Projectile impact effects on a 50 psi plug type coal mine seal

The current lack of projectile damage criteria for mine seals is assessed to determine if criteria should be developed. Impact experiments were performed on a full-scale 50 psi mine seal to determine failure modes, dynamic stress state, and assess risk to existing operational mine seals. Test projectiles were selected from common underground coal mine items propelled by means of a black powder projectile generator. Projectile velocities attained in testing ranged from approximately 100 to 650 ft/s (30 to 200 m/s). Dynamic strain was measured on the non-impact face to derive the state of stress and estimate failure criteria. Penetration models were used to estimate depth of penetration and compared to empirical data. Finite element analysis impact simulation was compared with empirical data and a critical impact velocity for rigid body projectiles of 20 to 30 lb (9 to 14 kg) was estimated to be in the range of 550 to 600 ft/s (168 to 183 m/s). Damage to the mine seal was observed and compared with numerical simulation to assess the need for defined projectile damage criteria to mine seals --Abstract, page iii

Improving value of clinical research - an evidence-based approach

Evidence suggests that 85% of biomedical research spending, i.e. 200 billion US dollars every year, goes to waste. In 2014, The Lancet published a series of five reviews showing how dividends from the investment in research might be increased at five stages - from the relevance and priorities of the questions being asked, to how the research is designed, conducted, and reported. Value and waste have since then become buzzwords in the academic as well as public debate surrounding health research. Although academic institutions are the major driving force of patient-oriented clinical research receiving large proportions of public funding they have been slow responders to the Series’ recommendations. Some of the identified underlying reasons include a lack of a common understanding of “value” as a concept and sparse practical guidance for academia on how to improve it. This work represents the first effort to formulate an academic response to The Lancet series on increasing value in clinical research by investigating the two distinct concepts in the equation: “Quality” and “cost”. In a first step, we systematically reviewed existing quality concepts, both in the medical literature and across international clinical research stakeholder groups. Precise definitions of quality were sparse, and stakeholder perspectives of crucial components of quality varied. Based on these findings, we then engaged international stakeholder representatives in the creation of a comprehensive, consensus-based framework for the quality of clinical research that is applicable to all study types and spans the entire lifecycle of a clinical study, i.e. from conceptualization of the research question to dissemination of study results. Primarily, it is designed to be operationalized in the academic setting and fully supports the REWARD Statement. This framework builds the foundation for a common understanding of the concept of “quality” and its practical assessment. At Swiss national level, the framework has triggered all stakeholders to convene in a first symposium on how to increase value of academic clinical research and serves as an agenda for future research on research. In a second step, we systematically reviewed the current evidence on the costs and associated resource use of Randomized Controlled Trials (RCTs), which we found to be sparse. Based on this, we laid the foundation for future study cost assessments in academia by (i) developing a comprehensive list of items for the retrospective and prospective assessment of costs, and (ii) generating first empirical evidence on main cost drivers in a case report on two academic RCTs. Although these two RCTs were conducted in very different settings and resulted in vastly different costs, the main drivers, i.e. personnel costs during conduct phase, were the same. In addition, we investigated the added value of two innovative aspects that affect both study quality and cost, i.e. risk-based trial monitoring and remote data collection. We show that both concepts may increase the cost-effectiveness of trial conduct and thereby increase value, but only if the methodology is further investigated and then, rigorously implemented. Although we did not take the initially envisioned cost-consequence approach, we have certainly created awareness on value and waste in the academic context and engaged the major stakeholders in fundamental discussions on how to improve the current situation. In the future, the costs occurred need to inform quality assessments of clinical studies in order to create a tool that creates “value”, rather than sole quality conformity. Furthermore, the willingness-to-pay of academic decision makers in resource-constrained settings will weigh into the value equation and needs further investigation in the future. The impact of this work - and whether it eventually increases value in the system - now critically depends on its rigorous implementation, evaluation, and refinement

Caring moments within an interprofessional healthcare team: Children and adolescent perspectives

Patients are now recognized as key partners to improve healthcare outcomes. Some organisations such as the WHO or the Canadian Interprofessional Health Collaborative (CIHC) encourage considering patients as partners in the interprofessional healthcare team. However, limited knowledge exists on patients’ perspective of interprofessional collaboration (IPC) and of their role in the collaborative process, particularly in pediatric settings. The experiences and perspectives of patients regarding IPC have to be considered in order to fully understand the concept of IPC and integrate it into practice. This qualitative study aimed at gaining a better understanding of the perspective of children of IPC, how it affects their experiences of care and how they perceive their own role within the interprofessional team. Semi-structured interviews were used in the pediatric service of a Swiss university hospital, with ten children and adolescents aged between 11-17 years. The participants described the interactions they observed between nurses and physicians and provided insights into how they perceived the quality of that relationship. A respectful relationship between nurses and physicians may have improved the experience of a caring environment. The participants did not perceive their role to be pivotal into the interprofessional relationship. The findings of this study indicate that the interactions between healthcare professionals have an influence on the perspectives and experiences of the participants of their hospitalisation and of IPC. However, integrating children and adolescents into collaborative process will need a change of paradigm and beliefs regarding IPC

Antilisterial Activity of Bacteriocins Produced by Lactic Bacteria Isolated from Dairy Products

Sixty-nine Lactic Acid Bacteria (LAB) and bifidobacteria were isolated and identified from Italian dairy products (raw milk, cream, butter, soft cheese and yoghurt) to find new antimicrobial compounds to use as food bio-preservatives. All the isolates were preliminarily screened by the deferred antagonism method for bacteriocin production. Afterwards, to evaluate the release of bacteriocin in liquid medium, the Cell-Free Supernatant Fluid (CFSF) of the best producers was tested by agar well diusion assay. The study allowed the selection of three bacteriocin producing strains (Enterococcus faecium E23, Bifidobacterium thermophilum B23 and Lactobacillus bulgaricus L21), endowed with the strongest and broadest inhibitory capability against the pathogen Listeria monocytogenes. The molecular characteristics and the chemical–physical properties of both producers and the respective bacteriocins were studied and compared. The results showed that E. faecium E23 was the best producer strain and its class IIa bacteriocins, called enterocin E23, exhibited a good spectrum of activity towards L. monocytogenes. Enterocin E23 was stable over a wide range of pH and at low temperatures for at least four months and, for this reason, it can be employed in refrigerated foods for the control of L. monocytogenes, the major concern in dairy products

Different B cell subpopulations show distinct patterns in their IgH repertoire metrics

Several human B cell subpopulations are recognised in the peripheral blood, which play distinct roles in the humoral immune response. These cells undergo developmental and maturational changes involving VDJ recombination, somatic hypermutation and class switch recombination, altogether shaping their immunoglobulin heavy chain (IgH) repertoire. Here, we sequenced the IgH repertoire of naïve, marginal zone, switched and plasma cells from 10 healthy adults along with matched unsorted and in silico separated CD19+ bulk B cells. Using advanced bioinformatic analysis and machine learning, we show that sorted B cell subpopulations are characterised by distinct repertoire characteristics on both the individual sequence and the repertoire level. Sorted subpopulations shared similar repertoire characteristics with their corresponding in silico separated subsets. Furthermore, certain IgH repertoire characteristics correlated with the position of the constant region on the IgH locus. Overall, this study provides unprecedented insight over mechanisms of B cell repertoire control in peripherally circulating B cell subpopulations. Keywords: B cells; diagnostics; human; immunoglobulin; immunology; inflammation; machine learning; prediction; repertoire

In vitro evaluation of the amoebicidal activity of rosemary (Rosmarinus officinalis L.) and cloves (Syzygium aromaticum L. Merr. & Perry) essential oils against Acanthamoeba polyphaga trophozoites

Several species of the genus Acanthamoeba cause human diseases. Treatment of infections involves various problems, emphasising the need to develop alternative antiprotozoal agents. We studied the anti-amoebic activity of Essential Oils (EOs), derived from rosemary (Rosmarinus officinalis L.) and cloves (Syzygium aromaticum L. Merr. & Perry), against Acanthamoeba polyphaga strain. The amoebicidal activity of cloves and rosemary EOs was preliminary demonstrated by the morphology change (modifications in the cell shape, the presence of precipitates in the cytoplasm, autophagic vesicles, membrane blends) of the treated trophozoites. The cell-counts, carried out after staining trophozoites with a Trypan blue solution, revealed that both EOs were active in a dose-dependent manner and in relation to the exposure time. This activity was evident after few hours, with encouraging results obtained in particular with cloves EO, able to act at the lower concentrations and after 1 h, probably for its high eugenol content (65.30%)

B-Cell Reconstitution After Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Background and objectives: Autologous hematopoietic stem cell transplantation (aHSCT) is increasingly used to treat aggressive forms of multiple sclerosis (MS). This procedure is believed to result in an immune reset and restoration of a self-tolerant immune system. Immune reconstitution has been extensively studied for T cells, but only to a limited extent for B cells. As increasing evidence suggests an important role of B cells in MS pathogenesis, we sought here to better understand reconstitution and the extent of renewal of the B-cell system after aHSCT in MS. Methods: Using longitudinal multidimensional flow cytometry and immunoglobulin heavy chain (IgH) repertoire sequencing following aHSCT with BCNU + Etoposide + Ara-C + Melphalan anti-thymocyte globulin, we analyzed the B-cell compartment in a cohort of 20 patients with MS in defined intervals before and up to 1 year after aHSCT and compared these findings with data from healthy controls. Results: Total B-cell numbers recovered within 3 months and increased above normal levels 1 year after transplantation, successively shifting from a predominantly transitional to a naive immune phenotype. Memory subpopulations recovered slowly and remained below normal levels with reduced repertoire diversity 1 year after transplantation. Isotype subclass analysis revealed a proportional shift toward IgG1-expressing cells and a reduction in IgG2 cells. Mutation analysis of IgH sequences showed that highly mutated memory B cells and plasma cells may transiently survive conditioning while the analysis of sequence cluster overlap, variable (IGHV) and joining (IGHJ) gene usage and repertoire diversity suggested a renewal of the late posttransplant repertoire. In patients with early cytomegalovirus reactivation, reconstitution of naive and memory B cells was delayed. Discussion: Our detailed characterization of B-cell reconstitution after aHSCT in MS indicates a reduced reactivation potential of memory B cells up to 1 year after transplantation, which may leave patients susceptible to infection, but may also be an important aspect of its mechanism of action

Discontinuation and non-publication of randomised clinical trials supported by the main public funding body in Switzerland: a retrospective cohort study.

The Swiss National Science Foundation (SNSF) promotes academic excellence through competitive selection of study proposals and rigorous evaluation of feasibility, but completion status and publication history of SNSF-supported randomised clinical trials (RCTs) remain unclear. The main objectives were to review all healthcare RCTs supported by the SNSF for trial discontinuation and non-publication, to investigate potential risk factors for trial discontinuation due to poor recruitment and non-publication, and to compare findings to other Swiss RCTs not supported by the SNSF. We established a retrospective cohort of all SNSF-supported RCTs for which recruitment and funding had ended in 2015 or earlier. For each RCT, two investigators independently searched corresponding publications in electronic databases. In addition, we approached all principal investigators to ask for additional publications and information about trial discontinuation. Teams of two investigators independently extracted details about study design, recruitment of participants, outcomes, analysis and sample size from the original proposal and, if available, from trial registries and publications. We used multivariable regression analysis to explore potential risk factors associated with discontinuation due to poor recruitment and with non-publication, and to compare our results with data from a previous cohort of Swiss RCTs not supported by the SNSF. We included 101 RCTs supported by the SNSF between 1986 and 2015. Eighty-seven (86%) principal investigators responded to our survey. Overall, 69 (68%) RCTs were completed, 26 (26%) RCTs were prematurely discontinued (all due to slow recruitment) and the completion status remained unclear for 6 (6%) RCTs. For analysing publication status, we excluded 4 RCTs for which follow-up was still ongoing and 9 for which manuscripts were still in preparation. Of the remaining 88 RCTs, 53 (60%) were published as full articles in peer-reviewed journals. Multivariable regression models suggested that discontinued trials were at higher risk for non-publication than completed trials (adjusted OR 7.61; 95% CI 2.44 to 27.09). Compared with other Swiss RCTs, the risk of discontinuation for SNSF-supported RCTs was higher than in industry-initiated RCTs (adjusted OR 3.84; 95% CI 1.68 to 8.74), but not significantly different from investigator-initiated RCTs not supported by the SNSF (adjusted OR 1.05; 95% CI 0.51 to 2.11). We found no evidence that the proportion of discontinued or unpublished RCTs decreased over the last 20 years. One out of four SNSF-supported RCTs were prematurely discontinued due to slow recruitment, 40% of all included RCTs and 70% of all discontinued RCTs were not published in peer-reviewed journals. There is a case to reconsider how public funding bodies such as the SNSF could improve their feasibility assessment and promote publication of RCTs irrespective of completion status

Die Rolle des Freibergerpferdes im Pferdemarkt Schweiz

Das Freiberger Pferd hat wie viele andere vergleichbare lokale, ursprüngliche europäische Pferderassen mit rückläufigen Bestandes- und Geburtenzahlen sowie einer fehlenden Rentabilität auf Stufe Produktion zu kämpfen. Agroscope, Schweizer Nationalgestüt SNG, untersuchte im Zuge der Erarbeitung eines Strategierapportes zur Erhaltung der Freibergerrasse die Marktkonformität des Freibergerpferdes (FM: franches-montagnes) mittels einer Umfrage bei Pferdeeigentümern sowie ergänzenden Experteninterviews. Die Ergebnisse lassen den Schluss zu, dass bei einer Mehrheit der befragten Pferdeeigentümer die persönlichen Erwartungen an ein Pferd mit der Beurteilung der Qualitäten und der generellen Wahrnehmung des Freibergerpferdes deckungsgleich sind. Daraus lässt sich ableiten, dass der FM über Qualitäten verfügt, die im Grundsatz im Freizeitpferdemarkt nachgefragt werden (einfacher Charakter, Polyvalenz, Robustheit, Gesundheit). Das Image des Markenbildes FM ist bei den nicht FM-Besitzern deutlich weniger positiv als bei den FM-Besitzern. Die Ergebnisse der Umfrage sowie der Experteninterviews zeigten, dass vor allem Anstrengungen zur Verbesserung der Vermarktung und des Images notwendig sind, um einen besseren Absatz von Freibergerpferden zu gewährleisten und damit auch langfristig einen Anstieg der Geburten zu erreichen