The tidyomics ecosystem: enhancing omic data analyses.

The growth of omic data presents evolving challenges in data manipulation, analysis and integration. Addressing these challenges, Bioconductor provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming offers a revolutionary data organization and manipulation standard. Here we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analyzing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas, spanning six data frameworks and ten analysis tools.

matchRanges: generating null hypothesis genomic ranges via covariate-matched sampling.

MOTIVATION: Deriving biological insights from genomic data commonly requires comparing attributes of selected genomic loci to a null set of loci. The selection of this null set is non-trivial, as it requires careful consideration of potential covariates, a problem that is exacerbated by the non-uniform distribution of genomic features including genes, enhancers, and transcription factor binding sites. Propensity score-based covariate matching methods allow the selection of null sets from a pool of possible items while controlling for multiple covariates; however, existing packages do not operate on genomic data classes and can be slow for large data sets making them difficult to integrate into genomic workflows. RESULTS: To address this, we developed matchRanges, a propensity score-based covariate matching method for the efficient and convenient generation of matched null ranges from a set of background ranges within the Bioconductor framework. AVAILABILITY AND IMPLEMENTATION: Package: https://bioconductor.org/packages/nullranges, Code: https://github.com/nullranges, Documentation: https://nullranges.github.io/nullranges.

bootRanges: flexible generation of null sets of genomic ranges for hypothesis testing.

MOTIVATION: Enrichment analysis is a widely utilized technique in genomic analysis that aims to determine if there is a statistically significant association between two sets of genomic features. To conduct this type of hypothesis testing, an appropriate null model is typically required. However, the null distribution that is commonly used can be overly simplistic and may result in inaccurate conclusions. RESULTS: bootRanges provides fast functions for generation of block bootstrapped genomic ranges representing the null hypothesis in enrichment analysis. As part of a modular workflow, bootRanges offers greater flexibility for computing various test statistics leveraging other Bioconductor packages. We show that shuffling or permutation schemes may result in overly narrow test statistic null distributions and over-estimation of statistical significance, while creating new range sets with a block bootstrap preserves local genomic correlation structure and generates more reliable null distributions. It can also be used in more complex analyses, such as accessing correlations between cis-regulatory elements (CREs) and genes across cell types or providing optimized thresholds, e.g. log fold change (logFC) from differential analysis. AVAILABILITY AND IMPLEMENTATION: bootRanges is freely available in the R/Bioconductor package nullranges hosted at https://bioconductor.org/packages/nullranges.

Provision of a Multidisciplinary Post-Suicidal, Community-Based Aftercare Program: A Longitudinal Study.

Suicide is a global concern with rates in Australia continuing to increase. Effective post-suicidal care is critical for reducing persistent suicidal behaviour. One model of care is that adopted by Alfred Health, delivering a multidisciplinary, hybrid clinical and non-clinical (psycho-social support), assertive outreach approach. This study measured improvements in resilience and wellbeing, changes to distress and suicidal ideation at least 6-months post-discharge from care. Thirty-one consumers participated including a one-on-one interview to gather qualitative feedback. There was a significant change on all outcome measures with large effect sizes. Participants had significantly reduced suicidal ideation and distress and increased coping self-efficacy, hope and well-being. The qualitative findings indicated that a key component to recovery was the staff. Limitations included a low sample size, and broad time range of follow-up data collection. Providing assertive, multidisciplinary, collaborative and outreach-focused post-suicidal care can increase and sustain protective psychological factors and reduced suicidal ideation in most individuals.

A Self-Help Manual for Psychological Distress and Quality of Life During a Haemopoietic Stem-Cell Transplant: An Effectiveness and Acceptability Pilot.

Haemopoietic stem-cell transplantation (HSCT) can be a highly distressing procedure that negatively impacts quality of life (QoL). Self-help interventions can help improve psychopathology and wellbeing in patients with physical illness, but have rarely been trialled with HSCT recipients. This study aimed to pilot the utility of a self-help manual intervention during the acute phase of HSCT. Forty autologous and allogeneic HSCT candidates were randomly assigned to a self-help manual intervention or treatment as usual (TAU). Psychological distress (BSI-18) and QoL (FACT-BMT-Vs4) were measured pre-, 2-3 weeks and 3 months post-HSCT. Linear mixed-effects analyses showed no significant group-time interaction for global QoL (p = .199) or global distress (p = .624). However, highlighting a protective role during admission, manual participants showed minimal QoL or somatic distress change at 2-3 weeks post-transplant compared with moderate-large effects for reduced QoL (d = 0.62) and increased somatic distress (d = - 0.81) for TAU patients. Thematic analysis suggests the manual helped prepare patients for transplant and provided strategies to improve distress and QoL. This pilot provides preliminary evidence for the benefit of a self-help manual during hospitalisation for a HSCT. More intensive, recovery-focussed care, however, may be needed to improve psychological health in the post-hospital period. Retrospectively registered trial (ANZCTR No. 12620001165976, 6th November 2020).

