Simultaneous switching of two different CO2-switchable amines in the same solution.

Most CO2-responsive systems operate by using a base in water that is expected to be mostly deprotonated when under an atmosphere of air and mostly protonated under an atmosphere of CO2. This concept has led to the development of many different CO2-responsive materials such as solvents, polymers, surfactants, and solutes. As CO2-responsive materials research continues, more complex systems may be developed, including systems containing two different bases with different basicities. Understanding the influence each base has on the protonation equilibrium of the other base is important for designing systems in which effective deprotonation and protonation occur. This article presents a model that can predict the solution pH and the % protonation of two different bases at various concentrations under air and CO2. Experimental data was collected to demonstrate the successful simultaneous switching of two amines and to evaluate the accuracy of the predictive model. The simultaneous switching of two different CO2-switchable amines in the same solution was determined to be possible but only if the amine concentrations and basicities are within certain ranges, and only if the pKaH values of the two bases differ by no more than 3 units.

Risk prevalence, readiness and confidence to change lifestyle risk factors among clients of community mental health services.

OBJECTIVE: People with mental health conditions have high rates of chronic physical diseases, partially attributable to lifestyle risks factors. This study examined risk prevalence among community mental health service clients, their readiness and confidence to change, and associations with participant characteristics. METHODS: Cross-sectional survey of adult clients from 12 community mental health services across 3 local health districts in New South Wales, Australia, collected from 2021 to 2022. Participants (n = 486) completed a telephone interview determining five risk factors, and readiness and confidence to change these. Multiple binary logistic regression models determined associations between readiness and confidence (for each risk), and participant characteristics (demographics and diagnosis). RESULTS: Participants most commonly reported a diagnosis of schizophrenia (36.7%) or depression (21.1%). Risk factors were prevalent: ranging from 26% (harmful alcohol use) to 97% (poor nutrition). High readiness was greatest for smoking (68%), weight (66%) and physical inactivity (63%), while confidence was highest for changing alcohol use (67%). Two significant associations were identified; females were more likely than males to have high readiness to change nutrition (odds ratio = 1.14, confidence interval = [1.13, 2.34], p = 0.0092), with males more likely to have high confidence to change physical activity (odds ratio = 0.91, confidence interval = [0.45, 0.99], p = 0.0109). CONCLUSIONS: Many participants were ready and confident to change risk factors. Gender influenced readiness to change nutrition and physical activity confidence. Training to upskill mental health clinicians in provision of preventive care that builds confidence and readiness levels may aid in supporting positive behaviour change.

Cognitive remediation in residential substance use treatment: A randomized stepped-wedge trial.

ABSTRACTExecutive dysfunction is common in individuals with substance use disorder (SUD) and presents a barrier to treatment engagement. The study aimed to investigate the effectiveness of cognitive remediation (CR) for improving executive functioning and treatment retention in patients with SUD, using a stepped-wedge cluster randomized controlled trial. The sample included 527 adults enrolled across ten residential SUD treatment providers in NSW, Australia. The intervention consisted of 12 hours of CR delivered over six weeks in a group format. The comparator was treatment-as-usual (TAU). Primary outcomes included self-reported executive functioning and proportion of treatment completed (PoTC), measured as the number of days in treatment divided by the planned treatment duration. Intention-to-treat analysis did not find significant differences for self-reported executive functioning (mean difference = -2.49, 95%CI [-5.07, 0.09], p = .059) or PoTC (adjusted mean ratio = 1.09, 95%CI [0.88, 1.36], p = .442). Due to high dropout from the intention-to-treat sample (56%) a post-hoc analysis was conducted using a per-protocol approach, in which CR was associated with improved self-reported executive functioning (mean difference = -3.33, 95%CI [-6.10, -0.57], p = .019) and improved likelihood of treatment graduation (adjusted odds ratio = 2.43, 95%CI [1.43, 4.11], p < .001). More research is required to develop a CR approach that results in service-wide treatment effectiveness.

Bringing bioinformatics to schools with the 4273pi project.

