The effectiveness and tolerability of trauma-focused psychotherapies for psychotic symptoms: A systematic review of trauma-focused psychotherapies.

INTRODUCTION: Psychological trauma is an established risk factor for psychosis. Trauma-focused psychotherapies (TFPT) have been suggested as a potential treatment for reducing psychotic symptoms in those who have experienced trauma. We therefore sought to investigate the effectiveness, tolerability, and acceptability of TFPT for psychotic symptoms. METHODS: We conducted a systematic review of studies of any form of TFPT that measured psychotic symptoms across a broad range of diagnoses. RESULTS: From 2584 papers initially identified, 17 studies (857 participants) met eligibility criteria. TFPT were found to be well tolerated, with very few adverse events. Acceptability was also high, with a mean dropout rate of 20%. CONCLUSIONS: Whilst the evidence of effectiveness for TFPT in reducing psychotic symptoms is weak, we found tentative evidence in favour of exposure-based interventions. Methodologically rigorous trials investigating the efficacy of TFPT for the treatment of psychotic symptoms are needed to assess this promising intervention.

A service evaluation of phased- and stepped-care psychological support for health and social care workers during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has disproportionally affected the mental health of health and social care workers (HSCWs), with many experiencing symptoms of depression, anxiety and post-traumatic stress disorder. Psychological interventions have been offered via mental health services and in-house psychology teams, but their effectiveness in this context is not well documented. AIMS: To evaluate a stepped-care psychological support pathway for HSCWs from Homerton Healthcare Foundation Trust in London, which offered psychological first aid, evidence-based psychological therapies and group-based well-being workshops. METHOD: The service evaluation used a pre-post approach to assess depression, anxiety, functional impairment and post-traumatic stress disorder symptom change for those who attended sessions of psychological first aid, low- or high-intensity cognitive-behavioural therapy or a combination of these. In addition, the acceptability of the psychological first aid sessions and well-being workshops was explored via feedback data. RESULTS: Across all interventions, statistically significant reductions of depression (d = 1.33), anxiety (d = 1.37) and functional impairment (d = 0.93) were observed, and these reductions were equivalent between the interventions, as well as the demographic and occupational differences between the HSCWs (ethnicity, staff group and redeployment status). HSCWs were highly satisfied with the psychological first aid and well-being workshops. CONCLUSIONS: The evaluation supports the utility of evidence-based interventions delivered as part of a stepped-care pathway for HSCWs with common mental health problems in the context of the COVID-19 pandemic. Given the novel integration of psychological first aid within the stepped-care model as a step one intervention, replication and further testing in larger-scale studies is warranted.

Media Contributions to a Chesapeake Bay Watershed Collective Identity? A Tale of Three Cities.

Although collective action is needed to address many environmental challenges, it cannot proceed in the absence of collective identity, that is, evidence of group belongingness expressed in or via communicative behavior. This study looked for evidence of a collective identity in newspaper articles that referenced the Chesapeake Bay Watershed. The data were drawn from local papers published in municipalities located at the headwaters of the Susquehanna River, midway down the Susquehanna, and where the river meets the Bay. Computerized content analysis assessed the frequency with which the Chesapeake Bay and watershed were mentioned alongside a set of keywords thought to represent different facets of identity (e.g., agriculture, fishing, swimming). The results showed substantial variation in frequency across time and place but low absolute levels of coverage of the Bay and the watershed. Multidimensional scaling revealed different structures to collective identity as a function of place. These differences in content may be attributable to varying demographic and environmental characteristics along with proximity to the Bay. But, to the extent that media contribute to collective identity among residents of the watershed at all, they do so in a complex and heterogeneous manner.

In Vitro Mitral Valve Model with Unrestricted Ventricular Access: Using Vacuum to Close the Valve and Enable Static Trans-Mitral Pressure.

Current in vitro models of the left heart establish the pressure difference required to close the mitral valve by sealing and pressurizing the ventricular side of the valve, limiting important access to the subvalvular apparatus. This paper describes and evaluates a system that establishes physiological pressure differences across the valve using vacuum on the atrial side. The subvalvular apparatus is open to atmospheric pressure and accessible by tools and sensors, establishing a novel technique for experimentation on atrioventricular valves. Porcine mitral valves were excised and closed by vacuum within the atrial chamber. Images were used to document and analyze closure of the leaflets. Papillary muscle force and regurgitant flow rate were measured to be 4.07 N at 120 mmHg and approximately 12.1 ml/s respectively, both of which are within clinically relevant ranges. The relative ease of these measurements demonstrates the usefulness of improved ventricular access at peak pressure/force closure.

A New Diploid Parthenogenetic Whiptail Lizard from Sonora, Mexico, Is the "Missing Link" in the Evolutionary Transition to Polyploidy.

AbstractTransitions between sexual and unisexual reproductive modes have significant consequences for the evolutionary trajectories of species. These transitions have occurred numerous times in vertebrates and are frequently mediated by hybridization events. Triploid unisexual vertebrates are thought to arise through hybridization between individuals of a diploid unisexual lineage and a sexual species, although additional evidence that confirms this mechanism is needed in numerous groups. North American whiptail lizards (Aspidoscelis) are notable for being one of the largest radiations of unisexual vertebrates, and the most diverse group of Aspidoscelis includes numerous triploid lineages that have no known diploid unisexual ancestors. This pattern of "missing" ancestors may result from the short evolutionary life span of unisexual lineages or the selective advantages of polyploidy, or it could suggest that alternative mechanisms of triploid formation are operating in nature. We leverage genomic, morphological, and karyotypic data to describe a new diploid unisexual whiptail and show that it is likely the unisexual progenitor of an extant triploid lineage, A. opatae. We also resolve patterns of polyploidization within the A. sexlineatus species group and test predictions about the phenotypic outcomes of hybridization.

Effectiveness of small group cognitive behavioural therapy for anxiety and depression in Ebola treatment centre staff in Sierra Leone.

Following the 2014 Ebola outbreak, South London and Maudsley NHS Foundation Trust (SLAM) were commissioned to provide a 'culturally appropriate, effective and sustainable' intervention to address the psychological needs of the Sierra Leonean Ebola Treatment Centre (ETC) staff. The study evaluated the effectiveness of group Cognitive Behavioural Therapy (CBT) developed to treat anxiety, depression and functional impairment amongst a sample of former ETC staff in Sierra Leone. Group comparisons explored whether the effect of the intervention differed dependent on the facilitators that delivered it, as well as whether it differed between former staff of high- and low-risk ETC roles. A sample of 253 former ETC staff attended the group CBT intervention comprised of eight sessions over six weeks. Outcome measures were administered upon entry and within two weeks after the intervention. At post-intervention, anxiety, depression and functional impairment significantly reduced. Reading ability (RA) was introduced as a covariate having impacted the outcomes. The intervention effect differed by facilitators delivering the sessions but not by ETC role risk. The implications of these results are discussed. Group CBT is a promising psychological intervention for treating the anxiety, depression and functional impairment of former ETC staff in Sierra Leone. Furthermore, as part of a stepped-care approach, it may provide a model for psychological support for staff that have worked on the frontline during future epidemics.

Complete characterization of the human immune cell transcriptome using accurate full-length cDNA sequencing.

The human immune system relies on highly complex and diverse transcripts and the proteins they encode. These include transcripts encoding human leukocyte antigen (HLA) receptors as well as B cell and T cell receptors (BCR and TCR). Determining which alleles an individual possesses for each HLA gene (high-resolution HLA typing) is essential to establish donor-recipient compatibility in organ and bone marrow transplantations. In turn, the repertoires of millions of unique BCR and TCR transcripts in each individual carry a vast amount of health-relevant information. Both short-read RNA-seq-based HLA typing and BCR/TCR repertoire sequencing (AIRR-seq) currently rely on our incomplete knowledge of the genetic diversity at HLA and BCR/TCR loci. Here, we generated over 10,000,000 full-length cDNA sequences at a median accuracy of 97.9% using our nanopore sequencing-based Rolling Circle Amplification to Concatemeric Consensus (R2C2) protocol. We used this data set to (1) show that deep and accurate full-length cDNA sequencing can be used to provide isoform-level transcriptome analysis for more than 9000 loci, (2) generate accurate sequences of HLA alleles, and (3) extract detailed AIRR data for the analysis of the adaptive immune system. The HLA and AIRR analysis approaches we introduce here are untargeted and therefore do not require prior knowledge of the composition or genetic diversity of HLA and BCR/TCR loci.

Total syntheses of spiroviolene and spirograterpene A: a structural reassignment with biosynthetic implications.

