Delayed discharge in inpatient psychiatric care: a systematic review.

BACKGROUND: Delayed discharge is problematic. It is financially costly and can create barriers to delivering best patient care, by preventing return to usual functioning and delaying admissions of others in need. This systematic review aimed to collate existing evidence on delayed discharge in psychiatric inpatient settings and to develop understanding of factors and outcomes of delays in these services. METHODS: A search of relevant literature published between 2002 and 2022 was conducted on Pubmed, PsycInfo and Embase. Studies of any design, which published data on delayed discharge from psychiatric inpatient care in high income countries were included. Studies examining child and adolescent, general medical or forensic settings were excluded. A narrative synthesis method was utilised. Quality of research was appraised using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Eighteen studies from England, Canada, Australia, Ireland, and Norway met the inclusion criteria. Six main reasons for delayed discharge were identified: (1) accommodation needs, (2) challenges securing community or rehabilitation support, (3) funding difficulties, (4) family/carer factors, (5) forensic considerations and (6) person being out of area. Some demographic and clinical factors were also found to relate to delays, such as having a diagnosis of schizophrenia or other psychotic disorder, cognitive impairment, and increased service input prior to admission. Being unemployed and socially isolated were also linked to delays. Only one study commented on consequences of delays for patients, finding they experienced feelings of lack of choice and control. Four studies examined consequences on services, identifying high financial costs. CONCLUSION: Overall, the findings suggest there are multiple interlinked factors relevant in delayed discharge that should be considered in practice and policy. Suggestions for future research are discussed, including investigating delayed discharge in other high-income countries, examining delayed discharge from child and forensic psychiatric settings, and exploring consequences of delays on patients and staff. We suggest that future research be consistent in terms used to define delayed discharge, to enhance the clarity of the evidence base. REVIEW REGISTRATION NUMBER ON PROSPERO: 292515. DATE OF REGISTRATION: 9th December 2021.

Rare, long-distance dispersal underpins genetic connectivity in the pink sea fan, Eunicella verrucosa.

Characterizing patterns of genetic connectivity in marine species is of critical importance given the anthropogenic pressures placed on the marine environment. For sessile species, population connectivity can be shaped by many processes, such as pelagic larval duration, oceanographic boundaries and currents. This study combines restriction-site associated DNA sequencing (RADseq) and passive particle dispersal modelling to delineate patterns of population connectivity in the pink sea fan, Eunicella verrucosa, a temperate octocoral. Individuals were sampled from 20 sites covering most of the species' northeast Atlantic range, and a site in the northwest Mediterranean Sea to inform on connectivity across the Atlantic-Mediterranean transition. Using 7510 neutral SNPs, a geographic cline of genetic clusters was detected, partitioning into Ireland, Britain, France, Spain (Atlantic), and Portugal and Spain (Mediterranean). Evidence of significant inbreeding was detected at all sites, a finding not detected in a previous study of this species based on microsatellite loci. Genetic connectivity was characterized by an isolation by distance pattern (IBD) (r 2 = 0.78, p < 0.001), which persisted across the Mediterranean-Atlantic boundary. In contrast, exploration of ancestral population assignment using the program ADMIXTURE indicated genetic partitioning across the Bay of Biscay, which we suggest represents a natural break in the species' range, possibly linked to a lack of suitable habitat. As the pelagic larval duration (PLD) is unknown, passive particle dispersal simulations were run for 14 and 21 days. For both modelled PLDs, inter-annual variations in particle trajectories suggested that in a long-lived, sessile species, range-wide IBD is driven by rare, longer dispersal events that act to maintain gene flow. These results suggest that oceanographic patterns may facilitate range-wide stepping-stone genetic connectivity in E. verrucosa and highlight that both oceanography and natural breaks in a species' range should be considered in the designation of ecologically coherent MPA networks.

mapmixture: An R package and web app for spatial visualisation of admixture and population structure.

