Real-world evaluation of an acceptance and commitment therapy-based group programme for breast cancer survivors with fear of cancer recurrence.

PURPOSE: To evaluate the effectiveness and acceptability of a 6-week acceptance and commitment therapy (ACT)-based group programme on participants' fear of cancer recurrence (FCR), quality of life (QoL), psychological distress and psychological flexibility at the end of the programme and 12-week follow-up. METHODS: A one-group, post-test service evaluation of a real-world psychological programme was carried out to evaluate collected outcome measures and attendance for a total of 21 groups facilitated between 2017 and 2019. Participants were breast cancer survivors who attended a 6-week group programme led by NHS clinicians. Descriptive statistics and repeated measures ANOVA analyses were carried out for each outcome measure. Attendance levels were examined to assess acceptability. RESULTS: A total of 97 group participants who had completed curative treatment for breast cancer took part. Of whom, 89% completed at least 4 of the 6 weekly group sessions and 76% attended the 12-week follow-up session. Eighty-four (87%) participants returned outcome measures at all three time points relative to group participation (T1 = pre, T2 = post T3 = 12-week follow-up). Group participants were female, mean age 51.9 years. FCR was highest at T1 (mean 25.2, SD 4.7), reduced T2 (mean 21.2, SD 5.4) and further lowered T3 (mean 19.5, SD 6.2). This difference was statistically significant (p < 0.001). QoL was lowest at T1 (mean 62.4, SD 15.7), increased T2 (mean 71.7, SD 18.1) and further increased at T3 (mean 75.9, SD 17.5). This difference was statistically significant (p < 0.001). Psychological distress measures were shown to reduce, and psychological flexibility increased. CONCLUSIONS: This real-world evaluation of an ACT-based group programme led to improvements in FCR, QoL, psychological distress and psychological flexibility in this population. This evaluation provides basis for further investigation to determine if these results can be replicated by controlled research design across diverse populations.

Sustainable Smart Cities-Social Media Platforms and Their Role in Community Neighborhood Resilience-A Systematic Review.

The COVID-19 pandemic took most communities off guard and has highlighted gaps in community preparedness and resilience in spite of the numerous technological advancements and the variety of available social media platforms that many relied on during lockdown periods. This served to emphasise the necessity for exploring the roles of social media and smart city technologies in mitigating pandemic impacts. In this systematic literature review, we examined twelve articles on social media usage and smart city technologies and their contributions to community resilience during COVID-19. The analysis focused on the use of social media platforms and smart city technologies during and after lockdown periods, examining their role in fostering community resilience. Results indicate that social media and smart city technologies were instrumental in helping communities adapt and recover from the pandemic. While past studies have examined community resilience, social media, or smart cities separately, there is limited literature collating insights on the three elements combined. We therefore argue that these technologies, employed collaboratively, enhance community resilience during crises. Nevertheless, further research is recommended, particularly on urban resilience and comparative analyses to deepen our understanding of the complex interplay between these variables.

The Role of Social Media in Building Pandemic Resilience in an Urban Community: A Qualitative Case Study.

This paper explores the influence of social media in fostering resilience within an urban spatial context, specifically in Bangalore, India, during the COVID-19 lockdown, a period marked by a surge in digital communication due to movement restrictions. To control the rapid spread of the virus, over 1.38 billion people were given stay-at-home orders by the government of India during the onset of the pandemic. The restrictions in movement forced individuals to shift to online modes of connection and communication. As the field of digital epidemiology, that is, the use of digital tools and data to understand and improve health took center stage during the pandemic, the focus shifted towards the social media landscape, which is often associated with its negative aspects, such as misinformation. However, this paper delves into social media's potential to build resilience on a local scale, particularly given its increased usage during the pandemic. Through in-depth online interviews with eight urban residents, we conducted a thematic analysis to understand social media's role during the lockdown. Results indicate that social media facilitated effective information exchange and fostered a sense of community. Furthermore, it engendered an environment conducive to prosocial behavior, a known resilience amplifier. We also highlight the importance of baseline context regarding the users directly engaged in social media data generation with respect to digital epidemiology analytics tools for large-scale social media data and the need for qualitative input feeding into their design. Our study highlights the need for a balanced perspective on social media use in times of crisis, recognizing its potential to boost community resilience in an urban setting, and further enriching digital epidemiology approaches.

