Considering occupational performance during recovery of distal radius fracture: A scoping review.

INTRODUCTION: Distal radius fracture (DRF) is one of the most common upper extremity fractures treated by hand therapists and can lead to chronic physical impairment and reduced occupational performance. This scoping review aimed to reveal what is currently known about occupational performance following DRF and to explore if and how occupational performance is defined and considered in the research. METHODS: This review was guided by the PRISMA-Scoping review and the Joanna Briggs Institute (JBI) guidelines. Relevant databases were searched, and studies that addressed occupation performance in adult participants following DRF were included. The findings were summarised according to the components of occupational performance (person, occupation, and environment), and quality was measured using the Mixed Methods Appraisal Tool. RESULTS: Forty-three articles met the eligibility criteria for inclusion. All of the studies discussed at least two components of occupational performance, while 25 recognised all three. The consideration of occupational performance was dominated by biomechanical issues associated with the person component (i.e. range of motion, strength). There was some acknowledgement of the psychosocial aspects of the person and, to a lesser extent, the environment, as well as the impact of both on return to occupational performance. CONCLUSION: Despite occupational performance being at the core of occupational therapy theory, its consideration within the context of research on DRF appears to be focussed on the person component of occupational performance and on biomechanical issues. Further research is recommended to determine how much this reflects current clinical practice and if a more comprehensive consideration of occupational performance will improve rates of recovery following DRF. CONSUMER AND COMMUNITY INVOLVEMENT: As part of the protocol development for this review, consumers and stakeholders were consulted. They provided feedback on clarity and importance of the research questions. PLAIN LANGUAGE SUMMARY: A distal radius fracture happens when you break the bone on the thumb side of your wrist. This type of injury often occurs when you fall and land on an outstretched hand. It is one of the more common injuries that hand therapists see in their practice. For some people, recovering from this fracture can take a long time and come with a lot of pain, difficulty moving, and emotional stress. These problems can make it hard to do everyday things like driving, cooking, or getting dressed. It can also affect both paid and unpaid work as well as leisure and social activities, making life more difficult for everyone involved. The findings from this review suggest that the current research usually focuses on how the body physically heals from this type of injury, but it does not pay as much attention to the emotional and social impact on healing. Also, it does not always discuss the activities that are important to the person, or the environment where they live, work, and socialise. This may show a gap in the research regarding our full comprehension of recovery from distal radius fractures. Taking a broader view and approach to recovery, considering a person's emotions, social life, environment, and daily activities, could help people recover fully and get back to their previous life routines and roles after this type of injury.

HLAEquity: Examining biases in pan-allele peptide-HLA binding predictors.

Peptide-HLA (pHLA) binding prediction is essential in screening peptide candidates for personalized peptide vaccines. Machine learning (ML) pHLA binding prediction tools are trained on vast amounts of data and are effective in screening peptide candidates. Most ML models report the ability to generalize to HLA alleles unseen during training ("pan-allele" models). However, the use of datasets with imbalanced allele content raises concerns about biased model performance. First, we examine the data bias of two ML-based pan-allele pHLA binding predictors. We find that the pHLA datasets overrepresent alleles from geographic populations of high-income countries. Second, we show that the identified data bias is perpetuated within ML models, leading to algorithmic bias and subpar performance for alleles expressed in low-income geographic populations. We draw attention to the potential therapeutic consequences of this bias, and we challenge the use of the term "pan-allele" to describe models trained with currently available public datasets.

The perspectives of participants with traumatic brain injury on prospective memory rehabilitation incorporating compensatory and metacognitive skills training.