The mapmixture R package and interactive web app are tools to aid visualisation of admixture and population structure in geographic space. The purpose of mapmixture is to enable and encourage molecular ecologists, and in particular population geneticists and phylogeneticists, to plot their admixture, ancestry or assignment results on a map when location information is available. mapmixture accepts data in the format typically generated by admixture analyses and visualises proportions to each genetic cluster per site as pie charts on a projected (optional) map. Combining this site-based map presentation approach with the routine individual-based presentation of admixture (structure) barplots will enhance interpretation of genetic-geographic patterns. Additionally, in the context of science communication, this enables clearer transfer of spatial genetic information to readers or listeners, and especially to audiences that do not have a background in genetics but who are able to use the genetic information as evidence in conservation management. The latest version of mapmixture is available on GitHub (https://github.com/tom-jenkins/mapmixture), which details installation instructions and examples of how to use the package and interactive web app.

Self-dehumanisation in voice hearers: the end of a continuum.

Background: Meta-dehumanisation and self-dehumanisation have been identified as potentially relevant phenomena for developing a deeper understanding of distress related to voice-hearing, particularly those experiencing voices as part of psychosis. Chadwick has previously argued that those with psychosis, including those who hear distressing voices, typically feel "dehumanised and set apart by their experiences of psychosis and trauma." The present study explores the subjective experience of self-dehumanisation in people who experience distressing voices, which was selected as a useful starting point to inform future research focused on understanding dehumanisation in people with psychosis. Methods: Qualitative data was obtained through twenty semi-structured interviews with self-identifying voice hearers and analysed using reflexive thematic analysis. This followed the recursive six phase procedure of Braun and Clarke, and this was conducted from a critical realist, contextualist position. Results: Reflexive thematic analysis of participant's experiences produced a core theme, Dehumanisation as the End of Experiential Continua, and six subthemes: Extent of Distressing Sensory Fragmentation; Sense of Belonging with Other Humans; Integrity of Self as a Private, Coherent Entity; Sense of Worth as a Human Being; Strength of Personal Agency; and Trust in Own Credibility and Reliability. Two further themes, The Push and Pull of Dehumanising Forces and Reclaiming Life through Humanising Forces, were identified. Findings were presented to a panel of five experts by experience, all with lived experience of psychosis and service-use; all five strongly endorsed the themes as fitting with and expressing their own experiences of self-dehumanisation. Conclusion: Reflexive thematic analysis of voice hearers' accounts identified self-dehumanisation as the endpoint where six experiential continua coalesce. Experiential movement along these continua was affected by a range of interpersonal, intrapersonal, and societal forces over time, including dehumanising attitudes of others and voice malevolence and omnipotence. Future research might examine if and how psychological therapies aimed at those experiencing distressing voices, such as people experiencing psychosis may address feelings of self-dehumanisation.

Palliative and End-of-Life Care for People Living with Motor Neurone Disease: Ongoing Challenges and Necessity for Shifting Directions.

Although the progressive clinical trajectory of motor neurone disease (MND) is widely understood, multiple challenges remain preventing optimal end-of-life care for this population with unique needs from the patient, carer and service provider perspectives. This paper reports on the experiences, gaps in service and unmet needs of MND patients and family carers and explores public health palliative care approaches that would facilitate coordinated and integrated care to respond to their changing needs. This is a qualitative study of responses to questions in an online consumer survey (353 respondents) in Western Australia (2020), focusing on a subset of 29 current and bereaved carers of people with MND who have used health services in the last five years. The analysis identified themes, highlighting the insufficient integration of services across health and social care; poor and unequal access to coordinated palliative care; significant gaps in the knowledge base of the workforce and a failure to meet the consumer expectations of person-centred care. For palliative care to be accessible to those living with MND and other under-served conditions, there needs to be a shift to more comprehensive, inclusive and sustainable options, such as the public health approach to palliative/end-of-life care that engages the assets of local communities in partnership with health services, one example being the "Compassionate Communities Connectors" model of care. Further considerations include advocacy for policy changes, fostering partnerships and developing indicators for evaluating the impact of the proposed models of care. The end result is not only better care but substantial savings for the health system.

The First Genome of the Cold-Water Octocoral, the Pink Sea Fan, Eunicella verrucosa.

Cold-water corals form an important part of temperate benthic ecosystems by increasing three-dimensionality and providing an important ecological substrate for other benthic fauna. However, the fragile three-dimensional structure and life-history characteristics of cold-water corals can leave populations vulnerable to anthropogenic disturbance. Meanwhile, the ability of temperate octocorals, particularly shallow-water species, to respond to adjustments in their environment linked to climate change has not been studied. This study reports the first genome assembly of the pink sea fan (Eunicella verrucosa), a temperate shallow-water octocoral species. We produced an assembly of 467 Mb, comprising 4,277 contigs and an N50 of 250,417 bp. In total, 213 Mb (45.96% of the genome) comprised repetitive sequences. Annotation of the genome using RNA-seq data derived from polyp tissue and gorgonin skeleton resulted in 36,099 protein-coding genes after 90% similarity clustering, capturing 92.2% of the complete Benchmarking Universal Single-Copy Orthologs (BUSCO) ortholog benchmark genes. Functional annotation of the proteome using orthology inference identified 25,419 annotated genes. This genome adds to the very few genomic resources currently available in the octocoral community and represents a key step in allowing scientists to investigate the genomic and transcriptomic responses of octocorals to climate change.

Mindfulness for voices: An experimental analogue study of the effect of manipulating response style to simulated voices in a non-clinical population.

OBJECTIVES: We aimed to investigate the effects of directly manipulating response style to simulated voice hearing on emotional and cognitive outcomes in a non-clinical population. DESIGN: A between-subjects design with one independent variable, response style (with two levels: mindful acceptance vs attentional avoidance). The dependent variables were subjective distress and anxiety (primary outcomes) and performance on a sustained attention task (secondary outcomes). METHODS: Participants were randomly assigned to one of two response styles (mindful acceptance vs. attentional avoidance). They completed a computerised attention task (continuous performance task) whilst listening to a simulation of voice hearing. Participants rated their experience of anxiety and distress before and after completing the sustained attention task which was used to measure their accuracy and response times. RESULTS: One hundred and one participants took part (mindful acceptance (n = 54); attentional avoidance (n = 47)). There were no statistically significant group differences on post-test distress and anxiety scores, correct response rate or response times on the computerised attention task. Participants reported a range of different response styles along the spectrum of avoidance to acceptance, but this had no association with their assigned experimental condition. Adherence to task instructions was therefore low. CONCLUSIONS: We are unable to conclude from this study whether experimentally inducing people to respond to voices under cognitively demanding conditions in an avoidant or accepting way has an impact on their emotional or cognitive outcomes. Further research should focus on the development of more robust and reliable procedures for inducing differences in response style under experimental conditions.

Predicting habitat suitability and range shifts under projected climate change for two octocorals in the north-east Atlantic.

Species distribution models have become a valuable tool to predict the distribution of species across geographic space and time. In this study, maximum entropy models were constructed for two temperate shallow-water octocoral species, the pink sea fan (Eunicella verrucosa) and dead man's fingers (Alcyonium digitatum), to investigate and compare habitat suitability. The study area covered the north-east Atlantic from the Bay of Biscay to the British Isles and southern Norway; this area includes both the northern range of E. verrucosa and the middle-northern range of A. digitatum. The optimal models for each species showed that, overall, slope, temperature at the seafloor and wave orbital velocity were important predictors of distribution in both species. Predictions of habitat suitability showed areas of present-day (1951-2000) suitable habitat where colonies have not yet been observed, particularly for E. verrucosa, where areas beyond its known northern range limit were identified. Moreover, analysis with future layers (2081-2100) of temperature and oxygen concentration predicted a sizable increase in habitat suitability for E. verrucosa beyond these current range limits under the Representative Concentration Pathway 8.5 scenario. This suggests that projected climate change may induce a potential range expansion northward for E. verrucosa, although successful colonisation would also be conditional on other factors such as dispersal and interspecific competition. For A. digitatum, this scenario of projected climate change may result in more suitable habitat in higher latitudes, but, as with E. verrucosa, there is a degree of uncertainty in the model predictions. Importantly, the results from this study highlight present-day areas of high habitat suitability which, if combined with knowledge on population density, could be used to identify priority areas to enhance protection and ensure the long-term survival of these octocoral species in the region.

Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19.

BACKGROUND AND PURPOSE: Despite the increasing number of reports on the spectrum of neurological manifestations of COVID-19 (neuro-COVID), few studies have assessed short- and long-term outcome of the disease. METHODS: This is a cohort study enrolling adult patients with neuro-COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro-covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as 'stable/improved' if the modified Rankin Scale score was equal to or lower than the pre-morbid score, 'worse' if the score was higher than the pre-morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months. RESULTS: From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non-hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow-up. CONCLUSIONS: Neuro-COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.

The complete mitochondrial genome of the pink sea fan, Eunicella verrucosa (Pallas, 1766).

The pink sea fan, Eunicella verrucosa (Pallas, 1766), inhabits rocky substrates across the northeast Atlantic and the western Mediterranean. Across much of its range it has been detrimentally affected by fishing. DNA from 17 E. verrucosa specimens was amplified by phi29-induced rolling circle amplification. Following purification by sodium acetate-ethanol precipitation, the circular genomic DNA was sequenced on an Illumina MiSeq v2. Specimens originated from sites along the west coast of Ireland, southwest Wales, southwest/southern England, northwest France, southern Portugal, and the Mediterranean coast of northeast Spain. All samples had identical mitochondrial genome sequences of 19,267 bp and included 14 protein-coding genes (including the mutS gene), two ribosomal RNA subunits (12S and 16S) and one methionine tRNA gene. Two genes (nad2 and nad5) overlapped by 13 bp; all other genes were separated by non-coding intergenic regions. All protein-coding genes had the same start codon (ATG) and a TAA or TAG stop codon, except for cox1 that terminated with the incomplete stop codon T--. The mitochondrial genome of E. verrucosa (MW588805) showed 99.72% similarity with that of a related sea fan species, Eunicella cavolini, with six SNPs and a 49 bp deletion between nad5 and nad4 in E. verrucosa distinguishing the two.

Whole genome genotyping reveals discrete genetic diversity in north-east Atlantic maerl beds.

Maerl beds are vital habitats for a diverse array of marine species across trophic levels, but they are increasingly threatened by human activities and climate change. Furthermore, little is known about the genetic diversity of maerl-forming species and the population structure of maerl beds, both of which are important for understanding the ability of these species to adapt to changing environments and for informing marine reserve planning. In this study, we used a whole genome genotyping approach to explore the population genomics of Phymatolithon calcareum, a maerl-forming red algal species, whose geographical distribution spans the north-east Atlantic, from Norway to Portugal. Our results, using 14,150 genome-wide SNPs (single nucleotide polymorphisms), showed that P. calcareum maerl beds across the north-east Atlantic are generally structured geographically, a pattern likely explained by low dispersal potential and limited connectivity between regions. Additionally, we found that P. calcareum from the Fal Estuary, south-west England, is genetically distinct from all other P. calcareum sampled, even from The Manacles, a site located only 13 km away. Further analysis revealed that this finding is not the result of introgression from two closely related species, Phymatolithon purpureum or Lithothamnion corallioides. Instead, this unique diversity may have been shaped over time by geographical isolation of the Fal Estuary maerl bed and a lack of gene flow with other P. calcareum populations. The genomic data presented in this study suggest that P. calcareum genetic diversity has accumulated over large temporal and spatial scales, the preservation of which will be important for maximizing the resilience of this species to changes in climate and the environment. Moreover, our findings underline the importance of managing the conservation of maerl beds across western Europe as distinct units, at a site-by-site level.

Diagnostic and investigative approach of consultant neurologists in a real-world clinical setting: A pilot study.

