The effects of spatial legacies following shifting management practices and fire on boreal forest age structure

Forest age structure and its spatial arrangement are important elements of sustainable forestry because of their effects on biodiversity and timber availability. Forest management objectives that include specific forest age structure may not be easily attained due to constraints imposed by the legacies of historical management and natural disturbance. We used a spatially explicit stochastic model to explore the synergetic effects of forest management and fire on boreal forest age structure. Specifically, we examined (1) the duration of spatial legacies of different management practices in the boreal forest, (2) how multiple shifts in management practices affect legacy duration and the spatial trajectories of forest age structure, and (3) how fire influences legacy duration and pattern development in combination with harvesting. Results based on 30 replicates of 500 years for each scenario indicate that (1) spatial legacies persist over 200 years and the rate at which legacies are overcome depends on whether new management targets are in synchrony with existing spatial pattern; (2) age specific goals were met faster after multiple management shifts due to the similar spatial scale of the preceding management types; (3) because large fires can erase the spatial pattern created by smaller disturbances, scenarios with fire had shorter lags than scenarios without fire. These results suggest that forest management goals can be accelerated by applying management at a similar spatial scale as existing spatial patterns. Also, management planning should include careful consideration of historical management as well as current and likely future disturbances

Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals

Developing self-regulation for dietary temptations: intervention effects on physical, self-regulatory and psychological outcomes

We aimed to investigate whether a self-regulatory skills intervention can improve weight loss-related outcomes. Fifty-five participants (M BMI = 32.60 ± 4.86) were randomized into self-regulation training and advice groups and received two training workshops and weekly practice tasks. The self-regulation training group was trained to use six self-regulatory skills: Delayed gratification, thought control, goal setting, self-monitoring, mindfulness, and coping. The advice group received dietary and physical activity advice for weight loss. Physical, self-regulatory, and psychological measures were taken at baseline, end of intervention (week 8) and at follow-up (week 12). Using intention-to-treat analysis, weight, waist circumference, body fat and body mass index (BMI) were significantly reduced at follow-up for both groups. There were significant increases in all six self-regulatory skills and the psychological measures of self-efficacy, self-regulatory success, and physical self-worth for both groups. Results indicate that self-regulatory skills training might be as effective as dietary and physical activity advice in terms of weight loss and related outcomes

Explorative visual analytics on interval-based genomic data and their metadata

Background: With the wide-spreading of public repositories of NGS processed data, the availability of user-friendly and effective tools for data exploration, analysis and visualization is becoming very relevant. These tools enable interactive analytics, an exploratory approach for the seamless "sense-making" of data through on-the-fly integration of analysis and visualization phases, suggested not only for evaluating processing results, but also for designing and adapting NGS data analysis pipelines. Results: This paper presents abstractions for supporting the early analysis of NGS processed data and their implementation in an associated tool, named GenoMetric Space Explorer (GeMSE). This tool serves the needs of the GenoMetric Query Language, an innovative cloud-based system for computing complex queries over heterogeneous processed data. It can also be used starting from any text files in standard BED, BroadPeak, NarrowPeak, GTF, or general tab-delimited format, containing numerical features of genomic regions; metadata can be provided as text files in tab-delimited attribute-value format. GeMSE allows interactive analytics, consisting of on-the-fly cycling among steps of data exploration, analysis and visualization that help biologists and bioinformaticians in making sense of heterogeneous genomic datasets. By means of an explorative interaction support, users can trace past activities and quickly recover their results, seamlessly going backward and forward in the analysis steps and comparative visualizations of heatmaps. Conclusions: GeMSE effective application and practical usefulness is demonstrated through significant use cases of biological interest. GeMSE is available at http://www.bioinformatics.deib.polimi.it/GeMSE/ , and its source code is available at https://github.com/Genometric/GeMSEunder GPLv3 open-source license

Sins of Omission

Little is known about the relative incidence of serious errors of omission versus errors of commission. Objective : To identify the most common substantive medical errors identified by medical record review. Design : Retrospective cohort study. Setting : Twelve Veterans Affairs health care systems in 2 regions. Participants : Stratified random sample of 621 patients receiving care over a 2-year period. Main Outcome Measure : Classification of reported quality problems. Methods : Trained physicians reviewed the full inpatient and outpatient record and described quality problems, which were then classified as errors of omission versus commission. Results : Eighty-two percent of patients had at least 1 error reported over a 13-month period. The average number of errors reported per case was 4.7 (95% confidence intervals [CI]: 4.4, 5.0). Overall, 95.7% (95% CI: 94.9%, 96.4%) of errors were identified as being problems with underuse. Inadequate care for people with chronic illnesses was particularly common. Among errors of omission, obtaining insufficient information from histories and physicals (25.3%), inadequacies in diagnostic testing (33.9%), and patients not receiving needed medications (20.7%) were all common. Out of the 2,917 errors identified, only 27 were rated as being highly serious, and 26 (96%) of these were errors of omission. Conclusions : While preventing iatrogenic injury resulting from medical errors is a critically important part of quality improvement, we found that the overwhelming majority of substantive medical errors identifiable from the medical record were related to people getting too little medical care, especially for those with chronic medical conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74567/1/j.1525-1497.2005.0152.x.pd

Too few staff, too many patients: A qualitative study of the impact on obstetric care providers and on quality of care in Malawi

Background: Shortages of staff have a significant and negative impact on maternal outcomes in low-income countries, but the impact on obstetric care providers in these contexts is less well documented. Despite the government of Malawi's efforts to increase the number of human resources for health, maternal mortality rates remain persistently high. Health workers' perceptions of insufficient staff or time to carry out their work can predict key variables concerning motivation and attrition, while the resulting sub-standard care and poor attitudes towards women dissuade women from facility-based delivery. Understanding the situation from the health worker perspective can inform policy options that may contribute to a better working environment for staff and improved quality of care for Malawi's women. Methods: A qualitative research design, using critical incident interviews, was used to generate a deep and textured understanding of participants' experiences. Eligible participants had performed at least one of the emergency obstetric care signal functions a in the previous three months and had experienced a demotivating critical incident within the same timeframe. Data were analysed using NVivo software. Results: Eighty-four interviews were conducted. Concerns about staff shortages and workload were key factors for over 40% of staff who stated their intention to leave their current post and for nearly two-thirds of the remaining health workers who were interviewed. The main themes emerging were: too few staff, too many patients; lack of clinical officers/doctors; inadequate obstetric skills; undermining performance and professionalism; and physical and psychological consequences for staff. Underlying factors were inflexible scheduling and staff allocations that made it impossible to deliver quality care. Conclusion: This study revealed the difficult circumstances under which maternity staff are operating and the professional and emotional toll this exacts. Systems failures and inadequate human resource management are key contributors to the gaps in provision of obstetric care and need to be addressed. Thoughtful strategies that match supply to demand, coupled with targeted efforts to support health workers, are necessary to mitigate the effects of working in this context and to improve the quality of obstetric care for women in Malawi

Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?

Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity. Yet, with regard to pharmacotherapy for obesity, we are far from true personalised medicine. We review the limited mechanistic data with four mono and combination pharmacotherapies, to assess the potential for tailoring their use to target specific obesogenic behaviours. Potential treatment options are considered, but in the absence of adequate research in respect to effects of these drugs on eating behaviour, neural activity and psychological substrates that underlie poorly controlled eating, we are far from definitive therapeutic recommendations. Specific mechanistic studies and broader behavioural phenotyping, possibly in conjunction with pharmacogenetic research, are required to characterise responders for distinct pharmacotherapeutic options

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding