A collaborative approach to exploring the future of Cancer treatment and care in relation to Precision Medicine: A design perspective.

The Precision Medicine and the Future of Cancer project was jointly conceived by the Innovation School at Glasgow School of Art and the Institute of Cancer Sciences at the University of Glasgow. Graduating year Product Design students from the Innovation School were presented with a challenge-based project to produce a vision of the future based on current trends that relate to Precision Medicine(PM) and Cancer treatment. This project involved working closely with scientists, clinicians, patients, industry and academic professionals from Glasgow University, staff at Queen Elizabeth University Hospital and Clinical Innovation Zone, staff at Beatson West of Scotland Cancer Centre, Patient Representatives and external design experts from Studio AndThen and GOODD design consultancy. The objective of this project was to investigate, in both analytical and speculative ways, future forms and functions of cancer treatment and care in relation to Precision Medicine, to develop future scenarios and design artefacts, services, and the experiences associated with them. One of the most significant societal shifts currently taking place within the field of PM is the transformation around what it means to be a patient and a professional working within this context. The public’s role is developing beyond once-passive patients into stakeholders valued within the medical industry and healthcare sector for their participation in clinical trials, and contribution towards policy-making and decision-making committees. This new dynamic is changing the traditional patient-doctor relationship and challenging the hegemony of medical practice at an institutional level. The impetus for this shift is relentless technological acceleration and increased scientific research, in particular driven by advances in PM. This project asked students to consider what will happen in a cancer landscape ten years from now, where PM has evolved to the extent that new forms of medical practice, cancer treatment and care transform how we interact with each other, with professionals and the world around us. The brief gave students the opportunity to reflect on the underlying complexities regarding the future of health, technological acceleration, post-capitalism and human agency, to envision a future world context, develop it as an experiential exhibit, and produce the designed products, services and experiences for the people who might live and work within it. The project was divided into two sections: The first was a collaborative stage where groups of students were assigned a specific area of focus from Social, Technological, Economic, Ethical, Educational, Political, Legal, Ecological [STEEEPLE]. These groups focused on researching and exploring their specific lenses and gathering as much information and understanding while working with external experts to further their knowledge. This group stage culminated in an exhibition of the collaborative understanding of what the future could look like in 10 years from now, after exploring the possible consequences of current actions. The second stage saw students explore their individual response to the world that had been defined in the first stage. Each student had their own response to the research by iteratively creating a design outcome that was appropriate to the subject matter. This culminated in each student having created a design product/service/experience relating to the future scenario. A full report (Project Process Journal [PPJ]) is included within the repository of each student which breaks down their process of designing and the outcome they have designed. The project aims to tackle the emerging possibilities where medical professionals and design can collaborate, to create a future where forms of medical practice are more preventative and are more appropriate for an aging population now and into the future. The deposited materials are arranged as follows: Readme files - two readme files relate to stage one and stage two of the project as outlined above. Overview poster - gives a visual overview of the structure and timeline of the project. Data folders - the data folders for stage one of the project are named for the lens through which each group viewed possible futures. The data folders for stage two of the project are named for the individual students who conducted the work

Impaired microbial N-acyl homoserine lactone signalling increases plant resistance to aphids across variable abiotic and biotic environments

Beneficial bacteria interact with plants using signalling molecules, such as N-acyl homoserine-lactones (AHLs). Although there is evidence that these molecules affect plant responses to pathogens, few studies have examined their effect on plant-insect and microbiome interactions, especially under variable soil conditions. We investigated the effect of the AHL-producing rhizobacterium Acidovorax radicis and its AHL-negative mutant (does not produce AHLs) on modulating barley (Hordeum vulgare) plant interactions with cereal aphids (Sitobion avenae) and earthworms (Dendrobaena veneta) across variable nutrient soils. Acidovorax radicis inoculation increased plant growth and suppressed aphids, with stronger effects by the AHL-negative mutant. However, effects varied between barley cultivars and the presence of earthworms altered interaction outcomes. Bacteria-induced plant defences differed between cultivars, and aphid exposure, with pathogenesis-related and WRKY pathways partly explaining the ecological effects in the more resistant cultivars. Additionally, we observed few but specific indirect effects via the wider root microbiome where the AHL-mutant strain influenced rare OTU abundances. We conclude that bacterial AHL-signalling disruption affects plant-microbial interactions by inducing different plant pathways, leading to increased insect resistance, also mediated by the surrounding biotic and abiotic environment. Understanding the mechanisms by which beneficial bacteria can reduce insect pests is a key research area for developing effective insect pest management strategies in sustainable agriculture