Transcriptomic Responses and Survival Mechanisms of Staphylococci to the Antimicrobial Skin Lipid Sphingosine.

Sphingosines are antimicrobial lipids that form part of the innate barrier to skin colonization by microbes. Sphingosine deficiencies can result in increased epithelial infections by bacteria including Staphylococcus aureus. Recent studies have focused on the potential use of sphingosine resistance or its potential mechanisms. We used RNA-Seq to identify the common d-sphingosine transcriptomic response of the transient skin colonizer S. aureus and the dominant skin coloniser S. epidermidis. A common d-sphingosine stimulon was identified that included downregulation of the SaeSR two-component system (TCS) regulon and upregulation of both the VraSR TCS and CtsR stress regulons. We show that the PstSCAB phosphate transporter, and VraSR offer intrinsic resistance to d-sphingosine. Further, we demonstrate increased sphingosine resistance in these staphylococci evolves readily through mutations in genes encoding the FarE-FarR efflux/regulator proteins. The ease of selecting mutants with resistance to sphingosine may impact upon staphylococcal colonization of skin where the lipid is present and have implications with topical therapeutic applications.

Identity-by-descent analyses for measuring population dynamics and selection in recombining pathogens.

Identification of genomic regions that are identical by descent (IBD) has proven useful for human genetic studies where analyses have led to the discovery of familial relatedness and fine-mapping of disease critical regions. Unfortunately however, IBD analyses have been underutilized in analysis of other organisms, including human pathogens. This is in part due to the lack of statistical methodologies for non-diploid genomes in addition to the added complexity of multiclonal infections. As such, we have developed an IBD methodology, called isoRelate, for analysis of haploid recombining microorganisms in the presence of multiclonal infections. Using the inferred IBD status at genomic locations, we have also developed a novel statistic for identifying loci under positive selection and propose relatedness networks as a means of exploring shared haplotypes within populations. We evaluate the performance of our methodologies for detecting IBD and selection, including comparisons with existing tools, then perform an exploratory analysis of whole genome sequencing data from a global Plasmodium falciparum dataset of more than 2500 genomes. This analysis identifies Southeast Asia as having many highly related isolates, possibly as a result of both reduced transmission from intensified control efforts and population bottlenecks following the emergence of antimalarial drug resistance. Many signals of selection are also identified, most of which overlap genes that are known to be associated with drug resistance, in addition to two novel signals observed in multiple countries that have yet to be explored in detail. Additionally, we investigate relatedness networks over the selected loci and determine that one of these sweeps has spread between continents while the other has arisen independently in different countries. IBD analysis of microorganisms using isoRelate can be used for exploring population structure, positive selection and haplotype distributions, and will be a valuable tool for monitoring disease control and elimination efforts of many diseases.

How Do Mental Health Nurses Define Success? A Comparative Study of Bed-Based and Community-Based Services.

Nursing is the single largest professional group within both hospital and community mental health care services, however the role of mental health nurses in under-defined. The nursing workforce is also coming under increasing pressure from internal and external requirements, and nurses themselves are on the frontline of providing patient care in what can be a risky and unpredictable workplace environment. This project explored via interview the ways in which mental health nurses experience and reflect on their personal and professional feelings of nursing success. Participants were 19 nurses who were employed in a range of bed-based and community mental health services in inner south eastern Melbourne. This study complies with the Consolidated Criteria for Reporting Qualitative Research (COREQ). The findings of the project align with existing evidence from the literature. Factors which helped mental health nurses feel successful included: therapeutic success; good teamwork; targeted education; and feedback. Barriers to success included: patients/clients do not engage or recover; poor communication amongst staff; lack of psychological safety in the workplace; and lack of respect from management. Nurses in community settings were more able than nurses in bed-based settings to: make effective use of clinical supervision; make use of targeted training and educational offerings; and practice therapeutically and holistically. Project results offer an opportunity to understand nurses' motivations and reward systems. Better understanding of these issues can improve the way mental health care services manage their workforce planning, maintain staff personal wellbeing, increase staff retention and ultimately improve patient/client care.

Emotional discomfort mediates the relationship between self-efficacy and subjective quality of life in people with schizophrenia.

BACKGROUND: In people with schizophrenia, self-efficacy (i.e. the belief in one's capability to perform particular tasks/skills) is associated with and motivates performance of social, health and independent living behaviours. Less well known is whether self-efficacy is associated with subjective quality of life (sQoL) or whether psychopathology impacts this relationship. AIMS: Measure whether greater self-efficacy is associated with greater community functioning and sQoL and whether emotional discomfort mediates this relationship. METHOD: Fifty-two community living people with schizophrenia completed measures of self-efficacy for everyday living and social situations, clinical symptoms, sQoL and community functioning. RESULTS: Greater everyday living and social self-efficacy was significantly correlated with greater sQoL and community functioning and lower emotional discomfort (p < 0.05). Only social self-efficacy was correlated with negative symptoms. The relationship between both aspects of self-efficacy and sQoL was, however, mediated by emotional discomfort. Greater confidence in performing social and everyday living behaviours therefore indirectly impacted sQoL through reducing emotional distress. CONCLUSIONS: Holding negative capability self-beliefs may contribute to poorer outcome for people with schizophrenia. Intervention aimed at facilitating recovery should therefore provide opportunities to develop knowledge and skills required for success in desired life roles and the belief that tasks required for success can be performed.

Unchanged cerebrovascular CO2 reactivity and hypercapnic ventilatory response during strict head-down tilt bed rest in a mild hypercapnic environment.

KEY POINTS: Carbon dioxide levels are mildly elevated on the International Space Station and it is unknown whether this chronic exposure causes physiological changes to astronauts. We combined ∼4 mmHg ambient PCO2 with the strict head-down tilt bed rest model of spaceflight and this led to the development of optic disc oedema in one-half of the subjects. We demonstrate no change in arterialized PCO2 , cerebrovascular reactivity to CO2 or the hypercapnic ventilatory response. Our data suggest that the mild hypercapnic environment does not contribute to the development of spaceflight associated neuro-ocular syndrome. ABSTRACT: Chronically elevated carbon dioxide (CO2 ) levels can occur in confined spaces such as the International Space Station. Using the spaceflight analogue 30 days of strict 6° head-down tilt bed rest (HDTBR) in a mild hypercapnic environment ( PCO2 = ∼4 mmHg), we investigated arterialized PCO2 , cerebrovascular reactivity and the hypercapnic ventilatory response in 11 healthy subjects (five females) before, on days 1, 9, 15 and 30 of bed rest (BR), and 6 and 13 days after HDTBR. During all HDTBR time points, arterialized PCO2 was not significantly different from the pre-HDTBR measured in the 6° HDT posture, with a mean (95% confidence interval) increase of 1.2 mmHg (-0.2 to 2.5 mmHg, P = 0.122) on day 30 of HDTBR. Respiratory acidosis was never detected, although a mild metabolic alkalosis developed on day 30 of HDTBR by a mean (95% confidence interval) pH change of 0.032 (0.022-0.043; P < 0.001), which remained elevated by 0.021 (0.011-0.031; P < 0.001) 6 days after HDTBR. Arterialized pH returned to pre-HDTBR levels 13 days after BR with a change of -0.001 (-0.009 to 0.007; P = 0.991). Compared to pre-HDTBR, cerebrovascular reactivity during and after HDTBR did not change. Baseline ventilation, ventilatory recruitment threshold and the slope of the ventilatory response were similar between pre-HDTBR and all other time points. Taken together, these data suggest that the mildly increased ambient PCO2 combined with 30 days of strict 6° HDTBR did not change arterialized PCO2 levels. Therefore, the experimental conditions were not sufficient to elicit a detectable physiological response.

SNP barcodes provide higher resolution than microsatellite markers to measure Plasmodium vivax population genetics.

