Radical innovation: making the right bets

Report published by Advanced Institute of Management ResearchOur research reveals that organisations, here in the UK and elsewhere, must face up to the complex challenges associated with exploring and developing radical ideas and innovations if they are to continue to be successful in the long term. ■ Discontinuous innovation – ‘doing something different’ innovation – is often the driver of sustained competitive advantage and shareholder value creation. As such the ability to support radical innovation is an essential organisational competence. ■ The decision-making process in which resources are allocated to innovation projects is extremely challenging, as the degree of uncertainty involved means that using conventional systems and processes often leads to radical ideas being rejected. ■ The research identifies twelve excuses that organisations use to justify their decision not to pursue radical innovation. Organisations must learn to recognise when they are making these excuses and find other ways of evaluating how to behave when faced with radical innovation. ■ The innovation selection environment that operates in organisations can be described in terms of four zones. In two of those zones, new strategies are required for innovation selection decision-making. ■ There are a number of promising strategies that can help organisations to back an innovation winner. These include: building alternative visions; bridge-building to/from outside the box; probe and learn method; using alternative evaluation and measurement criteria; mobilising sponsorship and championship; using alternative decision-making pathways; deploying alternative funding structures; using alternative – dedicated/devolved/decentralised – implementation structures; mobilising entrepreneurship inside and outside the firm. ■ Through a thorough understanding of the innovation selection process, organisations can avoid the pitfalls that lead to abandoning potentially marketwinning radical ideas. At the same time they can learn how to implement strategies that nurture and develop that all-important discontinuous innovation.Engineering and Physical Sciences Research Council (EPSRC)and Economic and Social Research Council (ESRC

In vitro wound healing assays - State of the art

Wound healing is essential for the restoration of the barrier function of the skin. During this process, cells at the wound edges proliferate and migrate, leading to re-epithelialization of the wound surface. Wound healing assays are used to study the molecular mechanisms of wound repair, as well as in the investigation of potential therapeutics and treatments for improved healing. Numerous models of wound healing have been developed in recent years. In this review, we focus on in vitro assays, as they allow a fast, cost-efficient and ethical alternative to animal models. This paper gives a general overview of 2-dimensional (2D) cell monolayer assays by providing a description of injury methods, as well as an evaluation of each assay's strengths and limitations. We include a section reviewing assays performed in 3-dimensional (3D) culture, which employ bioengineered skin models to capture complex wound healing mechanics like cell-matrix interactions and the interplay of different cell types in the healing process. Finally, we discuss in detail available software tools and algorithms for data analysis. © 2016 by De Gruyter

Pancreatic acinar cell carcinoma : an analysis of cell lineage markers, P53 expression, and Ki-ras mutation

In a series of 22 pancreatic acinar cell carcinomas, including two acinar cystadenocarcinomas, cellular differentiation was analyzed by immunocytochemistry and electron microscopy. In addition, overexpression of p53 protein and Ki-ras codon 12 mutation was studied. Four of the 20 noncystic acinar cell carcinomas showed a pure acinar pattern, nine an acinar-solid, and seven a solid pattern. All tumors stained for at least one of the following pancreatic acinar markers: trypsin (21 of 22), lipase (19 of 22), chymotrypsin (13 of 22), phospholipase A2 (nine of 22), and pancreatic stone protein (19 of 22). One-third of the tumors expressed neuroendocrine markers (synaptophysin, eight of 22; chromogranin A, six of 21) and duct cell markers (CA19.9, nine of 21; B72.3, six of 21). Cellular coexpression of trypsin and synaptophysin was demonstrated in one tumor. Electron microscopy revealed zymogen granules (nine of nine). In only one of 16 tumors a Ki-ras mutation at codon 12 was found, whereas in none of 19 tumors could overexpression of p53 protein be demonstrated. The results suggest that acinar cell carcinomas show obvious capacity to differentiate into several directions, but nevertheless constitute an entity different from ductal adenocarcinomas or endocrine tumors

Prevention and management of osteoporotic fractures by non-physician health professionals: a systematic literature review to inform EULAR points to consider

Objective To perform a systematic literature review (SLR) about the effect of non-pharmacological interventions delivered by non-physician health professionals to prevent and manage osteoporotic fractures. Methods Eight clinical questions based on two criteria guided the SLR: (1) adults >= 50 years at high risk of osteoporotic fracture and (2) interventions delivered by non-physician health professionals to prevent and manage osteoporotic fractures. Interventions focused on diagnostic procedures to identify risk of falling, therapeutic approaches and implementation strategies. Outcomes included fractures, falls, risk of falling and change in bone mineral density. Systematic reviews and randomised controlled trials were preferentially selected. Data were synthesised using a qualitative descriptive approach. Results Of 15 917 records, 43 articles were included. Studies were clinically and methodologically diverse. We identified sufficient evidence that structured exercise, incorporating progressive resistance training delivered to people who had undergone hip fracture surgery, and multicomponent exercise, delivered to people at risk of primary fracture, reduced risk of falling. The effectiveness of multidisciplinary fracture liaison services in reducing refracture rate was confirmed. There was insufficient evidence found to support the effectiveness of nutrients and falls prevention programmes in this patient population. Conclusion Despite study heterogeneity, our SLR showed beneficial effects of some interventions delivered by non-physician health professionals and the positive impact of multidisciplinary team working and patient educational approaches to prevent and manage osteoporotic fractures. These results informed a EULAR taskforce that developed points to consider for non-physician health professionals to prevent and manage osteoporotic fractures.This study was funded by the EULAR. Grant reference HPR 032.info:eu-repo/semantics/publishedVersio

Nature-based integration of migrants: A cross-national systematic literature review

Migration is as old as humankind, and the integration of people with a migration background is a hot topic worldwide. The focus on nature-based integration has increased over the last 20 years. Previous reviews discussing nature-based integration have focused mainly on Europe and the USA; this systematic quantitative review provides a global overview of the nature activity patterns, nature experiences, and possible hindrances migrants face. We reviewed 42 studies focusing on nature activity and the experiences of migrants. Our specific research questions were: (1) In the studies, what type of nature activities can be found in which people with a different migration background have participated or preferred? (2) How do nature activities and experiences affect the integration of people with different migration backgrounds? (3) What kind of negative nature experiences can act as hindrances in the integration of people with a migration background? Walking, sport, and gardening are the most reported physical activities by people with a different migration background, but migrants’ nature activity patterns differ at the levels of ethnicity and the individual. Nature activity patterns cannot be generalised for everyone with a different migration background, and tailored individual nature-based integration measures are needed. Elements that can promote integration are social interaction, emotional attachment, and a sense of belonging, whereas possible hindrances to the migrant’s integration are discrimination, the accessibility of nature, and a lack of information and communication. We conclude that nature activities have positive impacts on the integration of people with a migration background, and the human–nature relationship can be further extended to the human–nature–social relationship, but the empirical evidence is lacking, and nature-based integration effectiveness requires further investigation. We identify the need for a shift from nature-based integration to nature-based inclusion. This shift will require a participatory approach to incorporate the voices and experiences of people with a different migration background

The mecC-Harboring Region Is a Recombination Hot Spot in Staphylococcus stepanovicii

Introduction Horizontal gene transfer (HGT) is an important driver for resistance- and virulence factor accumulation in pathogenic bacteria such as Staphylococcus aureus. Methods Here, we have investigated the downstream region of the bacterial chromosomal attachment site (attB) for the staphylococcal cassette chromosome mec (SCCmec) element of a commensal mecC- positive Staphylococcus stepanovicii strain (IMT28705; ODD4) with respect to genetic composition and indications of HGT. S. stepanovicii IMT28705 was isolated from a fecal sample of a trapped wild bank vole (Myodes glareolus) during a screening study (National Network on “Rodent-Borne Pathogens”) in Germany. Whole genome sequencing (WGS) of IMT28705 together with the mecC- negative type strain CM7717 was conducted in order to comparatively investigate the genomic region downstream of attB (GenBank accession no. KR732654 and KR732653). Results The bank vole isolate (IMT28705) harbors a mecC gene which shares 99.2% nucleotide (and 98.5% amino acid) sequence identity with mecC of MRSA_LGA251. In addition, the mecC-encoding region harbors the typical blaZ-mecC-mecR1-mecI structure, corresponding with the class E mec complex. While the sequences downstream of attB in both S. stepanovicii isolates (IMT28705 and CM7717) are partitioned by 15 bp direct repeats, further comparison revealed a remarkable low concordance of gene content, indicating a chromosomal “hot spot” for foreign DNA integration and exchange. Conclusion Our data highlight the necessity for further research on transmission routes of resistance encoding factors from the environmental and wildlife resistome

A Look into the Melting Pot: The mecC-Harboring Region Is a Recombination Hot Spot in Staphylococcus stepanovicii

Publisher's version, source: http://dx.doi.org/10.1371/journal.pone.0147150.INTRODUCTION Horizontal gene transfer (HGT) is an important driver for resistance- and virulence factor accumulation in pathogenic bacteria such as Staphylococcus aureus. METHODS Here, we have investigated the downstream region of the bacterial chromosomal attachment site (attB) for the staphylococcal cassette chromosome mec (SCCmec) element of a commensal mecC-positive Staphylococcus stepanovicii strain (IMT28705; ODD4) with respect to genetic composition and indications of HGT. S. stepanovicii IMT28705 was isolated from a fecal sample of a trapped wild bank vole (Myodes glareolus) during a screening study (National Network on “Rodent-Borne Pathogens”) in Germany. Whole genome sequencing (WGS) of IMT28705 together with the mecC-negative type strain CM7717 was conducted in order to comparatively investigate the genomic region downstream of attB (GenBank accession no. KR732654 and KR732653). RESULTS The bank vole isolate (IMT28705) harbors a mecC gene which shares 99.2% nucleotide (and 98.5% amino acid) sequence identity with mecC of MRSA_LGA251. In addition, the mecC-encoding region harbors the typical blaZ-mecC-mecR1-mecI structure, corresponding with the class E mec complex. While the sequences downstream of attB in both S. stepanovicii isolates (IMT28705 and CM7717) are partitioned by 15 bp direct repeats, further comparison revealed a remarkable low concordance of gene content, indicating a chromosomal “hot spot” for foreign DNA integration and exchange. CONCLUSION Our data highlight the necessity for further research on transmission routes of resistance encoding factors from the environmental and wildlife resistome