Microbe‐induced plant resistance against insect pests depends on timing of inoculation but is consistent across climatic conditions

Abstract To cope with abiotic and biotic stressors, plants have developed mutualistic associations with beneficial soil microbes, but little is known about how extreme abiotic conditions impact on microbe‐induce resistance to insect herbivores. Extreme temperatures are often accompanied by extremes in plant water availability, which together reduce plant growth and change plant physiology. There are potential consequences for increasing plant susceptibility to biotic stresses, and this poses a real challenge for plant productivity. We evaluated how the effects of beneficial soil bacteria (Acidovorax radicis N35e) on barley plant growth and resultant resistance against aphid infestation (Sitobion avenae) were impacted by a single heatwave event across a plant water availability gradient. We also tested if timing of bacterial inoculation (before or after the temperature treatment) affected bacteria‐plant interactions on aphids. We found that heatwaves affected plant biomass allocation from above‐ground to below‐ground tissues. Inoculation with A. radicis led to reduction of aphid numbers, but depended on timing of inoculation, and led to stronger resistance when inoculations occurred closer to aphid infestation. Remarkably, microbe‐induced resistance against aphids was consistent across heatwave and water availability treatments. This study provides evidence that beneficial plant‐bacteria interactions may represent a potential solution for sustainable agricultural practices to enhance plant growth and response to insect pests under climate change. Future field trials should investigate the consistency of beneficial effects reported here for a better understanding of multispecies interactions in the context of global change. Read the free Plain Language Summary for this article on the Journal blog.</jats:p

Minimally Invasive Thoracoabdominal Esophagectomy Is Superior to Minimally Invasive Gastrectomy in Terms of Health-Related Quality of Life

Background and Objectives:There are two operative approaches for adenocarcinomas of the esophagogastric junction: thoracoabdominal esophagectomy or transhiatal extended gastrectomy. Both procedures can be performed minimally invasively. Dependent on the exact localization of the tumor, both approaches are feasible. Aim of this study was to compare the health-related quality of life (HRQOL) of patients after minimally invasive esophagectomy (MIE) with patients who underwent minimally invasive gastrectomy (MIG). Methods:All patients who underwent MIE or gastrectomy for malignoma since 2014 were identified from our clinical database. The identified patients were contacted and asked to fill out a quality of life questionnaire (QLQ) for general and gastrointestinal QOL (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25). Results:Global HRQOL scores were higher in patients after MIE than after MIG. After MIE, global HRQOL scores were close to the control population. In cancer-specific syndromes, patients after MIE reported lower symptom scores for financial problems, eating, reflux, and eating with others than patients after MIG. Conclusion:In terms of HRQOL, MIE proved superior to MIG in long-term follow-up in this study. Patients after MIE reported a HRQOL close to that of a healthy reference population

Transgender Girls Grow Tall: Adult Height Is Unaffected by GnRH Analogue and Estradiol Treatment

CONTEXT: Transgender adolescents can receive gonadotropin-releasing hormone analogues (GnRH) and gender-affirming hormone therapy (GAHT), but little is known about effects on growth and adult height. This is of interest since height differs between sexes and some transgender girls wish to limit their growth. OBJECTIVE: This work aims to investigate the effects of GnRHa and GAHT on growth, and the efficacy of growth-reductive treatment. METHODS: This retrospective cohort study took place at a specialized tertiary gender clinic. A total of 161 transgender girls were treated with GnRHa and estradiol at a regular dose (2 mg) or high growth-reductive doses of estradiol (6 mg) or ethinyl estradiol (EE, 100-200 µg). Main outcome measures included growth, adult height, and the difference from predicted adult height (PAH) and target height. RESULTS: Growth velocity and bone maturation decreased during GnRHa, but increased during GAHT. Adult height after regular-dose treatment was 180.4 ± 5.6 cm, which was 1.5 cm below PAH at the start GnRHa (95% CI, 0.2 cm to 2.7 cm), and close to target height (-1.1 cm; 95% CI, -2.5 cm to 0.3 cm). Compared to regular-dose treatment, high-dose estradiol and EE reduced adult height by 0.9 cm (95% CI, -0.9 cm to 2.8 cm) and 3.0 cm (95% CI, 0.2 cm to 5.8 cm), respectively. CONCLUSION: Growth decelerated during GnRHa and accelerated during GAHT. After regular-dose treatment, adult height was slightly lower than predicted at start of GnRHa, likely due to systematic overestimation of PAH as described in boys from the general population, but not significantly different from target height. High-dose EE resulted in greater reduction of adult height than high-dose estradiol, but this needs to be weighed against possible adverse effects

Incisional hernia repair by synthetic mesh prosthesis in patients with inflammatory bowel disease: a comparative analysis

Background!#!Patients with inflammatory bowel disease (IBD) have a high-life time risk undergoing abdominal surgery and are prone to develop incisional hernias (IH) in the postoperative course. Therefore, we investigated the role of IBD as perioperative risk factor in open ventral hernia repair (OVHR) as well as the impact of IBD on hernia recurrence during postoperative follow-up.!##!Methods!#!The postoperative course of 223 patients (Non-IBD (n = 199) and IBD (n = 34)) who underwent OVHR were compared by means of extensive group comparisons and binary logistic regressions. Hernia recurrence was investigated in the IBD group according to the Kaplan-Meier method and risk factors for recurrence determined by Cox regressions.!##!Results!#!General complications (≥ Clavien-Dindo I) occurred in 30.9% (72/233) and major complications (≥ Clavien-Dindo IIIb) in 7.7% (18/233) of the overall cohort with IBD being the single independent risk-factor for major complications (OR = 4.2, p = 0.007). Further, IBD patients displayed a recurrence rate of 26.5% (9/34) after a median follow-up of 36 months. Multivariable analysis revealed higher rates of recurrence in patients with ulcerative colitis (UC, 8/15, HR = 11.7) compared to patients with Crohn's disease (CD, 1/19, HR = 1.0, p = 0.021).!##!Conclusion!#!IBD is a significant risk factor for major postoperative morbidity after OVHR. In addition, individuals with IBD show high rates of hernia recurrence over time with UC patients being more prone to recurrence than patients with CD

Just as tall on testosterone; a neutral to positive effect on adult height of GnRHa and testosterone in trans boys

CONTEXT: Growth is an important topic for many transgender boys. However, few studies have investigated the impact of puberty suppression (PS) and gender affirming hormone treatment (GAHT) on growth and adult height. OBJECTIVE: To evaluate the effect of PS and GAHT on growth and adult height. DESIGN: Retrospective cohort study. SETTING: Specialised gender identity clinic. PARTICIPANTS: 146 transgender boys treated with GnRH analogues and testosterone who reached adult height. MAIN OUTCOME MEASURES: Growth, bone age (BA), adult height, and difference between adult height and predicted adult height (PAH) and midparental height. RESULTS: In those with BA ≤14 year at start (n = 61), a decrease in growth velocity and bone maturation during PS was followed by an increase during GAHT. Adult height was 172.0 ± 6.9 cm; height SDS was similar to baseline (0.1, 95% CI -0.2 to 0.4). Adult height was 3.9 ± 6.0 cm above midparental height and 3.0 ± 3.6 cm above PAH at start of PS. A younger BA at start PS was associated with an adult height significantly further above PAH. CONCLUSION: During PS, growth decelerated followed by an acceleration during GAHT. Although adult height SDS was similar to baseline, adult height was taller than predicted based on BA at baseline, especially in those who started treatment at a younger BA. It is reassuring that PS and GAHT do not have a negative impact on adult height in transgender boys and might even lead to a slightly taller adult height, especially in those who start at a younger age

Machine learning prediction model for postoperative outcome after perforated appendicitis

Purpose Appendectomy for acute appendicitis is one of the most common operative procedures worldwide in both childrenand adults. In particular, complicated (perforated) cases show high variability in individual outcomes. Here, we developedand validated a machine learning prediction model for postoperative outcome of perforated appendicitis.Methods Retrospective analyses of patients with clinically and histologically verified perforated appendicitis over 10 yearswere performed. Demographic and surgical baseline characteristics were used as competing predictors of single-patient out-comes along multiple dimensions via a random forest classifier with stratified subsampling. To assess whether complicationscould be predicted in new, individual cases, the ensuing models were evaluated using a replicated 10-fold cross-validation.Results A total of 163 patients were included in the study. Sixty-four patients underwent laparoscopic surgery, whereasninety-nine patients got a primary open procedure. Interval from admission to appendectomy was 9 ± 12 h and duration ofthe surgery was 74 ± 38 min. Forty-three patients needed intensive care treatment. Overall mortality was 0.6 % and morbid-ity rate was 15%. Severe complications as assessed by Clavien-Dindo > 3 were predictable in new cases with an accuracyof 68%. Need for ICU stay (> 24 h) could be predicted with an accuracy of 88%, whereas prolonged hospitalization (greaterthan 7–15 days) was predicted by the model with an accuracy of 76%.Conclusion We demonstrate that complications following surgery, and in particular, health care system-related outcomeslike intensive care treatment and extended hospitalization, may be well predicted at the individual level from demographicand surgical baseline characteristics through machine learning approaches

Ultra-Fine Polyethylene Hernia Meshes Improve Biocompatibility and Reduce Intraperitoneal Adhesions in IPOM Position in Animal Models

(1) Introduction: The intraperitoneal onlay mesh technique (IPOM) is widely used to repair incisional hernias. This method has advantages but suffers from complications due to intraperitoneal adhesion formation between the mesh and intestine. An ideal mesh minimizes adhesions and shows good biocompatibility. To address this, newly developed multifilamentous polyethylene (PET) meshes were constructed from sub-macrophage-sized monofilaments and studied regarding biocompatibility and adhesion formation. (2) Methods: We investigated fine (FPET, 72 filaments, 11 &micro;m diameter each) and ultra-fine multifilament (UFPET, 700 filaments, 3 &micro;m diameter each) polyethylene meshes for biocompatibility in subcutaneous implantation in rats. Adhesion formation was analyzed in the IPOM position in rabbits. Geometrically identical mono-filamentous polypropylene (PP) Bard Soft&reg; PP meshes were used for comparison. Histologic and immune-histologic foreign body reactions were assessed in 48 rats after 7 or 21 days (four mesh types, with two different mesh types per rat; n = 6 per mesh type). Additionally, two different mesh types each were placed in the IPOM position in 24 rabbits to compile the Diamond peritoneal adhesion score after the same timeframes. The biocompatibility and adhesion score differences were analyzed with the Kruskal&ndash;Wallis nonparametric statistical test. (3) Results: Overall, FPET and, especially, UFPET showed significantly smaller foreign body granulomas compared to PP meshes. Longer observation periods enhanced the differences. Immunohistology showed no significant differences in the cellular immune response and proliferation. UFPET demonstrated significantly reduced peritoneal adhesion formation compared to all other tested meshes after 21 days. (4) Conclusions: Overall, FPET and, especially, UFPET demonstrated their suitability for IPOM hernia meshes in animal models by improving major aspects of the foreign body reaction and reducing adhesion formation