Over the last few decades, the nature of life sciences research has changed enormously, generating a need for a workforce with a variety of computational skills such as those required to store, manage, and analyse the large biological datasets produced by next-generation sequencing. Those with such expertise are increasingly in demand for employment in both research and industry. Despite this, bioinformatics education has failed to keep pace with advances in research. At secondary school level, computing is often taught in isolation from other sciences, and its importance in biological research is not fully realised, leaving pupils unprepared for the computational component of Higher Education and, subsequently, research in the life sciences. The 4273pi Bioinformatics at School project (https://4273pi.org) aims to address this issue by designing and delivering curriculum-linked, hands-on bioinformatics workshops for secondary school biology pupils, with an emphasis on equitable access. So far, we have reached over 180 schools across Scotland through visits or teacher events, and our open education resources are used internationally. Here, we describe our project, our aims and motivations, and the practical lessons we have learned from implementing a successful bioinformatics education project over the last 5 years.

A Novel, Paresthesia-Free Spinal Cord Stimulation Waveform for Chronic Neuropathic Low Back Pain: Six-Month Results of a Prospective, Single-Arm, Dose-Response Study.

OBJECTIVES: The aim of this prospective, single-blinded, dose-response study was to evaluate the safety and efficacy of a novel, paresthesia-free (subperception) spinal cord stimulation (SCS) waveform designed to target dorsal horn dendrites for the treatment of chronic neuropathic low back pain (LBP). MATERIALS AND METHODS: Twenty-seven participants with chronic neuropathic LBP were implanted with a commercial SCS system after a successful trial of SCS therapy. Devices were programmed to deliver the investigative waveform (100 Hz, 1000 µs, T9/T10 bipole) at descending stimulation perception threshold amplitudes (80%, 60%, 40%). Programs were evaluated at six, ten, and 14 weeks, after which participants selected their preferred program, with more follow-up at 26 weeks (primary outcomes). Participants were blinded to the nature of the programming. Pain score (visual analog scale [VAS]), Brief Pain Inventory (BPI), quality of life (EQ-5D-5L), and health status (36-Item Short Form [SF-36]) were measured at baseline and follow-ups. Responder rate, treatment satisfaction, clinician global impression of change, and adverse events (AEs) also were evaluated. RESULTS: Mean (± SD) baseline VAS was 72.5 ± 11.2 mm. At 26 weeks (n = 26), mean change from baseline in VAS was -51.7 mm (95% CI, -60.7 to -42.7; p < 0.001), with 76.9% of participants reporting ≥50% VAS reduction, and 46.2% reporting ≥80% VAS reduction. BPI, EQ-5D-5L, and SF-36 scores were all statistically significantly improved at 26 weeks (p < 0.001), and 100% of participants were satisfied with their treatment. There were no unanticipated AEs related to the study intervention, device, or procedures. CONCLUSIONS: This novel, paresthesia-free stimulation waveform may be a safe and effective option for patients with chronic neuropathic LBP eligible for SCS therapy and is deliverable by all current commercial SCS systems. CLINICAL TRIAL REGISTRATION: This study is registered on anzctr.org.au with identifier ACTRN12618000647235.

Transcriptomic analysis reveals myometrial topologically associated domains linked to the onset of human term labour.

Changes in cell phenotype are thought to occur through the expression of groups of co-regulated genes within topologically associated domains (TADs). In this paper, we allocate genes expressed within the myometrium of the human uterus during the onset of term labour into TADs. Transformation of the myometrial cells of the uterus into a contractile phenotype during term human labour is the result of a complex interaction of different epigenomic and genomic layers. Recent work suggests that the transcription factor (TF) RELA lies at the top of this regulatory network. Using deep RNA sequencing (RNAseq) analysis of myometrial samples (n = 16) obtained at term from women undergoing caesarean section prior to or after the onset of labour, we have identified evidence for how other gene expression regulatory elements interact with TFs in the labour phenotype transition. Gene set enrichment analysis of our RNAseq data identified three modules of enriched genes (M1, M2 and M3), which in gene ontology studies are linked to matrix degradation, smooth muscle and immune gene signatures, respectively. These genes were predominantly located within chromosomal TADs suggesting co-regulation of expression. Our transcriptomic analysis also identified significant differences in the expression of long non-coding RNAs (lncRNA), microRNAs (miRNA) and TFs that were predicted to target genes within the TADs. Additionally, network analysis revealed 15 new lncRNA (MCM3AP-AS1, TUG1, MIR29B2CHG, HCG18, LINC00963, KCNQ1OT1, NEAT1, HELLPAR, SNHG16, NUTM2B-AS1, MALAT1, PSMA3-AS1, GABPB1-AS1, NORAD and NKILA) and 4 miRNA (mir-145, mir-223, mir-let-7a and mir-132) as top gene hubs with three TFs (NFKB1, RELA and ESR1) as master regulators. Together, these factors are likely to be involved in co-regulatory networks driving a myometrial transformation to generate an estrogen-sensitive phenotype. We conclude that lncRNA and miRNA targeting the estrogen receptor 1 and nuclear factor kappa B pathways play a key role in the initiation of human labour. For the first time, we perform an integrative analysis to present a multi-level genomic signature made of mRNA, non-coding RNA and TFs in the myometrium for spontaneous term labour.

Pathways linked to unresolved inflammation and airway remodelling characterize the transcriptome in two independent severe asthma cohorts.

BACKGROUND AND OBJECTIVE: Severe asthma (SA) is a heterogeneous disease. Transcriptomic analysis contributes to the understanding of pathogenesis necessary for developing new therapies. We sought to identify and validate mechanistic pathways of SA across two independent cohorts. METHODS: Transcriptomic profiles from U-BIOPRED and Australian NOVocastrian Asthma cohorts were examined and grouped into SA, mild/moderate asthma (MMA) and healthy controls (HCs). Differentially expressed genes (DEGs), canonical pathways and gene sets were identified as central to SA mechanisms if they were significant across both cohorts in either endobronchial biopsies or induced sputum. RESULTS: Thirty-six DEGs and four pathways were shared across cohorts linking to tissue remodelling/repair in biopsies of SA patients, including SUMOylation, NRF2 pathway and oxidative stress pathways. MMA presented a similar profile to HCs. Induced sputum demonstrated IL18R1 as a shared DEG in SA compared with healthy subjects. We identified enrichment of gene sets related to corticosteroid treatment; immune-related mechanisms; activation of CD4+ T cells, mast cells and IL18R1; and airway remodelling in SA. CONCLUSION: Our results identified differentially expressed pathways that highlight the role of CD4+ T cells, mast cells and pathways linked to ongoing airway remodelling, such as IL18R1, SUMOylation and NRF2 pathways, as likely active mechanisms in the pathogenesis of SA.

Using sound to understand protein sequence data: new sonification algorithms for protein sequences and multiple sequence alignments.

BACKGROUND: The use of sound to represent sequence data-sonification-has great potential as an alternative and complement to visual representation, exploiting features of human psychoacoustic intuitions to convey nuance more effectively. We have created five parameter-mapping sonification algorithms that aim to improve knowledge discovery from protein sequences and small protein multiple sequence alignments. For two of these algorithms, we investigated their effectiveness at conveying information. To do this we focussed on subjective assessments of user experience. This entailed a focus group session and survey research by questionnaire of individuals engaged in bioinformatics research. RESULTS: For single protein sequences, the success of our sonifications for conveying features was supported by both the survey and focus group findings. For protein multiple sequence alignments, there was limited evidence that the sonifications successfully conveyed information. Additional work is required to identify effective algorithms to render multiple sequence alignment sonification useful to researchers. Feedback from both our survey and focus groups suggests future directions for sonification of multiple alignments: animated visualisation indicating the column in the multiple alignment as the sonification progresses, user control of sequence navigation, and customisation of the sound parameters. CONCLUSIONS: Sonification approaches undertaken in this work have shown some success in conveying information from protein sequence data. Feedback points out future directions to build on the sonification approaches outlined in this paper. The effectiveness assessment process implemented in this work proved useful, giving detailed feedback and key approaches for improvement based on end-user input. The uptake of similar user experience focussed effectiveness assessments could also help with other areas of bioinformatics, for example in visualisation.

Add-on azithromycin reduces sputum cytokines in non-eosinophilic asthma: an AMAZES substudy.

Add-on azithromycin (AZM) significantly reduces exacerbations in poorly controlled asthma irrespective of disease phenotype. In a predefined substudy of the original AMAZES protocol (500 mg, three times a week for 48 weeks), we report that AZM treatment reduces key sputum inflammatory proteins (interleukin (IL)-6, IL-1ß and extracellular DNA), which is more evident in non-eosinophilic asthma (NEA). Moreover, AZM reduced Haemophilus influenzae load only in NEA. Our data support the anti-inflammatory effects of AZM in poorly controlled asthma. Prospective studies are required to identify patients that derive greatest benefit from AZM add-on therapy.