Lifestyle coaching is feasible in fatigued brain tumor patients: A phase I/feasibility, multi-center, mixed-methods randomized controlled trial.

Background: There are no effective treatments for brain tumor-related fatigue. We studied the feasibility of two novel lifestyle coaching interventions in fatigued brain tumor patients. Methods: This phase I/feasibility multi-center RCT recruited patients with a clinically stable primary brain tumor and significant fatigue (mean Brief Fatigue Inventory [BFI] score ≥ 4/10). Participants were randomized in a 1-1-1 allocation ratio to: Control (usual care); Health Coaching ("HC", an eight-week program targeting lifestyle behaviors); or HC plus Activation Coaching ("HC + AC", further targeting self-efficacy). The primary outcome was feasibility of recruitment and retention. Secondary outcomes were intervention acceptability, which was evaluated via qualitative interview, and safety. Exploratory quantitative outcomes were measured at baseline (T0), post-interventions (T1, 10 weeks), and endpoint (T2, 16 weeks). Results: n = 46 fatigued brain tumor patients (T0 BFI mean = 6.8/10) were recruited and 34 were retained to endpoint, establishing feasibility. Engagement with interventions was sustained over time. Qualitative interviews (n = 21) suggested that coaching interventions were broadly acceptable, although mediated by participant outlook and prior lifestyle. Coaching led to significant improvements in fatigue (improvement in BFI versus control at T1: HC=2.2 points [95% CI 0.6, 3.8], HC + AC = 1.8 [0.1, 3.4], Cohen's d [HC] = 1.9; improvement in FACIT-Fatigue: HC = 4.8 points [-3.7, 13.3]; HC + AC = 12 [3.5, 20.5], d [HC and AC] = 0.9). Coaching also improved depressive and mental health outcomes. Modeling suggested a potential limiting effect of higher baseline depressive symptoms. Conclusions: Lifestyle coaching interventions are feasible to deliver to fatigued brain tumor patients. They were manageable, acceptable, and safe, with preliminary evidence of benefit on fatigue and mental health outcomes. Larger trials of efficacy are justified.

Developing an e-Prehabilitation System of Care for Young Adults Diagnosed With Cancer: User-Centered Design Study.

BACKGROUND: A diagnosis of cancer in adolescence or young adulthood can pose many different and unique challenges for individuals, as well as their families and friends. Drawing on the concept of prehabilitation, the provision of high-quality, accessible, timely, reliable, and appropriate information, care, and support for young adults with cancer and their families is critical to ensure that they feel equipped and empowered to make informed decisions relating to their treatment and care. Increasingly, digital health interventions offer opportunities to augment current health care information and support provision. Co-designing these digital health interventions can help to ensure that they are meaningful and relevant to the patient cohort, thereby maximizing their accessibility and acceptability. OBJECTIVE: This study had 4 primary interlinked objectives: understand the support needs of young adults with cancer at the time of diagnosis, understand the potential role of a digital health solution to assist in the delivery of prehabilitation for young adults with cancer, identify appropriate technologies and technological platforms for a digital prehabilitation system of care, and develop a prototype for a digital prehabilitation system of care. METHODS: This was a qualitative study using interviews and surveys. Young adults aged 16 to 26 years diagnosed with cancer within the last 3 years were invited to participate in individual user-requirement interviews or surveys. Health care professionals specializing in the treatment and care of young adults with cancer and digital health professionals working in the industry were also interviewed or completed a survey. Consensus feedback interviews were conducted with 3 young adults and 2 health care professionals after the development of the first generation of the prototype app. RESULTS: In total, 7 individual interviews and 8 surveys were completed with young adults with a range of cancer diagnoses. Moreover, 6 individual interviews and 9 surveys were completed with health care professionals, and 3 digital health professionals participated in one-on-one interviews. A prototype app with the working name of Cancer Helpmate was developed based on these collective participant data. Overall, feedback from participants across the data collection activities suggests that the concept for the app was positive during these developmental stages. Further insightful ideas for the app's future development were also identified. CONCLUSIONS: Young adults with cancer and health care professionals are responsive to the need for more digitally driven services to be developed. Further development of an app such as Cancer Helpmate, which incorporates key features and functionalities directly informed by users, could help to augment the support provided to young adults with cancer.

Atypical TDP-43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP.

We describe an autosomal dominant, multi-generational, amyotrophic lateral sclerosis (ALS) pedigree in which disease co-segregates with a heterozygous p.Y374X nonsense mutation within TDP-43. Mislocalization of TDP-43 and formation of insoluble TDP-43-positive neuronal cytoplasmic inclusions is the hallmark pathology in >95% of ALS patients. Neuropathological examination of the single case for which CNS tissue was available indicated typical TDP-43 pathology within lower motor neurons, but classical TDP-43-positive inclusions were absent from motor cortex. The mutated allele is transcribed and translated in patient fibroblasts and motor cortex tissue, but overall TDP-43 protein expression is reduced compared to wild-type controls. Despite absence of TDP-43-positive inclusions we confirmed deficient TDP-43 splicing function within motor cortex tissue. Furthermore, urea fractionation and mass spectrometry of motor cortex tissue carrying the mutation revealed atypical TDP-43 protein species but not typical C-terminal fragments. We conclude that the p.Y374X mutation underpins a monogenic, fully penetrant form of ALS. Reduced expression of TDP-43 combined with atypical TDP-43 protein species and absent C-terminal fragments extends the molecular phenotypes associated with TDP-43 mutations and with ALS more broadly. Future work will need to include the findings from this pedigree in dissecting the mechanisms of TDP-43-mediated toxicity.

Needle to needle robot-assisted manufacture of cell therapy products.

Advanced therapeutic medicinal products (ATMPs) have emerged as novel therapies for untreatable diseases, generating the need for large volumes of high-quality, clinically-compliant GMP cells to replace costly, high-risk and limited scale manual expansion processes. We present the design of a fully automated, robot-assisted platform incorporating the use of multiliter stirred tank bioreactors for scalable production of adherent human stem cells. The design addresses a needle-to-needle closed process incorporating automated bone marrow collection, cell isolation, expansion, and collection into cryovials for patient delivery. AUTOSTEM, a modular, adaptable, fully closed system ensures no direct operator interaction with biological material; all commands are performed through a graphic interface. Seeding of source material, process monitoring, feeding, sampling, harvesting and cryopreservation are automated within the closed platform, comprising two clean room levels enabling both open and closed processes. A bioprocess based on human MSCs expanded on microcarriers was used for proof of concept. Utilizing equivalent culture parameters, the AUTOSTEM robot-assisted platform successfully performed cell expansion at the liter scale, generating results comparable to manual production, while maintaining cell quality postprocessing.

Austere Fasciotomy: Alternative Equipment for Performance in the Field.

