermediate of respiratory Complex II
Authors: Sharma Pankaj , Maklashina Elena , Cecchini Gary , Iverson T. M.
Published: January 2018

Flavin is covalently attached to the protein scaffold in ~10% of flavoenzymes. However, the mechanism of covalent modification is unclear, due in part to challenges in stabilizing assembly intermediates. Here, we capture the structure of an assembly intermediate of the Escherichiacoli Complex II (quinol:fumarate reductase (FrdABCD)). The structure contains the E. coli FrdA subunit bound to covalent FAD and crosslinked with its assembly factor, SdhE. The structure contains two global conformational changes as compared to prior structures of the mature protein: the rotation of a domain within the FrdA subunit, and the destabilization of two large loops of the FrdA subunit, which may create a tunnel to the active site. We infer a mechanism for covalent flavinylation. As supported by spectroscopic and kinetic analyses, we suggest that SdhE shifts the conformational equilibrium of the FrdA active site to disfavor succinate/fumarate interconversion and enhance covalent flavinylation.
Myelination of Purkinje axons is critical for resilient synaptic transmission in the deep cerebellar nucleus
Authors: Barron Tara , Saifetiarova Julia , Bhat Manzoor A. , Kim Jun Hee
Published: January 2018

The roles of myelin in maintaining axonal integrity and action potential (AP) propagation are well established, but its role in synapse maintenance and neurotransmission remains largely understudied. Here, we investigated how Purkinje axon myelination regulates synaptic transmission in the Purkinje to deep cerebellar nuclei (DCN) synapses using the Long Evans Shaker (LES) rat, which lacks compact myelin and thus displays severe locomotion deficits. DCN neurons fired spontaneous action potentials (APs), whose frequencies were dependent on the extent of myelin. In the LES cerebellum with severe myelin deficiency, DCN neurons were hyper-excitable, exhibiting spontaneous AP firing at a much higher frequency compared to those from wild type (LE) and heterozygote (LEHet) rats. The hyper-excitability in LES DCN neurons resulted from reduced inhibitory GABAergic inputs from Purkinje cells to DCN neurons. Corresponding with functional alterations including failures of AP propagation, electron microscopic analysis revealed anatomically fewer active zones at the presynaptic terminals of Purkinje cells in both LEHet and LES rats. Taken together, these studies suggest that proper axonal myelination critically regulates presynaptic terminal structure and function and directly impacts synaptic transmission in the Purkinje cell-DCN cell synapse in the cerebellum.
Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers
Authors: Morimoto Nobuyuki , Takei Riho , Wakamura Masaru , Oishi Yoshifumi , Nakayama Masafumi , Suzuki Makoto , Yamamoto Masaya , Winnik Françoise M.
Published: January 2018

Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but little is known on how to enhance their effectiveness through structural properties of polymeric carriers. To address this issue, we prepared 8 copolymers of 3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate and poly(ethyleneglycol) methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 < M
n
 < 74.0 kg/mol) with two different endgroups. We labeled them with Rho groups attached along the chain or on one of the two endgroups (α or ω). From studies by flow cytometry and confocal fluorescence microscopy of the copolymers internalization in HeLa cells in the absence and presence of pharmacological inhibitors, we established that the polymers cross the cell membrane foremost by translocation and also by endocytosis, primarily clathrin-dependent endocytosis. The most effective mitochondrial entry was achieved by copolymers of M
n
 < 30.0 kg/mol, lightly grafted with PEG chains (< 5 mol %) labeled with Rho in the ω-position. Our findings may be generalized to the uptake and mitochondrial targeting of prodrugs and imaging agents with a similar polymeric scaffold.
Nucleation and Ostwald Growth of Particles in Fe-O-Al-Ca Melt
Authors: Wang Linzhu , Li Junqi , Yang Shufeng , Chen Chaoyi , Jin Huixin , Li Xiang
Published: January 2018

Tremendous focus has been put on the control of particle size distribution which effects the grain structure and mechanical properties of resulting metallic materials, and thus nucleation and growth of particles in solution should be clarified. This study uses classical nucleation theory and Ostwald ripening theory to probe the relationship between the compositions of Fe-O-Al-Ca melts and the behavior of particles under the condition of no external stirring. Our experimental data suggest that decreasing the initial Ca addition and Al addition is conductive to the increase of nucleation rate for calcium aluminate particles, which exhibits a same change trend with that predicted from classical nucleation theory. Based on the experimental evidence for particles size distribution in three-dimensional, we demonstrate that Ostwald ripening is the predominate mechanism on the coarsening of particles in Fe-O-Al-Ca melt at early stage of deoxidation under the condition of no external stirring but not at later stage.
Near infrared harvesting dye-sensitized solar cells enabled by rare-earth upconversion materials
Authors: Li Deyang , Ågren Hans , Chen Guanying
Published: January 2018

Dye-sensitized solar cells (DSSCs) have been deemed as promising alternatives to silicon solar cells for the conversion of clean sunlight energy into electricity.
Concentration dependent supramolecular interconversions of triptycene-based cubic, prismatic, and tetrahedral structures
Authors: Chakraborty Sourav , Endres Kevin J. , Bera Ranajit , Wojtas Lukasz , Moorefield Charles N. , Saunders Mary Jane , Das Neeladri , Wesdemiotis Chrys , Newkome George R.
Published: January 2018

New insight into the molecular fission–fusion process is obtained with the characterization of a stable intermediate prismatic cage.
Potential- and concentration-dependent self-assembly structures at solid/liquid interfaces
Authors: Cai Zhen-Feng , Yan Hui-Juan , Wang Dong , Wan Li-Jun
Published: January 2018

We report the potential and concentration controlled assembly of an alkyl-substituted benzo[1,2-b:4,5-b′]dithiophene (DDBDT) on an Au(111) electrode byin situelectrochemical scanning tunneling microscopy (ECSTM).
A new mechanism for internal nucleophilic substitution reactions
Authors: Aurell María J. , González-Cardenete Miguel A. , Zaragozá Ramón J.
Published: January 2018

A new mechanism, through two transition structures, is postulated for internal nucleophilic substitution reactions (SNi).
On the capacity of a class of K‐user Gaussian broadcast channel with states known at the transmitter
Authors: Ghabeli Leila
Published: January 2018

This studies the capacity of a class of K‐user Gaussian broadcast channels with additive i.i.d. Gaussian state sequences which are non‐causally known at the transmitter (GBC‐SKT). The transmitter wishes to reliably communicate both a common and a private message to each receiver, thus attempting to simultaneously pre‐code the common message against different states presented in channel outputs. The authors first derive the approximate capacity for the 2‐user GBC‐SKT to within 1.25  bits per channel use (bpcu) for all channel parameters and state variances. Then they extended the result to derive the approximate capacity for a class of K‐user GBC‐SKT to within 1.5 bpcu. In the capacity‐approaching strategy, the channel input is obtained as the superposition of two codewords: a bottom codeword treating the channel state as noise and a top codeword pre‐coded against the channel state at each user for a portion of the transmission block length or power. For the outer bound, they use the fact that the capacity should be decreasing in state variance in order to get to the tighter outer bound for high values of state variances.
Vertex‐level three‐dimensional shape deformability measurement based on line segment advection
Authors: Li Yuelong , Hancock Edwin R. , Xiao Zhitao , Geng Lei , Wu Jun , Zhang Fang , Li Chunqing
Published: January 2018

Measuring the intrinsic deformability of arbitrary small‐scale subdivision of a shape is an interesting meanwhile valuable research topic. Such measurement can be directly utilised as a reliable criteria to partition shape into small components and then assist in shape modelling and description. Compared to global modelling, through constructing subdivision‐based complex shape description, the accuracy and flexibility of shape representation can be significantly improved. In this study, the authors propose a line segment advection (LSA)‐based vertex‐level three‐dimensional shape deformability measuring method. It can highlight the deformability characteristics of each shape part in any scale and size. The measurement is realised mainly based on the advection of line segments connecting neighbouring shape mesh vertices. For 3D shapes, since the line segment of triangular mesh facet directly reflects the minimal neighbourhood relationships and mesh microstructure, its advection can capture the finest details of shape deformability. Then, after transferring that information into neighbouring vertices, a vertex‐level shape deformability measurement can be acquired. Besides, to demonstrate the value of the proposed measuring method to shape partitioning and piecewise shape modelling, a straightforward shape partitioning method is introduced as well. Extensive experiments on three publicly available databases are conducted to verify the effectiveness of proposed methods.
New class of frequency selective surface based on non‐resonant elements with high stability
Authors: Taghizadeh Mahdi , Maddahali Mohsen
Published: January 2018

The authors designed and fabricated a new frequency selective surface (FSS) based on non‐resonant elements. Unlike other FSSs, which use aperture element this one utilises patch element to achieve band‐pass response. Simulation shows that the new FSS has a large bandwidth and a stable response regarding to the change of incident angle.
DZ Chamaeleontis: a bona fide photoevaporating disc
Authors: Canovas H. , Montesinos B. , Schreiber M. R. , Cieza L. A. , Eiroa C. , Meeus G. , de Boer J. , Ménard F. , Wahhaj Z. , Riviere-Marichalar P. , Olofsson J. , Garufi A. , Rebollido I. , van Holstein R. G. , Caceres C. , Hardy A. , Villaver E.
Published: January 2018

Context. DZ Cha is a weak-lined T Tauri star (WTTS) surrounded by a bright protoplanetary disc with evidence of inner disc clearing. Its narrow Hα line and infrared spectral energy distribution suggest that DZ Cha may be a photoevaporating disc.

Aims. We aim to analyse the DZ Cha star + disc system to identify the mechanism driving the evolution of this object.

Methods. We have analysed three epochs of high resolution optical spectroscopy, photometry from the UV up to the sub-mm regime, infrared spectroscopy, and J-band imaging polarimetry observations of DZ Cha.

Results. Combining our analysis with previous studies we find no signatures of accretion in the Hα line profile in nine epochs covering a time baseline of ~20 yr. The optical spectra are dominated by chromospheric emission lines, but they also show emission from the forbidden lines [SII] 4068 and [OI] 6300Å that indicate a disc outflow. The polarized images reveal a dust depleted cavity of ~7 au in radius and two spiral-like features, and we derive a disc dust mass limit of Mdust< 3 MEarth from the sub-mm photometry. No stellar (M⋆> 80 MJup) companions are detected down to 0.̋07 (~8 au, projected).

Conclusions. The negligible accretion rate, small cavity, and forbidden line emission strongly suggests that DZ Cha is currently at the initial stages of disc clearing by photoevaporation. At this point the inner disc has drained and the inner wall of the truncated outer disc is directly exposed to the stellar radiation. We argue that other mechanisms like planet formation or binarity cannot explain the observed properties of DZ Cha. The scarcity of objects like this one is in line with the dispersal timescale (≲105 yr) predicted by this theory. DZ Cha is therefore an ideal target to study the initial stages of photoevaporation.
The Caviar software package for the astrometric reduction of Cassini ISS images: description and examples
Authors: Cooper N. J. , Lainey V. , Meunier L.-E. , Murray C. D. , Zhang Q.-F. , Baillie K. , Evans M. W. , Thuillot W. , Vienne A.
Published: January 2018

Aims. Caviar is a software package designed for the astrometric measurement of natural satellite positions in images taken using the Imaging Science Subsystem (ISS) of the Cassini spacecraft. Aspects of the structure, functionality, and use of the software are described, and examples are provided. The integrity of the software is demonstrated by generating new measurements of the positions of selected major satellites of Saturn, 2013–2016, along with their observed minus computed (O−C) residuals relative to published ephemerides.

Methods. Satellite positions were estimated by fitting a model to the imaged limbs of the target satellites. Corrections to the nominal spacecraft pointing were computed using background star positions based on the UCAC5 and Tycho2 star catalogues. UCAC5 is currently used in preference to Gaia-DR1 because of the availability of proper motion information in UCAC5.

Results. The Caviar package is available for free download. A total of 256 new astrometric observations of the Saturnian moons Mimas (44), Tethys (58), Dione (55), Rhea (33), Iapetus (63), and Hyperion (3) have been made, in addition to opportunistic detections of Pandora (20), Enceladus (4), Janus (2), and Helene (5), giving an overall total of 287 new detections. Mean observed-minus-computed residuals for the main moons relative to the JPL SAT375 ephemeris were − 0.66 ± 1.30 pixels in the line direction and 0.05 ± 1.47 pixels in the sample direction. Mean residuals relative to the IMCCE NOE-6-2015-MAIN-coorb2 ephemeris were −0.34 ± 0.91 pixels in the line direction and 0.15 ± 1.65 pixels in the sample direction. The reduced astrometric data are provided in the form of satellite positions for each image. The reference star positions are included in order to allow reprocessing at some later date using improved star catalogues, such as later releases of Gaia, without the need to re-estimate the imaged star positions.