Taming the beast : Exploring the lived experience of relapsing remitting multiple sclerosis using a life history approach

Multiple Sclerosis (MS) is a complex neurological disease affecting the central nervous system and is driven by a complex autoimmune cascade. The peak age of onset is between the ages of 20 and 40 years and shows a female preponderance of 3:1. The most common form of the disease affecting 85% of people living with the illness is called relapsing remitting MS (RRMS), and is characterised by unpredictable relapses or exacerbations which usually last a few weeks before returning to baseline function. There is the possibility of disease progression and non-reversible disability after many years. RRMS is also characterised by a complicated array of symptoms which may affect sensory function, motor function, vision, gait, cognition, mood, bladder, bowel and sexual function. There is currently no curative treatment for RRMS, although recently there have been major advances in more efficacious treatments called disease modifying therapies (DMTs) to control relapses and possibly future disability. The aim of this study was to gain insights and understanding into the lived experience of RRMS in order to inform patient-centred nursing care. Although there is an abundance of literature dealing with various aspects of the MS experience, there is a paucity of literature specifically exploring the general life experience of living with the disease and considering a broader understanding. Life history methodology, a form of focused ethnography, was used to explore the illness experience across the lifespan of 13 study participants living with RRMS. Semi-structured interviews were used to gather data and later transcribed by the researcher, before undergoing data analysis. Braun and Clarke’s (2006) method of thematic data analysis ensured a systematic and robust exploration of the lived experience and revealed eight key themes, 30 subthemes and 44 sub-subthemes, providing clarity and insight into the experience of living with RRMS. Several novel findings were revealed by the thematic analysis including an appreciation of the importance of early life events prior to the onset of RRMS and their potential impact on later coping, adjustment and resilience after diagnosis. A key study finding was of people living with RRMS experiencing “Surplus Suffering”, a form of suffering over and above that caused by the disease itself and inflicted most often by health care professionals and significant others. Other themes explored concepts of “Piecing together the Puzzle” of RRMS at the beginning of the journey, “(Re)defining self” in the wake of an RRMS diagnosis, “Battling the Demons” that RRMS uncovers, dealing with invisible symptoms of the disease, managing the DMTs necessary to control the disease and their side effects, and ultimately “Taming the Beast” that is RRMS and “Holding Hands with Hope”. The life history approach revealed these themes to be reflective of the ebbs and flows of life, intertwining with each other and changing positions of importance according to life events, whether directly related to RRMS or indirectly related. Numerous recommendations for clinical practice in MS care have been developed from the study findings which are anticipated to improve clinical care and to enhance the quality of life for people living with RRMS, along the life trajectory

Meeting the Needs of New Teachers Through Mentoring, Induction, and Teacher Support

Providing new teacher induction is an important practice that is common in schools around the world (Wong, Britton, and Ganser 2005). Teacher induction and mentoring programs have been found to reduce the rate of new teacher attrition, increase job satisfaction, and efficacy (Ingersoll and Smith 2004). Mentoring has been the main form of teacher induction used in the United States since the early 1980′s (Fideler and Haselkorn1999)

Droplet digital PCR based detection of EGFR mutations in advanced lung cancer patient liquid biopsies : a comparison of circulating tumour DNA extraction kits

Background: Mutations in the epidermal growth factor receptor gene, EGFR, predict response or resistance to first generation tyrosine kinase inhibitors in non-small cell lung cancer. These biomarkers can now be conveniently detected from liquid biopsies, however technical details of these assays are still being refined. Objective: To compare detection of four different non-small cell lung cancer (NSCLC) associated EGFR mutations from patient ctDNA isolated with five different ctDNA isolation kit. Methods: Droplet digital PCR (ddPCR) assays detecting four EGFR mutations were developed. ctDNA was isolated with five kits from plasma samples, one pleural and one ascites fluid from nine NSCLC patients with known EGFR mutations. ctDNA fragment sizes and concentrations were also assessed. Results: Each kit isolated DNA from all samples which contained an expected dominant DNA fragment of ~ 170 base pairs. Normalised for plasma input, one kit produced ctDNA extracts which consistently enabled the highest cop n umber detection for all EGFR variants, and importantly was able to validate mutations in all patient samples. Other kits stood out in regards to cost economy as well as ease and speed of processing but were less efficient and one kit was found to be incompatible with ddPCR. Conclusion: This study demonstrated successful ctDNA isolation from plasma, pleural fluid and ascites by four of five ctDNA isolation kits. The QIAmp circulating nucleic acid kit produced consistently the most sensitive detection of EGFR variants. While other kits allow for lower volume plasma input down to 0.1 ml, are faster, more economical and simpler to use, they are challenged by very low ctDNA concentrations in plasma

Dbf2–Mob1 drives relocalization of protein phosphatase Cdc14 to the cytoplasm during exit from mitosis

Exit from mitosis is characterized by a precipitous decline in cyclin-dependent kinase (Cdk) activity, dissolution of mitotic structures, and cytokinesis. In Saccharomyces cerevisiae, mitotic exit is driven by a protein phosphatase, Cdc14, which is in part responsible for counteracting Cdk activity. Throughout interphase, Cdc14 is sequestered in the nucleolus, but successful anaphase activates the mitotic exit network (MEN), which triggers dispersal of Cdc14 throughout the cell by a mechanism that has remained unknown. In this study, we show that a MEN component, protein kinase Dbf2–Mob1, promotes transfer of Cdc14 to the cytoplasm and consequent exit from mitosis by direct phosphorylation of Cdc14 on serine and threonine residues adjacent to a nuclear localization signal (NLS), thereby abrogating its NLS activity. Our results define a mechanism by which the MEN promotes exit from mitosis

A rapid application emissions-to-impacts tool for scenario assessment: Probabilistic Regional Impacts from Model patterns and Emissions (PRIME)

Climate policies evolve quickly, and new scenarios designed around these policies are used to illustrate how they impact global mean temperatures using simple climate models (or climate emulators). Simple climate models are extremely efficient although limited to showing only the global picture. Within the Intergovernmental Panel on Climate Change (IPCC) framework, there is a need to understand the regional impacts of scenarios that include the most recent science and policy decisions quickly to support government in negotiations. To address this, we present PRIME (Probabilistic Regional Impacts from Model patterns and Emissions), a new flexible probabilistic framework which aims to provide an efficient means to run new scenarios without the significant overheads of larger more complex Earth system models (ESMs). PRIME provides the capability to include the most recent models, science and scenarios to run ensemble simulations on multi-centennial timescales and include analysis of many variables that are relevant and important for impacts assessments. We use a simple climate model to provide the global temperatures to scale the patterns from a large number of the CMIP6 ESMs. These provide the inputs to a weather generator and a land-surface model, which generates an estimate of the land-surface impacts from the emissions scenarios. Here we test PRIME using known scenarios in the form of the Shared Socioeconomic Pathways (SSPs) to demonstrate that PRIME reproduces the climate response to a range of emissions scenarios, as shown in the IPCC reports. We show results for a range of scenarios including the SSP5-8.5 high emissions scenario, which was used to define the patterns; SSP1-2.6, a mitigation scenario with low emissions and SSP5-3.4-OS, an overshoot scenario. PRIME correctly represents the climate response for these known scenarios, which gives us confidence that PRIME will be useful for rapidly providing probabilistic spatially resolved information for novel climate scenarios; substantially reducing the time between the scenarios being released and being used in impacts assessments

Preimaginal Stages of the Emerald Ash Borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae): An Invasive Pest on Ash Trees (Fraxinus)

This study provides the most detailed description of the immature stages of Agrilus planipennis Fairmaire to date and illustrates suites of larval characters useful in distinguishing among Agrilus Curtis species and instars. Immature stages of eight species of Agrilus were examined and imaged using light and scanning electron microscopy. For A. planipennis all preimaginal stages (egg, instars I-IV, prepupa and pupa) were described. A combination of 14 character states were identified that serve to identify larvae of A. planipennis. Our results support the segregation of Agrilus larvae into two informal assemblages based on characters of the mouthparts, prothorax, and abdomen: the A. viridis and A. ater assemblages, with A. planipennis being more similar to the former. Additional evidence is provided in favor of excluding A. planipennis from the subgenus Uragrilus

an international multi center serum protein electrophoresis accuracy and m protein isotyping study part i factors impacting limit of quantitation of serum protein electrophoresis

AbstractBackgroundSerum protein electrophoresis (SPEP) is used to quantify the serum monoclonal component or M-protein, for diagnosis and monitoring of monoclonal gammopathies. Significant imprecision and inaccuracy pose challenges in reporting small M-proteins. Using therapeutic monoclonal antibody-spiked sera and a pooled beta-migrating M-protein, we aimed to assess SPEP limitations and variability across 16 laboratories in three continents.MethodsSera with normal, hypo- or hypergammaglobulinemia were spiked with daratumumab, Dara (cathodal migrating), or elotuzumab, Elo (central-gamma migrating), with concentrations from 0.125 to 10 g/L (n = 62) along with a beta-migrating sample (n = 9). Provided with total protein (reverse biuret, Siemens), laboratories blindly analyzed samples according to their SPEP and immunofixation (IFE) or immunosubtraction (ISUB) standard operating procedures. Sixteen laboratories reported the perpendicular drop (PD) method of gating the M-protein, while 10 used tangent skimming (TS). A mean percent recovery range of 80%–120% was set as acceptable. The inter-laboratory %CV was calculated.ResultsGamma globulin background, migration pattern and concentration all affect the precision and accuracy of quantifying M-proteins by SPEP. As the background increases, imprecision increases and accuracy decreases leading to overestimation of M-protein quantitation especially evident in hypergamma samples, and more prominent with PD. Cathodal migrating M-proteins were associated with less imprecision and higher accuracy compared to central-gamma migrating M-proteins, which is attributed to the increased gamma background contribution in M-proteins migrating in the middle of the gamma fraction. There is greater imprecision and loss of accuracy at lower M-protein concentrations.ConclusionsThis study suggests that quantifying exceedingly low concentrations of M-proteins, although possible, may not yield adequate accuracy and precision between laboratories