BACKGROUND: Acute compartment syndrome (ACS) following extremity trauma requires rapid fasciotomy to avoid significant morbidity and limb loss. Four-compartment fasciotomy of the leg is a surgical procedure typically performed in the operating room; however, casualties who cannot be rapidly transported may need fasciotomies in the prehospital setting. In the absence of traditional operating instruments (e.g., scalpel, long Metzenbaum scissors, electrocautery), alternative means of fasciotomy may be needed. We undertook a proof-of-concept study using cadaver models to determine whether leg fasciotomies could be performed with alternative devices compared with the surgical standard. METHODS: Two-incision, four-compartment fasciotomies were performed on fresh, never-frozen, non-embalmed cadaver legs using a scalpel for the initial skin incision, followed by release of the fascia using one of the following instruments: 5.5-in curved Mayo scissors; Benchmade rescue hook (model BM-5BLKW); rescue hook on the Leatherman Raptor multitool (model 831741-FFP); Leatherman Z-Rex multitool rescue hook (model LM93408); or No. 10 PenBlade (model PB-M-10- CAS). The procedures were performed by a surgeon. Skin and fascia incisional lengths were recorded along with a subjective impression of the performance for each device. Post-procedural dissection was performed to identify associated injuries to the muscle, superficial peroneal nerve, and the greater saphenous vein (GSV). RESULTS: All devices were able to adequately release the fascia in all four compartments. All rescue hooks (Benchmade, Raptor, and Z-Rex) required a "pull technique" and a skin incision of equal length to the fascia incision. The PenBlade was used in a "push technique," similar to the standard scissor fasciotomy through a smaller skin incision. There was one superficial peroneal nerve transection with the rescue hooks, but there were no GSV injuries or significant muscle damage with any instrument. CONCLUSION: Four-compartment fasciotomy can be performed with readily available alternative equipment such as rescue hooks and the PenBlade. Hook-type devices require longer skin incisions compared with scissors and the PenBlade. In contested environments, patients with ACS may require fasciotomy prior to evacuation to surgical teams; training combat medics in the use of these alternative instruments in the field may preserve life and limb.

Assessing geographic and industry-related trends in bladder cancer in Ontario: A population-based study.

INTRODUCTION: Bladder cancer (BC) is the fifth most prevalent cancer in Canada, with 9000 Canadians diagnosed each year. While smoking is the most important risk factor, environmental and occupational carcinogens have been found to significantly contribute to BC rates. As Canada is highly reliant on natural resource industries, this study seeks to identify geographical and industry-related trends of BC rates in Ontario. METHODS: The 1991 and 2001 Canadian Census Health and Environment Cohort (CanCHEC; Statistics Canada) was used, along with individual years of census data. Maps identifying hot and cold spots for BC within Ontario were generated, and the former were assessed for industry patterns between location and BC rates. Cox proportional hazards models were run for each age cohort to predict the likelihood of developing BC by industry of work. RESULTS: Significant geographical and industrial trends in BC rates were identified. For 1991-2001, hot spots included the Cochrane, Manitoulin, Parry Sound, and Sudbury (90% confidence interval [CI]), and Nipissing and Temiskaming (95% CI) regions. Toronto and York were cold spots. Concurrently, metal (p=0.039), paper and publishing (p=0.0062), and wood and furniture (p<0.0001) industries had increased rates of BC. Notably, these industries had high employment density in our hot spot areas and low density in our cold spots. CONCLUSIONS: Significant geographical and industrial BC trends were found in Northern Ontario regions reliant on heavy employment in natural resource-based industries, such as forestry, agriculture, and wood/paper. These findings may inform future screening guidelines and aid in identifying individuals at risk of BC development.

Extended dual antiplatelet therapy with ticagrelor 60 mg in patients with prior myocardial infarction: The design of ALETHEIA, a multi-country observational study.

INTRODUCTION: Clinical guidelines recommend extended treatment with dual antiplatelet therapy (DAPT) with ticagrelor 60 mg (twice daily) beyond 12 months in high-risk patients with a history of myocardial infarction (MI) who have previously tolerated DAPT and are not at heightened bleeding risk. However, evidence on patterns of use and associated clinical outcomes in routine clinical practice is limited. METHODS: ALETHEIA is an observational, multi-country study, designed to describe characteristics, treatment persistence, and bleeding and cardiovascular (CV) outcomes in post-MI patients who initiate ticagrelor 60 mg in routine clinical practice (NCT04568083). The study will include electronic health data in the United States (US; Medicare, commercial claims) and Europe (Sweden, Italy, United Kingdom, Germany). Characteristics will be described among patients with and without ticagrelor 60 mg ≥1 year post-MI. Assuming an a priori threshold of 5000 person-years on-treatment is met, to ensure sufficient precision, clinical outcomes (bleeding and CV events) among patients treated with ticagrelor 60 mg will be assessed. Risk factors for clinical outcomes and treatment discontinuation will be assessed in patients with ticagrelor 60 mg and meta-analysis used to combine estimates across databases. Cohort selection will initiate from the ticagrelor 60 mg US and European approval dates and end February 2020. An estimated total of 7250 patients prescribed ticagrelor 60 mg are expected to be included. DISCUSSION: An increased understanding of patterns of ticagrelor 60 mg use and associated clinical outcomes among high-risk patients with a prior MI is needed. The a priori specified stepwise approach adapted in this observational study is expected to generate useful evidence for clinical decision-making and treatment optimization.

Scale-up of an intensified bioprocess for the expansion of bovine adipose-derived stem cells (bASCs) in stirred tank bioreactors.

Cultivated meat is an emerging field, aiming to establish the production of animal tissue for human consumption in an in vitro environment, eliminating the need to raise and slaughter animals for their meat. To realise this, the expansion of primary cells in a bioreactor is needed to achieve the high cell numbers required. The aim of this study was to develop a scalable, microcarrier based, intensified bioprocess for the expansion of bovine adipose-derived stem cells as precursors of fat and muscle tissue. The intensified bioprocess development was carried out initially in spinner flasks of different sizes and then translated to fully controlled litre scale benchtop bioreactors. Bioprocess intensification was achieved by utilising the previously demonstrated bead-to-bead transfer phenomenon and through the combined addition of microcarrier and medium to double the existing surface area and working volume in the bioreactor. Choosing the optimal time point for the additions was critical in enhancing the cell expansion. A significant fold increase of 114.19 ± 1.07 was obtained at the litre scale in the intensified bioprocess compared to the baseline (**p < .005). The quality of the cells was evaluated pre- and post-expansion and the cells were found to maintain their phenotype and differentiation capacity.

Expansion of human mesenchymal stem/stromal cells on temporary liquid microcarriers.

BACKGROUND: Traditional large-scale culture systems for human mesenchymal stem/stromal cells (hMSCs) use solid microcarriers as attachment substrates. Although the use of such substrates is advantageous because of the high surface-to-volume ratio, cell harvest from the same substrates is a challenge as it requires enzymatic treatment, often combined with agitation. Here, we investigated a two-phase system for expansion and non-enzymatic recovery of hMSCs. Perfluorocarbon droplets were dispersed in a protein-rich growth medium and were used as temporary liquid microcarriers for hMSC culture. RESULTS: hMSCs successfully attached to these liquid microcarriers, exhibiting similar morphologies to those cultured on solid ones. Fold increases of 3.03 ± 0.98 (hMSC1) and 3.81 ± 0.29 (hMSC2) were achieved on day 9. However, the maximum expansion folds were recorded on day 4 (4.79 ± 0.47 (hMSC1) and 4.856 ± 0.7 (hMSC2)). This decrease was caused by cell aggregation upon reaching confluency due to the contraction of the interface between the two phases. Cell quality, as assessed by differentiation, cell surface marker expression and clonogenic ability, was retained post expansion on the liquid microcarriers. Cell harvesting was achieved non-enzymatically in two steps: first by inducing droplet coalescence and then aspirating the interface. Quality characteristics of hMSCs continued to be retained even after inducing droplet coalescence. CONCLUSION: The prospect of a temporary microcarrier that can be used to expand cells and then 'disappear' for cell release without using proteolytic enzymes is a very exciting one. Here, we have demonstrated that hMSCs can attach and proliferate on these perfluorocarbon liquid microcarriers while, very importantly, retaining their quality.

Design and development of a new ambr250® bioreactor vessel for improved cell and gene therapy applications.

The emergence of cell and gene therapies has generated significant interest in their clinical and commercial potential. However, these therapies are prohibitively expensive to manufacture and can require extensive time for development due to our limited process knowledge and understanding. The automated ambr250® stirred-tank bioreactor platform provides an effective platform for high-throughput process development. However, the original dual pitched-blade 20 mm impeller and baffles proved sub-optimal for cell therapy candidates that require suspension of microcarriers (e.g. for the culture of adherent human mesenchymal stem cells) or other particles such as activating Dynabeads® (e.g. for the culture of human T-cells). We demonstrate the development of a new ambr250® stirred-tank bioreactor vessel which has been designed specifically to improve the suspension of microcarriers/beads and thereby improve the culture of such cellular systems. The new design is unbaffled and has a single, larger elephant ear impeller. We undertook a range of engineering and physical characterizations to determine which vessel and impeller configuration would be most suitable for suspension based on the minimum agitation speed (NJS) and associated specific power input (P/V)JS. A vessel (diameter, T, = 60 mm) without baffles and incorporating a single elephant ear impeller (diameter 30 mm and 45° pitch-blade angle) was selected as it had the lowest (P/V)JS and therefore potentially, based on Kolmogorov concepts, was the most flexible system. These experimentally-based conclusions were further validated firstly with computational fluid dynamic (CFD) simulations and secondly experimental studies involving the culture of both T-cells with Dynabeads® and hMSCs on microcarriers. The new ambr250® stirred-tank bioreactor successfully supported the culture of both cell types, with the T-cell culture demonstrating significant improvements compared to the original ambr250® and the hMSC-microcarrier culture gave significantly higher yields compared with spinner flask cultures. The new ambr250® bioreactor vessel design is an effective process development tool for cell and gene therapy candidates and potentially for autologous manufacture too.

Effect of the Abdominal Aortic and Junctional Tourniquet on chest compressions in a swine model of ventricular fibrillation.

INTRODUCTION: Mortality for out-of-hospital cardiac arrest is high when traditional chest compressions are used without adjuncts. The abdominal aortic and junctional tourniquet (AAJT) is a device with a wedge-shaped air bladder that occludes the aortic bifurcation, augmenting blood flow to the heart and brain. Previously, the addition of AAJT during chest compression led to an increase in rate of survival in a model of traumatic cardiac arrest. HYPOTHESIS: This study was designed to determine if application of the AAJT would lead to more effective chest compressions as measured by improved hemodynamic parameters and an increased rate of return of spontaneous circulation (ROSC). METHODS: Yorkshire swine (n = 6 per group) underwent general anesthesia and instrumentation. Ventricular fibrillation (Vfib) was electrically induced and animals were allocated into groups with or without the AAJT. The AAJT was inflated if selected after four minutes of compressions. Following a total of ten minutes of compressions, the animals entered into a ten-minute advanced cardiac life support phase. Hemodynamics and blood gas measurements were compared between groups. RESULTS: ROSC or cardioversion from Vfib was not achieved in either group. The AAJT group had improved hemodynamic parameters with significantly higher carotid diastolic pressure and higher blood flow in the carotid artery (p = 0.016 and 0.028 respectively). However, no significant differences were observed with coronary perfusion pressure or end tidal CO2. CONCLUSION: The AAJT did not confer a survival advantage during chest compressions, but hemodynamic improvements were observed while the AAJT was in place.

Bioprocess development for scalable production of cultivated meat.

