Objective measurement of sedentary behaviour using accelerometers

Background: Sedentary behaviour (SB) is an important risk factor for a number of chronic diseases. Although gaps remain in our knowledge of the elements of SB most associated with reduced health outcomes, measuring SB is important, especially in less active patient populations where treatment-related changes may be seen first in changes in SB.Methods: We review current published work in the measurement of SB to make recommendations for SB measurement in clinical studies.Results: To help move our understanding of the area forward, we propose a set of derived measures of SB that can be easily understood and interpreted.Conclusion: Although there is more work required to determine and validate the most clinically relevant and sensitive measures of SB, there is enough understanding of how to measure SB to enable its inclusion in study protocols

Analysis of Variance in Neuroreceptor Ligand Imaging Studies

Radioligand positron emission tomography (PET) with dual scan paradigms can provide valuable insight into changes in synaptic neurotransmitter concentration due to experimental manipulation. The residual t-test has been utilized to improve the sensitivity of the t-test in PET studies. However, no further development of statistical tests using residuals has been proposed so far to be applied in cases when there are more than two conditions. Here, we propose the residual f-test, a one-way analysis of variance (ANOVA), and examine its feasibility using simulated [11C]raclopride PET data. We also re-visit data from our previously published [11C]raclopride PET study, in which 10 individuals underwent three PET scans under different conditions. We found that the residual f-test is superior in terms of sensitivity than the conventional f-test while still controlling for type 1 error. The test will therefore allow us to reliably test hypotheses in the smaller sample sizes often used in explorative PET studies

Pre-Whaling Genetic Diversity and Population Ecology in Eastern Pacific Gray Whales: Insights from Ancient DNA and Stable Isotopes

Commercial whaling decimated many whale populations, including the eastern Pacific gray whale, but little is known about how population dynamics or ecology differed prior to these removals. Of particular interest is the possibility of a large population decline prior to whaling, as such a decline could explain the ∼5-fold difference between genetic estimates of prior abundance and estimates based on historical records. We analyzed genetic (mitochondrial control region) and isotopic information from modern and prehistoric gray whales using serial coalescent simulations and Bayesian skyline analyses to test for a pre-whaling decline and to examine prehistoric genetic diversity, population dynamics and ecology. Simulations demonstrate that significant genetic differences observed between ancient and modern samples could be caused by a large, recent population bottleneck, roughly concurrent with commercial whaling. Stable isotopes show minimal differences between modern and ancient gray whale foraging ecology. Using rejection-based Approximate Bayesian Computation, we estimate the size of the population bottleneck at its minimum abundance and the pre-bottleneck abundance. Our results agree with previous genetic studies suggesting the historical size of the eastern gray whale population was roughly three to five times its current size

Acceptability of a theory-based sedentary behaviour reduction intervention for older adults ('On Your Feet to Earn Your Seat').

Background: Adults aged 60 years and over spend most time sedentary and are the least physically active of all age groups. This early-phase study explored acceptability of a theory-based intervention to reduce sitting time and increase activity in older adults, as part of the intervention development process. Methods: An 8-week uncontrolled trial was run among two independent samples of UK adults aged 60–75 years. Sample 1, recruited from sheltered housing on the assumption that they were sedentary and insufficiently active, participated between December 2013 and March 2014. Sample 2, recruited through community and faith centres and a newsletter, on the basis of self-reported inactivity (<150 weekly minutes of moderate-to-vigorous activity) and sedentary behaviour (≥6 h mean daily sitting), participated between March and August 2014. Participants received a booklet offering 16 tips for displacing sitting with light-intensity activity and forming activity habits, and self-monitoring ‘tick-sheets’. At baseline, 4-week, and 8-week follow-ups, quantitative measures were taken of physical activity, sedentary behaviour, and habit. At 8 weeks, tick-sheets were collected and a semi-structured interview conducted. Acceptability was assessed for each sample separately, through attrition and adherence to tips, ANOVAs for behaviour and habit changes, and, for both samples combined, thematic analysis of interviews. Results: In Sample 1, 12 of 16 intervention recipients completed the study (25 % attrition), mean adherence was 40 % (per-tip range: 15–61 %), and there were no clear patterns of changes in sedentary or physical activity behaviour or habit. In Sample 2, 23 of 27 intervention recipients completed (15 % attrition), and mean adherence was 58 % (per-tip range: 39–82 %). Sample 2 decreased mean sitting time and sitting habit, and increased walking, moderate activity, and activity habit. Qualitative data indicated that both samples viewed the intervention positively, found the tips easy to follow, and reported health and wellbeing gains. Conclusions: Low attrition, moderate adherence, and favourability in both samples, and positive changes in Sample 2, indicate the intervention was acceptable. Higher attrition, lower adherence, and no apparent behavioural impact among Sample 1 could perhaps be attributable to seasonal influences. The intervention has been refined to address emergent acceptability problems. An exploratory controlled trial is underway

