Public health guidelines for physical activity during pregnancy from around the world: a scoping review.

BACKGROUND AND OBJECTIVE: Despite the known health benefits of physical activity (PA), pregnancy is a time of marked decline in PA levels. To provide women with reliable and trustworthy information, and to encourage greater participation in PA during pregnancy, many governments have developed guidelines for PA during pregnancy. Our aim was to synthesise the most recent public health guidelines on PA during pregnancy from different countries in order to understand the nature and extent of advice that is available. DESIGN: Scoping review. DATA SOURCES: Search of the grey literature, direct contact with international experts, screening of relevant academic literature and citation searching. ELIGIBILITY CRITERIA: Public health guidelines developed or endorsed by government departments published since 2010. RESULTS: Our search located 30 eligible guidelines, published in 11 different languages. There is remarkable concordance in the advice offered. For women with uncomplicated pregnancy, guidelines recommend: 150-300 min/week of moderate intensity aerobic activity; pelvic floor and muscle strengthening exercises; modification of some exercises (eg, supine position); and provide lists of warning signs to cease activity (eg, persistent dizziness, vaginal bleeding) and activities that should be avoided (eg, if high risk of falling/collision). Few guidelines offer specific advice for highly active women (eg, athletes), or trimester-specific or culturally specific considerations. CONCLUSIONS: This review provides a summary of public health recommendations for PA during pregnancy around the world. The challenge is now to ensure that all who provide healthcare for women understand the guidelines and encourage safe participation in PA during pregnancy.

BioReader: a text mining tool for performing classification of biomedical literature.

BACKGROUND: Scientific data and research results are being published at an unprecedented rate. Many database curators and researchers utilize data and information from the primary literature to populate databases, form hypotheses, or as the basis for analyses or validation of results. These efforts largely rely on manual literature surveys for collection of these data, and while querying the vast amounts of literature using keywords is enabled by repositories such as PubMed, filtering relevant articles from such query results can be a non-trivial and highly time consuming task. RESULTS: We here present a tool that enables users to perform classification of scientific literature by text mining-based classification of article abstracts. BioReader (Biomedical Research Article Distiller) is trained by uploading article corpora for two training categories - e.g. one positive and one negative for content of interest - as well as one corpus of abstracts to be classified and/or a search string to query PubMed for articles. The corpora are submitted as lists of PubMed IDs and the abstracts are automatically downloaded from PubMed, preprocessed, and the unclassified corpus is classified using the best performing classification algorithm out of ten implemented algorithms. CONCLUSION: BioReader supports data and information collection by implementing text mining-based classification of primary biomedical literature in a web interface, thus enabling curators and researchers to take advantage of the vast amounts of data and information in the published literature. BioReader outperforms existing tools with similar functionalities and expands the features used for mining literature in database curation efforts. The tool is freely available as a web service at http://www.cbs.dtu.dk/services/BioReader.

A review of public health guidelines for postpartum physical activity and sedentary behavior from around the world.

BACKGROUND: The period following pregnancy is a critical time window when future habits with respect to physical activity (PA) and sedentary behavior (SB) are established; therefore, it warrants guidance. The purpose of this scoping review was to summarize public health-oriented country-specific postpartum PA and SB guidelines worldwide. METHODS: To identify guidelines published since 2010, we performed a (a) systematic search of 4 databases (CINAHL, Global Health, PubMed, and SPORTDiscus), (b) structured repeatable web-based search separately for 194 countries, and (c) separate web-based search. Only the most recent guideline was included for each country. RESULTS: We identified 22 countries with public health-oriented postpartum guidelines for PA and 11 countries with SB guidelines. The continents with guidelines included Europe (n = 12), Asia (n = 5), Oceania (n = 2), Africa (n = 1), North America (n = 1), and South America (n = 1). The most common benefits recorded for PA included weight control/management (n = 10), reducing the risk of postpartum depression or depressive symptoms (n = 9), and improving mood/well-being (n = 8). Postpartum guidelines specified exercises to engage in, including pelvic floor exercises (n = 17); muscle strengthening, weight training, or resistance exercises (n = 13); aerobics/general aerobic activity (n = 13); walking (n = 11); cycling (n = 9); and swimming (n = 9). Eleven guidelines remarked on the interaction between PA and breastfeeding; several guidelines stated that PA did not impact breast milk quantity (n = 7), breast milk quality (n = 6), or infant growth (n = 3). For SB, suggestions included limiting long-term sitting and interrupting sitting with PA. CONCLUSION: Country-specific postpartum guidelines for PA and SB can help promote healthy behaviors using a culturally appropriate context while providing specific guidance to public health practitioners.

"I Felt I Was Actually Inside the Movie" An Exploratory Study into Children's Views of Staging a Physically Active Experience, with Implications for Future Interventions.

Current levels of inactivity suggest novel approaches are needed to engage children in physical activity (PA), and enjoyment is a strong motivator for children's PA engagement. A physically active experience (PAE) was proposed as a way to use entertainment, education, (e)aesthetics and escapist methods to promote PA to children in a way that is immersive and enables them to actively partake whilst enjoying their experience. In this current mixed methods study, three physically active experiences based on popular children's movies were designed and staged, in order to explore children's views on staging a PAE and provide implications for future PA interventions. Seventeen children (boys n = nine, girls n = eight) between the ages of nine and ten years provided feedback on the experiences. The children watched a pre-recorded video presenting the physically active experiences and then completed a survey including affective forecasting responses, which was followed by participation in an online focus group where views on the experiences were explored further. For all three experiences, the mean anticipated affective response for valence was between "fairly good" and "good", and for arousal between "a bit awake" and "awake". Further, when asked, the children reported wanting to take part in the experiences (experience 1: 82.4%, experience 2: 76.5%, experience 3: 64.7%). The qualitative data revealed that children felt that they would enjoy the sessions, feel immersed in their environment, transported away from reality, and that they would be able to learn something new regarding PA. These results support the implementation of a PAE to engage children in enjoyable PA; future interventions should use these findings to engage children in a PAE, examining their actual responses to the activities.

'A Physically Active Experience': Setting the Stage for a New Approach to Engage Children in Physical Activity Using Themed Entertainment Experiences.

Despite the multiple health benefits that result from engaging in physical activity, data suggest that children are moving less. Novel approaches to engaging children in physical activity are needed to address this public health concern. Recently, a new definition of physical activity was proposed that emphasizes, among other things, the fact that physical activity is deeply affective, emotional and situated in spaces that shape the experience. With the need to increase engagement in physical activity and this new proposed definition, this paper presents a more novel approach to addressing this problem through staging a physically active experience. The idea draws upon the well-established area of experience economy, which aims to engage those partaking in an educational, (e)aesthetic, escapist, and entertaining way. When staging something as an experience, the focus is on engagement. By staging physical activity as an experience, it is proposed that children can actively partake in physical activity in a way that is focused on the experience offered. This review explains the notion of experience economy and provides examples of how it could be applied to children's physical activity. By creating an aesthetically pleasing, escapist and entertaining environment where children can learn and engage in physical activity, a more engaging positive experience of physical activity can be offered. Future research should examine the staging of physically active experiences for children and evaluate the practical implementation and effectiveness of this new approach to increasing children's engagement in physical activity.

Study Design: Human Leukocyte Antigen Class I Molecule A∗02-Chimeric Antigen Receptor Regulatory T Cells in Renal Transplantation.

Introduction: Cell therapy with regulatory T cells (Tregs) in solid organ transplantation is a promising approach for the prevention of graft rejection and induction of immunologic tolerance. Previous clinical studies have demonstrated the safety of Tregs in renal transplant recipients. Antigen-specific Tregs, such as chimeric antigen receptor (CAR)-Tregs, are expected to be more efficacious than polyclonal Tregs in homing to the target antigen. We have developed an autologous cell therapy (TX200-TR101) where a human leukocyte antigen (HLA) class I molecule A∗02 (HLA-A∗02)-CAR is introduced into autologous naive Tregs from a patient with HLA-A∗02-negative end-stage renal disease (ESRD) awaiting an HLA-A∗02-positive donor kidney. Methods: This article describes the design of the STEADFAST study, a first-in-human, phase I/IIa, multicenter, open-label, single-ascending dose, dose-ranging study to assess TX200-TR101 in living-donor renal transplant recipients. Up to 15 transplant recipients will receive TX200-TR101 and will be followed up for a total of 84 weeks post-transplant, alongside a control cohort of up to 6 transplant recipients. All transplant recipients will receive a standard of care immunosuppressive regimen, with the intent of intensified tapering of the regimen in the TX200-TR101 cohort. Results: The primary end point is the incidence and severity of treatment-emergent adverse events (AEs) within 28 days post-TX200-TR101 infusion. Other end points include additional safety parameters, clinical and renal outcome parameters, and the evaluation of biomarkers. Conclusion: The STEADFAST study represents the next frontier in adoptive cell therapies. TX200-TR101 holds great potential to prevent immune-mediated graft rejection and induce immunologic tolerance after HLA-A∗02-mismatched renal transplantation.

Evaluating Evidence-Based Content, Features of Exercise Instruction, and Expert Involvement in Physical Activity Apps for Pregnant Women: Systematic Search and Content Analysis.

BACKGROUND: Guidelines for physical activity and exercise during pregnancy recommend that all women without contraindications engage in regular physical activity to improve both their own health and the health of their baby. Many women are uncertain how to safely engage in physical activity and exercise during this life stage and are increasingly using mobile apps to access health-related information. However, the extent to which apps that provide physical activity and exercise advice align with current evidence-based pregnancy recommendations is unclear. OBJECTIVE: This study aims to conduct a systematic search and content analysis of apps that promote physical activity and exercise in pregnancy to examine the alignment of the content with current evidence-based recommendations; delivery, format, and features of physical activity and exercise instruction; and credentials of the app developers. METHODS: Systematic searches were conducted in the Australian App Store and Google Play Store in October 2020. Apps were identified using combinations of search terms relevant to pregnancy and exercise or physical activity and screened for inclusion (with a primary focus on physical activity and exercise during pregnancy, free to download or did not require immediate paid subscription, and an average user rating of ≥4 out of 5). Apps were then independently reviewed using an author-designed extraction tool. RESULTS: Overall, 27 apps were included in this review (Google Play Store: 16/27, 59%, and App Store: 11/27, 41%). Two-thirds of the apps provided some information relating to the frequency, intensity, time, and type principles of exercise; only 11% (3/27) provided this information in line with current evidence-based guidelines. Approximately one-third of the apps provided information about contraindications to exercise during pregnancy and referenced the supporting evidence. None of the apps actively engaged in screening for potential contraindications. Only 15% (4/27) of the apps collected information about the user's current exercise behaviors, 11% (3/27) allowed users to personalize features relating to their exercise preferences, and a little more than one-third provided information about developer credentials. CONCLUSIONS: Few exercise apps designed for pregnancy aligned with current evidence-based physical activity guidelines. None of the apps screened users for contraindications to physical activity and exercise during pregnancy, and most lacked appropriate personalization features to account for an individual's characteristics. Few involved qualified experts during the development of the app. There is a need to improve the quality of apps that promote exercise in pregnancy to ensure that women are appropriately supported to engage in exercise and the potential risk of injury, complications, and adverse pregnancy outcomes for both mother and child is minimized. This could be done by providing expert guidance that aligns with current recommendations, introducing screening measures and features that enable personalization and tailoring to individual users, or by developing a recognized system for regulating apps.

Cost sensitive hierarchical document classification to triage PubMed abstracts for manual curation.

BACKGROUND: The Immune Epitope Database (IEDB) project manually curates information from published journal articles that describe immune epitopes derived from a wide variety of organisms and associated with different diseases. In the past, abstracts of scientific articles were retrieved by broad keyword queries of PubMed, and were classified as relevant (curatable) or irrelevant (not curatable) to the scope of the database by a Naïve Bayes classifier. The curatable abstracts were subsequently manually classified into categories corresponding to different disease domains. Over the past four years, we have examined how to further improve this approach in order to enhance classification performance and to reduce the need for manual intervention. RESULTS: Utilizing 89,884 abstracts classified by a domain expert as curatable or uncuratable, we found that a SVM classifier outperformed the previously used Naïve Bayes classifier for curatability predictions with an AUC of 0.899 and 0.854, respectively. Next, using a non-hierarchical and a hierarchical application of SVM classifiers trained on 22,833 curatable abstracts manually classified into three levels of disease specific categories we demonstrated that a hierarchical application of SVM classifiers outperformed non-hierarchical SVM classifiers for categorization. Finally, to optimize the hierarchical SVM classifiers' error profile for the curation process, cost sensitivity functions were developed to avoid serious misclassifications. We tested our design on a benchmark dataset of 1,388 references and achieved an overall category prediction accuracy of 94.4%, 93.9%, and 82.1% at the three levels of categorization, respectively. CONCLUSIONS: A hierarchical application of SVM algorithms with cost sensitive output weighting enabled high quality reference classification with few serious misclassifications. This enabled us to significantly reduce the manual component of abstract categorization. Our findings are relevant to other databases that are developing their own document classifier schema and the datasets we make available provide large scale real-life benchmark sets for method developers.

Can Earth's Mightiest Heroes Help Children Be Physically Active? Exploring the Immersive Qualities of Les Mills' and Marvel's "Move Like the Avengers" Video.

There have been calls for more enjoyable Physical Activity (PA) interventions which focus on ensuring a positive affective response. This study explored how using a narrative, characters, and music in a video-led PA session might influence the sense of immersion and impact the affective response. One hundred and thirty-six participants (boys n = 65, girls n = 71) were recruited, 85% aged between 7 and 11 years old. Participants completed the "Move Like the Avengers" PA video created by Les Mills and Marvel, then complete a survey answering questions on their post activity affective responses, and the use of immersive elements. Positive average affective responses were found (valence mean score: 3.6 ± 2.2, arousal mean score: 5.1 ± 1.0). Analysis revealed the narrative with characters indirectly mediate the valence response through creating a sense of immersion (ßstd = 0.122 [95%CI 0.013 to 0.231]; p = 0.012). Musical elements had both a direct (ßstd = 0.449 [95%CI 0.264 to 0.634]; p < 0.001), and an indirect (ßstd = 0.122 [95%CI 0.014 to 0.229]; p = 0.011) effect upon valence and a direct effect upon arousal (ßstd = 0.244 [95%CI 0.006 to 0.482]; p = 0.021). These promising results provide justification for future research into children's immersive PA.

A Rapid Review of Communication Strategies for Physical Activity Guidelines and Physical Activity Promotion: A Review of Worldwide Strategies.

BACKGROUND: To support the strategy development for communication of the updated physical activity (PA) guidelines, the UK Chief Medical Officers' Expert Panel for Communication was created. METHODS: To help inform this process, a rapid review was performed to identify and describe how other nations are communicating their PA guidelines and PA generally. Elements of the health-enhancing physical activity policy audit tool created by the World Health Organization were used to investigate all 195 countries. RESULTS: Seventy-seven countries had their own guidelines; 53 used the World Health Organization guidelines, and for 65 countries, no guidelines could be found. For the communication, 27 countries used infographics; 56 had government policies/documents, and 11 used a mass media campaign. Only 6 of these had been evaluated. Although many countries used infographics, there were no associated evaluations. As such, any future communication strategies should incorporate an evaluation. Mass media campaigns had the strongest evidence base, proving to be an effective strategy, particularly when incorporating aspects of social marketing. CONCLUSION: This review provides an insight into strategies countries worldwide have taken to communicate PA guidelines and PA promotion. These should be carefully considered when deciding how best to communicate and promote PA guidelines.

Evaluating the results of resistance training using ultrasound or flexed arm circumference: A case for keeping it simple?

BACKGROUND: The present study aimed to compare changes in muscle size when measured by ultrasound (US) muscle thickness (MT) and arm circumference (AC) using data from young men. METHODS: The investigation involved data from three previous studies involving a total of 67 young men who performed resistance training (RT) for 10-12 weeks. Before and after the training period, elbow flexor MT was evaluated by US and AC was measured. We conducted two-stage individual patient data random-effects meta-analyses using both Frequentist and Bayesian hypothesis testing. One-sample analyses examined the absence or presence of a change in both MT and AC, and paired analyses examined whether these differed from one another or equivalent. RESULTS: One-sample analysis supported that both AC (+4.9%; tp=0.0002; BF10=6,255,759,515) and MT (+3.9%; P<0.0001; BF10=7,958,241,773) suggested that change in muscle size had occurred. Frequentist paired comparisons suggested that the estimates of change between both AC and MT measures did not significantly differ (P=0.1092), but were not statistically equivalent. Bayesian paired comparisons, however, suggested that MT estimates where greater in magnitude than AC estimates for change in muscle size (BF10=16.39174). CONCLUSION: Both MT and AC are able to detect RT-induced changes in muscle size of the upper arm, but that the magnitude of changes may differ. Thus, care should be taken when comparing or combining estimates using either approach. RELEVANCE FOR PATIENTS: The use of AC might be considered as a practical and low-cost alternative to detect changes in muscle size.

Physical Activity, Mental and Personal Well-Being, Social Isolation, and Perceptions of Academic Attainment and Employability in University Students: The Scottish and British Active Students Surveys.

BACKGROUND: Physical activity (PA) promotes health and well-being. For students, university represents a transitional period, including increased independence over lifestyle behaviors, in addition to new stressors and barriers to engaging in PA. It is, therefore, important to monitor PA trends in students to gain a greater understanding about the role it might play in physical and mental well-being, as well as other factors, such as attainment and employability. METHODS: Cross-sectional surveys were conducted in 2016 in Scottish universities and colleges, and in 2017 in universities and colleges across the United Kingdom, and the data were pooled for the present study (N = 11,650). Cumulative ordinal logistic regression was used to model the association between PA levels and mental and personal well-being, social isolation, and perceptions of academic attainment and employability. RESULTS: Only 51% of the respondents met the recommended levels of moderate to vigorous PA per week. There was a linear relationship between PA levels and all outcomes, with better scores in more active students. CONCLUSIONS: UK university students are insufficiently active compared with the general population of 16- to 24-year olds. Yet, students with higher PA report better outcomes for mental and personal well-being, social isolation, and perceptions of academic attainment and employability.

Heart rate, energy expenditure, and affective responses from children participating in trampoline park sessions compared with traditional extra-curricular sports clubs.

BACKGROUND: Lack of physical activity (PA) is becoming an issue in younger populations. Trampoline parks are newly popular environments for PA yet research on their use is scarce. Thus the present study compared heart rate, energy expenditure, and affective responses in children participating in trampoline park sessions compared with extracurricular sports clubs. METHODS: Children (aged 6-11 years; N.=16 females, N.=10 males) participated in 3 trampoline park sessions and 3 extracurricular sports club sessions lasting ~45 minutes over 3 weeks. Heart rate, energy expenditure, and affective responses through the circumplex model, were measured. RESULTS: Both conditions elicited moderate-vigorous PA. Average heart rate (mean difference [95%CIs]=27.6 fc [23.5 to 31.8]), peak heart rate (mean difference [95%CIs]=24.2 fc [20.8 to 27.6]) and energy expenditure (mean difference [95%CIs]=3.2 kcals.min-1 [2.7 to 3.6]) were all significantly higher for the trampoline sessions. Affective responses for both conditions elicited feelings of "excitement." CONCLUSIONS: Both extracurricular sports clubs and trampoline park activities provide moderate-vigorous PA, though the latter may result in higher heart rate and energy expenditure responses. Both however produce similar positive affective responses. As such, both could be valuable options for PA opportunities for children.

Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study.

BACKGROUND: Wiskott-Aldrich syndrome is a rare, life-threatening, X-linked primary immunodeficiency characterised by microthrombocytopenia, infections, eczema, autoimmunity, and malignant disease. Lentiviral vector-mediated haemopoietic stem/progenitor cell (HSPC) gene therapy is a potentially curative treatment that represents an alternative to allogeneic HSPC transplantation. Here, we report safety and efficacy data from an interim analysis of patients with severe Wiskott-Aldrich syndrome who received lentiviral vector-derived gene therapy. METHODS: We did a non-randomised, open-label, phase 1/2 clinical study in paediatric patients with severe Wiskott-Aldrich syndrome, defined by either WAS gene mutation or absent Wiskott-Aldrich syndrome protein (WASP) expression or a Zhu clinical score of 3 or higher. We included patients who had no HLA-identical sibling donor available or, for children younger than 5 years of age, no suitable 10/10 matched unrelated donor or 6/6 unrelated cord blood donor. After treatment with rituximab and a reduced-intensity conditioning regimen of busulfan and fludarabine, patients received one intravenous infusion of autologous CD34+ cells genetically modified with a lentiviral vector encoding for human WAS cDNA. The primary safety endpoints were safety of the conditioning regimen and safety of lentiviral gene transfer into HSPCs. The primary efficacy endpoints were overall survival, sustained engraftment of genetically corrected HSPCs, expression of vector-derived WASP, improved T-cell function, antigen-specific responses to vaccinations, and improved platelet count and mean platelet volume normalisation. This interim analysis was done when the first six patients treated had completed at least 3 years of follow-up. The planned analyses are presented for the intention-to-treat population. This trial is registered with ClinicalTrials.gov (number NCT01515462) and EudraCT (number 2009-017346-32). FINDINGS: Between April 20, 2010, and Feb 26, 2015, nine patients (all male) were enrolled of whom one was excluded after screening; the age range of the eight treated children was 1·1-12·4 years. At the time of the interim analysis (data cutoff April 29, 2016), median follow-up was 3·6 years (range 0·5-5·6). Overall survival was 100%. Engraftment of genetically corrected HSPCs was successful and sustained in all patients. The fraction of WASP-positive lymphocytes increased from a median of 3·9% (range 1·8-35·6) before gene therapy to 66·7% (55·7-98·6) at 12 months after gene therapy, whereas WASP-positive platelets increased from 19·1% (range 4·1-31·0) to 76·6% (53·1-98·4). Improvement of immune function was shown by normalisation of in-vitro T-cell function and successful discontinuation of immunoglobulin supplementation in seven patients with follow-up longer than 1 year, followed by positive antigen-specific response to vaccination. Severe infections fell from 2·38 (95% CI 1·44-3·72) per patient-year of observation (PYO) in the year before gene therapy to 0·31 (0·04-1·11) per PYO in the second year after gene therapy and 0·17 (0·00-0·93) per PYO in the third year after gene therapy. Before gene therapy, platelet counts were lower than 20 × 109 per L in seven of eight patients. At the last follow-up visit, the platelet count had increased to 20-50 × 109 per L in one patient, 50-100 × 109 per L in five patients, and more than 100 × 109 per L in two patients, which resulted in independence from platelet transfusions and absence of severe bleeding events. 27 serious adverse events in six patients occurred after gene therapy, 23 (85%) of which were infectious (pyrexia [five events in three patients], device-related infections, including one case of sepsis [four events in three patients], and gastroenteritis, including one case due to rotavirus [three events in two patients]); these occurred mainly in the first 6 months of follow-up. No adverse reactions to the investigational drug product and no abnormal clonal proliferation or leukaemia were reported after gene therapy. INTERPRETATION: Data from this study show that gene therapy provides a valuable treatment option for patients with severe Wiskott-Aldrich syndrome, particularly for those who do not have a suitable HSPC donor available. FUNDING: Italian Telethon Foundation, GlaxoSmithKline, and Orchard Therapeutics.

Evolving Industry Partnerships and Investments in Cell and Gene Therapies.

Cell and gene therapies hold the promise of providing significant and durable health gains to patients in many disease states and have recently elicited significant investor and partner interest. We cover the current state of industry partnerships and investments, highlight what makes a partnership advantageous, and discuss implications for stem cell therapies.

An ontology for major histocompatibility restriction.

BACKGROUND: MHC molecules are a highly diverse family of proteins that play a key role in cellular immune recognition. Over time, different techniques and terminologies have been developed to identify the specific type(s) of MHC molecule involved in a specific immune recognition context. No consistent nomenclature exists across different vertebrate species. PURPOSE: To correctly represent MHC related data in The Immune Epitope Database (IEDB), we built upon a previously established MHC ontology and created an ontology to represent MHC molecules as they relate to immunological experiments. DESCRIPTION: This ontology models MHC protein chains from 16 species, deals with different approaches used to identify MHC, such as direct sequencing verses serotyping, relates engineered MHC molecules to naturally occurring ones, connects genetic loci, alleles, protein chains and multi-chain proteins, and establishes evidence codes for MHC restriction. Where available, this work is based on existing ontologies from the OBO foundry. CONCLUSIONS: Overall, representing MHC molecules provides a challenging and practically important test case for ontology building, and could serve as an example of how to integrate other ontology building efforts into web resources.

Cost of Stem Cell-Based Tissue-Engineered Airway Transplants in the United Kingdom: Case Series.

Stem cell-based tissue-engineered tracheas are at an early stage in their product development cycle. Tens of patients have been treated worldwide in predominantly compassionate use settings, demonstrating significant promise. This potentially life-saving treatment is complex, and the cost and its implications for such treatments are yet to be fully understood. The costs are compounded by varying strategies for graft preparation and transplant, resulting in differing clinical and laboratory costs from different research groups. In this study, we present a detailed breakdown of the clinical and manufacturing costs for three of the United Kingdom (UK) patients treated with such transplants. All three patients were treated under Compassionate Use legislation, within the UK National Health Service (NHS) hospital setting. The total costs for the three UK patients treated ranged from $174,420 to $740,500. All three patients were in a state of poor health at time of treatment and had a number of complexities in addition to the restricted airway. This is the first time a cost analysis has been made for a tissue-engineered organ and provides a benchmark for future studies, as well as comparative data for use in reimbursement considerations.

Turning Regenerative Medicine Breakthrough Ideas and Innovations into Commercial Products.

The TERMIS-Europe (EU) Industry committee intended to address the two main critical issues in the clinical/commercial translation of Advanced Therapeutic Medicine Products (ATMP): (1) entrepreneurial exploitation of breakthrough ideas and innovations, and (2) regulatory market approval. Since January 2012, more than 12,000 publications related to regenerative medicine and tissue engineering have been accepted for publications, reflecting the intense academic research activity in this field. The TERMIS-EU 2014 Industry Symposium provided a reflection on the management of innovation and technological breakthroughs in biotechnology first proposed to contextualize the key development milestones and constraints of allocation of financial resources, in the development life-cycle of radical innovation projects. This was illustrated with the biofuels story, sharing similarities with regenerative medicine. The transition was then ensured by an overview of the key identified challenges facing the commercialization of cell therapy products as ATMP examples. Real cases and testimonies were then provided by a palette of medical technologies and regenerative medicine companies from their commercial development of cell and gene therapy products. Although the commercial development of ATMP is still at the proof-of-concept stage due to technology risks, changing policies, changing markets, and management changes, the sector is highly dynamic with a number of explored therapeutic approaches, developed by using a large diversity of business models, both proposed by the experience, pitfalls, and successes of regenerative medicine pioneers, and adapted to the constraint resource allocation and environment in radical innovation projects.

Substantial gaps in knowledge of Bordetella pertussis antibody and T cell epitopes relevant for natural immunity and vaccine efficacy.

The recent increase in whooping cough in vaccinated populations has been attributed to waning immunity associated with the acellular vaccine. The Immune Epitope Database (IEDB) is a repository of immune epitope data from the published literature and includes T cell and antibody epitopes for human pathogens. The IEDB conducted a review of the epitope literature, which revealed 300 Bordetella pertussis-related epitopes from 39 references. Epitope data are currently available for six virulence factors of B. pertussis: pertussis toxin, pertactin, fimbrial 2, fimbrial 3, adenylate cyclase and filamentous hemagglutinin. The majority of epitopes were defined for antibody reactivity; fewer T cell determinants were reported. Analysis of available protective correlates data revealed a number of candidate epitopes; however few are defined in humans and few have been shown to be protective. Moreover, there are a limited number of studies defining epitopes from natural infection versus whole cell or acellular/subunit vaccines. The relationship between epitope location and structural features, as well as antigenic drift (SNP analysis) was also investigated. We conclude that the cumulative data is yet insufficient to address many fundamental questions related to vaccine failure and this underscores the need for further investigation of B. pertussis immunity at the molecular level.