OBJECTIVE: Patient feedback is rarely gathered systematically in cognitive rehabilitation research. This study examined the perceptions and experiences of people with traumatic brain injury (TBI) who participated in a trial of a 6-session educational program for the rehabilitation of prospective memory (PM) impairment. METHODS: A mixed methods design was used with 47 participants with TBI who completed a compensatory strategy training program (COMP) or COMP plus metacognitive strategy training program (COMP-MST) delivered by an occupational therapist. Data were collected via a participant survey, extracts from progress notes, and audiotaped discussions about learnings from the program during the final session. RESULTS: Participants from both programs were highly satisfied and perceived improvements in everyday PM performance post-intervention. Elements that were highly valued include setting individualised client-centred goals, repetitive training of strategy use, establishing habits and routines, and receiving experiential, verbal, and written feedback.Changes including more therapy sessions were recommended. CONCLUSIONS: Both the COMP and COMP-MST programs were perceived as effective by participants with TBI in improving their PM performance in everyday life using compensatory strategies such as assistive technology. PRACTICE IMPLICATIONS: Routine collection of patient feedback on cognitive rehabilitation can provide valuable information to support person-centred implementation of clinical practice guidelines.

The Presence of Pseudo-nitzschia australis in North Atlantic Aquaculture Sites, Implications for Monitoring Amnesic Shellfish Toxins.

The farming of shellfish plays an important role in providing sustainable economic growth in coastal, rural communities in Scotland and acts as an anchor industry, supporting a range of ancillary jobs in the processing, distribution and exporting industries. The Scottish Government is encouraging shellfish farmers to double their economic contribution by 2030. These farmers face numerous challenges to reach this goal, among which is the problem caused by toxin-producing microplankton that can contaminate their shellfish, leading to harvesting site closure and the recall of product. Food Standards Scotland, a non-ministerial department of the Scottish Government, carries out a monitoring programme for both the toxin-producing microplankton and the toxins in shellfish flesh, with farms being closed when official thresholds for any toxin are breached. The farm remains closed until testing for the problematic toxin alone, often diarrhetic shellfish toxin (DST), shows the site to have dropped below the regulatory threshold. While this programme has proved to be robust, questions remain regarding the other toxins that may be present at a closed site. In this study, we tested archival material collected during site closures but only tested for DSTs as part of the official control monitoring. We found the presence of amnesic shellfish toxin (AST) in low concentrations in the majority of sites tested. In one case, the level of AST breached the official threshold. This finding has implications for AST monitoring programmes around Europe.

PepSim: T-cell cross-reactivity prediction via comparison of peptide sequence and peptide-HLA structure.

Introduction: Peptide-HLA class I (pHLA) complexes on the surface of tumor cells can be targeted by cytotoxic T-cells to eliminate tumors, and this is one of the bases for T-cell-based immunotherapies. However, there exist cases where therapeutic T-cells directed towards tumor pHLA complexes may also recognize pHLAs from healthy normal cells. The process where the same T-cell clone recognizes more than one pHLA is referred to as T-cell cross-reactivity and this process is driven mainly by features that make pHLAs similar to each other. T-cell cross-reactivity prediction is critical for designing T-cell-based cancer immunotherapies that are both effective and safe. Methods: Here we present PepSim, a novel score to predict T-cell cross-reactivity based on the structural and biochemical similarity of pHLAs. Results and discussion: We show our method can accurately separate cross-reactive from non-crossreactive pHLAs in a diverse set of datasets including cancer, viral, and self-peptides. PepSim can be generalized to work on any dataset of class I peptide-HLAs and is freely available as a web server at pepsim.kavrakilab.org.

SARS-Arena: Sequence and Structure-Guided Selection of Conserved Peptides from SARS-related Coronaviruses for Novel Vaccine Development.