Predictors of 30-Day Mortality Among Dutch Patients Undergoing Colorectal Cancer Surgery, 2011-2016

IMPORTANCE Quality improvement programs for colorectal cancer surgery have been introduced with benchmarking based on quality indicators, such as mortality. Detailed (pre)operative characteristics may offer relevant information for proper case-mix correction. OBJECTIVE To investigate the added value of machine learning to predict quality indicators for colorectal cancer surgery and identify previously unrecognized predictors of 30-day mortality based on a large, nationwide colorectal cancer registry that collected extensive data on comorbidities. DESIGN, SETTING, AND PARTICIPANTS All patients who underwent resection for primary colorectal cancer registered in the Dutch ColoRectal Audit between January 1, 2011, and December 31, 2016, were included. Multiple machine learning models (multivariable logistic regression, elastic net regression, support vector machine, random forest, and gradient boosting) were made to predict quality indicators. Model performance was compared with conventionally used scores. Risk factors were identified by logistic regression analyses and Shapley additive explanations (ie, SHAP values). Statistical analysis was performed between March 1 and September 30, 2020. MAIN OUTCOMES AND MEASURES The primary outcome of this cohort study was 30-day mortality. Prediction models were trained on a training set by performing 5-fold cross-validation, and outcomes were measured by the area under the receiver operating characteristic curve on the test set. Machine learning was further used to identify risk factors, measured by odds ratios and SHAP values. RESULTS This cohort study included 62 501 records, most patients were male (35 116 [56.2%]), were aged 61 to 80 years (41 560 [66.5%]), and had an American Society of Anesthesiology score of II (35 679 [57.1%]). A 30-day mortality rate of 2.7% (n = 1693) was found. The area under the curve of the best machine learning model for 30-day mortality (0.82; 95% CI, 0.79-0.85) was significantly higher than the American Society of Anesthesiology score (0.74; 95% CI, 0.71-0.77; P &lt; .001), Charlson Comorbidity Index (0.66; 95% CI, 0.63-0.70; P &lt; .001), and preoperative score to predict postoperative mortality (0.73; 95% CI, 0.70-0.77; P &lt; .001). Hypertension, myocardial infarction, chronic obstructive pulmonary disease, and asthma were comorbidities with a high risk for increased mortality. Machine learning identified specific risk factors for a complicated course, intensive care unit admission, prolonged hospital stay, and readmission. Laparoscopic surgery was associated with a decreased risk for all adverse outcomes. CONCLUSIONS AND RELEVANCE This study found that machine learning methods outperformed conventional scores to predict 30-day mortality after colorectal cancer surgery, identified specific patient groups at risk for adverse outcomes, and provided directions to optimize benchmarking in clinical audits.</p

Growth hormone deficiency in adult survivors of childhood brain tumors treated with radiation

Objective: Growth hormone deficiency (GHD) is the most common endocrine la te effect in irradiated survivors of childhood brain tumors. This study a imed to determine the prevalence of GHD in adults treated with proton or photon irradiation for a brain tumor in childhood and to detect undiagnosed GHD. Design: This study is a cross-sectional study. Methods: We investigated GHD in 5-year survivors from two health region s in Denmark treated for childhood brain tumors with cranial or craniospinal irradiation in the period 1997–2015. Medical charts were reviewed for endocrinological and other health data. Survivors without a growth hormone (GH) test at final height wer e invited to a GH stimulation test. Results: Totally 41 (22 females) survivors with a median age of 21.7 ye ars (range: 15.1– 33.8 years) at follow-up and 14.8 years (range: 5.1–23.4 years) since diagnosis were included; 11 were treated with proton and 30 with photon irradiation; 18 of 21 survivors were previously found to have GHD; 16 of 20 survivors with no G H test at final height were tested, 8 (50 %) had GHD. In total, 26 of 41 patients (63% ) had GHD. Insulin-like growth factor-1 (IGF-1) is associated poorly with the insulin t olerance test (ITT). Conclusion: This study identified a high prevalence of undiagnosed GHD in s urvivors with no GH test at final height. The results stress the importance of screening for GHD at final height in survivors of childhood brain tumors with prior exposure to cranial irradiation, irrespective of radiation modality and IGF-1. Significance statement: This cross-sectional study reports a prevalence of 63% of GHD in irradiated childhood brain tumor survivors. Furthermore, the study identified a considerable number of long-term survivors without a GH test at final height, of whom, 50% subsequently were shown to have undiagnosed GHD. Additional ly, this study confirmed that a normal serum IGF-1 measurement cannot exclude t he diagnosis of GHD in irradiated survivors. This illustrates the need for improvements in the diagnostic approach to GHD after reaching final height in childhood brain t umor survivors at risk of GHD. In summary, our study stresses the need for GHD testing in all adult survivors treated with cranial irradiation for a brain tumor in childhood irrespe ctive of radiation modality