New Concepts of Fluorescent Probes for Specific Detection of DNA Sequences: Bis-Modified Oligonucleotides in Excimer and Exciplex Detection

The detection of single base mismatches in DNA is important for diagnostics, treatment of genetic diseases, and identification of single nucleotide polymorphisms. Highly sensitive, specific assays are needed to investigate genetic samples from patients. The use of a simple fluorescent nucleoside analogue in detection of DNA sequence and point mutations by hybridisation in solution is described in this study. The 5′-bispyrene and 3′-naphthalene oligonucleotide probes form an exciplex on hybridisation to target in water and the 5′-bispyrene oligonucleotide alone is an adequate probe to determine concentration of target present. It was also indicated that this system has a potential to identify mismatches and insertions. The aim of this work was to investigate experimental structures and conditions that permit strong exciplex emission for nucleic acid detectors, and show how such exciplexes can register the presence of mismatches as required in SNP analysis. This study revealed that the hybridisation of 5′-bispyrenyl fluorophore to a DNA target results in formation of a fluorescent probe with high signal intensity change and specificity for detecting a complementary target in a homogeneous system. Detection of SNP mutations using this split-probe system is a highly specific, simple, and accessible method to meet the rigorous requirements of pharmacogenomic studies. Thus, it is possible for the system to act as SNP detectors and it shows promise for future applications in genetic testing

Quantifying the impact of climate change on drought regimes using the Standardised Precipitation Index

The study presents a methodology to characterise short- or long-term drought events, designed to aid understanding of how climate change may affect future risk. An indicator of drought magnitude, combining parameters of duration, spatial extent and intensity, is presented based on the Standardised Precipitation Index (SPI). The SPI is applied to observed (1955–2003) and projected (2003–2050) precipitation data from the Community Integrated Assessment System (CIAS). Potential consequences of climate change on drought regimes in Australia, Brazil, China, Ethiopia, India, Spain, Portugal and the USA are quantified. Uncertainty is assessed by emulating a range of global circulation models to project climate change. Further uncertainty is addressed through the use of a high-emission scenario and a low stabilisation scenario representing a stringent mitigation policy. Climate change was shown to have a larger effect on the duration and magnitude of long-term droughts, and Australia, Brazil, Spain, Portugal and the USA were highlighted as being particularly vulnerable to multi-year drought events, with the potential for drought magnitude to exceed historical experience. The study highlights the characteristics of drought which may be more sensitive under climate change. For example, on average, short-term droughts in the USA do not become more intense but are projected to increase in duration. Importantly, the stringent mitigation scenario had limited effect on drought regimes in the first half of the twenty-first century, showing that adaptation to drought risk will be vital in these regions

Prioritising surveillance for alien organisms transported as stowaways on ships travelling to South Africa

The global shipping network facilitates the transportation and introduction of marine and terrestrial organisms to regions where they are not native, and some of these organisms become invasive. South Africa was used as a case study to evaluate the potential for shipping to contribute to the introduction and establishment of marine and terrestrial alien species (i.e. establishment debt) and to assess how this varies across shipping routes and seasons. As a proxy for the number of species introduced (i.e. 'colonisation pressure') shipping movement data were used to determine, for each season, the number of ships that visited South African ports from foreign ports and the number of days travelled between ports. Seasonal marine and terrestrial environmental similarity between South African and foreign ports was then used to estimate the likelihood that introduced species would establish. These data were used to determine the seasonal relative contribution of shipping routes to South Africa's marine and terrestrial establishment debt. Additionally, distribution data were used to identify marine and terrestrial species that are known to be invasive elsewhere and which might be introduced to each South African port through shipping routes that have a high relative contribution to establishment debt. Shipping routes from Asian ports, especially Singapore, have a particularly high relative contribution to South Africa's establishment debt, while among South African ports, Durban has the highest risk of being invaded. There was seasonal variation in the shipping routes that have a high relative contribution to the establishment debt of the South African ports. The presented method provides a simple way to prioritise surveillance effort and our results indicate that, for South Africa, port-specific prevention strategies should be developed, a large portion of the available resources should be allocated to Durban, and seasonal variations and their consequences for prevention strategies should be explored further. (Résumé d'auteur

Appendix perforation in appendix duplication in a man: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although appendix duplication is diagnosed as a rare congenital anomaly of the alimentary tract in childhood, a few adult cases have also been reported. Here we report a case of appendix duplication with perforated appendicitis co-existing with acute appendicitis in an adult patient.</p> <p>Case presentation</p> <p>A 33-year-old Caucasian man was admitted to our Emergency Department with right-sided lower-quadrant pain that we explored for presumed complicated appendicitis. On exploration, a perforated inflamed appendix was found coexisting with a second inflamed appendix which was subserosal and retrocecal. Appendectomies were performed, and the pathological examination confirmed the signs of acute inflammation in both appendixes.</p> <p>Conclusion</p> <p>Surgeons in emergency services should be aware of anatomical anomalies such as duplication and malposition of the appendix, even in patients with a history of previous appendectomy, because misdiagnosis of appendix duplication may lead to a poor clinical outcome and medicolegal issues.</p

OSCE best practice guidelines—applicability for nursing simulations

Background: Objective structured clinical examinations (OSCEs) have been used for many years within healthcare programmes as a measure of students’ and clinicians’ clinical performance. OSCEs are a form of simulation and are often summative but may be formative. This educational approach requires robust design based on sound pedagogy to assure practice and assessment of holistic nursing care. As part of a project testing seven OSCE best practice guidelines (BPGs) across three sites, the BPGs were applied to an existing simulation activity. The aim of this study was to determine the applicability and value of the OSCE BPGs in an existing formative simulation. Methods: A mixed methods approach was used to address the research question: in what ways do OSCE BPGs align with simulations. The BPGs were aligned and compared with all aspects of an existing simulation activity offered to first-year nursing students at a large city-based university, prior to their first clinical placement in an Australian healthcare setting. Survey questions, comprised of Likert scales and free-text responses, used at other sites were slightly modified for reference to simulation. Students’ opinions about the refined simulation activity were collected via electronic survey immediately following the simulation and from focus groups. Template analysis, using the BPGs as existing or a priori thematic codes, enabled interpretation and illumination of the data from both sources.Results: Few changes were made to the existing simulation plan and format. Students’ responses from surveys (n = 367) and four focus groups indicated that all seven BPGs were applicable for simulations in guiding their learning, particularly in the affective domain, and assisting their perceived needs in preparing for upcoming clinical practice. Discussion: Similarities were found in the intent of simulation and OSCEs informed by the BPGs to enable feedback to students about holistic practice across affective, cognitive and psychomotor domains. The similarities in this study are consistent with findings from exploring the applicability of the BPGs for OSCEs in other nursing education settings, contexts, universities and jurisdictions. The BPGs also aligned with other frameworks and standards often used to develop and deliver simulations. Conclusions: Findings from this study provide further evidence of the applicability of the seven OSCE BPGs to inform the development and delivery of, in this context, simulation activities for nurses. The manner in which simulation is offered to large cohorts requires further consideration to meet students’ needs in rehearsing the registered nurse role

OSCE Best Practice Guidelines – applicability for nursing simulations

Background: Objective structured clinical examinations (OSCEs) have been used for many years within healthcare programmes as a measure of students’ and clinicians’ clinical performance. OSCEs are a form of simulation and are often summative but may be formative. This educational approach requires robust design based on sound pedagogy to assure practice and assessment of holistic nursing care. As part of a project testing seven OSCE best practice guidelines (BPGs) across three sites, the BPGs were applied to an existing simulation activity. The aim of this study was to determine the applicability and value of the OSCE BPGs in an existing formative simulation. Methods: A mixed methods approach was used to address the research question: in what ways do OSCE BPGs align with simulations. The BPGs were aligned and compared with all aspects of an existing simulation activity offered to first-year nursing students at a large city-based university, prior to their first clinical placement in an Australian healthcare setting. Survey questions, comprised of Likert scales and free-text responses, used at other sites were slightly modified for reference to simulation. Students’ opinions about the refined simulation activity were collected via electronic survey immediately following the simulation and from focus groups. Template analysis, using the BPGs as existing or a priori thematic codes, enabled interpretation and illumination of the data from both sources.Results: Few changes were made to the existing simulation plan and format. Students’ responses from surveys (n = 367) and four focus groups indicated that all seven BPGs were applicable for simulations in guiding their learning, particularly in the affective domain, and assisting their perceived needs in preparing for upcoming clinical practice. Discussion: Similarities were found in the intent of simulation and OSCEs informed by the BPGs to enable feedback to students about holistic practice across affective, cognitive and psychomotor domains. The similarities in this study are consistent with findings from exploring the applicability of the BPGs for OSCEs in other nursing education settings, contexts, universities and jurisdictions. The BPGs also aligned with other frameworks and standards often used to develop and deliver simulations. Conclusions: Findings from this study provide further evidence of the applicability of the seven OSCE BPGs to inform the development and delivery of, in this context, simulation activities for nurses. The manner in which simulation is offered to large cohorts requires further consideration to meet students’ needs in rehearsing the registered nurse role

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Spring-Block Model Reveals Region-Like Structures

A mechanical spring-block model is used for realizing an objective space partition of settlements from a geographic territory in region-like structures. The method is based on the relaxation-dynamics of the spring-block system and reveals in a hierarchical manner region-like entities at different spatial scales. It takes into account in an elegant manner both the spatiality of the elements and the connectivity relations among them. Spatiality is taken into account by using the geographic coordinates of the settlements, and by detecting the neighbors with the help of a Delaunay triangulation. Connectivity between neighboring settlements are quantified using a Pearson-like correlation for the relative variation of a relevant socio-economic parameter (population size, GDP, tax payed per inhabitant, etc.). The method is implemented in an interactive JAVA application and it is applied with success for an artificially generated society and for the case of USA, Hungary and Transylvania