Traditional farm-based products based on livestock are one of the main contributors to greenhouse gas emissions. Cultivated meat is an alternative that mimics animal meat, being produced in a bioreactor under controlled conditions rather than through the slaughtering of animals. The first step in the production of cultivated meat is the generation of sufficient reserves of starting cells. In this study, bovine adipose-derived stem cells (bASCs) were used as starting cells due to their ability to differentiate towards both fat and muscle, two cell types found in meat. A bioprocess for the expansion of these cells on microcarriers in spinner flasks was developed. Different cell seeding densities (1,500, 3,000, and 6,000 cells/cm2 ) and feeding strategies (80%, 65%, 50%, and combined 80%/50% medium exchanges) were investigated. Cell characterization was assessed pre- and postbioprocessing to ensure that bioprocessing did not negatively affect bASC quality. The best growth was obtained with the lowest cell seeding density (1,500 cells/cm2 ) with an 80% medium exchange performed (p < .0001) which yielded a 28-fold expansion. The ability to differentiate towards adipogenic, osteogenic, and chondrogenic lineages was retained postbioprocessing and no significant difference (p > .5) was found in clonogenicity pre- or postbioprocessing in any of the feeding regimes tested.

Demonstrating the Manufacture of Human CAR-T Cells in an Automated Stirred-Tank Bioreactor.

Chimeric antigen receptor T-cell (CAR-T) therapies have proven clinical efficacy for the treatment of hematological malignancies. However, CAR-T cell therapies are prohibitively expensive to manufacture. The authors demonstrate the manufacture of human CAR-T cells from multiple donors in an automated stirred-tank bioreactor. The authors successfully produced functional human CAR-T cells from multiple donors under dynamic conditions in a stirred-tank bioreactor, resulting in overall cell yields which were significantly better than in static T-flask culture. At agitation speeds of 200 rpm and greater (up to 500 rpm), the CAR-T cells are able to proliferate effectively, reaching viable cell densities of >5 × 106 cells ml-1 over 7 days. This is comparable with current expansion systems and significantly better than static expansion platforms (T-flasks and gas-permeable culture bags). Importantly, engineered T-cells post-expansion retained expression of the CAR gene and retained their cytolytic function even when grown at the highest agitation intensity. This proves that power inputs used in this study do not affect cell efficacy to target and kill the leukemia cells. This is the first demonstration of human CAR-T cell manufacture in stirred-tank bioreactors and the findings present significant implications and opportunities for larger-scale allogeneic CAR-T production.

Establishing the scalable manufacture of primary human T-cells in an automated stirred-tank bioreactor.

Advanced cell and gene therapies such as chimeric antigen receptor T-cell immunotherapies (CAR-T), present a novel therapeutic modality for the treatment of acute and chronic conditions including acute lymphoblastic leukemia and non-Hodgkin lymphoma. However, the development of such immunotherapies requires the manufacture of large numbers of T-cells, which remains a major translational and commercial bottleneck due to the manual, small-scale, and often static culturing systems used for their production. Such systems are used because there is an unsubstantiated concern that primary T-cells are shear sensitive, or prefer static conditions, and therefore do not grow as effectively in more scalable, agitated systems, such as stirred-tank bioreactors, as compared with T-flasks and culture bags. In this study, we demonstrate that not only T-cells can be cultivated in an automated stirred-tank bioreactor system (ambr® 250), but that their growth is consistently and significantly better than that in T-flask static culture, with equivalent cell quality. Moreover, we demonstrate that at progressively higher agitation rates over the range studied here, and thereby, higher specific power inputs (P/M W kg-1 ), the higher the final viable T-cell density; that is, a cell density of 4.65 ± 0.24 × 106 viable cells ml-1 obtained at the highest P/M of 74 × 10-4 W kg-1 in comparison with 0.91 ± 0.07 × 106 viable cells ml-1 at the lowest P/M of 3.1 × 10-4 W kg-1 . We posit that this improvement is due to the inability at the lower agitation rates to effectively suspend the Dynabeads®, which are required to activate the T-cells; and that contact between them is improved at the higher agitation rates. Importantly, from the data obtained, there is no indication that T-cells prefer being grown under static conditions or are sensitive to fluid dynamic stresses within a stirred-tank bioreactor system at the agitation speeds investigated. Indeed, the opposite has proven to be the case, whereby, the cells grow better under higher agitation speeds while maintaining their quality. This study is the first demonstration of primary T-cell ex vivo manufacture activated by Dynabeads® in an automated stirred-tank bioreactor system such as the ambr® 250 and the findings have the potential to be applied to multiple other cell candidates for advanced therapy applications.