Microdissection of Shoot Meristem Functional Domains

The shoot apical meristem (SAM) maintains a pool of indeterminate cells within the SAM proper, while lateral organs are initiated from the SAM periphery. Laser microdissection–microarray technology was used to compare transcriptional profiles within these SAM domains to identify novel maize genes that function during leaf development. Nine hundred and sixty-two differentially expressed maize genes were detected; control genes known to be upregulated in the initiating leaf (P0/P1) or in the SAM proper verified the precision of the microdissections. Genes involved in cell division/growth, cell wall biosynthesis, chromatin remodeling, RNA binding, and translation are especially upregulated in initiating leaves, whereas genes functioning during protein fate and DNA repair are more abundant in the SAM proper. In situ hybridization analyses confirmed the expression patterns of six previously uncharacterized maize genes upregulated in the P0/P1. P0/P1-upregulated genes that were also shown to be downregulated in leaf-arrested shoots treated with an auxin transport inhibitor are especially implicated to function during early events in maize leaf initiation. Reverse genetic analyses of asceapen1 (asc1), a maize D4-cyclin gene upregulated in the P0/P1, revealed novel leaf phenotypes, less genetic redundancy, and expanded D4-CYCLIN function during maize shoot development as compared to Arabidopsis. These analyses generated a unique SAM domain-specific database that provides new insight into SAM function and a useful platform for reverse genetic analyses of shoot development in maize

The Dopamine Augmenter L-DOPA Does Not Affect Positive Mood in Healthy Human Volunteers

Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans

Dynamic Effective Connectivity of Inter-Areal Brain Circuits

Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity (or, more precisely, causal connectivity), related to the elusive question “Which areas cause the present activity of which others?”. Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study mesoscale network motifs of interacting cortical areas, modeled as large random networks of spiking neurons or as simple rate units. Through a causal analysis of time-series of model neural activity, we show that different dynamical states generated by a same structural connectivity motif correspond to distinct effective connectivity motifs. Such effective motifs can display a dominant directionality, due to spontaneous symmetry breaking and effective entrainment between local brain rhythms, although all connections in the considered structural motifs are reciprocal. We show then that transitions between effective connectivity configurations (like, for instance, reversal in the direction of inter-areal interactions) can be triggered reliably by brief perturbation inputs, properly timed with respect to an ongoing local oscillation, without the need for plastic synaptic changes. Finally, we analyze how the information encoded in spiking patterns of a local neuronal population is propagated across a fixed structural connectivity motif, demonstrating that changes in the active effective connectivity regulate both the efficiency and the directionality of information transfer. Previous studies stressed the role played by coherent oscillations in establishing efficient communication between distant areas. Going beyond these early proposals, we advance here that dynamic interactions between brain rhythms provide as well the basis for the self-organized control of this “communication-through-coherence”, making thus possible a fast “on-demand” reconfiguration of global information routing modalities

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce