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Friction stir processing (FSP) is a solid-state processing technique that has proven to be an efficient surface modification process for producing aluminium matrix composites (AMCs). However, practical challenges still occur during the processing of AMCs even though extensive progress has been made in recent years. In the present study, the influence of FSP process parameters on the tensile property of Al-Ni-Fe composite has been investigated. The process parameters studied were rotational speed and advancing speed. The rotational speed varied between 600 and 1000 rpm while the advancing speed varied between 70 and 210 mm/min. The rotational speed was kept constant at each setting and the advancing speed varied. Other processing parameters were kept constant throughout the experiments. The results were compared with those of the base metal (Al). The results showed that the tensile strength decreased as the advancing speed increased. The highest tensile strength was obtained at a rotational speed of 1000 rpm and an advancing speed of 70 mm/min.

Aluminium alloys has been favoured in many applications because of its exciting properties which include light weight and corrosion resistance. However, susceptibility to pitting corrosion and intergranular corrosion (IGC) are some of the drawbacks of aluminium. The surface of aluminium can be modified to improve its corrosion resistance properties. Surface modification is a surface engineering process that is performed to alter the properties of material surface to improve its service life. Friction stir processing (FSP) is a relatively new and an important solid state material surface modification process. In this study, investigation on the influence of FSP processing parameters on the resulting corrosion resistance surface properties of pure commercial aluminium and Ni-40Fe-10Ti surface composite using friction stir processing technique was conducted. The processing parameters that were studied are tool rotational speed and transverse speed, while all other processing parameters were kept constant. The corrosion behaviour was studied using three-electrode electrochemical cell, and the microstructure of the corroded samples was studied using optical microscope (OM). The results showed that the addition of Ni, Fe and Ti caused a decrease in the anodic and cathodic current densities. The set of processing parameters that resulted in the lowest corrosion rate are the rotational speed of 600 rpm and transverse speed of 70 mm/min.

An international project developed, quality-tested, and measured isotope-delta values of 10 new food matrix reference materials (RMs) for hydrogen, carbon, nitrogen, oxygen, and sulfur stable isotope-ratio measurements to support food authenticity testing and food provenance verification. These new RMs, USGS82 to USGS91, will enable users to normalize measurements of samples to isotope-delta scales. The RMs include (i) two honeys from Canada and tropical Vietnam, (ii) two flours from C3 (rice) and C4 (millet) plants, (iii) four vegetable oils from C3 (olive, peanut) and C4 (corn) plants, and (iv) two collagen powders from marine fish and terrestrial mammal origins. An errors-in-variables regression model included the uncertainty associated with the measured and assigned values of the RMs, and it was applied centrally to normalize results and obtain consensus values and measurement uncertainties. Utilization of these new RMs should facilitate mutual compatibility of stable isotope data if accepted normalization procedures are applied and documented.

STATEMENT: The International Society for Cellular and Gene Therapies (ISCT) and the International Society for Extracellular Vesicles (ISEV) recognize the potential of extracellular vesicles (EVs, including exosomes) from mesenchymal stromal cells (MSCs) and possibly other cell sources as treatments for COVID-19. Research and trials in this area are encouraged. However, ISEV and ISCT do not currently endorse the use of EVs or exosomes for any purpose in COVID-19, including but not limited to reducing cytokine storm, exerting regenerative effects or delivering drugs, pending the generation of appropriate manufacturing and quality control provisions, pre-clinical safety and efficacy data, rational clinical trial design and proper regulatory oversight. (C) 2020 International Society for Cell and Gene Therapy. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Background The panel of fluid- and imaging-based biomarkers available for neurodegenerative disease research is growing and has the potential to close important gaps in research and the clinic. With this growth and increasing use, appropriate implementation and interpretation are paramount. Various biomarkers feature nuanced differences in strengths, limitations, and biases that must be considered when investigating disease etiology and clinical utility. For example, neuropathological investigations of Alzheimer’s disease pathogenesis can fall in disagreement with conclusions reached by biomarker-based investigations. Considering the varied strengths, limitations, and biases of different research methodologies and approaches may help harmonize disciplines within the neurodegenerative disease field. Purpose of review Along with separate review articles covering fluid and imaging biomarkers in this issue of Alzheimer’s Research and Therapy, we present the result of a discussion from the 2019 Biomarkers in Neurodegenerative Diseases course at the University College London. Here, we discuss themes of biomarker use in neurodegenerative disease research, commenting on appropriate use, interpretation, and considerations for implementation across different neurodegenerative diseases. We also draw attention to areas where biomarker use can be combined with other disciplines to understand issues of pathophysiology and etiology underlying dementia. Lastly, we highlight novel modalities that have been proposed in the landscape of neurodegenerative disease research and care.