BACKGROUND: Genomic surveillance of malaria parasite populations has the potential to inform control strategies and to monitor the impact of interventions. Barcodes comprising large numbers of single nucleotide polymorphism (SNP) markers are accurate and efficient genotyping tools, however may need to be tailored to specific malaria transmission settings, since 'universal' barcodes can lack resolution at the local scale. A SNP barcode was developed that captures the diversity and structure of Plasmodium vivax populations of Papua New Guinea (PNG) for research and surveillance. METHODS: Using 20 high-quality P. vivax genome sequences from PNG, a total of 178 evenly spaced neutral SNPs were selected for development of an amplicon sequencing assay combining a series of multiplex PCRs and sequencing on the Illumina MiSeq platform. For initial testing, 20 SNPs were amplified in a small number of mono- and polyclonal P. vivax infections. The full barcode was then validated by genotyping and population genetic analyses of 94 P. vivax isolates collected between 2012 and 2014 from four distinct catchment areas on the highly endemic north coast of PNG. Diversity and population structure determined from the SNP barcode data was then benchmarked against that of ten microsatellite markers used in previous population genetics studies. RESULTS: From a total of 28,934,460 reads generated from the MiSeq Illumina run, 87% mapped to the PvSalI reference genome with deep coverage (median = 563, range 56-7586) per locus across genotyped samples. Of 178 SNPs assayed, 146 produced high-quality genotypes (minimum coverage = 56X) in more than 85% of P. vivax isolates. No amplification bias was introduced due to either polyclonal infection or whole genome amplification (WGA) of samples before genotyping. Compared to the microsatellite panels, the SNP barcode revealed greater variability in genetic diversity between populations and geographical population structure. The SNP barcode also enabled assignment of genotypes according to their geographic origins with a significant association between genetic distance and geographic distance at the sub-provincial level. CONCLUSIONS: High-throughput SNP barcoding can be used to map variation of malaria transmission dynamics at sub-national resolution. The low cost per sample and genotyping strategy makes the transfer of this technology to field settings highly feasible.

Exploring behaviours of concern including aggression, self-harm, sexual harm and absconding within an Australian inpatient mental health service.

OBJECTIVE: Patients admitted to mental health services may exhibit behaviours of concern (BOCs) such as aggression, self-harm, absconding and sexual harm. BOCs can lead to restrictive interventions, which have adverse effects on patients, carers and staff. This paper aims to explore the nature and outcome of BOCs within an adult inpatient mental health setting. METHODS: A retrospective audit was conducted at a metropolitan inpatient service between 1 August 2016 and 31 July 2017. The frequency, nature and outcomes of BOC episodes were described and thematic analysis was used to summarise BOC antecedents. RESULTS: A BOC was documented for 179 (18.2%) patients who also showed high rates of drug abuse, homelessness and longer admission. Most self-harm and sexual harm events occurred outside of normal business hours. Medications and verbal de-escalation were commonly used interventions. Episodes of deliberate self-harm were likely to result in patient and staff injury or mechanical restraint, whereas aggression was associated with seclusion. Mental state, care engagement, physiological stress and situational stressor were identified as BOC antecedents. CONCLUSION: Multiple forms of BOCs were experienced with mental state, physical and interpersonal contributors identified. Improving multidisciplinary input into early assessment and treatment of BOC causes is needed to improve safety.

Structurally conserved erythrocyte-binding domain in Plasmodium provides a versatile scaffold for alternate receptor engagement.

Understanding how malaria parasites gain entry into human red blood cells is essential for developing strategies to stop blood stage infection. Plasmodium vivax preferentially invades reticulocytes, which are immature red blood cells. The organism has two erythrocyte-binding protein families: namely, the Duffy-binding protein (PvDBP) and the reticulocyte-binding protein (PvRBP) families. Several members of the PvRBP family bind reticulocytes, specifically suggesting a role in mediating host cell selectivity of P. vivax. Here, we present, to our knowledge, the first high-resolution crystal structure of an erythrocyte-binding domain from PvRBP2a, solved at 2.12 Å resolution. The monomeric molecule consists of 10 α-helices and one short ß-hairpin, and, although the structural fold is similar to that of PfRh5--the essential invasion ligand in Plasmodium falciparum--its surface properties are distinct and provide a possible mechanism for recognition of alternate receptors. Sequence alignments of the crystallized fragment of PvRBP2a with other PvRBPs highlight the conserved placement of disulfide bonds. PvRBP2a binds mature red blood cells through recognition of an erythrocyte receptor that is neuraminidase- and chymotrypsin-resistant but trypsin-sensitive. By examining the patterns of sequence diversity within field isolates, we have identified and mapped polymorphic residues to the PvRBP2a structure. Using mutagenesis, we have also defined the critical residues required for erythrocyte binding. Characterization of the structural features that govern functional erythrocyte binding for the PvRBP family provides a framework for generating new tools that block P. vivax blood stage infection.

Neurocognitive and Self-efficacy Benefits of Cognitive Remediation in Schizophrenia: A Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to evaluate the impact of computer-assisted "drill-and-strategy" cognitive remediation (CR) for community-dwelling individuals with schizophrenia on cognition, everyday self-efficacy, and independent living skills. METHODS: Fifty-six people with schizophrenia or schizoaffective disorder were randomized into CR or computer game (CG) playing (control), and offered twenty 1-hr individual sessions in a group setting over 10 weeks. Measures of cognition, psychopathology, self-efficacy, quality of life, and independent living skills were conducted at baseline, end-group and 3 months following intervention completion. RESULTS: Forty-three participants completed at least 10 sessions and the end-group assessment. Linear mixed-effect analyses among completers demonstrated a significant interaction effect for global cognition favoring CR (p=.028). CR-related cognitive improvement was sustained at 3-months follow-up. At end-group, 17 (77%) CR completers showed a reliable improvement in at least one cognitive domain. A significant time effect was evident for self-efficacy (p=.028) with both groups improving over time, but no significant interaction effect was observed. No significant effects were found for other study outcomes, including the functional measure. CONCLUSIONS: Computer-assisted drill-and-strategy CR in schizophrenia improved cognitive test performance, while participation in both CR and CG playing promoted enhancements in everyday self-efficacy. Changes in independent living skills did not appear to result from CR, however. Adjunctive psychosocial rehabilitation is likely necessary for improvements in real-world community functioning to be achieved. (JINS, 2018, 24, 549-562).

The role of aggression-related early maladaptive schemas and schema modes in aggression in a prisoner sample.

Contemporary social-cognitive aggression theory and extant empirical research highlights the relationship between certain Early Maladaptive Schemas (EMSs) and aggression in offenders. To date, the related construct of schema modes, which presents a comprehensive and integrated schema unit, has received scant empirical attention. Furthermore, EMSs and schema modes have yet to be examined concurrently with respect to aggressive behavior. This study examined associations between EMSs, schema modes, and aggression in an offender sample. Two hundred and eight adult male prisoners completed self-report psychological tests measuring their histories of aggression, EMSs, and schema modes. Regression analyses revealed that EMSs were significantly associated with aggression but did not account for a unique portion of variance once the effects of schema modes were taken into account. Three schema modes, Enraged Child, Impulsive Child, and Bully and Attack, significantly predicted aggression. These findings support the proposition that schema modes characterized by escalating states of anger, rage, and impulsivity characterize aggressive offenders. In this regard, we call attention to the need to include schema modes in contemporary social-cognitive aggression theories, and suggest that systematic assessment and treatment of schema modes has the potential to enhance outcomes with violent offenders.

Single session family therapy in youth mental health: can it help?

OBJECTIVE: The objective of this study was to assess the effectiveness of single session therapy in meeting the needs of young people and their families on first presentation to a mental health service. METHOD: We conducted a quantitative analysis of routinely collected data using self- and family member-reported session and outcome rating scales. RESULTS: Both young people and their family members rate single session therapy sessions highly. In addition, both young people and their families rate the young person's mental health and well-being to have improved after the single session therapy intervention, with mothers rating the young person's improvement most highly. CONCLUSIONS: Single session therapy is an effective tool in improving both self- and parent-rated individual, interpersonal, social and overall well-being for young people presenting to a mental health service.

Are people with severe mental illness ready for online interventions? Access and use of the Internet in Australian mental health service users.

OBJECTIVES: The Internet is increasingly used in mental health service delivery, but there are significant potential barriers to Internet access for persons with severe mental illness (SMI). There is a need to understand this group's access to, and confidence with using, the Internet, and current views on using online resources as part of mental healthcare. METHOD: A survey was conducted of 100 consumers attending a specialist mental health service in Melbourne, Australia. RESULTS: Approximately three-quarters of participants had regular access to the Internet, and two-thirds used the Internet weekly or more. Half of the sample used email at least weekly, and a third were regular users of social networking sites. Internet access was often via mobile devices. Only a minority of participants used the Internet for mental health information, with video streaming and general websites accessed more often than peer forums for mental health content. Most participants were positive about their mental health worker using tablet computers with them in appointments for delivery of mental health materials. CONCLUSION: Most people with SMI are active Internet users and, therefore, able to use interventions online.