Ten Simple Rules for Reproducible Research in Jupyter Notebooks

Reproducibility of computational studies is a hallmark of scientific methodology. It enables researchers to build with confidence on the methods and findings of others, reuse and extend computational pipelines, and thereby drive scientific progress. Since many experimental studies rely on computational analyses, biologists need guidance on how to set up and document reproducible data analyses or simulations. In this paper, we address several questions about reproducibility. For example, what are the technical and non-technical barriers to reproducible computational studies? What opportunities and challenges do computational notebooks offer to overcome some of these barriers? What tools are available and how can they be used effectively? We have developed a set of rules to serve as a guide to scientists with a specific focus on computational notebook systems, such as Jupyter Notebooks, which have become a tool of choice for many applications. Notebooks combine detailed workflows with narrative text and visualization of results. Combined with software repositories and open source licensing, notebooks are powerful tools for transparent, collaborative, reproducible, and reusable data analyses

Observational Signatures of Self-Destructive Civilisations

We address the possibility that intelligent civilisations that destroy themselves could present signatures observable by humanity. Placing limits on the number of self-destroyed civilisations in the Milky Way has strong implications for the final three terms in Drake's Equation, and would allow us to identify which classes of solution to Fermi's Paradox fit with the evidence (or lack thereof). Using the Earth as an example, we consider a variety of scenarios in which humans could extinguish their own technological civilisation. Each scenario presents some form of observable signature that could be probed by astronomical campaigns to detect and characterise extrasolar planetary systems. Some observables are unlikely to be detected at interstellar distances, but some scenarios are likely to produce significant changes in atmospheric composition that could be detected serendipitously with next-generation telescopes. In some cases, the timing of the observation would prove crucial to detection, as the decay of signatures is rapid compared to humanity's communication lifetime. In others, the signatures persist on far longer timescales.Comment: 35 pages, 2 figures, accepted for publication in the International Journal of Astrobiolog

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E–09 and 4.10E–18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD

Salivary testosterone and cortisol levels in borderline personality disorder before and after a 12-week group dialectical behavior therapy intervention

BackgroundBorderline Personality Disorder (BPD) is a chronic, debilitating, and difficult to treat condition. BPD has recently been linked to steroid hormone dysregulation and medical conditions characterized by disturbed androgen metabolism. This study aimed to investigate cortisol and testosterone levels in BPD, and changes in hormones following psychological treatment.MethodsParticipants with BPD (n = 33) completed a 12-week Dialectical Behavior Therapy group program. Pre and post salivary testosterone and cortisol were analyzed. Baseline hormones in the BPD group were compared to age-and-sex matched controls (n = 33). Non-parametric tests were utilized to investigate group differences, pre-post treatment hormone and symptom changes, and associations between symptoms and hormone levels.ResultsParticipants with BPD had significantly higher testosterone levels than controls. Mean testosterone levels in females with BPD were double that of female controls. Testosterone and cortisol levels were related, and some BPD symptoms were associated with with hormone levels. BPD symptoms reduced significantly with treatment, however pre to post hormone levels did not change.ConclusionsThis study supports an association between BPD symptoms and neuroendocrine dysfunction at baseline, however we found no reduction in hormone dysfunction post treatment. Further research into relationships between stress signaling and neuroendocrine disturbances in BPD may inform aetiological and treatment models.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12618000477224. Registered on 3 April 2018

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E–09 and 4.10E–18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.publishedVersio

Evaluation of a brief intervention within a stepped care whole of service model for personality disorder

Background Although there is growing evidence that stepped models of care are useful for providing appropriate, person centered care, there are very few studies applied to personality disorders. A brief, four session, psychological treatment intervention for personality disorder within a whole of service stepped care model was evaluated. The intervention stepped between acute emergency crisis mental health services and longer-term outpatient treatments. Methods Study 1 used service utilization data from 191 individuals referred to the brief intervention at a single community health site in a metropolitan health service. Proportions of individuals retained across the intervention and the referral pathways accessed following the intervention were examined. Study 2 examined 67 individuals referred to the brief intervention across 4 different sites in metropolitan health services. A range of measures of symptoms and quality of life were administered at the first and last session of the intervention. Effect sizes were calculated to examine mean changes across the course of the intervention. Results Study 1 found that 84.29% of individuals referred to the intervention attended at least 1 session, 60.21% attended 2 sessions or more and 41.89% attended 3 or more sessions. 13.61% of the sample required their care to be stepped up within the service, whereas 29.31% were referred to other treatment providers following referral to the intervention. Study 2 found a significant reduction in borderline personality disorder symptom severity and distress following the intervention, and an increase in quality of life. The largest reduction was found for suicidal ideation (d = 1.01). Conclusions Brief psychological intervention was a useful step between acute services and longer-term treatments in this stepped model of care for personality disorder. Suicide risk and symptom severity reduced and quality of life improved, with only a small proportion of individuals requiring ongoing support from the health service following the intervention

Assessing the efficacy of a stepped-care group treatment programme for borderline personality disorder: study protocol for a pragmatic trial

Abstract Background Borderline personality disorder (BPD) is a high prevalence and serious mental health disorder that has historically challenged the finite resources of health services. Despite empirical evidence supporting structured psychological therapy as the first line of treatment, there remains significant barriers in providing timely access to evidence-based treatment for this population. The primary aim of this study is to evaluate the effectiveness of providing a stepped-care structured psychological group treatment to individuals with BPD within local mental health services. The secondary aims of the study are to identify the variables that predict the need to step up or down in care and the effectiveness of treatment on psychosocial functioning. Methods Participants seeking treatment at two community mental health services will be invited to participate. Randomised controlled trial assignment will be to either (i) group skills treatment or (ii) treatment as usual. Group treatment will be offered via a stepped-care pathway with participants initially attending a 12-week group with the option of a subsequent 16-week group. The criteria for inclusion in continuing treatment includes meeting > 4 BPD diagnostic criteria or severity on GAF (< 65) at the completion of the 12-week group. Data will be collected at baseline and at five follow-up time points over a 12-month period. Discussion This pragmatic trial will provide valuable information regarding the effectiveness of a progressive stepped-care group treatment for individuals with BPD in the real-world setting of a community mental health service. It will further the current understanding of variables that predict treatment dose and duration. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12618000477224 . Registered on 3 April 201

Privacy-Preserving Indexing of Documents on the Network

We address the problem of providing privacy-preserving search over distributed access-controlled content. Indexed documents can be easily reconstructed from conventional (inverted) indexes used in search. The need to avoid breaches of access-control through the index requires the index hosting site to be fully secured and trusted by by all participating content providers. This level of trust is impractical in the increasingly common case where multiple competing organizations or individuals wish to selectively share content. We propose a solution that eliminates the need of such a trusted authority. The solution builds a centralized privacy-preserving index in conjunction with a distributed access-control enforcing search protocol. The new index provides strong and quantifiable privacy guarantees that hold even if the entire index is made public. Experiments on a real-life dataset validate performance of the scheme. The appeal of our solution is two-fold: (a) Content providers maintain complete control in defining access groups and ensuring its compliance, and (b) System implementors retain tunable knobs to balance privacy and e#ciency concerns for their particular domains