Transcriptomics of biopsies identifies novel genes and pathways linked to neutrophilic inflammation in severe asthma.

BACKGROUND: Severe asthma is a complex disease. Transcriptomic profiling has contributed to understanding the pathogenesis of asthma, especially type-2 inflammation. However, there is still poor understanding of non-type-2 asthma, and consequently, there are limited treatment options. OBJECTIVE: The aim of this study was to identify differentially expressed genes (DEGs) and pathways in endobronchial biopsies associated with inflammatory phenotypes of severe asthma. METHODS: This cross-sectional study examined endobronchial biopsies from 47 adults with severe asthma (neutrophilic asthma (NA) n = 9, eosinophilic asthma (EA) n = 22 and paucigranulocytic asthma (PGA) n = 16) and 13 healthy controls (HC). RNA was extracted and transcriptomic profiles generated (Illumina Humanref-12 V4) and analysed using GeneSpring GX14.9.1. Pathway identification using Ingenuity Pathway Analysis. RESULTS: NA had the most distinct profile, with signature of 60 top-ranked DEGs (FC >±2) including genes associated with innate immunity response, neutrophil degranulation and IL-10 signalling. NA presented enrichment to pathways previously linked to neutrophilic inflammation; dendritic cell maturation, Th1, TREM1, inflammasome, Th17 and p38 MAPK, as well as novel links to neuroinflammation, NFAT and PKCθ signalling. EA presented similar transcriptomic profiles to PGA and HC. Despite the higher proportion of bacterial colonization in NA, no changes were observed in the transcriptomic profiles of severe asthma culture positive compared with severe asthma culture negative. CONCLUSIONS & CLINICAL RELEVANCE: NA features a distinct transcriptomic profile with seven pathways enriched in NA compared to EA, PGA and HC. All those with severe asthma had significant enrichment for SUMOylation, basal cell carcinoma signalling and Wnt/ß-catenin pathways compared to HC, despite high-dose inhaled corticosteroids. These findings contribute to the understanding of mechanistic pathways in endobronchial biopsies associated with NA and identify potential novel treatment targets for severe asthma.

Sputum TNF markers are increased in neutrophilic and severe asthma and are reduced by azithromycin treatment.

BACKGROUND: The AMAZES randomized controlled trial demonstrated that long-term low-dose azithromycin treatment reduces exacerbations of poorly controlled asthma, but the therapeutic mechanisms remain unclear. Dysregulation of the inflammatory tumour necrosis factor (TNF) pathway is implicated in asthma and could be suppressed by azithromycin. We aimed to determine the inflammatory and clinical associations of soluble TNF signalling proteins (TNF receptors [TNFR] 1 and 2, TNF) in sputum and serum, and to test the effect of 48 weeks of azithromycin vs placebo on TNF markers. METHODS: Sputum supernatant and serum TNFR1, TNFR2 (n = 142; 75 azithromycin-treated, 67 placebo-treated) and TNF (n = 48; 22 azithromycin-treated, 26 placebo-treated) were measured by ELISA in an AMAZES trial sub-population at baseline and end of treatment. Baseline levels were compared between sputum inflammatory phenotypes, severe/non-severe asthma and frequent/non-frequent exacerbators. Effect of azithromycin on markers was tested using linear mixed models. RESULTS: Baseline sputum TNFR1 and TNFR2 were significantly increased in neutrophilic vs non-neutrophilic asthma phenotypes, while serum markers did not differ. Sputum TNFR1 and TNFR2 were increased in severe asthma and correlated with poorer lung function, worse asthma control and increasing age. Serum TNFR1 was also increased in severe asthma. Sputum and serum TNFR2 were increased in frequent exacerbators. Azithromycin treatment significantly reduced sputum TNFR2 and TNF relative to placebo, specifically in non-eosinophilic participants. CONCLUSIONS: We demonstrate dysregulation of TNF markers, particularly in the airways, that relates to clinically important phenotypes of asthma including neutrophilic and severe asthma. Suppression of dysregulated TNF signalling by azithromycin could contribute to its therapeutic mechanism.

Disordered eating, body image concerns, and weight control behaviors in primary school aged children: A systematic review and meta-analysis of universal-selective prevention interventions.

