A case of familial frontotemporal dementia caused by a progranulin gene mutation.

After Alzheimer's disease, Frontotemporal dementia (FTD) is the most common cause of early-onset dementia. Several genetic mutations have been identified in familial FTD, with mutations in progranulin (GRN) accounting for approximately 20-25% of familial FTD cases and about 10% of total FTD cases. We report the case of a familial FTD patient with atypical parkinsonism who was found to have GRN frontotemporal dementia (GRN-FTD) with a pathogenic splice site mutation (c.709-2A > G) and notable phenotypic heterogeneity among family members.

Development of a European Centre of Excellence (Coe) for Research in Continuing Professional Development (UPGRADE).

The European Centre of Excellence (CoE) for Research in Continuing Professional Development (UPGRADE) is a pan-European network of researchers, clinicians, regulators, educators, and professional bodies, established in 2020 through a consensus group of experts, who defined its mission, vision, values, aims and objectives. The Centre's aim is to advance the science of Continuing Professional Development (CPD) for healthcare professionals through research and dissemination of best practices for CPD. Debate among UPGRADE partners and interchange of research data will yield best practices across countries to optimise quality CPD programmes. Collaboration, information exchange and communication among CPD experts will be facilitated through UPGRADE via an online Community of Inquiry (CoI). UPGRADE aims to evolve as a driving force network of academics and health professional leaders in research, education, professional regulation, and clinical practice whose collaborative work ensures quality and safe person-centred care. UPGRADE members are from 22 European countries, represented by strategic leaders in diverse sectors of health, policy, academia, and professional organisations. Three research-working groups constitute the pillars of UPGRADE, which addresses gaps in research, collect and create critical databases, and solidify the effectiveness of CPD.

Capturing, the experiences of undergraduate student nurses undertaking a pre-registration nursing degree course using an adapted experience based co-design approach.

BACKGROUND: The quality of student experience in higher education plays an increasingly important role in attracting and retaining pre-registration nurses. Identifying and understanding the students' experiences of their course is a necessary step in the move towards improving the student experience. Experience Based Co-design (EBCD) is successfully established as an effective process for improving patient experience in a health care setting. This study presents the use of EBCD outside of healthcare, specifically in a higher education setting. OBJECTIVES: To capture, explore and understand the experiences of students' undertaking a pre-registration (adult) nursing course, and co-design potential improvements for future experiences through the application of an EBCD approach. METHODS: An adapted EBCD approach was utilised for gaining insight into what shapes students' experience of the nursing course and to collaboratively produce priority recommendations for course improvement. Semi-structured interviews, emotional touchpoint mapping and co-design events were conducted with undergraduate nursing students (n = 22) and staff stakeholders in a pre-registration (adult) nursing course (n = 19). Findings were analysed using the 'Six phases of thematic analysis' (Braun & Clarke, 2006). RESULTS: Students had varied experiences on the nursing course, both positive and negative, particularly with student support. Three priority recommendations for course improvement were identified from the findings including: facilitating and supporting student development of independent study skills, enhancing student support in the clinical practice placement environment and clarifying and enhancing the role of the academic advisor. CONCLUSIONS: Findings from this study highlight areas for improvement on a pre-registration nursing course that could impact future students' experience. Furthermore, this study appears to be the first documented as using EBCD in a higher education setting with the focus on students, that enabled students and staff stakeholders in the nursing course to co-design priority recommendations for course improvement.

Genetic Variability of Palm Lethal Decline Phytoplasmas in the Caribbean Basin and Florida, U.S.A., Based on a Multilocus Analysis.

Palm lethal decline phytoplasmas are an important group of plant pathogens that cause death in a variety of palm species throughout the Caribbean basin and the southeastern United States. The 16SrIV-D phytoplasma was introduced to the state of Florida, United States; it has since caused severe economic losses to the green industries of Florida and is threating natural ecosystems because of its ability to infect the native palm Sabal palmetto. In this study, the genetic variability of the 16SrIV-D phytoplasma was assessed over a 10-year period to determine if multiple introductions had occurred or if natural mutations were occurring. Furthermore, the genetic variability of the palm lethal decline phytoplasma group (16SrIV) was assessed with a multiple locus analysis using the 16S ribosomal RNA gene, the 16S-23S intergenic spacer region, and secA and groEL genes. Overall, no variability of the 16SrIV-D phytoplasma was documented in Florida over a 10-year period. The multilocus analysis showed support for three distinct species of the phytoplasma in the Caribbean basin that infect palms and further support that the 16SrIV-C from Tanzania is not closely related. Furthermore, 16SrIV-B and 16SrIV-D were found to be the same phytoplasma based on 100% identity between the two based on intergenic spacer region, secA, and groEL analysis. This study represents the first robust, multilocus analysis of palm-infecting phytoplasmas from the Caribbean and sheds light on the phylogeny and evolution of the group.

Development of Aplastic Anemia during Treatment of Anaplastic Astrocytoma with Temozolomide.

Temozolomide (TMZ) is an oral alkylating agent that is considered the standard therapy in primary intracranial malignancies. The medication is well tolerated with a most common side effect of bone marrow suppression that is encountered in a small proportion of patients, often reversible with medication discontinuation and supportive treatment. Rarely, aplastic anemia can develop during treatment with TMZ. Here, we present a case of a patient who developed aplastic anemia following treatment with TMZ. We offer a review of the existing literature to have a better understanding of the causative effect and to examine the characteristics and outcomes when aplastic anemia develops during treatment with TMZ.

Presence of 16SrIV phytoplasmas of subgroups A, D and E in planthopper Haplaxius crudus Van Duzee insects in Yucatán, Mexico.

The present study was carried out to determine if group 16SrIV phytoplasmas, causing lethal yellowing (LY) disease, are present in Haplaxius crudus Van Duzee (Hemiptera: Cixiidae) insects associated with palms in Yucatán, Mexico. Haplaxius crudus feral insects were captured from palm foliage at two locations (Chicxulub Puerto and CICY, Mérida, where LY-type diseases are active) and evaluated individually for the presence of phytoplasma DNA by a group 16SrIV-specific nested PCR assay. The results showed positive detection in H. crudus insects in a proportion of 2.7% (of the total 2726 analyzed) during a 3-year period of study. The percentage of detection was different for each site, 5.9% positive of 799 insects from Mérida and 1.7% of 1927 from Chicxulub Puerto. Positive detections were also obtained in extracts from 5.3 to 1.2% of males and females, respectively. Sequencing and in silico RFLP and phylogenetic analyses of PCR-amplified rDNA products indicated that H. crudus insects from Chicxulub Puerto harbored phytoplasma strains of subgroups 16SrIV-A or 16SrIV-D, whereas in insects from Mérida the strains found were 16SrIV-A, 16SrIV-D or 16SrIV-E. The diversity of subgroup strains detected in H. crudus coincided with strains previously identified in palms showing LY-type disease syndromes in Yucatán thereby implicating H. crudus as a candidate vector of 16SrIV phytoplasmas in this region of Mexico.

Digital PCR Technology for Detection of Palm-Infecting Phytoplasmas Belonging to Group 16SrIV that Occur in Florida.

Phytoplasmas are an economically important group of plant pathogens that negatively impact a wide variety of plants in agricultural and natural ecosystems. In Florida, palm trees are essential elements in the nursery and landscaping industries that suffer from diseases caused by phytoplasmas that are related to each other but are classified in two different subgroups, 16SrIV-A and 16SrIV-D. In this study, a TaqMan assay was developed for digital polymerase chain reaction (dPCR) to detect both palm-infecting phytoplasmas found in Florida. When compared with real-time PCR assays and nested PCR assays, dPCR was capable of detecting the phytoplasmas at much lower concentrations than was possible by using real-time PCR and nested PCR. Additionally, the assay was capable of detecting 16SrIV-B phytoplasma as well as isolates representing the 16SrI and 16SrIII phytoplasma groups. Due to sequence identity of primer annealing regions across diverse phytoplasmas, the assay is likely to be successful for detection of a wide variety of phytoplasmas. The increased sensitivity of this dPCR assay over real-time PCR will allow for earlier detection of phytoplasma infection in palm trees, as well as for screening of salivary glands of candidate insect vector species. These advantages should aid timely management decisions to reduce disease spread and rapid determination of phytoplasma transmission by vectors.

'Candidatus Phytoplasma wodyetiae', a new taxon associated with yellow decline disease of foxtail palm (Wodyetia bifurcata) in Malaysia.