PURPOSE: Whilst core curricula in neurology are nationally standardised, in real-world clinical practice, different approaches may be taken by individual consultants. The aims of this study were to investigate differences by assessing: (a) variance in diagnostic and investigative practice, using a case-based analysis of inter-rater agreement; (b) potential importance of any differences in terms of patient care; (c) relationships between clinical experience, diagnostic certainty, diagnostic peer-agreement and investigative approach. The objective was to develop novel individualised metrics to facilitate reflection and appraisal. METHODS: Three neurologists with 6-23 years' experience at consultant level provided diagnosis, certainty (10-point Likert scale), and investigative approach for 200 consecutive general neurology outpatients seen by a newly qualified consultant in 2015. Diagnostic agreement was evaluated by percentage agreement. The potential importance of any diagnostic differences on patient outcome was assigned a score (6-point Likert scale) by the evaluating neurologist. Associations between diagnostic agreement, certainty and investigative approach were assessed using Spearman correlation, logistic and ordinal regression, and reported as individualised metrics for each rater. RESULTS: Diagnostic peer-agreement was 3/3, 2/3 and 1/3 in 55.5%, 31.0% and 13.5% of cases, respectively. In 15.5%, differences in patient management were judged potentially important. Investigation rates were 42%-73%. Mean diagnostic certainty ranged from 6.63/10 (SD 1.98) to 7.72/10 (SD 2.20) between least and most experienced consultants. Greater diagnostic certainty was associated with greater diagnostic peer-agreement (individual-rater regression coefficients 0.33-0.44, P < .01) and lower odds of arranging investigations (individual-rater odds ratios 0.56-0.71, P < .01). CONCLUSIONS: It appears that variance in diagnostic and investigative practice between consultant neurologists exists and may result in differing management. Mean diagnostic certainty was associated with greater diagnostic peer-agreement and lower investigation rates. Metrics reflecting concordance with peers, and relationships to diagnostic confidence, could be developed in larger cohorts to inform reflective practice.

Historical translocations and stocking alter the genetic structure of a Mediterranean lobster fishery.

Stocking is often used to supplement wild populations that are overexploited or have collapsed, yet it is unclear how this affects the genetic diversity of marine invertebrate populations. During the 1970s, a lobster stock enhancement program was carried out around the island of Corsica in the Mediterranean using individuals translocated from the Atlantic coast of France. This included the release of thousands of hatchery-reared postlarval lobsters and several adult individuals, but no monitoring plan was established to assess whether these animals survived and recruited to the population. In this study, we sampled European lobster (Homarus gammarus) individuals caught around Corsica and tested whether they showed Atlantic ancestry. Due to a natural marked phylogeographic break between Atlantic and Mediterranean lobsters, we hypothesized that lobsters with dominant (>0.50) Atlantic ancestry were descended from historical stocking releases. Twenty Corsican lobsters were genotyped at 79 single nucleotide polymorphisms, and assignment analysis showed that the majority (13) had dominant Atlantic ancestry. This suggests that the hatchery stocking program carried out in Corsica during the 1970s, using individuals translocated from the Atlantic coast of France, has likely augmented local recruitment but at a cost of altering the genetic structure of the Corsican lobster population.

Crossing the pond: genetic assignment detects lobster hybridisation.

American lobsters (Homarus americanus) imported live into Europe as a seafood commodity have occasionally been released or escaped into the wild, within the range of an allopatric congener, the European lobster (H. gammarus). In addition to disease and competition, introduced lobsters threaten native populations through hybridisation, but morphological discriminants used for species identification are unable to discern hybrids, so molecular methods are required. We tested an array of 79 single nucleotide polymorphisms (SNPs) for their utility to distinguish 1,308 H. gammarus from 38 H. americanus and 30 hybrid offspring from an American female captured in Sweden. These loci provide powerful species assignment in Homarus, enabling the robust identification of hybrid and American individuals among a survey of European stock. Moreover, a subset panel of the 12 most powerful SNPs is sufficient to separate the two pure species, even when tissues have been cooked, and can detect the introduced component of hybrids. We conclude that these SNP loci can unambiguously identify hybrid lobsters that may be undetectable via basic morphology, and offer a valuable tool to investigate the prevalence of cryptic hybridisation in the wild. Such investigations are required to properly evaluate the potential for introgression of alien genes into European lobster populations.

Harnessing genomics to fast-track genetic improvement in aquaculture.

Aquaculture is the fastest-growing farmed food sector and will soon become the primary source of fish and shellfish for human diets. In contrast to crop and livestock production, aquaculture production is derived from numerous, exceptionally diverse species that are typically in the early stages of domestication. Genetic improvement of production traits via well-designed, managed breeding programmes has great potential to help meet the rising seafood demand driven by human population growth. Supported by continuous advances in sequencing and bioinformatics, genomics is increasingly being applied across the broad range of aquaculture species and at all stages of the domestication process to optimize selective breeding. In the future, combining genomic selection with biotechnological innovations, such as genome editing and surrogate broodstock technologies, may further expedite genetic improvement in aquaculture.