The recent natural product isolates spiroviolene and spirograterpene A are two relatively non-functionalized linear triquinane terpenes with a large number of structural homologies. Nevertheless, three significant areas of structural disparity exist based on their original assignments, one of which implies a key stereochemical divergence early in their respective biosyntheses. Herein, using two known bicyclic ketone intermediates, a core Pd-catalyzed Heck cyclization sequence, and several chemoselective transformations, we describe concise total syntheses of both natural product targets and propose that the structure of spiroviolene should be reassigned. As a result, these natural products possess greater homology than previously anticipated.

A ligation-based single-stranded library preparation method to analyze cell-free DNA and synthetic oligos.

BACKGROUND: Cell-free DNA (cfDNA), present in circulating blood plasma, contains information about prenatal health, organ transplant reception, and cancer presence and progression. Originally developed for the genomic analysis of highly degraded ancient DNA, single-stranded DNA (ssDNA) library preparation methods are gaining popularity in the field of cfDNA analysis due to their efficiency and ability to convert short, fragmented DNA into sequencing libraries without altering DNA ends. However, current ssDNA methods are costly and time-consuming. RESULTS: Here we present an efficient ligation-based single-stranded library preparation method that is engineered to produce complex libraries in under 2.5 h from as little as 1 nanogram of input DNA without alteration to the native ends of template molecules. Our method, called Single Reaction Single-stranded LibrarY or SRSLY, ligates uniquely designed Next-Generation Sequencing (NGS) adapters in a one-step combined phosphorylation/ligation reaction that foregoes end-polishing. Using synthetic DNA oligos and cfDNA, we demonstrate the efficiency and utility of this approach and compare with existing double-stranded and single-stranded approaches for library generation. Finally, we demonstrate that cfDNA NGS data generated from SRSLY can be used to analyze DNA fragmentation patterns to deduce nucleosome positioning and transcription factor binding. CONCLUSIONS: SRSLY is a versatile tool for converting short and fragmented DNA molecules, like cfDNA fragments, into sequencing libraries while retaining native lengths and ends.

Realizing the potential of full-length transcriptome sequencing.

Long-read sequencing holds great potential for transcriptome analysis because it offers researchers an affordable method to annotate the transcriptomes of non-model organisms. This, in turn, will greatly benefit future work on less-researched organisms like unicellular eukaryotes that cannot rely on large consortia to generate these transcriptome annotations. However, to realize this potential, several remaining molecular and computational challenges will have to be overcome. In this review, we have outlined the limitations of short-read sequencing technology and how long-read sequencing technology overcomes these limitations. We have also highlighted the unique challenges still present for long-read sequencing technology and provided some suggestions on how to overcome these challenges going forward. This article is part of a discussion meeting issue 'Single cell ecology'.

A qualitative study assessing the feasibility of implementing a group cognitive-behavioural therapy-based intervention in Sierra Leone.

Mental health support in Sierra Leone is sparse, and qualitative research into the feasibility of implementing psychological interventions is equally underdeveloped. Following the 2014 Ebola virus disease outbreak, South London and Maudsley NHS Trust were commissioned to develop a psychological intervention that UK clinicians could train national staff with minimal psychological experience to deliver to their peers. Following the completion of the stepped care, group-based cognitive-behavioural therapy intervention, qualitative interviews were conducted with the national team to identify key barriers and enablers to implementation of and engagement with this intervention. This article describes the key themes that came out of those interviews, and discusses the implications of these findings for future clinical teams.

Asymmetric pyrone Diels-Alder reactions enabled by dienamine catalysis.

Despite the proven value in utilizing pyrone dienes to create molecular complexity via Diels-Alder reactions with varied dienophiles, few examples of effective catalytic, asymmetric variants of this process have been developed. Herein, we show that the use of Jørgensen-Hayashi-type catalysts can convert an array of α,ß-unsaturated aldehydes into chiral dienamines that can formally add in a Diels-Alder fashion to a number of electron-deficient pyrones of the coumalate-type to generate optically active [2.2.2]-bicyclic lactones. In most cases, the reactions proceed with good to excellent diastereo- and enantiocontrol (up to 99% ee). Models to explain that stereoselectivity, as well as several additional transformations of the resultant products, are also presented.

Molecular tools that block maturation of the nuclear lamin A and decelerate cancer cell migration.

Lamin A contributes to the structure of nuclei in all mammalian cells and plays an important role in cell division and migration. Mature lamin A is derived from a farnesylated precursor protein, known as prelamin A, which undergoes post-translational cleavage catalyzed by the zinc metalloprotease STE24 (ZPMSTE24). Accumulation of farnesylated prelamin A in the nuclear envelope compromises cell division, impairs mitosis and induces an increased expression of inflammatory gene products. ZMPSTE24 has been proposed as a potential therapeutic target in oncology. A library of peptidomimetic compounds were synthesized and screened for their ability to induce accumulation of prelamin A in cancer cells and block cell migration in pancreatic ductal adenocarcinoma cells. The results of this study suggest that inhibitors of lamin A maturation may interfere with cell migration, the biological process required for cancer metastasis.

Improving nanopore read accuracy with the R2C2 method enables the sequencing of highly multiplexed full-length single-cell cDNA.

High-throughput short-read sequencing has revolutionized how transcriptomes are quantified and annotated. However, while Illumina short-read sequencers can be used to analyze entire transcriptomes down to the level of individual splicing events with great accuracy, they fall short of analyzing how these individual events are combined into complete RNA transcript isoforms. Because of this shortfall, long-distance information is required to complement short-read sequencing to analyze transcriptomes on the level of full-length RNA transcript isoforms. While long-read sequencing technology can provide this long-distance information, there are issues with both Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) long-read sequencing technologies that prevent their widespread adoption. Briefly, PacBio sequencers produce low numbers of reads with high accuracy, while ONT sequencers produce higher numbers of reads with lower accuracy. Here, we introduce and validate a long-read ONT-based sequencing method. At the same cost, our Rolling Circle Amplification to Concatemeric Consensus (R2C2) method generates more accurate reads of full-length RNA transcript isoforms than any other available long-read sequencing method. These reads can then be used to generate isoform-level transcriptomes for both genome annotation and differential expression analysis in bulk or single-cell samples.

Tn5Prime, a Tn5 based 5' capture method for single cell RNA-seq.

RNA-sequencing (RNA-seq) is a powerful technique to investigate and quantify entire transcriptomes. Recent advances in the field have made it possible to explore the transcriptomes of single cells. However, most widely used RNA-seq protocols fail to provide crucial information regarding transcription start sites. Here we present a protocol, Tn5Prime, that takes advantage of the Tn5 transposase-based Smart-seq2 protocol to create RNA-seq libraries that capture the 5' end of transcripts. The Tn5Prime method dramatically streamlines the 5' capture process and is both cost effective and reliable. By applying Tn5Prime to bulk RNA and single cell samples, we were able to define transcription start sites as well as quantify transcriptomes at high accuracy and reproducibility. Additionally, similar to 3' end-based high-throughput methods like Drop-seq and 10× Genomics Chromium, the 5' capture Tn5Prime method allows the introduction of cellular identifiers during reverse transcription, simplifying the analysis of large numbers of single cells. In contrast to 3' end-based methods, Tn5Prime also enables the assembly of the variable 5' ends of the antibody sequences present in single B-cell data. Therefore, Tn5Prime presents a robust tool for both basic and applied research into the adaptive immune system and beyond.

Training peers to treat Ebola centre workers with anxiety and depression in Sierra Leone.

BACKGROUND: Following the 2014 Ebola virus disease (EVD) outbreak in West Africa, the UK Department for International Development funded South London and Maudsley National Health Service (NHS) to develop a psychological intervention that ex-Ebola Treatment Centre (ETC) staff could be trained to deliver to their peers to improve mental health in Sierra Leone. AIM: The two key aims were to assess the feasibility of training a national team to deliver a cognitive behavioural therapy (CBT)-based group intervention, and to evaluate the effectiveness of the overall intervention within this population. METHODS: UK clinicians travelled to Sierra Leone to train a small team of ex-ETC staff in a three-phased CBT-based intervention. Standardised clinical measures, as well as bespoke measures, were applied with participants through the intervention to assess changes in mental health symptomology, and the effectiveness of the intervention. RESULTS: The results found improvements across all factors of mental health in the bespoke measure from phase 1 to phase 3. Additionally, the majority of standardised clinical measures showed improvements between phase 2 and the start of phase 3, and pre- and post-phase 3. CONCLUSION: Overall, the findings suggest that it is possible to train staff from ETCs to deliver effective CBT interventions to peers. The implications of these results are discussed, including suggestions for future research and clinical intervention implementation within this population. The limitations of this research are also addressed.

Therapeutic leukocytapheresis in infants and children with leukemia and hyperleukocytosis: A single institution experience.

BACKGROUND: Hyperleukocytosis, defined as white blood cell (WBC) count above 100 × 109 /L, has high early morbidity and mortality from leukostasis-related complications, namely intracranial hemorrhage and pulmonary distress. Initiating chemotherapy without prior leukocytoreduction may lead to tumor lysis syndrome (TLS). Therapeutic leukocytapheresis (TL) is used as one leukocytoreductive intervention; however, its safety and efficacy in pediatric leukemia has not been established. The purpose of this study is to evaluate safety of TL in pediatric patients and assess the efficacy of TL in reducing WBC count in pediatric leukemia. METHODS: Retrospective chart review was conducted on 14 patients with acute lymphoblastic leukemia (ALL) and 5 with acute myeloid leukemia (AML) who underwent TL during the period 2000-2014 at a single institution. RESULTS: Mean WBC count of 19 patients who received TL was 483.2 × 109 /L (547.1 in ALL, 304.3 in AML); a portion of patients presented with central nervous system symptoms (15%), respiratory symptoms (10%), or both (10%). TL reduced WBC count (mean 50.7% reduction after a single TL procedure; additional 17.1% reduction after a second TL procedure in 6 patients). Short-term survival immediately following TL was 100% without any major procedural complication. Mean survival time in patients with AML was 1.5 years and with ALL was 6.5 years. CONCLUSIONS: TL significantly reduces WBC number in pediatric leukemia patients as young as 22 days old. In our retrospective study, TL was not associated with any significant complications and suggests that TL is a safe initial procedure in pediatric leukemia.

Nanopore long-read RNAseq reveals widespread transcriptional variation among the surface receptors of individual B cells.

Understanding gene regulation and function requires a genome-wide method capable of capturing both gene expression levels and isoform diversity at the single-cell level. Short-read RNAseq is limited in its ability to resolve complex isoforms because it fails to sequence full-length cDNA copies of RNA molecules. Here, we investigate whether RNAseq using the long-read single-molecule Oxford Nanopore MinION sequencer is able to identify and quantify complex isoforms without sacrificing accurate gene expression quantification. After benchmarking our approach, we analyse individual murine B1a cells using a custom multiplexing strategy. We identify thousands of unannotated transcription start and end sites, as well as hundreds of alternative splicing events in these B1a cells. We also identify hundreds of genes expressed across B1a cells that display multiple complex isoforms, including several B cell-specific surface receptors. Our results show that we can identify and quantify complex isoforms at the single cell level.

Dissociation mediates the relationship between childhood maltreatment and subclinical psychosis.

More than a third of the population report childhood adversity, and these experiences are associated with an increased risk of clinical and subclinical psychosis. The reason why some people go on to develop mental health problems and others do not is a key question for study. It has been hypothesized that dissociative processes mediate the relationship between early adversity and psychosis. The current study assessed whether dissociation, and specifically depersonalization (one component of dissociation), plays a mediating role in the relationship between childhood maltreatment and both hallucination proneness and delusional ideation. The study used a cross-sectional design and recruited a student sample to assess these relationships in a nonclinical group. Dissociation mediated the relationship between early maltreatment and both hallucination proneness and delusional ideation. In terms of specific dissociative processes, depersonalization did not mediate hallucination proneness or delusional ideation. Absorption mediated hallucination proneness; dissociative amnesia (negatively) and absorption mediated delusional ideation. It is likely that dissociation interferes with the encoding of traumatic information in nonclinical as well as clinical groups and in certain ways. Absorption may be particularly relevant. For some people, traumatic memories may intrude into conscious awareness in adulthood as psychotic-type experience.

Highly Accurate Sequencing of Full-Length Immune Repertoire Amplicons Using Tn5-Enabled and Molecular Identifier-Guided Amplicon Assembly.

Ab repertoire sequencing is a powerful tool to analyze the adaptive immune system. To sequence entire Ab repertoires, amplicons are created from Ab H chain (IgH) transcripts and sequenced on a high-throughput sequencer. The field of immune repertoire sequencing is growing rapidly and the protocols used are steadily improving; however, thus far, immune repertoire sequencing protocols have not been able to sequence full-length immune repertoires including the entire IgH V region and enough of the IgH C region to identify isotype subtypes. In this study, we present a method that combines Tn5 transposase and molecular identifiers for the highly accurate sequencing of amplicons >500 bp using Illumina short read paired-end sequencing. We then apply this method to Ab H chain amplicons to sequence the first, to our knowledge, highly accurate full-length immune repertoire.