Landscape-grown foxtail palm (Wodyetia bifurcata A. K. Irvine) trees displaying symptoms of severe foliar chlorosis, stunting, general decline and mortality reminiscent of coconut yellow decline disease were observed in Bangi, Malaysia, during 2012. DNA samples from foliage tissues of 15 symptomatic palms were analysed by employing a nested PCR assay primed by phytoplasma universal ribosomal RNA operon primer pairs, P1/P7 followed by R16F2n/R2. The assay yielded amplicons of a single band of 1.25 kb from DNA samples of 11 symptomatic palms. Results from cloning and sequence analysis of the PCR-amplified 16S rRNA gene segments revealed that, in three palms, three mutually distinct phytoplasmas comprising strains related to 'Candidatus Phytoplasma asteris' and 'Candidatus Phytoplasma cynodontis', as well as a novel phytoplasma, were present as triple infections. The 16S rRNA gene sequence derived from the novel phytoplasma shared less than 96 % nucleotide sequence identity with that of each previously describedspecies of the provisional genus 'Ca. Phytoplasma', justifying its recognition as the reference strain of a new taxon, 'Candidatus Phytoplasma wodyetiae'. Virtual RFLP profiles of the R16F2n/R2 portion of the 16S rRNA gene and the pattern similarity coefficient value (0.74) supported the delineation of 'Ca. Phytoplasma wodyetiae' as the sole representative subgroup A member of a new phytoplasma ribosomal group, 16SrXXXVI.

Detecting and Differentiating Phytoplasmas Belonging to Subgroups 16SrIV-A and 16SrIV-D Associated With Lethal Declines of Palms in Florida Using qPCR and High-Resolution Melt Analysis (HRMA).

Lethal yellowing (LY) and Texas Phoenix palm decline (TPPD) are two important phytoplasma diseases of palms in Florida. Both have been responsible for major economic losses historically and remain a constant threat to the sustainability of palm production in the landscaping and nursery industries in Florida. These two diseases cause rapid, lethal decline in afflicted palms, so rapid detection and identification is crucial to implement appropriate management strategies to reduce further spread and losses. In this study, a qPCR assay was developed to detect and identify the causal agents of LY and TPPD. Based on sequence data of the 16S gene for the 16SrIV-A phytoplasma (LY) and the 16SrIV-D phytoplasma (TPPD), two regions were identified in the gene that possessed sufficient variation to yield amplicons with measurable differences in melting temperature based on high resolution melt analysis (HRMA). One region was in the 5' region and the other was located in the 3' region of the gene. Products from both regions yielded amplicons with significantly different melting temperatures between the two phytoplasma strains. This research allows for the detection and identification of phytoplasmas in palms rapidly by eliminating many lengthy and post-PCR steps commonly used in phytoplasma identification.

Novel application of three-dimensional technologies in a case of dismemberment.

This case study reports the novel application of three-dimensional technologies such as micro-CT and 3D printing to the forensic investigation of a complex case of dismemberment. Micro-CT was successfully employed to virtually align severed skeletal elements found in different locations, analyse tool marks created during the dismemberment process, and virtually dissect a charred piece of evidence. High resolution 3D prints of the burnt human bone contained within were created for physical visualisation to assist the investigation team. Micro-CT as a forensic radiological method provided vital information and the basis for visualisation both during the investigation and in the subsequent trial making it one of the first examples of such technology in a UK court.

'Candidatus Phytoplasma hispanicum', a novel taxon associated with Mexican periwinkle virescence disease of Catharanthus roseus.

Mexican periwinkle virescence (MPV) phytoplasma was originally discovered in diseased plants of Madagascar periwinkle (Catharanthus roseus) in Yucatán, Mexico. On the basis of results from RFLP analysis of PCR-amplified 16S rRNA gene sequences, strain MPV was previously classified as the first known member of phytoplasma group 16SrXIII, and a new subgroup (16SrXIII-A) was established to accommodate MPV phytoplasma. Phylogenetic analysis of 16S rRNA gene sequences indicated that strain MPV represents a lineage distinct from previously described 'CandidatusPhytoplasma' species. Nucleotide sequence alignments revealed that strain MPV shared less than 97.5 % 16S rRNA gene sequence similarity with all previously described 'Ca.Phytoplasma' species. Based on unique properties of the DNA, we propose recognition of Mexican periwinkle virescence phytoplasma strain MPV as representative of a novel taxon, 'CandidatusPhytoplasma hispanicum'.

Complete Genome Sequence of Spiroplasma kunkelii Strain CR2-3x, Causal Agent of Corn Stunt Disease in Zea mays L.

Spiroplasma kunkelii causes corn stunt disease of Zea mays L. in the Americas. Here, we report the nucleotide sequence of the 1,463,926-bp circular chromosome and four plasmids of strain CR2-3x. This information will facilitate studies of Spiroplasma pathogenicity and evolutionary adaptations to transkingdom parasitism in plants and insect vectors.

