Performance-based building and innovation: Balancing client and industry needs

One reason for the interest in performance-based building is that it is commonly advocated as a powerful way of enhancing innovation performance by articulating building performance outcomes, and by offering relevant procurement actors the discretion to innovate to meet these performance requirements more effectively and/or efficiently. The paper argues that the current approach to performance-based building assumes that relevant actors have the capacity, ability and motivation to innovate from a business perspective. It is proposed that the prevailing conceptualization of PBB is too restrictive and should be broadened explicitly to accommodate the required business logic that must be in place before actors will innovate. The relevant performance-based building and innovation literature is synthesized to support the assertion. The paper concludes with an innovation-focused definition of performance-based building

Differential expression analysis with global network adjustment

<p>Background: Large-scale chromosomal deletions or other non-specific perturbations of the transcriptome can alter the expression of hundreds or thousands of genes, and it is of biological interest to understand which genes are most profoundly affected. We present a method for predicting a gene’s expression as a function of other genes thereby accounting for the effect of transcriptional regulation that confounds the identification of genes differentially expressed relative to a regulatory network. The challenge in constructing such models is that the number of possible regulator transcripts within a global network is on the order of thousands, and the number of biological samples is typically on the order of 10. Nevertheless, there are large gene expression databases that can be used to construct networks that could be helpful in modeling transcriptional regulation in smaller experiments.</p> <p>Results: We demonstrate a type of penalized regression model that can be estimated from large gene expression databases, and then applied to smaller experiments. The ridge parameter is selected by minimizing the cross-validation error of the predictions in the independent out-sample. This tends to increase the model stability and leads to a much greater degree of parameter shrinkage, but the resulting biased estimation is mitigated by a second round of regression. Nevertheless, the proposed computationally efficient “over-shrinkage” method outperforms previously used LASSO-based techniques. In two independent datasets, we find that the median proportion of explained variability in expression is approximately 25%, and this results in a substantial increase in the signal-to-noise ratio allowing more powerful inferences on differential gene expression leading to biologically intuitive findings. We also show that a large proportion of gene dependencies are conditional on the biological state, which would be impossible with standard differential expression methods.</p> <p>Conclusions: By adjusting for the effects of the global network on individual genes, both the sensitivity and reliability of differential expression measures are greatly improved.</p&gt

Structure and function of a spectrin-like regulator of bacterial cytokinesis

© 2014 Macmillan Publishers Limited. All rights reserved. Bacterial cell division is facilitated by a molecular machine - the divisome - that assembles at mid-cell in dividing cells. The formation of the cytokinetic Z-ring by the tubulin homologue FtsZ is regulated by several factors, including the divisome component EzrA. Here we describe the structure of the 60-kDa cytoplasmic domain of EzrA, which comprises five linear repeats of an unusual triple helical bundle. The EzrA structure is bent into a semicircle, providing the protein with the potential to interact at both N- and C-termini with adjacent membrane-bound divisome components. We also identify at least two binding sites for FtsZ on EzrA and map regions of EzrA that are responsible for regulating FtsZ assembly. The individual repeats, and their linear organization, are homologous to the spectrin proteins that connect actin filaments to the membrane in eukaryotes, and we thus propose that EzrA is the founding member of the bacterial spectrin family

Tooth wear: the view of the anthropologist

Anthropologists have for many years considered human tooth wear a normal physiological phenomenon where teeth, although worn, remain functional throughout life. Wear was considered pathological only if pulpal exposure or premature tooth loss occurred. In addition, adaptive changes to the stomatognathic system in response to wear have been reported including continual eruption, the widening of the masticatory cycle, remodelling of the temporomandibular joint and the shortening of the dental arches from tooth migration. Comparative studies of many different species have also documented these physiological processes supporting the idea of perpetual change over time. In particular, differential wear between enamel and dentine was considered a physiological process relating to the evolution of the form and function of teeth. Although evidence of attrition and abrasion has been known to exist among hunter-gatherer populations for many thousands of years, the prevalence of erosion in such early populations seems insignificant. In particular, non-carious cervical lesions to date have not been observed within these populations and therefore should be viewed as ‘modern-day’ pathology. Extrapolating this anthropological perspective to the clinical setting has merits, particularly in the prevention of pre-mature unnecessary treatment