Background: Despite increased recognition of cognitive impairment in Multiple System Atrophy (MSA), its neuroanatomical correlates are not well defined. We aimed to explore cognitive profiles in MSA with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) and their relationship to frontostriatal structural and metabolic changes. Methods: Detailed clinical and neuropsychological evaluation was performed together with diffusion tensor imaging (DTI) and [ 18F]-fluoro-deoxyglucose positron emission tomography ([ 18F]-FDG-PET) in patients with MSA-P (n = 11) and PD (n = 11). We compared clinical and neuropsychological data to healthy controls (n = 9) and correlated neuropsychological data with imaging findings in MSA-P and PD. Results: Patients with MSA-P showed deficits in executive function (Trail Making Test B-A) and scored higher in measures of depression and anxiety compared to those with PD and healthy controls. Widespread frontostriatal white matter tract reduction in fractional anisotropy was seen in MSA-P and PD compared to an imaging control group. Stroop Test interference performance correlated with [ 18F]-FDG uptake in the bilateral dorsolateral prefrontal cortex (DLPFC) and with white matter integrity between the striatum and left inferior frontal gyrus (IFG) in PD. Trail Making Test performance correlated with corticostriatal white matter integrity along tracts from the bilateral IFG in MSA-P and from the right DLPFC in both groups. Conclusion: Executive dysfunction was more prominent in patients with MSA-P compared to PD. DLPFC metabolism and frontostriatal white matter integrity seem to be a driver of executive function in PD, whereas alterations in corticostriatal white matter integrity may contribute more to executive dysfunction in MSA-P.

The threat of bovine respiratory disease (BRD) for cattle operations is exacerbated by increasing prevalence of antimicrobial resistance (AMR) in Mannheimia haemolytica, a leading cause of BRD. Characterization of AMR in M. haemolytica by culture and susceptibility testing is complicated by uncertainty regarding the number of colonies that must be selected to accurately characterize AMR phenotypes (antibiograms) and genotypes in a culture. The study objective was to assess phenotypic and genotypic diversity of M. haemolytica isolates on nasopharyngeal swabs (NPS) from 28 cattle at risk for BRD or with BRD. NPS were swabbed onto five consecutive blood agar plates; after incubation up to 20 M. haemolytica colonies were selected per plate (up to 100 colonies per NPS). Phenotype was determined by measuring minimum inhibitory concentrations (MIC) for 11 antimicrobials and classifying isolates as resistant or not. Genotype was indirectly determined by matrix-assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF MS). NPS from 11 of 28 cattle yielded at least one M. haemolytica isolate; median (range) of isolates per NPS was 48 (1–94). NPS from seven cattle yielded one phenotype, 3 NPS yielded two, and 1 NPS yielded three; however, within a sample all phenotypic differences were due to only one MIC dilution. On each NPS all M. haemolytica isolated were the same genotype; genotype 1 was isolated from three NPS and genotype two was isolated from eight. Diversity of M. haemolytica on bovine NPS was limited, suggesting that selection of few colonies might adequately identify relevant phenotypes and genotypes.

BackgroundSafe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed to select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar to those in adults, and was safe and well tolerated in young children.MethodsInternational Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is a phase 1-2 ongoing multicentre, open-label, non-comparative study of dolutegravir. A 5 mg dispersible tablet formulation of dolutegravir was studied in children aged 4 weeks to less than 6 years old, weighing at least 3 kg, with HIV RNA of greater than 1000 copies per mL and no previous treatment with integrase strand transfer inhibitor recruited from IMPAACT clinical research sites in Africa, the Americas, and Asia. Doses were selected on the basis of intensive pharmacokinetic evaluation on days 5-10, with safety and tolerability assessed up to 48 weeks. The primary objectives of this study are to evaluate the pharmacokinetics of dolutegravir in combination with optimised background therapy and to establish the dose of dolutegravir that achieves the targeted 24-h trough concentration and 24-h area under the curve for infants, children, and adolescents with HIV-1, to establish the safety and tolerability of dolutegravir at 24 and 48 weeks, and to select a dose that achieves similar exposure to the dolutegravir 50 mg once daily dose in adults. This analysis included participants treated with the proposed dose of dolutegravir dispersible tablets in two stages for each of three age cohorts. This trial is registered at ClinicalTrials.gov (NCT01302847) and is ongoing.FindingsWe recruited 181 participants from April 20, 2011, to Feb 19, 2020; of these, 96 received dolutegravir dispersible tablets. This analysis included 73 (35, 48% female) participants who received the final proposed dose with median (range) age of 1 year (0·1 to 6·0), weight (minimum-maximum) of 8·5 kg (3·7 to 18·5), plasma HIV-1 RNA concentration of 4·2 log10 copies per mL (2·1 to 7·0), and CD4% of 24·0% (0·3 to 49·0); 64 (87·7%) were treatment-experienced. The selected dose within each age cohort (≥2 years to

This research was conducted to determine whether early participation in cardiac rehabilitation (CR) reduces readmissions following heart failure (HF) hospitalization.A retrospective quasiexperimental comparison group design was used. Electronic medical records were abstracted for HF patients discharged between March 2013 and December 2017. The treatment group was defined as patients with HF who attended ≥1 CR session within 6 wk following discharge. The comparison group was defined as patients with HF without additional HF hospitalizations during the previous year, discharged to home/self-care, and did not attend CR within 6 wk. Readmission rates at 30 d and 6 wk were compared between groups using χ 2 analysis and logistic regression.Out of 8613 patients with HF, 205 (2.4%) attended ≥1 CR within 6 wk post-discharge. The treatment group had lower, but not statistically significant, readmission rates than the comparison group for 30-d readmissions for HF ( P = .13), and 6-wk readmission rates for HF ( P = .05). The treatment group had lower all-cause readmissions at 30 d (P.01) and 6 wk ( P.01) than the comparison group. Multivariable logistic regression revealed that early CR attendance was associated with reduced 30-d all-cause readmissions (adjusted OR = 0.4: 95% CI, 0.2-0.7) and 6-wk all-cause readmissions (adjusted OR = 0.5: 95% CI, 0.3-0.8).This study contributes to the existing evidence for allowing early unrestricted CR participation with the aim of improving the health of patients with HF and reducing rehospitalization rates.

BACKGROUND: Markers of cerebrovascular disease are common in dementia, and may be present before dementia onset. However, their clinical relevance in midlife adults at risk of future dementia remains unclear. We investigated whether the Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score was associated with markers of cerebral small vessel disease (SVD), and if it predicted future progression of SVD. We also determined its relationship to systemic inflammation, which has been additionally implicated in dementia and SVD. METHODS: Cognitively healthy midlife participants were assessed at baseline (n=185) and 2-year follow-up (n=158). To assess SVD, we quantified white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), microbleeds and lacunes. We derived composite scores of SVD burden, and subtypes of hypertensive arteriopathy and cerebral amyloid angiopathy. Inflammation was quantified using serum C-reactive protein (CRP) and fibrinogen. RESULTS: At baseline, higher CAIDE scores were associated with all markers of SVD and inflammation. Longitudinally, CAIDE scores predicted greater total (p, Research grants from the UK Alzheimer's Society, the US Alzheimer’s Association and philanthropic donations. This work was funded by a grant for the PREVENT-Dementia programme from the UK Alzheimer’s Society (grant numbers 178 and 264), and the PREVENT-Dementia study is also supported by the US Alzheimer’s Association (grant number TriBEKa-17–519007) and philanthropic donations. AL is supported by the Lee Kuan Yew Fitzwilliam PhD Scholarship and the Tan Kah Kee Postgraduate Scholarship. JDS is a Wellcome clinical PhD fellow funded on grant 203914/Z/16/Z to the Universities of Manchester, Leeds, Newcastle and Sheffield. EM is supported by Alzheimer’s Society Junior Research Fellowship (RG 9611). LS is supported by the Cambridge NIHR Biomedical Research Centre (BRC) and Alzheimer’s Research UK (ARUK-SRF2017B-1). HSM is supported by an NIHR Senior Investigator award. JOB and HSM receive infrastructural support from the Cambridge NIHR Biomedical Research Centre (BRC). This research was supported by the NIHR Cambridge BRC (BRC-1215-20014). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Acknowledgements: This work received financial support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EMIF grant agreement no. 115372. This work also received in-kind sponsoring from GE Healthcare in the form of flutemetamol cassettes for production of the radiotracer at the Wolfson Molecular Imaging Centre using GE’s FASTlab system. This work has also been supported by the Erasmus+ programme of the European Union. The European Commission support for the production of this publication does not constitute an endorsement of the contents which reflects the views only of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein. SFC is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. We are very grateful to the individuals who participated in this study and their long dedication to ageing research. This study also would not have been possible without operational support colleagues at the Wolfson Molecular Imaging Centre and the research nurses and radiographers at the NIHR Manchester Clinical Research Facility within Manchester Royal Infirmary., Funder: EU/EFPIA Innovative Medicines Initiative Joint Undertaking EMIF grant agreement #°115372 NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), Amyloid-beta (Aβ) deposition is common in cognitively unimpaired (CU) elderly >85 years. This study investigated amyloid distribution and evaluated three published in vivo amyloid-PET staging schemes from a cognitively unimpaired (CU) cohort aged 84.9 ± 4.3 years (n = 75). SUV-based principal component analysis (PCA) was applied to 18F-flutemetamol PET data to determine an unbiased regional covariance pattern of tracer uptake across grey matter regions. PET staging schemes were applied to the data and compared to the PCA output. Concentration of p-tau181 was measured in blood plasma. The PCA revealed three distinct components accounting for 91.2% of total SUV variance. PC1 driven by the large common variance of uptake in neocortical and striatal regions was significantly positively correlated with global SUVRs, APOE4 status and p-tau181 concentration. PC2 represented mainly non-specific uptake in typical amyloid-PET reference regions, and PC3 the occipital lobe. Application of the staging schemes demonstrated that the majority of the CU cohort (up to 93%) were classified as having pathological amount and distribution of Aβ. Good correspondence existed between binary (+/-) classification and later amyloid stages, however, substantial differences existed between schemes for low stages with 8-17% of individuals being unstageable, i.e., not following the sequential progression of Aβ deposition. In spite of the difference in staging outcomes there was broad spatial overlap between earlier stages and PC1, most prominently in default mode network regions. This study critically evaluated the utility of in vivo amyloid staging from a single PET scan in CU elderly and found that early amyloid stages could not be consistently classified. The majority of the cohort had pathological Aβ, thus, it remains an open topic what constitutes abnormal brain Aβ in the oldest-old and what is the best method to determine that.

Extracellular vesicles (EVs) are small cargo‐bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell‐to‐cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes. These small biological particles are also deregulated in disease. As we approach the 75th anniversary of the first experiments in which EVs were unknowingly isolated, it seems right to take stock and look back on how the field started, and has since exploded into its current state. Here we review the early experiments, summarise key findings that have propelled the field, describe the growth of an organised EV community, discuss the current state of the field, and identify key challenges that need to be addressed.

Sub-Saharan Africa suffers from a persistent shortage of engineering skills required to drive industry in this dynamic era of rapid technological changes. This has been exacerbated by the mismatch of skills produced by universities and those required by industry, partly attributed to lack of access to modern equipment and technology by engineering academics to adequately dispatch appropriate skills to future engineers. A recent audit conducted in Zimbabwe revealed a 62% skills deficit, mainly in the engineering and technology sectors. The University of Zimbabwe, in collaboration with six other institutions of higher learning in Southern Africa embarked on and successfully managed the Enriching Engineering Education Program from 2013 to 2015, financially supported by the Royal Academy of Engineering. This project was aimed at enhancing the quality and relevance of engineering graduates and this was accomplished through secondments of engineering academics to industry to improve their skills and access to modern equipment, knowledge sharing workshops and conferences to boost the quality of research as well as continuous professional development training for engineering academics and technicians. This initiative was largely successful, based on student evaluations, buy-in and support from local industries as well as the number of industrial design projects and innovations that were generated, some of which have since been patented and commercialized. These achievements motivated other institutions to join and the initiative has been expanded to the Higher Education Partnerships for Sub-Saharan Africa. This paper outlines the activities and achievements of this initiative and demonstrates how the expanded version will utilize two approaches of design thinking and systems thinking for capacity building and sustainability in engineering education and regional integration.

Burnout results from experiencing persistent work-related stressors. We introduce and update a model of whole-person well-being to manage or mitigate the stressors that may otherwise generate burnout. The updated model incorporates Nursing Leadership Influence on Professional Burnout. The model was affirmed by original research at Carilion Clinic, Roanoke, Virginia, with 1296 nurses. Nurses exhibiting higher socio-relational well-being and lower depersonalization of patients experienced far lower emotional exhaustion—a core element of burnout and depression. Practical actions nurse leaders can take to promote greater well-being among nurses are reviewed.

Extracellular vesicles (EVs) are small lipid-enclosed particles that can carry various types of cargo, including proteins, nucleic acids and metabolites. They are known to be released by all cell types and can be taken up by other cells, leading to the transfer of the cargo they carry. As such, they represent an important type of intercellular signalling and a natural mechanism for transferring macromolecules between cells. This ability to transfer cargo could be harnessed to deliver therapeutic molecules. Indeed, a growing body of work has described the attempt by the field to utilise EVs to deliver a range of therapeutics including RNAi, CRISPR/Cas9 and chemotherapeutics, to a specific target tissue. However, there are numerous barriers associated with the use of EVs as therapeutic vehicles, including the challenge of efficiently loading therapeutics into EVs, avoiding clearance of the EVs from circulation, targeting the correct tissue type and the inefficiency of internalisation and functional delivery of the cargo. Despite these difficulties, EVs represent a tremendous therapeutic opportunity, both for the delivery of exogenous cargo, as well as the therapeutic benefit of targeting aberrant EV signalling or treating patients with natural EVs, such as those released by mesenchymal stem cells. This review describes current knowledge on the therapeutic potential of EVs and the challenges faced by the field. Many of these challenges are due to a lack of complete understanding of EV function, but further research in this area should continue to yield new solutions that will lead to the use of EVs in the clinic.

Objectives There has been significant discussion about the quality of burnout research, especially with regard to abbreviated measurements of burnout and/or well-being. The purpose of this study was to compare a single-item, investigator-developed question measuring perceived well-being with validated multi-item measures of burnout and well-being. Methods Between 2016 and 2017, healthcare professionals and medical students at a large academic hospital system were sent an online survey measuring the risk of burnout (Maslach Burnout Inventory), well-being (Physician or Nurse Well-Being Self-Assessment Tool), and perception of personal well-being (Burnout-Thriving Index [BTI], an investigator-developed, single-item measure). Analyses included linear and multiple regression and Pearson correlations. Results The study sample included 1365 medical students, frontline nurses, resident physicians, supervising physicians or fellows, and advanced care practitioners. There were significant differences in all Maslach Burnout Inventory and Physician or Nurse Well-Being Self-Assessment Tool subscale scores based on BTI score (all P 80% sensitivity for high emotional exhaustion, depersonalization, and low personal accomplishment. Conclusions The BTI may be used to screen for individuals who could benefit from completing a full burnout assessment and may be used to collect a quick "big picture" impression of burnout and well-being at a healthcare institution. Further research is needed to compare BTI score with known consequences of burnout and to explore differences in the relation between BTI score and psychoemotional wellness in different professional groups.

We present three children with tinea incognito initially misdiagnosed as allergic contact dermatitis to face masks. All three patients presented with pruritic erythematous patches and plaques across the malar cheek and nose. This case series suggests that clinicians should keep a broad differential when evaluating mask-related facial dermatoses in children.

Acute myocardial infarction rapidly increases blood neutrophils (2 hours). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 hours after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (30 minutes) release of extracellular vesicles (EVs), which have emerged as an important means of cell-cell signalling and are thus a potential mechanism for communicating with remote tissues.Here, we show that injury to the myocardium rapidly mobilises neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to arrival at the injured tissue. Time course analysis of plasma EV composition revealed a rapid and selective increase in EVs bearing VCAM-1. These EVs, which were also enriched for miRNA-126, accumulated preferentially in the spleen where they induced local inflammatory gene and chemokine protein expression, and mobilised splenic-neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing we generated VCAM-1-deficient EC-EVs and showed that its deletion removed the ability of EC-EVs to provoke the mobilisation of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model.Our findings show a novel EV-dependent mechanism for the rapid mobilisation of neutrophils to peripheral blood from a splenic reserve and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells.Peripheral blood neutrophils are rapidly elevated following acute myocardial infarction (AMI) and prior to alterations in systemic cytokines. Extracellular vesicles (EVs) are membrane enclosed particles that carry protein and miRNAs and are rapidly liberated from endothelial cells (EC). Here, we show that following AMI EC-derived-EVs (EC-EVs) mediate neutrophil mobilisation from the spleen via EC-EV-VCAM-1 and induce transcriptional activation of neutrophils in the blood to favour miRNA-126-mRNA targets; miRNA-126 antagomir treatment lowers infarct size. EC-EV-VCAM-1 and EC-EV-miRNA-126 are novel mechanisms that mobilise splenic reserve of neutrophils, a previously unidentified source of neutrophils in sterile ischaemic injury.

Synopsis Free-swimming planktonic larvae are a key stage in the development of many marine phyla, and studies of these organisms have contributed to our understanding of major genetic and evolutionary processes. Although transitory, these larvae often attain a remarkable degree of tissue complexity, with well-defined musculature and nervous systems. Among the best studied are larvae belonging to the phylum Echinodermata, but with work largely focused on the pluteus larvae of sea urchins (class Echinoidea). The greatest diversity of larval strategies among echinoderms is found in the class Asteroidea (sea stars), organisms that are rapidly emerging as experimental systems for genetic and developmental studies. However, the bipinnaria larvae of sea stars have only been studied in detail in a small number of species and although they have been relatively well described neuro-anatomically, they are poorly understood neurochemically. Here, we have analyzed embryonic development and bipinnaria larval anatomy in the common North Atlantic sea star Asterias rubens, using a variety of staining methods in combination with confocal microscopy. Importantly, the chemical complexity of the nervous system of bipinnaria larvae was revealed through use of a diverse set of antibodies, with identification of at least three centers of differing neurochemical signature within the previously described nervous system: the anterior apical organ, oral region, and ciliary bands. Furthermore, the anatomy of the musculature and sites of cell division in bipinnaria larvae was analyzed. Comparisons of developmental progression and molecular anatomy across the Echinodermata provided a basis for hypotheses on the shared evolutionary and developmental processes that have shaped this group of animals. We conclude that bipinnaria larvae appear to be remarkably conserved across ∼200 million years of evolutionary time and may represent a strong evolutionary and/or developmental constraint on species utilizing this larval strategy.

Background Acute myocardial infarction (AMI) induces transcriptional activation of monocytes en route to the injured myocardium, in part driven by endothelial cell derived extracellular vesicles (EC-EV), which contain proteins and microRNA (miRNA) cargo. However, neutrophils are the first immune cells to arrive at sites of injury and mediate further damage to the ischemic myocardium. Here, we describe for the first time how neutrophils are released from the spleen in AMI and show that this is driven by EC-EV signalling. Methods and results Experimental AMI in wild-type mice caused a significant increase in peripheral blood neutrophils and a simultaneous reduction in splenic-neutrophil number (P Conclusions (I) Neutrophil deployment from the spleen is a novel finding in acute injury and interactions with (II) EC-EV may mediate their splenic liberation and (III) activation following AMI, en route to the injured myocardium. The splenic neutrophil reserve may be a novel therapeutic target in AMI to modulate the inflammatory response before recruitment of cells to sites of injury.

Simple Summary Drug resistance still represents the main reason for therapy failure in cancer patients. In the last decade, extracellular vesicles (EVs), a heterogeneous group of particles implicated in cell-to-cell communication, have been shown to substantially contribute to this phenomenon. This review summarizes the molecular mechanisms underlying the EV-mediated development of chemoresistance, shedding light on the potential role of these vesicles as both diagnostic/prognostic markers and therapeutic targets. Abstract Extracellular vesicles (EVs) have recently emerged as crucial modulators of cancer drug resistance. Indeed, it has been shown that they can directly sequester anti-tumor drugs, decreasing their effective concentration at target sites. Moreover, they facilitate the horizontal transfer of specific bioactive cargoes able to regulate proliferative, apoptotic, and stemness programs in recipient cells, potentially conferring a resistant phenotype to drug-sensitive cancer cells. Finally, EVs can mediate the communication between the tumor and both stromal and immune cells within the microenvironment, promoting treatment escape. In this context, clarifying the EV-driven resistance mechanisms might improve not only tumor diagnosis and prognosis but also therapeutic outcomes. Detailed cellular and molecular events occurring during the development of EV-mediated cancer drug resistance are described in this review article.