The pandemic caused by the SARS-CoV-2 virus, the agent responsible for the COVID-19 disease, has affected millions of people worldwide. There is constant search for new therapies to either prevent or mitigate the disease. Fortunately, we have observed the successful development of multiple vaccines. Most of them are focused on one viral envelope protein, the spike protein. However, such focused approaches may contribute for the rise of new variants, fueled by the constant selection pressure on envelope proteins, and the widespread dispersion of coronaviruses in nature. Therefore, it is important to examine other proteins, preferentially those that are less susceptible to selection pressure, such as the nucleocapsid (N) protein. Even though the N protein is less accessible to humoral response, peptides from its conserved regions can be presented by class I Human Leukocyte Antigen (HLA) molecules, eliciting an immune response mediated by T-cells. Given the increased number of protein sequences deposited in biological databases daily and the N protein conservation among viral strains, computational methods can be leveraged to discover potential new targets for SARS-CoV-2 and SARS-CoV-related viruses. Here we developed SARS-Arena, a user-friendly computational pipeline that can be used by practitioners of different levels of expertise for novel vaccine development. SARS-Arena combines sequence-based methods and structure-based analyses to (i) perform multiple sequence alignment (MSA) of SARS-CoV-related N protein sequences, (ii) recover candidate peptides of different lengths from conserved protein regions, and (iii) model the 3D structure of the conserved peptides in the context of different HLAs. We present two main Jupyter Notebook workflows that can help in the identification of new T-cell targets against SARS-CoV viruses. In fact, in a cross-reactive case study, our workflows identified a conserved N protein peptide (SPRWYFYYL) recognized by CD8+ T-cells in the context of HLA-B7+. SARS-Arena is available at https://github.com/KavrakiLab/SARS-Arena.

Efficacy of Prospective Memory Rehabilitation Plus Metacognitive Skills Training for Adults With Traumatic Brain Injury: A Randomized Controlled Trial.

BACKGROUND: Prospective memory (PM) failure can limit independence and productivity following traumatic brain injury (TBI). Compensatory strategy use may ameliorate the effect of PM impairment on daily life but requires sufficient self-awareness. Metacognitive skills training (MST) can facilitate self-awareness and strategy use and may improve the efficacy of PM rehabilitation. OBJECTIVE: To evaluate the effectiveness of compensatory strategy training (COMP) with an MST component (COMP-MST) for reducing everyday PM failure and improving psychosocial integration in adults with moderate-severe TBI, compared to COMP alone and a control condition. Secondary aims were to evaluate the effect of training on psychometric PM test scores, strategy use, self-awareness, and level of care. METHODS: Assessor and participant-blinded randomized controlled trial with 52 participants (77% male, mean age = 39.0. SD = 13.6) allocated to 3 groups: COMP-MST, COMP, and waitlist control. Interventions were delivered over 6 weekly sessions. Measures were collected pre- and post-intervention and 3-month follow-up. Data were analyzed using unstructured linear mixed-effects modeling for repeated measures and planned contrasts between time-points for each group. RESULTS: The models showed no significant differences between the groups on primary or secondary outcome measures. Significant pre-post intervention improvements were found for significant other's ratings of everyday PM failure for both intervention groups but not the control group, with medium to large effect sizes. Clinically relevant improvements on primary outcomes were found for participants across all 3 groups. CONCLUSIONS: This study found no significant benefits of combining MST with COMP for improving everyday PM and psychosocial integration. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry https://www.anzctr.org.au/ ACTRN12615000996561.

Multisite randomised controlled trial of trauma-focused cognitive behaviour therapy for psychosis to reduce post-traumatic stress symptoms in people with co-morbid post-traumatic stress disorder and psychosis, compared to treatment as usual: study protocol for the STAR (Study of Trauma And Recovery) trial.

BACKGROUND: People with psychosis have high rates of trauma, with a post-traumatic stress disorder (PTSD) prevalence rate of approximately 15%, which exacerbates psychotic symptoms such as delusions and hallucinations. Pilot studies have shown that trauma-focused (TF) psychological therapies can be safe and effective in such individuals. This trial, the largest to date, will evaluate the clinical effectiveness of a TF therapy integrated with cognitive behaviour therapy for psychosis (TF-CBTp) on post-traumatic stress symptoms in people with psychosis. The secondary aims are to compare groups on cost-effectiveness; ascertain whether TF-CBTp impacts on a range of other meaningful outcomes; determine whether therapy effects endure; and determine acceptability of the therapy in participants and therapists. METHODS: Rater-blind, parallel arm, pragmatic randomised controlled trial comparing TF-CBTp + treatment as usual (TAU) to TAU only. Adults (N = 300) with distressing post-traumatic stress and psychosis symptoms from five mental health Trusts (60 per site) will be randomised to the two groups. Therapy will be manualised, lasting 9 months (m) with trained therapists. We will assess PTSD symptom severity (primary outcome); percentage who show loss of PTSD diagnosis and clinically significant change; psychosis symptoms; emotional well-being; substance use; suicidal ideation; psychological recovery; social functioning; health-related quality of life; service use, a total of four times: before randomisation; 4 m (mid-therapy); 9 m (end of therapy; primary end point); 24 m (15 m after end of therapy) post-randomisation. Four 3-monthly phone calls will be made between 9 m and 24 m assessment points, to collect service use over the previous 3 months. Therapy acceptability will be assessed through qualitative interviews with participants (N = 35) and therapists (N = 5-10). An internal pilot will ensure integrity of trial recruitment and outcome data, as well as therapy protocol safety and adherence. Data will be analysed following intention-to-treat principles using generalised linear mixed models and reported according to Consolidated Standards of Reporting Trials-Social and Psychological Interventions Statement. DISCUSSION: The proposed intervention has the potential to provide significant patient benefit in terms of reductions in distressing symptoms of post-traumatic stress, psychosis, and emotional problems; enable clinicians to implement trauma-focused therapy confidently in this population; and be cost-effective compared to TAU through reduced service use. TRIAL REGISTRATION: ISRCTN93382525 (03/08/20).

Improving self-awareness of prospective memory function after TBI using experiential feedback on a board game activity: An observational study.

This study investigated whether experiential and video feedback on performance of prospective memory (PM) tasks embedded within a board game activity improved self-awareness of PM function in adults with moderate-severe traumatic brain injury. An observational pre-post study design with 26 participants from a larger trial of a 6-session PM rehabilitation programme. Sessions 3 and 4 included a board game activity with embedded time-, event-, and activity-based PM tasks. Verbal feedback was provided by therapists during the game and video feedback afterwards. Self-ratings of performance were used to divide the sample into under-estimators (n = 7), accurate estimators (n = 9) and over-estimators (n = 10) of actual PM performance. The discrepancy between self- and therapist ratings of PM performance was measured before and after the game, and following video feedback, and compared between timepoints using non-parametric statistics. Post-task self-evaluations were more accurate than pre-task self-evaluations for the under- and over-estimator groups. Under-estimators showed significant improvement in accuracy of ratings for activity-based PM. Over-estimators showed improvement for event-based PM. Further improvements after video feedback were not significant. The board game activity provided a vehicle for experiential feedback and a means of engaging both those with impaired self-awareness and heightened self-awareness of PM in cognitive rehabilitation.

DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins.

An unprecedented research effort has been undertaken in response to the ongoing COVID-19 pandemic. This has included the determination of hundreds of crystallographic structures of SARS-CoV-2 proteins, and numerous virtual screening projects searching large compound libraries for potential drug inhibitors. Unfortunately, these initiatives have had very limited success in producing effective inhibitors against SARS-CoV-2 proteins. A reason might be an often overlooked factor in these computational efforts: receptor flexibility. To address this issue we have implemented a computational tool for ensemble docking with SARS-CoV-2 proteins. We have extracted representative ensembles of protein conformations from the Protein Data Bank and from in silico molecular dynamics simulations. Twelve pre-computed ensembles of SARS-CoV-2 protein conformations have now been made available for ensemble docking via a user-friendly webserver called DINC-COVID (dinc-covid.kavrakilab.org). We have validated DINC-COVID using data on tested inhibitors of two SARS-CoV-2 proteins, obtaining good correlations between docking-derived binding energies and experimentally-determined binding affinities. Some of the best results have been obtained on a dataset of large ligands resolved via room temperature crystallography, and therefore capturing alternative receptor conformations. In addition, we have shown that the ensembles available in DINC-COVID capture different ranges of receptor flexibility, and that this diversity is useful in finding alternative binding modes of ligands. Overall, our work highlights the importance of accounting for receptor flexibility in docking studies, and provides a platform for the identification of new inhibitors against SARS-CoV-2 proteins.

Diversity and regional distribution of harmful algal events along the Atlantic margin of Europe.

The IOC-ICES-PICES Harmful Algal Event Database (HAEDAT) was used to describe the diversity and spatiotemporal distribution of harmful algal events along the Atlantic margin of Europe from 1987 - 2018. The majority of events recorded are caused by Diarrhetic Shellfish Toxins (DSTs). These events are recorded annually over a wide geographic area from southern Spain to northern Scotland and Iceland, and are responsible for annual closures of many shellfish harvesting areas. The dominant causative dinoflagellates, members of the morphospecies 'Dinophysis acuminata complex' and D. acuta, are common in the waters of the majority of countries affected. There are regional differences in the causative species associated with PST events; the coasts of Spain and Portugal with the dinoflagellates Alexandrium minutum and Gymnodinium catenatum, north west France/south west England/south Ireland with A. minutum, and Scotland/Faroe Islands/Iceland with A. catenella. This can influence the duration and spatial scale of PST events as well as the toxicity of shellfish. The diatom Pseudo-nitzschia australis is the most widespread Domoic Acid (DA) producer, with records coming from Spain, Portugal, France, Ireland and the UK. Amnesic Shellfish Toxins (ASTs) have caused prolonged closures for the scallop fishing industry due to the slow depuration rate of DA. Amendments to EU shellfish hygiene regulations introduced between 2002 and 2005 facilitated end-product testing and sale of adductor muscle. This reduced the impact of ASTs on the scallop fishing industry and thus the number of recorded HAEDAT events. Azaspiracids (AZAs) are the most recent toxin group responsible for events to be characterised in the ICES area. Events associated with AZAs have a discrete distribution with the majority recorded along the west coast of Ireland. Ciguatera Poisoning (CP) has been an emerging issue in the Canary Islands and Madeira since 2004. The majority of aquaculture and wild fish mortality events are associated with blooms of the dinoflagellate Karenia mikimotoi and raphidophyte Heterosigma akashiwo. Such fish killing events occur infrequently yet can cause significant mortalities. Interannual variability was observed in the annual number of HAEDAT areas with events associated with individual shellfish toxin groups. HABs represent a continued risk for the aquaculture industry along the Atlantic margin of Europe and should be accounted for when considering expansion of the industry or operational shifts to offshore areas.

DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins.

MOTIVATION: Recent efforts to computationally identify inhibitors for SARS-CoV-2 proteins have largely ignored the issue of receptor flexibility. We have implemented a computational tool for ensemble docking with the SARS-CoV-2 proteins, including the main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp). RESULTS: Ensembles of other SARS-CoV-2 proteins are being prepared and made available through a user-friendly docking interface. Plausible binding modes between conformations of a selected ensemble and an uploaded ligand are generated by DINC, our parallelized meta-docking tool. Binding modes are scored with three scoring functions, and account for the flexibility of both the ligand and receptor. Additional details on our methods are provided in the supplementary material. AVAILABILITY: dinc-covid.kavrakilab.org. SUPPLEMENTARY INFORMATION: Details on methods for ensemble generation and docking are provided as supplementary data online. CONTACT: geancarlo.zanatta@ufc.br , kavraki@rice.edu.

HLA-Arena: A Customizable Environment for the Structural Modeling and Analysis of Peptide-HLA Complexes for Cancer Immunotherapy.

