Student resilience : exploring the positive case for resilience

Resilience is a word that is increasingly being used alongside student welfare, but what is meant by resilience? This paper takes a closer look at the subject of student resilience and I hope will encourage greater debate, exploration and fresh perspectives. As the paper outlines, while the study of student resilience is still very much in its infancy in the UK, there is recognition that student mental wellbeing is a growing challenge, and one which needs greater consideration. While overall student satisfaction at UK universities is rightly high, it has become clear that not all students find the transition to university life a straightforward one. Unite Students provides a home to around 50,000 students across the UK and our own research findings from the past few years demonstrate that some students can and do face difficulties. This is what prompted us to dedicate a significant portion of our annual Unite Students Insight Report in 2016 to finding out more about students’ own views on resilience by trying to identify some of the challenges surrounding student mental health, isolation and stress. These research insights support the detailed operational data from which we and our partner universities have seen an increase in welfare-related incidents over the last two years, and which encourage us to continually review and improve our operational processes and support services

Die Auswirkungen Ketamin-basierter Narkoseprotokolle auf den intraokularen Druck bei der Katze – eine prospektive randomisierte Blindstudie: Die Auswirkungen Ketamin-basierter Narkoseprotokolle auf denintraokularen Druck bei der Katze– eine prospektive randomisierte Blindstudie

Der Einsatz von Ketamin erfolgt in der Humananästhesie, vor allem aufgrund seiner vielfältigen Nebenwirkungen, nur noch nach strenger Indikation. In der Veterinärmedizin ist Ketamin tierartenübergreifend für die Injektionsnarkose weit verbreitet. Um den bekannten Nebenwirkungen vorzubeugen, wird Ketamin mit verschiedenen anderen Anästhetika kombiniert und stellt so ein sicheres Narkoseverfahren bei Tieren dar. Eine besondere Herausforderung ist die Anästhesie bei ophthalmologischen Patienten unter Berücksich-tigung der Kontrolle des Intraokularen Drucks (IOP). In diesem Zusammenhang gibt es in der Literatur widersprüchliche Angaben zur Auswirkung von Ketamin auf den IOP beim Menschen und verschiedenen Tierarten. Auch für die Auswirkungen von Propofol und der endotrachealen Intubation auf den IOP existieren widersprüchliche Aussagen. In der vorliegenden Arbeit wurde untersucht, ob gängige Ketamin-Kombinationsnarkosen bei der augengesunden Katze einen Einfluss auf den IOP haben. Angeregt durch Berichte in der Literatur wurde zudem untersucht, ob die Applikation von Propofol sowie die endotracheale Intubation den IOP bei der Katze beeinflussen. Methodik: Untersucht wurden 48 adulte, augengesunde Katzen, die dem chirurgischen Patientengut der Klinik für Kleintiere der Universität Leipzig entstammten. Es handelt sich um eine prospektive, randomisierte Blindstudie. Die Patienten wurden vier Untersuchungsgruppen zugeordnet. Zur intramuskulären Narkoseeinleitung erhielten Tiere der KX-Gruppe Ketamin (10 mg/kg) und Xylazin (1 mg/kg), der KXAtr-Gruppe Ketamin (10 mg/kg), Xylazin (1 mg/kg) und Atropin (0,025 mg/kg), der KA-Gruppe Ketamin (20 mg/kg) und Acepromazin (0,5 mg/kg) und der KM-Gruppe Ketamin (10 mg/kg) und Medetomidin (50 g/kg). Bei allen Patienten wurde mittels Tono-Pen® XL zu verschiedenen Zeitpunkten der IOP bestimmt: vor Narkoseeinleitung (Ausgangswert), nach Narkoseeinleitung nach 5, Zusammenfassung 86 10, 15 und 20 Minuten und direkt nach der Intubation sowie final nach Beendigung der Narkose während der Aufwachphase. Einige Tiere erhielten zur Vertiefung der Narkose vor der Intubation Propofol. Im Anschluss erfolgte eine ophthalmologische Untersuchung der Patienten, um eine Augenerkrankung auszuschließen. Ergebnisse: Der mittlere Ausgangs-IOP aller Tiere beträgt 15,8 mmHg. Mit p = 0,756 besteht kein signifikanter Unterschied zwischen den Gruppen. Getrennt nach linken (OS) und rechten (OD) Augen ist der mittlere IOP 15,7 und 15,8 mmHg. Dieser Unterschied ist nicht signifikant (p = 0,442). Daher wird für die Auswertung der Mittelwert aller 6 Datenpunkte pro Tier und Messzeitpunkt zugrunde gelegt. Im Vergleich zum Ausgangswert zeigt die KX-Gruppe keine signifikanten IOP-Änderungen. Die KXAtr-Gruppe und die KM-Gruppe weisen zur Final-Messung einen signifikanten IOP-Abfall um 16 % (p = 0,012) bzw. 17 % (p = 0,021) im Vergleich zum Ausgangswert auf. Die KA-Gruppe zeigt zur 15-Minuten-Messung den stärksten IOP-Abfall mit 21 % Prozent (p = 0,001) gegenüber dem Ausgangswert. Ab der 10-Minuten-Messung bis zur post-Intubations-Messung ist der IOP-Abfall der KA-Gruppe signifikant. Für die Gesamtstichprobe hat die Intubation keinen signifikanten Einfluss auf den IOP (p = 0,063). Die Gabe von Propofol zur Vertiefung der Narkose bei einzelnen Tieren hat ebenfalls keinen signifikanten Einfluss auf den IOP (p = 0,42). Schlussfolgerung: Die verwendeten Ketamin-basierten Narkoseprotokolle bewirken bei der augengesunden Katze keinen signifikanten IOP-Anstieg. Die Gruppen KX, KXAtr und KM gewährleisten für den Zeitraum von 20 Minuten nach Narkoseeinleitung einen relativ stabilen IOP. Trotz des signifikanten IOP-Abfalls in der KA-Gruppe sind sämtliche IOP-Schwankungen aller Gruppen klinisch nicht relevant. Die gemessenen IOP-Werte bewegen sich alle im physiologischen Bereich. Zudem geben die Ergebnisse keinen Hinweis auf eine IOP-Steigerung infolge Propofolgabe und Intubation bei der Katze.Ketamine is used in human medicine based on strict indications, mainly due to its numerous side effects. In veterinary medicine however Ketamine is commonly used to induce anesthesia intramuscularly throughout all species. To minimize the well known side effects Ketamine is used in combination with several other anesthetics and thus represents a safe anesthetic procedure in animals. Ophthalmological patients are a particular challenge for anesthetists with regard to maintaining the intraocular pressure (IOP). Conflicting data can be found in the literature about the effects of Ketamine on IOP in humans and various animal species. The literature also contains various statements about the effects of Propofol and endotracheal intubation on IOP. In this clinical trial we investigated the effects of commonly used Ketamine-based anesthetic protocols on IOP in cats. Motivated by conflicting statements in the literature the analysis of the effects of Propofol and endotracheal intubation on IOP was included in the study. Methods: This is a prospective, randomized, blinded study. 48 adult cats without ophthalmological abnormalities, recruited from the pool of admitted surgical patients of the Department of Small Animal Medicine of the University of Leipzig were included in the study. The patients were assigned to one of the following four groups and anesthesia was induced intramuscularly. Cats in the KX-group were induced with Ketamine (10 mg/kg) and Xylazine (1 mg/kg). Cats in the KXAtr-group were induced with Ketamine (10 mg/kg), Xylazine (1 mg/kg) and Atropine (0,025 mg/kg). Cats in the KA-group were induced with Ketamine (20 mg/kg) and Acepromazine (0,5 mg/kg). Cats in the KM-group were induced with Ketamine (10 mg/kg) and Medetomidine (50 g/kg). In all patients the IOP was measured three times per eye using the Tono-Pen® XL at particular times: baseline IOP before induction of anesthesia, at 5, 10, 15 and 20 minutes after induction of anesthesia, after intubation and final IOP after completion of surgery. Some cats received a single bolus of Propofol to be able to tolerate endotracheal intubation. After the final IOP-measurement all Zusammenfassung 88 cats were subjected to an ophthalmological examination, including slitlamp biomicroscopy and gonioscopy, in order to exclude patients with ophthalmological pathologies. Results: The mean baseline IOP for all animals is 15,8 mmHg (SD 4,0). There is no significant difference between the four groups (p = 0,756). The mean IOP for the right (OD) and left eyes (OS) of all patients was 15,8 mmHg and 15,7 mmHg, respectively. There is no significant difference between right (OD) and left eyes (OS) (p = 0,442). Therefore all further analyses are based on the mean of all six data points per animal and measuring time. The KX-group shows no significant IOP-change relative to baseline-IOP. The KXAtr and KM-group show a significant decrease in IOP of 16 % and 17 %, respectively, at the final measurement compared with baseline-IOP. The KA-group shows a significant decrease in IOP starting at 10 minutes after induction of anesthesia until the post-intubation measurement. The maximum decrease in IOP in this group is 21 % relative to baseline-IOP 15 minutes after induction of anesthesia. For the total data no significant influence of endotracheal intubation on IOP could be detected (p = 0,063). The application of Propofol in a total of 14 cats has no significant effect on IOP (p = 0,42). Conclusion: The Ketamine-based anesthetic protocols used in this study do not cause a significant increase in IOP in cats without ophthalmological abnormalities. The KX, KXAtr and KM-group ensure a relatively stable IOP for the time period of 20 minutes after induction of anesthesia. Despite the significant IOP-decrease in the KA-group none of the IOP-changes in all groups examined are of clinical relevance. All of the collected IOP-values are within the physiological range for cats. There is no evidence for an increase in IOP caused by endotracheal intubation or the application of Propofol

Feasibility of combined upper and lower gastrointestinal endoscopic biopsy in the common marmoset (Callithrix jacchus) to evaluate gastrointestinal diseases

Background: Chronic gastroenteropathies, including gluten sensitivity and marmoset wasting syndrome, frequently occur in captive colonies of common marmosets (Callithrix jacchus). Early identification and diagnosis of affected animals are desirable. Endoscopic examination of the colon in marmosets is described, but the small intestine can harbor significant mucosal lesions not representing those in the colon. Evaluating the small intestine currently requires invasive surgical biopsies due to the small patient size, carrying a risk of severe complications. Methods: Endoscopic intubation and multisite biopsy of the duodenum/proximal jejunum are demonstrated in 10 marmosets under general anesthesia. Results: Esophagogastroduodenoscopy with colonoscopy efficiently aid in examining the gastrointestinal tract and obtaining an antemortem histologic diagnosis in marmosets with chronic gastrointestinal signs. Conclusions: This minimally invasive technique is feasible in marmosets. Future investigations into the pathogenesis of chronic gastroenteropathies will benefit from these data, leading to improved animal welfare and better individual and colony health management

Comparison of Breast Cancer to Healthy Control Tissue Discovers Novel Markers with Potential for Prognosis and Early Detection

This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically ‘normal’ breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors

A discussion paper: Do national maternity policy reviews take account of the education and training of the future midwifery workforce? An example from England

The development and provision of maternity services globally are continuing to receive much attention in order to improve care and safety for women and babies. In the UK national reviews of the maternity services have taken place, with local services taking forward specific pilot projects to support the implementations of policy recommendations. This paper argues that, in order to meet the requirements of change in maternity services, there also needs to be a prompt review of the education of student midwives in order to be confident that the workforce of the future is equipped to implement these changes successfully. Using changes to national policy in England, this paper raises the question of the need for flexible national education standards, to ensure a curriculum can meet the needs of the changing workforce without the need for constant revision of the curriculum

Leadership in Compassionate Care: Final Report 2012

This report reflects the initiation, planning, running and the important outcomes emerging from the Leadership in Compassionate Care Programme. The team worked in close partnership across the School of Nursing, Midwifery and Social Care, Edinburgh Napier University and NHS Lothian. This report also shares the highlights, challenges and solutions to embed compassionate care education and nursing practice.Additional co-authors: Fiona Smith, Stephen DM Smith, Ria Tocher, and Anne Waug

Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease

Fabry disease is an X-linked lysosomal storage disorder caused by loss of alpha-galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of glycosphingolipids in multiple cells and tissues. FLT190, an investigational gene therapy, is currently being evaluated in a Phase 1/2 clinical trial in patients with Fabry disease (NCT04040049). FLT190 consists of a potent, synthetic capsid (AAVS3) containing an expression cassette with a codon-optimized human GLA cDNA under the control of a liver-specific promoter FRE1 (AAV2/S3-FRE1-GLAco). For mouse studies FLT190 genome was pseudotyped with AAV8 for efficient transduction. Preclinical studies in a murine model of Fabry disease (Gla-deficient mice), and non-human primates (NHPs) showed dose-dependent increases in plasma α-Gal A with steady-state observed 2 weeks following a single intravenous dose. In Fabry mice, AAV8-FLT190 treatment resulted in clearance of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in plasma, urine, kidney, and heart; electron microscopy analyses confirmed reductions in storage inclusion bodies in kidney and heart. In NHPs, α-Gal A expression was consistent with the levels of hGLA mRNA in liver, and no FLT190-related toxicities or adverse events were observed. Taken together, these studies demonstrate preclinical proof-of-concept of liver-directed gene therapy with FLT190 for the treatment of Fabry disease

Novel protective role for MAP kinase phosphatase 2 in inflammatory arthritis

Objectives: We have previously shown mitogen-activated protein kinase phosphatase 2 (MKP-2) to be a key regulator of proinflammatory cytokines in macrophages. In the study presented here, we investigated the role of MKP-2 in inflammatory arthritis with a particular focus on neutrophils. Methods: T o achieve this, we subjected MKP-2 deficient and wild type mice to collagen antibody induced arthritis, an innate model of arthritis, and determined disease pathology. To further our investigation, we depleted neutrophils in a prophylactic and therapeutic fashion. Last, we used chemotaxis assays to analyse the impact of MKP- 2 deletion on neutrophil migration. Results MKP-2-/- mice showed a significant increase in disease pathology linked to elevated levels of proarthritic cytokines and chemokines TNF-α, IL-6 and MCP-1 in comparison to wild type controls. This phenotype is prevented or abolished after administration of neutrophil depleting antibody prior or after onset of disease, respectively. While MCP-1 levels were not affected, neutrophil depletion diminished TNF-α and reduced IL-6, thus linking these cytokines to neutrophils. In vivo imaging showed that MKP-2-/- mice had an increased influx of neutrophils into affected joints, which was higher and potentially prolonged than in wild type animals. Furthermore, using chemotaxis assays we revealed that MKP-2 deficient neutrophils migrate faster towards a Leukotriene B4 gradient. This process correlated with a reduced phosphorylation of ERK in MKP-2-/- neutrophils. Conclusions: T his is the first study to show a protective role for MKP-2 in inflammatory arthritis

Adeno-associated virus gene therapy prevents progression of kidney disease in genetic models of nephrotic syndrome

Gene therapy for kidney diseases has proven challenging. Adeno-associated virus (AAV) is used as a vector for gene therapy targeting other organs, with particular success demonstrated in monogenic diseases. We aimed to establish gene therapy for the kidney by targeting a monogenic disease of the kidney podocyte. The most common cause of childhood genetic nephrotic syndrome is mutations in the podocyte gene NPHS2, encoding podocin. We used AAV-based gene therapy to rescue this genetic defect in human and mouse models of disease. In vitro transduction studies identified the AAV-LK03 serotype as a highly efficient transducer of human podocytes. AAV-LK03–mediated transduction of podocin in mutant human podocytes resulted in functional rescue in vitro, and AAV 2/9–mediated gene transfer in both the inducible podocin knockout and knock-in mouse models resulted in successful amelioration of kidney disease. A prophylactic approach of AAV 2/9 gene transfer before induction of disease in conditional knockout mice demonstrated improvements in albuminuria, plasma creatinine, plasma urea, plasma cholesterol, histological changes, and long-term survival. A therapeutic approach of AAV 2/9 gene transfer 2 weeks after disease induction in proteinuric conditional knock-in mice demonstrated improvement in urinary albuminuria at days 42 and 56 after disease induction, with corresponding improvements in plasma albumin. Therefore, we have demonstrated successful AAV-mediated gene rescue in a monogenic renal disease and established the podocyte as a tractable target for gene therapy approaches

Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization

Background: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization.Methods: In vitro structural analysis followed by in vivo protein expression studies served in assessing the integrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunization trials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutinin H1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinations using pDNA for influenza was nebulized and delivered via a respirator to sheep.Results: The SAW nebulizer was effective at generating pDNA aerosols with sizes optimal for deep lung delivery. Successful gene expression was observed in mouse lung epithelial cells, when SAW-nebulized pDNA was delivered to male Swiss mice via intratracheal instillation. Effective systemic and mucosal antibody responses were found in rats via post-nebulized, condensed fluid instillation. Significantly, we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNA encoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation.Conclusion: Given the difficulty of inducing functional antibody responses for DNA vaccination in large animals, we report here the first instance of successful aerosolized inhalation delivery of a pDNA vaccine in a large animal model relevant to human lung development, structure, physiology, and disease, using a novel, low-power (<1 W) surface acoustic wave (SAW) hand-held nebulizer to produce droplets of pDNA with a size range suitable for delivery to the lower respiratory airways. © 2014 Rajapaksa et al.; licensee BioMed Central Ltd