Free-swimming planktonic larvae are a key stage in the development of many marine phyla, and studies of these organisms have contributed to our understanding of major genetic and evolutionary processes. Although transitory, these larvae often attain a remarkable degree of tissue complexity, with well-defined musculature and nervous systems. Amongst the best studied are larvae belonging to the phylum Echinodermata, but with work largely focused on the pleuteus larvae of sea urchins (class Echinoidea). The greatest diversity of larval strategies amongst echinoderms is found in the class Asteroidea (sea-stars), organisms that are rapidly emerging as experimental systems for genetic and developmental studies. However, the bipinnaria larvae of sea stars have only been studied in detail in a small number of species and the full complexity of the nervous system is, in particular, poorly understood. Here we have analysed embryonic development and bipinnaria larval anatomy in the common North Atlantic sea-starAsterias rubens, employing use of a variety of staining methods in combination with confocal microscopy. Importantly, the complexity of the nervous system of bipinnaria larvae was revealed in greater detail than ever before, with identification of at least three centres of neuronal complexity: the anterior apical organ, oral region and ciliary bands. Furthermore, the anatomy of the musculature and sites of cell division in bipinnaria larvae were analysed. Comparisons of developmental progression and molecular anatomy across the Echinodermata provided a basis for hypotheses on the shared evolutionary and developmental processes that have shaped this group of animals. We conclude that bipinnaria larvae appear to be remarkably conserved across ~200 million years of evolutionary time and may represent a strong evolutionary and/or developmental constraint for species utilizing this larval strategy.

The ultimate expectation from any innovations that are nurtured through incubation and product development was to commercialise them for wealth creation, entrepreneurships and industrialisation. Several centres of excellence have been established in Southern Africa, either housed at or in collaboration with tertiary institutions, some of which have been actively involved in incubation of innovative ideas and start-ups. However, most of these innovations have not been taken beyond the innovation hubs due to several reasons such as lack of investors and adequate support from government or industry. This chapter explores ways in which ideas generated by academics can be ‘nourished’ and packaged to attract investment from industry in order to prepare them for start-ups that can be commercialised and possibly from which spin-off companies can emerge. This was accomplished by considering typical cases of this nature at universities in Southern Africa, with a view to use the developed knowledge to encourage the bridging of the gap between academia and industry.

Despite rapid and dynamic changes in technology and the disruptive but necessary innovations orchestrated by the fourth Industrial Revolution that required the production of goods and services in industry to be driven by technology and knowledge transfer from tertiary institutions, the gap between academia and industry remained wide. This has been attributed to several reasons including the shortages and mismatch of skills between those produced by universities and those required by industry. This book focuses on research carried out in Southern Africa to address these challenges using systems thinking modelling as detailed in the previous chapters. This is the penultimate chapter that integrates the various sub-models to universally model the bridge between academia and industry under the broad categories of technology, training and policies. The case studies used in the book and indeed this chapter were derived from institutions and industries collaborating under the Southern Africa Engineering Education Network (SAE2Net). The various avenues proposed in the book were verified and validated for their usefulness and the impact they had on bringing industry closer to academia.

While collaborations between polytechnics and industry existed and were well pronounced in the earlier revolutions where apprenticeship training was key to driving industry, the relationship between industry and universities was not well pronounced. The transformations in the engineering education sector, especially from the third to the fourth Industrial Revolution, saw the introduction of industrial attachments for both the traditional and technical universities. This was partly in response to the demands for appropriate skills due to the fourth Industrial Revolution and it was also meant to address the gap created by the conversion of polytechnics to universities. This chapter focusses on the collaborations between various tertiary institutions, both the traditional and technical universities, and industry partners in Southern Africa from 2011 to 2020, in order to establish effectiveness of such relationships and how this could be synthesised and modelled using systems thinking for repeatability and sustainability in capacity building in order to bridge the gap between academia and industry.

The direct and dynamic relationship linking academia with industry has been the ability by academia to provide practical solutions and innovations to solve industry’s challenges. In recent years and in response to the rapid changes in technology, higher education institutions have invested in innovation hubs for incubating novel ideas as well as technology and industrial parks for developing the same ideas to commercialisation. This chapter focusses on business incubation principles and the establishment of innovation hubs, science and technology parks by institutions under the Southern Africa Engineering Education Network (SAE2Net), how these have prospered and how the technology parks improved technology transfer. Although SAE2Net members are situated in the same region, this chapter also analyses how the different country environments affected the development of such parks. Success variable factors for product development and sustainability of the parks as well as constraints and challenges were analysed to enhance bridging of the gap between academia and industry through science and technology innovations.