Study design of 'FRIENDS for Life': process and effect evaluation of an indicated school-based prevention programme for childhood anxiety and depression

Background: Anxiety disorders and depression are highly prevalent in children and affect their current and future functioning. 'FRIENDS for Life' is a cognitive-behavioural programme teaching children skills to cope more effectively with feelings of anxiety and depression. Although 'FRIENDS for Life' is increasingly being implemented at Dutch schools, its effectiveness as a preventive intervention in Dutch schools has never been investigated. The aim of the study is to evaluate the effectiveness of 'FRIENDS for Life' as an indicated school-based prevention programme for children with early or mild signs of anxiety or depression. Methods/Design. This study is a controlled trial with one pre-intervention and three post-intervention measurements (directly after, and 6 and 12 months after the end of the programme). The study sample consists of children aged 10-12 years (grades 6, 7 and 8 of Dutch primary schools), who show symptoms of anxiety or depressive disorder. Data are collected through self-report, teacher report and peer nomination. A process evaluation is conducted to investigate programme integrity (whether the programme has been executed according to protocol) and to evaluate children's and parents' opinions about 'FRIENDS for Life' using online focus groups and interviews. Discussion. The present study will provide insight into the effectiveness of 'FRIENDS for Life' as an indicated school-based prevention programme for children with early or mild signs of anxiety or depression

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS

Cost-effectiveness of financial incentives to promote adherence to depot antipsychotic medication: economic evaluation of a cluster-randomised controlled trial

Background: Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Methods: Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Findings: Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving 'good' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5%at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence. Interpretation: Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention. Trial Registration: ISRCTN.com 7776928

Disturbance and stress - different meanings in ecological dynamics?

There is an increasing frequency of papers addressing disturbance and stress in ecology without clear delimitation of their meaning. Some authors use the terms disturbance and stress exclusively as impacts, while others use them for the entire process, including both causes and effects. In some studies, the disturbance is considered as a result of a temporary impact, which is positive for the ecosystem, while stress is a negative, debilitating impact. By developing and testing simple theoretical models, the authors propose to differentiate disturbance and stress by frequency. If the frequency of the event enables the variable to reach a dynamic equilibrium which might be exhibited without this event, then the event (plus its responses) is a disturbance for the system. If frequency prevents the variable’s return to similar pre-event dynamics and drives or shifts it to a new trajectory, then we are facing stress. The authors propose that changes triggered by the given stimuli can be evaluated on an absolute scale, therefore, direction of change of the variable must not be used to choose one term or the other, i.e. to choose between stress and disturbance

Predictors of Change Following Cognitive-Behavioral Treatment of Children with Anxiety Problems: A Preliminary Investigation on Negative Automatic Thoughts and Anxiety Control

The purpose of the present study was to evaluate negative automatic thoughts and anxiety control as predictors of change produced by cognitive-behavioral treatment of youths with anxiety disorders. Forty-five high-anxious children aged between 9 and 12 years who were selected from the primary school population, received a standardized CBT intervention that was provided in a group format. Before and after the intervention, children completed scales of negative automatic thoughts and perceived control over anxiety-related events as well as a questionnaire for measuring DSM-defined anxiety disorders symptoms, which was the outcome measure. Results indicated that CBT was effective in reducing children’s anxiety symptoms. Most importantly, the reduction of anxiety disorders symptoms was significantly associated with a decrease in negative automatic thoughts and an increase of anxiety control, which provides support for the notion that these variables are candidate mediators of CBT in anxious youths