OBJECTIVE: Body image concerns and extreme weight control behaviors frequently develop in childhood indicating an important age group for the implementation of universal-selective prevention approaches. This systematic review aimed to evaluate the effect of universal-selective prevention interventions addressing disordered eating, body image concerns, and/or extreme weight control behaviors in children aged 6-12 years. METHOD: Nine databases were searched up to April 2021. Studies were included if they delivered a universal-selective prevention intervention to children aged 6-12 years and reported outcomes relating to body image, disordered eating, or weight control behaviors. The review was conducted in line with the PRISMA Guidelines. RESULTS: A total of 42 articles describing 39 studies included in the review, with most (n = 24; 57%) classified as neutral quality. Thirty studies implemented an eating disorder specific universal-selective program and nine implemented lifestyle interventions plus content to address disordered eating risk factors. Meta-analysis (n = 16 studies) revealed an improvement in body image-related outcomes across all studies (standardized mean difference [SMD] 0.26 [95%CI 0.01, 0.51]); with a high level of heterogeneity (Î2 = 89.9%; p < .01). Meta-analysis according to gender revealed a general improvement in body image-related outcomes for girls (SMD 0.40 [95%CI 0.07, 0.73]), but not boys (SMD 0.23 [95%CI -0.24, 0.70]). DISCUSSION: By investigating child, parental and teaching interventions and including outcomes such as weight control and disordered eating behaviors, a trend toward a reduction in eating disorder risk factors was observed, particularly body image-related outomes in girls. Future directions include embedded disordered eating prevention materials within existing lifestyle interventions and inclusion of more diverse samples.

OBJETIVO: Las preocupaciones sobre la imagen corporal y los comportamientos de control de peso extremo se desarrollan con frecuencia en la infancia, lo que indica un grupo de edad importante para la implementación de enfoques de prevención universal-selectiva. Esta revisión sistemática tuvo como objetivo evaluar el efecto de las intervenciones de prevención universal-selectivas que abordan la alimentación disfuncional, los problemas de imagen corporal y/o los comportamientos extremos de control de peso en niños de 6 a 12 años de edad. MÉTODO: Se realizaron búsquedas en nueve bases de datos hasta abril 2021. Se incluyeron estudios que habían incluido una intervención de prevención universal-selectiva en niños de 6 a 12 años de edad e informaron resultados relacionados con la imagen corporal, la alimentación disfuncional o los comportamientos de control de peso. El examen se llevó a cabo de conformidad con los lineamientos PRISMA. RESULTADOS: Un total de 42 artículos que describieron 39 estudios incluidos en la revisión, con la mayoría (n = 24; 57%) de calidad neutra. Treinta estudios implementaron un programa selectivo universal específico de trastornos de la conducta alimentaria y nueve implementaron intervenciones de estilo de vida más contenido para abordar la alimentación disfuncional. El metanálisis (n = 16 estudios) reveló una mejoría en los resultados relacionados con la imagen corporal en todos los estudios (DME 0,26 [IC95%: 0,00 a 0,53]); con un alto nivel de heterogeneidad (Î2 = 91,1%; p < 0,01). El metanálisis según el sexo reveló una mejora general en los resultados relacionados con la imagen corporal para las niñas (DME 0,40 [IC95%: 0,07 a 0,73]), pero no para los niños (DME 0,23 [IC95%: −0,24 a 0,70]). DISCUSIÓN: Al investigar las intervenciones tanto de los padres como de la enseñanza e incluir resultados como el control de peso y las conductas alimentarias de riesgo, se observó una tendencia hacia una reducción de los factores de riesgo de los trastornos de la conducta alimentaria. En concreto, mejoras en las variables relacionadas con la imagen corporal, especialmente en las niñas. Las direcciones futuras incluyen materiales de prevención de la alimentación disfuncional incorporados dentro de las intervenciones de estilo de vida existentes y la inclusión de muestras más diversas. PALABRAS CLAVE: Niños, trastornos de la conducta alimentaria y de la alimentación, alimentación disfuncional, prevención, imagen corporal, revisión sistemática, metanálisis.

Optimum maternal healthcare service utilization and infant mortality in Ethiopia.