PURPOSE: HLA protein receptors play a key role in cellular immunity. They bind intracellular peptides and display them for recognition by T-cell lymphocytes. Because T-cell activation is partially driven by structural features of these peptide-HLA complexes, their structural modeling and analysis are becoming central components of cancer immunotherapy projects. Unfortunately, this kind of analysis is limited by the small number of experimentally determined structures of peptide-HLA complexes. Overcoming this limitation requires developing novel computational methods to model and analyze peptide-HLA structures. METHODS: Here we describe a new platform for the structural modeling and analysis of peptide-HLA complexes, called HLA-Arena, which we have implemented using Jupyter Notebook and Docker. It is a customizable environment that facilitates the use of computational tools, such as APE-Gen and DINC, which we have previously applied to peptide-HLA complexes. By integrating other commonly used tools, such as MODELLER and MHCflurry, this environment includes support for diverse tasks in structural modeling, analysis, and visualization. RESULTS: To illustrate the capabilities of HLA-Arena, we describe 3 example workflows applied to peptide-HLA complexes. Leveraging the strengths of our tools, DINC and APE-Gen, the first 2 workflows show how to perform geometry prediction for peptide-HLA complexes and structure-based binding prediction, respectively. The third workflow presents an example of large-scale virtual screening of peptides for multiple HLA alleles. CONCLUSION: These workflows illustrate the potential benefits of HLA-Arena for the structural modeling and analysis of peptide-HLA complexes. Because HLA-Arena can easily be integrated within larger computational pipelines, we expect its potential impact to vastly increase. For instance, it could be used to conduct structural analyses for personalized cancer immunotherapy, neoantigen discovery, or vaccine development.

Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins.

BACKGROUND: Docking large ligands, and especially peptides, to protein receptors is still considered a challenge in computational structural biology. Besides the issue of accurately scoring the binding modes of a protein-ligand complex produced by a molecular docking tool, the conformational sampling of a large ligand is also often considered a challenge because of its underlying combinatorial complexity. In this study, we evaluate the impact of using parallelized and incremental paradigms on the accuracy and performance of conformational sampling when docking large ligands. We use five datasets of protein-ligand complexes involving ligands that could not be accurately docked by classical protein-ligand docking tools in previous similar studies. RESULTS: Our computational evaluation shows that simply increasing the amount of conformational sampling performed by a protein-ligand docking tool, such as Vina, by running it for longer is rarely beneficial. Instead, it is more efficient and advantageous to run several short instances of this docking tool in parallel and group their results together, in a straightforward parallelized docking protocol. Even greater accuracy and efficiency are achieved by our parallelized incremental meta-docking tool, DINC, showing the additional benefits of its incremental paradigm. Using DINC, we could accurately reproduce the vast majority of the protein-ligand complexes we considered. CONCLUSIONS: Our study suggests that, even when trying to dock large ligands to proteins, the conformational sampling of the ligand should no longer be considered an issue, as simple docking protocols using existing tools can solve it. Therefore, scoring should currently be regarded as the biggest unmet challenge in molecular docking.

Variability of Amnesic Shellfish Toxin and Pseudo-nitzschia occurrence in bivalve molluscs and water samples-Analysis of ten years of the official control monitoring programme.

As the official control laboratory for marine biotoxins within Great Britain, the Centre for Environment, Fisheries and Aquaculture Science, in conjunction with the Scottish Association for Marine Science, has amassed a decade's worth of data regarding the prevalence of the toxins associated with Amnesic Shellfish Poisoning within British waters. This monitoring involves quantitative HPLC-UV analysis of shellfish domoic acid concentration, the causative toxin for Amnesic Shellfish Poisoning, and water monitoring for Pseudo-nitzschia spp., the phytoplankton genus that produces domoic acid. The data obtained since 2008 indicate that whilst the occurrence of domoic acid in shellfish was generally below the maximum permitted limit of 20 mg/kg, there were a number of toxic episodes that breached this limit. The data showed an increase in the frequency of both domoic acid occurrence and toxic events, although there was considerable annual variability in intensity and geographical location of toxic episodes. A particularly notable increase in domoic acid occurrence in England was observed during 2014. Comparison of Scottish toxin data and Pseudo-nitzschia cell densities during this ten-year period revealed a complex relationship between the two measurements. Whilst the majority of events were associated with blooms, absolute cell densities of Pseudo-nitzschia did not correlate with domoic acid concentrations in shellfish tissue. This is believed to be partly due to the presence of a number of different Pseudo-nitzschia species in the water that can exhibit variable toxin production. These data highlight the requirement for tissue monitoring as part of an effective monitoring programme to protect the consumer, as well as the benefit of more detailed taxonomic discrimination of the Pseudo-nitzschia genus to allow greater accuracy in the prediction of shellfish toxicity.

Variability and profiles of lipophilic toxins in bivalves from Great Britain during five and a half years of monitoring: azaspiracids and yessotoxins.

Cefas has been responsible for the delivery of official control biotoxin testing of bivalve molluscs from Great Britain for just over a decade. Liquid chromatography tandem mass spectrometric (LC-MS/MS) methodology has been used for the quantitation of lipophilic toxins (LTs) since 2011. The temporal and spatial distribution of okadaic acid group toxins and profiles in bivalves between 2011 and 2016 have been recently reported. Here we present data on the two other groups of regulated lipophilic toxins, azaspiracids (AZAs) and yessotoxins (YTXs), over the same period. The latter group has also been investigated for a potential link with Protoceratium reticulatum and Lingulodinium polyedra, both previously recognised as YTXs producing phytoplankton. On average, AZAs were quantified in 3.2% of all tested samples but notable inter-annual variation in abundance was observed. The majority of all AZA contaminated samples were found between July 2011 and August 2013 in Scotland, while only two, three-month long, AZA events were observed in 2015 and 2016 in the south-west of England. Maximum concentrations were generally reached in late summer or early autumn. Reasons for AZAs persistence during the 2011/2012 and 2012/2013 winters are discussed. Only one toxin profile was identified, represented by both AZA1 and AZA2 toxins at an approximate ratio of 2 : 1, suggesting a single microalgal species was the source of AZAs in British bivalves. Although AZA1 was always the most dominant toxin, its proportion varied between mussels, Pacific oysters and surf clams. The YTXs were the least represented group among regulated LTs. YTXs were found almost exclusively on the south-west coast of Scotland, with the exception of 2013, when the majority of contaminated samples originated from the Shetland Islands. The highest levels were recorded in the summer months and followed a spike in Protoceratium reticulatum cell densities. YTX was the most dominant toxin in shellfish, further strengthening the link to P. reticulatum as the YTX source. Neither homo-YTX, nor 45-OH homo-YTX were detected throughout the monitored period. 45-OH YTX, thought to be a shellfish metabolite associated with YTX elimination, contributed on average 26% in mussels. Although the correlation between 45-OH YTX abundance and the speed of YTX depuration could not be confirmed, we noted the half-life of YTX was more than two-times longer in queen scallops, which contained 100% YTX, than in mussels. No other bivalve species were affected by YTXs. This is the first detailed evaluation of AZAs and YTXs occurrences and their profiles in shellfish from Great Britain over a period of multiple years.

Concordance between the Awareness Questionnaire and Self-Awareness of Deficits Interview for identifying impaired self-awareness in individuals with traumatic brain injury in the community.