Single nucleotide polymorphisms reveal a genetic cline across the north-east Atlantic and enable powerful population assignment in the European lobster.

Resolving stock structure is crucial for fisheries conservation to ensure that the spatial implementation of management is commensurate with that of biological population units. To address this in the economically important European lobster (Homarus gammarus), genetic structure was explored across the species' range using a small panel of single nucleotide polymorphisms (SNPs) previously isolated from restriction-site-associated DNA sequencing; these SNPs were selected to maximize differentiation at a range of both broad and fine scales. After quality control and filtering, 1,278 lobsters from 38 sampling sites were genotyped at 79 SNPs. The results revealed a pronounced phylogeographic break between the Atlantic and Mediterranean basins, while structure within the Mediterranean was also apparent, partitioned between lobsters from the central Mediterranean and the Aegean Sea. In addition, a genetic cline across the north-east Atlantic was revealed using both putatively neutral and outlier SNPs, but the precise driver(s) of this clinal pattern-isolation by distance, secondary contact, selection across an environmental gradient, or a combination of these factors-remains undetermined. Putatively neutral markers differentiated lobsters from Oosterschelde, an estuary on the Dutch coast, a finding likely explained by past bottlenecks and limited gene flow with adjacent North Sea populations. Building on the findings of our spatial genetic analysis, we were able to test the accuracy of assigning lobsters at various spatial scales, including to basin of origin (Atlantic or Mediterranean), region of origin and sampling location. The predictive model assembled using 79 SNPs correctly assigned 99.7% of lobsters not used to build the model to their basin of origin, but accuracy decreased to region of origin and again to sampling location. These results are of direct relevance to managers of lobster fisheries and hatcheries, and provide the basis for a genetic tool for tracing the origin of European lobsters in the food supply chain.

Absence of evidence is not evidence of absence: Nanopore sequencing and complete assembly of the European lobster (Homarus gammarus) mitogenome uncovers the missing nad2 and a new major gene cluster duplication.

BACKGROUND: The recently published complete mitogenome of the European lobster (Homarus gammarus) that was generated using long-range PCR exhibits unusual gene composition (missing nad2) and gene rearrangements among decapod crustaceans with strong implications in crustacean phylogenetics. Such atypical mitochondrial features will benefit greatly from validation with emerging long read sequencing technologies such as Oxford Nanopore that can more accurately identify structural variation. RESULTS: We re-sequenced the H. gammarus mitogenome on an Oxford Nanopore Minion flowcell and performed a long-read only assembly, generating a complete mitogenome assembly for H. gammarus. In contrast to previous reporting, we found an intact mitochondrial nad2 gene in the H. gammarus mitogenome and showed that its gene organization is broadly similar to that of the American lobster (H. americanus) except for the presence of a large tandemly duplicated region with evidence of pseudogenization in one of each duplicated protein-coding genes. CONCLUSIONS: Using the European lobster as an example, we demonstrate the value of Oxford Nanopore long read technology in resolving problematic mitogenome assemblies. The increasing accessibility of Oxford Nanopore technology will make it an attractive and useful tool for evolutionary biologists to verify new and existing unusual mitochondrial gene rearrangements recovered using first and second generation sequencing technologies, particularly those used to make phylogenetic inferences of evolutionary scenarios.

Biomarkers in Motor Neuron Disease: A State of the Art Review.

Motor neuron disease can be viewed as an umbrella term describing a heterogeneous group of conditions, all of which are relentlessly progressive and ultimately fatal. The average life expectancy is 2 years, but with a broad range of months to decades. Biomarker research deepens disease understanding through exploration of pathophysiological mechanisms which, in turn, highlights targets for novel therapies. It also allows differentiation of the disease population into sub-groups, which serves two general purposes: (a) provides clinicians with information to better guide their patients in terms of disease progression, and (b) guides clinical trial design so that an intervention may be shown to be effective if population variation is controlled for. Biomarkers also have the potential to provide monitoring during clinical trials to ensure target engagement. This review highlights biomarkers that have emerged from the fields of systemic measurements including biochemistry (blood, cerebrospinal fluid, and urine analysis); imaging and electrophysiology, and gives examples of how a combinatorial approach may yield the best results. We emphasize the importance of systematic sample collection and analysis, and the need to correlate biomarker findings with detailed phenotype and genotype data.