Service user involvement in practitioner education: Movement politics and transformative change.

This paper will attempt to celebrate both key developments and best practice involving the users of health and social care services in programmes of practitioner education in a UK context, and offer a critical appraisal of the extent to which such initiatives meet some of the more transformative objectives sought by service user activists for change. The approach is largely that of a discussion paper but we will illustrate some of the themes relating to movement activism with selected data. These data relate to earlier research and two specially convened focus groups within the Comensus initiative at the University of Central Lancashire; itself constituted as a piece of participatory action research. We conclude that universities represent paradoxical sites for the facilitation of debate and learning relevant to key issues of social justice and change. As such, they are places that can impede or support movement aims. Particular strategic responses might be more likely to engender progressive outcomes. These ought to include the presence of critically engaged academic staff operating within a scholarly culture that fosters forms of deliberative democratic decision making.

'Candidatus Phytoplasma palmicola', associated with a lethal yellowing-type disease of coconut (Cocos nucifera L.) in Mozambique.

In this study, the taxonomic position and group classification of the phytoplasma associated with a lethal yellowing-type disease (LYD) of coconut (Cocos nucifera L.) in Mozambique were addressed. Pairwise similarity values based on alignment of nearly full-length 16S rRNA gene sequences (1530 bp) revealed that the Mozambique coconut phytoplasma (LYDM) shared 100% identity with a comparable sequence derived from a phytoplasma strain (LDN) responsible for Awka wilt disease of coconut in Nigeria, and shared 99.0-99.6% identity with 16S rRNA gene sequences from strains associated with Cape St Paul wilt (CSPW) disease of coconut in Ghana and Côte d'Ivoire. Similarity scores further determined that the 16S rRNA gene of the LYDM phytoplasma shared <97.5% sequence identity with all previously described members of 'Candidatus Phytoplasma'. The presence of unique regions in the 16S rRNA gene sequence distinguished the LYDM phytoplasma from all currently described members of 'Candidatus Phytoplasma', justifying its recognition as the reference strain of a novel taxon, 'Candidatus Phytoplasma palmicola'. Virtual RFLP profiles of the F2n/R2 portion (1251 bp) of the 16S rRNA gene and pattern similarity coefficients delineated coconut LYDM phytoplasma strains from Mozambique as novel members of established group 16SrXXII, subgroup A (16SrXXII-A). Similarity coefficients of 0.97 were obtained for comparisons between subgroup 16SrXXII-A strains and CSPW phytoplasmas from Ghana and Côte d'Ivoire. On this basis, the CSPW phytoplasma strains were designated members of a novel subgroup, 16SrXXII-B.

The identification of individuals by observational gait analysis using closed circuit television footage.

This study investigated the ability of individuals with experience in gait analysis to identify people by observing features of gait recorded by closed circuit television cameras (CCTV). Seven experienced analysts each viewed five samples of footage. Each sample showed a "target walker" and five "suspect walkers." The task of the experienced analysts was to determine which, if any, of the "suspect walkers" was the "target walker." All of the participant "walkers" wore identical loose fitting clothing to mask anatomical and body contour features, and balaclavas to obscure facial features. The overall results showed that the experienced analysts made a correct decision in 124 of 175 cases (71%), significantly better than would have been expected to have occurred by chance (p<0.05). A significant variation in correct decisions (p<0.05) was shown to occur between the various angles from which the footage was recorded, footage recorded in the saggital plane showing the highest number of correct decisions. Significantly more correct decisions (p<0.05) were also shown to occur when the footage of the "target walker" and that of the "suspect walker" were taken from the same angle. The results suggest that individuals with experience in gait analysis perform well in the comparative identification of suspects from CCTV footage, and therefore do have a role to play as expert witnesses in this field.

DNA extraction from arborescent monocots and how to deal with other challenging hosts.

Detection of pathogen DNA by polymerase chain reaction (PCR) assays is the most widely used method for diagnosing phytoplasma diseases. Reliable and efficient detection of phytoplasmas, especially in woody perennial plants, is challenging due to the unusually low abundance and sporadic distribution of phytoplasmas within infected host tissues. Detection success depends largely upon the host species and sampling procedures and, to a lesser extent, on the protocol used for DNA extraction. Here we describe a simple, straightforward, nondestructive stem sampling protocol to confirm phytoplasma infection of palms and other arborescent monocots of large stature. The protocol requires minimal processing of excised tissues and yields phytoplasma DNA preparations in suitable quantity for reliable detection by nested PCR assays.