OBJECTIVE: To investigate concordance between the Awareness Questionnaire (AQ) and Self-Awareness of Deficits Interview (SADI) for identifying impaired self-awareness in the community after traumatic brain injury. DESIGN: A retrospective file audit was conducted to retrieve data on the AQ and SADI for participants with traumatic brain injury involved in previous studies on community-based outcomes. Concordance between the AQ and SADI was examined using receiver operating characteristic curves for different scores on each measure. PARTICIPANTS: A total of 80 individuals with moderate-to-severe traumatic brain injury (81% male, mean age 2.25 years, standard deviation (SD) 11.5 years) living in the community. METHODS: Participants were administered the AQ and SADI and their significant other completed the AQ and SADI checklist. RESULTS: Consistency of classification of impaired self-awareness between the AQ and SADI was high (i.e. 80-84%) based on scores reflecting good sensitivity and specificity. Corresponding scores on the 2 measures and rates of impaired self-awareness were as follows: SADI > 3~AQ discrepancy > 4 (45-48% with impaired self-awareness); SADI > 4~AQ discrepancy > 9 (26-34% with impaired self-awareness); SADI > 5~AQ discrepancy >12 (13-26% with impaired self-awareness). CONCLUSION: The AQ and SADI yielded consistent information regarding the presence of impaired self-awareness in community-based individuals with traumatic brain injury. The choice of measure may depend on how the tool is being used to guide rehabilitation planning.

Retraction Note: detangling PPI networks to uncover functionally meaningful clusters.

The authors have retracted this article [1]. After publication they discovered a technical error in the Louvain algorithm with bounded cluster sizes. Correction of this error substantially changed the results for this algorithm and the conclusions drawn in the article were found to be incorrect. The authors will submit a new manuscript for peer review.

Dinophysis acuta in Scottish Coastal Waters and Its Influence on Diarrhetic Shellfish Toxin Profiles.

Diarrhetic shellfish toxins produced by the dinoflagellate genus Dinophysis are a major problem for the shellfish industry worldwide. Separate species of the genus have been associated with the production of different analogues of the okadaic acid group of toxins. To evaluate the spatial and temporal variability of Dinophysis species and toxins in the important shellfish-harvesting region of the Scottish west coast, we analysed data collected from 1996 to 2017 in two contrasting locations: Loch Ewe and the Clyde Sea. Seasonal studies were also undertaken, in Loch Ewe in both 2001 and 2002, and in the Clyde in 2015. Dinophysis acuminata was present throughout the growing season during every year of the study, with blooms typically occurring between May and September at both locations. The appearance of D. acuta was interannually sporadic and, when present, was most abundant in the late summer and autumn. The Clyde field study in 2015 indicated the importance of a temperature front in the formation of a D. acuta bloom. A shift in toxin profiles of common mussels (Mytilus edulis) tested during regulatory monitoring was evident, with a proportional decrease in okadaic acid (OA) and dinophysistoxin-1 (DTX1) and an increase in dinophysistoxin-2 (DTX2) occurring when D. acuta became dominant. Routine enumeration of Dinophysis to species level could provide early warning of potential contamination of shellfish with DTX2 and thus determine the choice of the most suitable kit for effective end-product testing.

Detangling PPI networks to uncover functionally meaningful clusters.

BACKGROUND: Decomposing a protein-protein interaction network (PPI network) into non-overlapping clusters or communities, sometimes called "network modules," is an important way to explore functional roles of sets of genes. When the method to accomplish this decomposition is solely based on purely graph-theoretic measures of the interconnection structure of the network, this is often called unsupervised clustering or community detection. In this study, we compare unsupervised computational methods for decomposing a PPI network into non-overlapping modules. A method is preferred if it results in a large proportion of nodes being assigned to functionally meaningful modules, as measured by functional enrichment over terms from the Gene Ontology (GO). RESULTS: We compare the performance of three popular community detection algorithms with the same algorithms run after the network is pre-processed by removing and reweighting based on the diffusion state distance (DSD) between pairs of nodes in the network. We call this "detangling" the network. In almost all cases, we find that detangling the network based on the DSD distance reweighting provides more meaningful clusters. CONCLUSIONS: Re-embedding using the DSD distance metric, before applying standard community detection algorithms, can assist in uncovering GO functionally enriched clusters in the yeast PPI network.