Shrub establishment favoured and grass dominance reduced in acid heath grassland systems cleared of invasive Rhododendron ponticum.

Rhododendron ponticum L. is a damaging invasive alien species in Britain, favouring the moist, temperate climate, and the acidic soils of upland areas. It outshades other species and is thought to create a soil environment of low pH that may be higher in phytotoxic phenolic compounds. We investigated native vegetation restoration and R. ponticum regeneration post-clearance using heathland sites within Snowdonia National Park, Wales; one site had existing R. ponticum stands and three were restoring post-clearance. Each site also had an adjacent, uninvaded control for comparison. We assessed whether native vegetation restoration was influenced post-invasion by soil chemical properties, including pH and phytotoxic compounds, using Lactuca sativa L. (lettuce) bioassays supported by liquid chromatography-mass spectroscopy (LC-MSn). Cleared sites had higher shrub and bare ground cover, and lower grass and herbaceous species cover relative to adjacent uninvaded control sites; regenerating R. ponticum was also observed on all cleared sites. No phenolic compounds associated with R. ponticum were identified in any soil water leachates, and soil leachates from cleared sites had no inhibitory effect in L. sativa germination assays. We therefore conclude that reportedly phytotoxic compounds do not influence restoration post R. ponticum clearance. Soil pH however was lower beneath R. ponticum and on cleared sites, relative to adjacent uninvaded sites. The lower soil pH post-clearance may have favoured shrub species, which are typically tolerant of acidic soils. The higher shrub cover on cleared sites may have greater ecological value than unaffected grass dominated sites, particularly given the recent decline in such valuable heathland habitats. The presence of regenerating R. ponticum on all cleared sites however highlights the critical importance of monitoring and re-treating sites post initial clearance.

Meta-analysis of northeast Atlantic marine taxa shows contrasting phylogeographic patterns following post-LGM expansions.

BACKGROUND: Comparative phylogeography enables the study of historical and evolutionary processes that have contributed to shaping patterns of contemporary genetic diversity across co-distributed species. In this study, we explored genetic structure and historical demography in a range of coastal marine species across the northeast Atlantic to assess whether there are commonalities in phylogeographic patterns across taxa and to evaluate whether the timings of population expansions were linked to the Last Glacial Maximum (LGM). METHODS: A literature search was conducted using Web of Science. Search terms were chosen to maximise the inclusion of articles reporting on population structure and phylogeography from the northeast Atlantic; titles and abstracts were screened to identify suitable articles within the scope of this study. Given the proven utility of mtDNA in comparative phylogeography and the availability of these data in the public domain, a meta-analysis was conducted using published mtDNA gene sequences. A standardised methodology was implemented to ensure that the genealogy and demographic history of all mtDNA datasets were reanalysed in a consistent and directly comparable manner. RESULTS: Mitochondrial DNA datasets were built for 21 species. The meta-analysis revealed significant population differentiation in 16 species and four main types of haplotype network were found, with haplotypes in some species unique to specific geographical locations. A signal of rapid expansion was detected in 16 species, whereas five species showed evidence of a stable population size. Corrected mutation rates indicated that the majority of expansions were estimated to have occurred after the earliest estimate for the LGM (∼26.5 Kyr), while few expansions were estimated to have pre-dated the LGM. CONCLUSION: This study suggests that post-LGM expansion appeared to be common in a range of marine taxa, supporting the concept of rapid expansions after the LGM as the ice sheets started to retreat. However, despite the commonality of expansion patterns in many of these taxa, phylogeographic patterns appear to differ in the species included in this study. This suggests that species-specific evolutionary processes, as well as historical events, have likely influenced the distribution of genetic diversity of marine taxa in the northeast Atlantic.