BACKGROUND: Ethiopia has one of the highest rates of infant mortality in the world. Utilization of maternal healthcare during pregnancy, at delivery, and after delivery is critical to reducing the risk of infant mortality. Studies in Ethiopia have shown how infant survival is affected by utilization of maternal healthcare services, however, no studies to date have investigated the relationship between optimum utilization of maternal healthcare services utilization and infant mortality. Therefore, this study examined the effect of optimum utilization of maternal healthcare service on infant mortality in Ethiopia based on the World Health Organization (WHO, 2010) guidelines. METHODS: We used nationally representative cross-sectional data from the Ethiopian Demographic and Health Survey (EDHS). Sampling weights were applied to adjust for the non-proportional allocation of the sample to the nine regions and two city administrations as well as the sample difference across urban and rural areas. A total of 7193 most recent births from mothers who had provided complete information on infant mortality, ANC visits, tetanus injections, place of delivery and skilled birth attendance during pregnancy were included. The EDHS was conducted from January to June 2016. We applied a multivariate logistic regression analysis to estimate the relationship between optimum maternal healthcare service utilization and infant mortality in Ethiopia. RESULTS: The findings from this study showed that optimum maternal healthcare service utilization had a significant association with infant mortality after adjusting for other socioeconomic characteristics. This implies that increased maternal healthcare service utilization decreases the rate of infant mortality in Ethiopia. The main finding from this study indicated that infant mortality was reduced by approximately 66% among mothers who had high utilization of maternal healthcare services compared to mothers who had not utilized maternal healthcare services (AOR = 0.34; 95%CI: 0.16-0.75; p-value = 0.007). Furthermore, infant mortality was reduced by approximately 46% among mothers who had low utilization of maternal healthcare services compared to mothers who had not utilized any maternal healthcare services (AOR = 0.54; 95%CI: 0.31-0.97; p-value = 0.040). CONCLUSIONS: From this study, we concluded that optimum utilization of maternal healthcare services during pregnancy, at delivery and after delivery might reduce the rate of infant mortality in Ethiopia.

Human Biomarker Exposure From Cigarettes Versus Novel Heat-Not-Burn Devices: A Systematic Review and Meta-Analysis.

INTRODUCTION: Novel tobacco products require independent research to assess their safety. This study assessed the current literature for trials comparing levels of biomarkers of exposure (BoE) between conventional cigarettes (CC) and heat-not-burn (HNB) devices. METHODS: Ten databases were searched using terms including: "heat not burn," "iqos," "teeps," "mrtp," "tobacco heating," and "glo" between January 1, 2010 and August 13, 2019. Randomized controlled trials (RCTs) assessing comparative BoE levels in humans using either CC or novel HNB devices were eligible. BoE were tabulated, and differences between the intervention and control groups were analyzed and combined using a random-effects meta-analysis. RESULTS: Ten nonblinded, RCTs were eligible, involving a total of 1766 participants. Studies regularly reported on 12 BoE (including nicotine). HNB devices assessed included the "IQOS" and "glo" devices and "precursor" (being developed) HNB devices. In comparison to CC, all 12 BoEs assessed were significantly lower for participants assigned to an HNB device. In comparison to smoking abstinence, HNB devices were statistically equivalent for eight BoEs and significantly elevated for four BoEs. CONCLUSIONS: This review found that the potential for harm to humans is reduced when using HNB devices compared to CC as indicated by significant reductions in BoE levels. Whilst these results support tobacco manufacturer claims of improved safety, the small number of studies included, limited range of BoE assessed, and involvement of the tobacco industry necessitate further independent research to confirm the HNB devices as being a safer alternative to CC. IMPLICATIONS: This study supports claims made by tobacco manufacturers on the improved safety of HNB tobacco devices in comparison to CC. These novel devices lead to reduced exposure to key biomarkers, which are linked to the health consequences attributed to tobacco use. This has strong implications for international public health as well as further research and policy development relating to the safety aspects and legalities of novel tobacco products.

Plant-pollinator network structural properties differentially affect pollen transfer dynamics and pollination success.

Plant-pollinator network studies have uncovered important generalities in the structure of these communities, rapidly advancing our understanding of the underlying drivers of such a structure. In spite of this, however, it is still unclear how changes in structural network properties influence overall plant pollination success. One key limitation is the lack of information on the relationship between network structural properties and aspects of pollination and plant reproductive success. Here, we estimate four plant species network structural metrics (interaction strength, weighted degree, closeness centrality, and specialization level), commonly used to describe their importance within plant-pollinator networks, at two different sites, and evaluate their effects on pollen deposition and pollen tube success. We found a positive effect of plant-pollinator specialization and a negative effect of closeness centrality on heterospecific pollen load size. We also found a marginal negative effect of closeness centrality on pollen tube success. Our results suggest that increasing plant-pollinator specialization within nested communities (pollinated by one or very few generalist insect species) may result in high levels of heterospecific pollen transfer. Furthermore, the differential effects of plant-pollinator network metrics on pollination success (pollen receipt and pollen tube success), highlight the need to integrate quantity (e.g. visitation rate) and quality (e.g. pollen delivery) aspects of pollination to achieve a more mechanistic understanding of the relationship between plant-pollinator network structure and function. Such knowledge is key to evaluate the resilience and stability of plant-pollinator communities and the services they provide in the face of increasing human disturbances.

PyLCP: A Python package for computing laser cooling physics.

We present a Python object-oriented computer program for simulating various aspects of laser cooling physics. Our software is designed to be both easy to use and adaptable, allowing the user to specify the level structure, magnetic field profile, or the laser beams' geometry, detuning, and intensity. The program contains three levels of approximation for the motion of the atom, applicable in different regimes offering cross checks for calculations and computational efficiency depending on the physical situation. We test the software by reproducing well-known phenomena, such as damped Rabi flopping, electromagnetically induced transparency, stimulated Raman adiabatic passage, and optical molasses. We also use our software package to quantitatively simulate recoil-limited magneto-optical traps, like those formed on the narrow 1S0 → 3P1 transition in 88Sr and 87Sr.

A stepped wedge cluster randomised trial of a cognitive remediation intervention in alcohol and other drug (AOD) residential treatment services.

BACKGROUND: Executive functioning impairment is common in substance use disorder and is a major risk factor for poor treatment outcomes, including treatment drop-out and relapse. Cognitive remediation interventions seek to improve executive functioning and offer a promising approach to increase the efficacy of alcohol and other drug (AOD) treatments and improve long-term therapeutic outcomes. This protocol describes a study funded by the NSW Agency for Clinical Innovation that assesses the effectiveness of delivering a six-week group-based intervention of cognitive remediation in an ecologically valid sample of people attending residential AOD treatment services. We primarily aim to investigate whether cognitive remediation will be effective in improving executive functioning and treatment retention rates. We will also evaluate if cognitive remediation may reduce long-term AOD use and rates of health service utilisation, as well as improve personal goal attainment, quality of life, and client satisfaction with treatment. In addition, the study will involve an economic analysis of the cost of delivering cognitive remediation. METHODS/DESIGN: The study uses a stepped wedge cluster randomised design, where randomisation will occur at the cluster level. Participants will be recruited from ten residential AOD treatment services provided by the non-government sector. The intervention will be delivered in 12 one-hour group-based sessions over a period of six weeks. All participants who are expected to receive treatment for the duration of the six-week intervention will be asked to participate in the study. The clusters of participants who are randomly assigned to the treatment condition will complete cognitive remediation in addition to treatment as usual (TAU). Primary and secondary outcome assessments will be conducted at pre-cognitive remediation/TAU phase, post-cognitive remediation/TAU phase, two-month follow-up, four-month follow-up, six-month follow-up, and eight-month follow-up intervals. DISCUSSION: This study will provide comprehensive data on the effect of delivering a cognitive remediation intervention within residential AOD treatment services. If shown to be effective, cognitive remediation may be incorporated as an adjunctive intervention in current treatment programs. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register (ANZCTR): ACTRN12618001190291 . Prospectively registered 17th July 2018.

Increasing the capacity of policy agencies to use research findings: a stepped-wedge trial.