An e-Prehabilitation System of Care for Teenagers and Young Adults Diagnosed With Cancer: Protocol for a Qualitative Co-Design Study.

BACKGROUND: A diagnosis of cancer in young adulthood can pose many different and unique challenges for individuals. The provision of adequate and appropriate information as well as care and support for teenagers and young adults at the time of diagnosis is central to their health care experience going forward. Moreover, appropriate and accessible information provision is critical to ensure that young individuals with cancer feel equipped and empowered to make decisions about, and be involved in, their treatment and recovery throughout their experience; this is a concept known as prehabilitation. As digital interventions and resources that support teenagers and young adults with cancer are an increasingly desirable part of health care provision, this study will focus on the development of an age- and population-appropriate electronic prehabilitation (e-Prehabilitation) system of care. OBJECTIVE: We will conduct an exploratory, co-design research project that will inform the development of an e-Prehabilitation system of care to support teenagers and young adults diagnosed with cancer. A collaborative approach to data collection and prototype design will ensure that a patient-centered approach is embedded throughout. METHODS: A qualitative, co-design study utilizing surveys, interviews, and focus group discussions is being conducted with teenagers and young adults, health care professionals, and technologists. RESULTS: This research study is in progress; recruitment and data collection activities have commenced and findings are expected in early 2019. CONCLUSIONS: The findings of this study will have important implications for informing the future development and evaluation of an e-Prehabilitation system of care to support teenagers and young adults diagnosed with cancer. REGISTERED REPORT IDENTIFIER: RR1-10.2196/10287.

The Role of Magnetic Resonance Imaging in Optimizing Injury Management in Air Force Pararescuemen, Combat Rescue Officers, and Survival Specialists.

Operators perform physically demanding jobs associated with a variety of overuse and acute musculoskeletal injuries. The current management of musculoskeletal complaints in the Air Force includes plane radiographs and 6 weeks of physical therapy (PT) before consideration of orthopedic consultation and magnetic resonance imaging (MRI); however, MRI shows a clear advantage compared with plane radiographs. We conducted a performance improvement project and conclude that (1) MRI allowed for definitive diagnosis as well as definitive triage for care in a timely manner, (2) guidelines for ordering lumbosacral MRIs should be followed and not ordered for pain that is not progressive and severe or not associated with a neurological finding, and (3) because of the risk of X-ray exposure in patients in their 20 and 30s, X-rays should be avoided in this setting unless definitely indicated.

Multivariate monitoring for the industrialisation of a continuous wet granulation tableting process.

The pharmaceutical industry is undergoing a significant change in product development and manufacturing strategies with the progressive shift from batch to continuous processes. These typically feature vast volumes of data generated by the numerous sensors connected to several unit operations running over the period of several hours or even days and that demand the application of increasingly efficient tools for process understanding, monitoring and control. This paper describes the use of multivariate statistical process modeling by means of chemometric methods to monitor the continuous wet granulation tableting process for a drug product currently under development. Models are tailored to the different units that make up the continuous tableting line, from material feeding and granulation up to tablet compression, where the solutions devised reflect the different dynamics of each unit and are used as maintenance and intervention tools to optimise manufacturing and associated operations retrospectively as well as in real-time, as part of the product industrialisation programme.