'Candidatus Phytoplasma malaysianum', a novel taxon associated with virescence and phyllody of Madagascar periwinkle (Catharanthus roseus).

This study addressed the taxonomic position and group classification of a phytoplasma responsible for virescence and phyllody symptoms in naturally diseased Madagascar periwinkle plants in western Malaysia. Unique regions in the 16S rRNA gene from the Malaysian periwinkle virescence (MaPV) phytoplasma distinguished the phytoplasma from all previously described 'Candidatus Phytoplasma' species. Pairwise sequence similarity scores, calculated through alignment of full-length 16S rRNA gene sequences, revealed that the MaPV phytoplasma 16S rRNA gene shared 96.5 % or less sequence similarity with that of previously described 'Ca. Phytoplasma' species, justifying the recognition of the MaPV phytoplasma as a reference strain of a novel taxon, 'Candidatus Phytoplasma malaysianum'. The 16S rRNA gene F2nR2 fragment from the MaPV phytoplasma exhibited a distinct restriction fragment length polymorphism (RFLP) profile and the pattern similarity coefficient values were lower than 0.85 with representative phytoplasmas classified in any of the 31 previously delineated 16Sr groups; therefore, the MaPV phytoplasma was designated a member of a new 16Sr group, 16SrXXXII. Phytoplasmas affiliated with this novel taxon and the new group included diverse strains infecting periwinkle, coconut palm and oil palm in Malaysia. Three phytoplasmas were characterized as representatives of three distinct subgroups, 16SrXXXII-A, 16SrXXXII-B and 16SrXXXII-C, respectively.

Safety and feasibility of patient transfer by helicopter for primary percutaneous coronary intervention.

AIM: Delayed treatment of patients undergoing transfer for primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) may reduce treatment benefits compared with fibrinolysis at the referring institution. We evaluated the feasibility of helicopter transfer of Whangarei patients to Auckland City Hospital for PPCI. METHOD: Clinical records of patients transferred from Whangarei to Auckland City Hospital by helicopter for PPCI were reviewed and clinical data reported. RESULTS: Between May 2010 and August 2011, 24 patients (19 male, median age 63 years, range 41-79 years) underwent helicopter transfer PPCI from Whangarei. Overall, median time to reperfusion was 125 minutes (IQR 117-147 minutes). For the 9 patients presenting within working hours (weekdays 8am-5pm), the median reperfusion time was 122 minutes (IQR 105-136 minutes), compared with 134 minutes (IQR 117-159 minutes) in the 15 patients presenting outside working hours. One patient achieved reperfusion within 90 minutes from presentation while 8/24 achieved reperfusion within 120 minutes. All patients survived to hospital discharge, as did 23/24 at 30 day follow-up. CONCLUSION: Helicopter transfer for PPCI from Whangarei to Auckland City Hospital is a feasible treatment strategy for patients presenting with STEMI. Improvements in treatment times are required if the full benefits of this strategy are to be realised.

Coordination of cell differentiation and migration in mathematical models of caudal embryonic axis extension.

Vertebrate embryos display a predominant head-to-tail body axis whose formation is associated with the progressive development of post-cranial structures from a pool of caudal undifferentiated cells. This involves the maintenance of active FGF signaling in this caudal region as a consequence of the restricted production of the secreted factor FGF8. FGF8 is transcribed specifically in the caudal precursor region and is down-regulated as cells differentiate and the embryo extends caudally. We are interested in understanding the progressive down-regulation of FGF8 and its coordination with the caudal movement of cells which is also known to be FGF-signaling dependent. Our study is performed using mathematical modeling and computer simulations. We use an individual-based hybrid model as well as a caricature continuous model for the simulation of experimental observations (ours and those known from the literature) in order to examine possible mechanisms that drive differentiation and cell movement during the axis elongation. Using these models we have identified a possible gene regulatory network involving self-repression of a caudal morphogen coupled to directional domain movement that may account for progressive down-regulation of FGF8 and conservation of the FGF8 domain of expression. Furthermore, we have shown that chemotaxis driven by molecules, such as FGF8 secreted in the stem zone, could underlie the migration of the caudal precursor zone and, therefore, embryonic axis extension. These mechanisms may also be at play in other developmental processes displaying a similar mode of axis extension coupled to cell differentiation.