BACKGROUND: This paper describes the trial of a novel intervention, Supporting Policy In health with evidence from Research: an Intervention Trial (SPIRIT). It examines (1) the feasibility of delivering this kind of programme in practice; (2) its acceptability to participants; (3) the impact of the programme on the capacity of policy agencies to engage with research; and (4) the engagement with and use of research by policy agencies. METHODS: SPIRIT was a multifaceted, highly tailored, stepped-wedge, cluster-randomised, trial involving six health policy agencies in Sydney, Australia. Agencies were randomly allocated to one of three start dates to receive the 1-year intervention programme. SPIRIT included audit, feedback and goal setting; a leadership programme; staff training; the opportunity to test systems to facilitate research use in policies; and exchange with researchers. Outcome measures were collected at each agency every 6 months for 30 months. RESULTS: Participation in SPIRIT was associated with significant increases in research use capacity at staff and agency levels. Staff reported increased confidence in research use skills, and agency leaders reported more extensive systems and structures in place to support research use. Self-report data suggested there was also an increase in tactical research use among agency staff. Given the relatively small numbers of participating agencies and the complexity of their contexts, findings suggest it is possible to effect change in the way policy agencies approach the use of research. This is supported by the responses on the other trial measures; while these were not statistically significant, on 18 of the 20 different measures used, the changes observed were consistent with the hypothesised intervention effect (that is, positive impacts). CONCLUSIONS: As an early test of an innovative approach, SPIRIT has demonstrated that it is possible to increase research engagement and use in policy agencies. While more work is needed to establish the replicability and generalisability of these findings, this trial suggests that building staff skills and organisational structures may be effective in increasing evidence use.

Managing Asthma in Pregnancy (MAP) trial: FENO levels and childhood asthma.

BACKGROUND: The single-center double-blind, randomized controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FENO) in combination with asthma symptoms (FENO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (Australian New Zealand Clinical Trials Registry, no. 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FENO group. However, the effect of FENO-guided management on the development of asthma in the offspring is unknown. OBJECTIVE: We sought to investigate the effect of FENO-guided asthma management during pregnancy on asthma incidence in childhood. METHODS: A total of 179 mothers consented to participate in the Growing into Asthma (GIA) double-blind follow-up study with the primary aim to determine the effect of FENO-guided asthma management on childhood asthma incidence. RESULTS: A total of 140 children (78%) were followed up at 4 to 6 years of age. FENO-guided as compared to symptoms-only approach significantly reduced doctor-diagnosed asthma (25.9% vs 43.2%; odds ratio [OR], 0.46, 95% CI, 0.22-0.96; P = .04). Furthermore, frequent wheeze (OR, 0.27; 95% CI, 0.09-0.87; P = .03), use of short-acting ß-agonists (OR, 0.49; 95% CI, 0.25-0.97; P = .04), and emergency department visits for asthma (OR, 0.17; 95% CI, 0.04-0.76; P = .02) in the past 12 months were less common in children born to mothers from the FENO group. Doctor-diagnosed asthma was associated with common risk alleles for early onset asthma at gene locus 17q21 (P = .01 for rs8069176; P = .03 for rs8076131), and higher airways resistance (P = .02) and FENO levels (P = .03). A causal mediation analysis suggested natural indirect effects of FENO-guided asthma management on childhood asthma through "any use" and "time to first change in dose" of inhaled corticosteroids during the MAP trial (OR: 0.83; 95% CI: 0.59-0.99, and OR: 0.90; 95% CI: 0.70-1.03, respectively). CONCLUSIONS: FENO-guided asthma management during pregnancy prevented doctor-diagnosed asthma in the offspring at preschool age, in part mediated through changes in use and dosing of inhaled corticosteroids during the MAP trial.

Xenolog classification.

Motivation: Orthology analysis is a fundamental tool in comparative genomics. Sophisticated methods have been developed to distinguish between orthologs and paralogs and to classify paralogs into subtypes depending on the duplication mechanism and timing, relative to speciation. However, no comparable framework exists for xenologs: gene pairs whose history, since their divergence, includes a horizontal transfer. Further, the diversity of gene pairs that meet this broad definition calls for classification of xenologs with similar properties into subtypes. Results: We present a xenolog classification that uses phylogenetic reconciliation to assign each pair of genes to a class based on the event responsible for their divergence and the historical association between genes and species. Our classes distinguish between genes related through transfer alone and genes related through duplication and transfer. Further, they separate closely-related genes in distantly-related species from distantly-related genes in closely-related species. We present formal rules that assign gene pairs to specific xenolog classes, given a reconciled gene tree with an arbitrary number of duplications and transfers. These xenology classification rules have been implemented in software and tested on a collection of ∼13 000 prokaryotic gene families. In addition, we present a case study demonstrating the connection between xenolog classification and gene function prediction. Availability and Implementation: The xenolog classification rules have been implemented in N otung 2.9, a freely available phylogenetic reconciliation software package. http://www.cs.cmu.edu/~durand/Notung . Gene trees are available at http://dx.doi.org/10.7488/ds/1503 . Contact: durand@cmu.edu. Supplementary information: Supplementary data are available at Bioinformatics online.