Spine system equivalence: A new protocol for standardized multi-axis comparison tests

This is the final version of the paper.Accurately replicating the in-vivo loads of the spine is a critical aspect of in-vitro spine testing, but the complexity of this structure renders this challenging. The design and control capabilities of multi-axis spine systems vary considerably, and though recommendations have been made [1, 2], standardized in-vitro methods have not yet been established. As such, it is often difficult to compare different biomechanical studies [3]. The aim of this study was to use international standards [4, 5], and spine testing recommendations [1-3] to develop a standardized protocol for the evaluation of different multi-axis spinal test systems. The protocol was implemented on three six-axis spine systems, and the data used to establish stiffness and phase angle limits. [...]This research was supported by the Catherine Sharpe Foundation, the Enid Linder Foundation, the Higher Education Innovation Fund, and the University of Bath Alumni Fund

The equivalence of multi-axis spine systems: Recommended stiffness limits using a standardized testing protocol

Author's accepted manuscriptFinal version available from Elsevier via the DOI in this recordThe complexity of multi-axis spine testing often makes it challenging to compare results from different studies. The aim of this work was to develop and implement a standardized testing protocol across three six-axis spine systems, compare them, and provide stiffness and phase angle limits against which other test systems can be compared. Standardized synthetic lumbar specimens (n = 5), comprising three springs embedded in polymer at each end, were tested on each system using pure moments in flexion–extension, lateral bending, and axial rotation. Tests were performed using sine and triangle waves with an amplitude of 8 Nm, a frequency of 0.1 Hz, and with axial preloads of 0 and 500 N. The stiffness, phase angle, and R2 value of the moment against rotation in the principal axis were calculated at the center of each specimen. The tracking error was adopted as a measure of each test system to minimize non-principal loads, defined as the root mean squared difference between actual and target loads. All three test systems demonstrated similar stiffnesses, with small (<14%) but significant differences in 4 of 12 tests. More variability was observed in the phase angle between the principal axis moment and rotation, with significant differences in 10 of 12 tests. Stiffness and phase angle limits were calculated based on the 95% confidence intervals from all three systems. These recommendations can be used with the standard specimen and testing protocol by other research institutions to ensure equivalence of different spine systems, increasing the ability to compare in vitro spine studies.This research was completed with the support of the Catherine Sharpe Foundation, the Enid Linder Foundation, and the University of Bath Alumni Fun

Emergence of structural and dynamical properties of ecological mutualistic networks

Mutualistic networks are formed when the interactions between two classes of species are mutually beneficial. They are important examples of cooperation shaped by evolution. Mutualism between animals and plants plays a key role in the organization of ecological communities. Such networks in ecology have generically evolved a nested architecture independent of species composition and latitude - specialists interact with proper subsets of the nodes with whom generalists interact. Despite sustained efforts to explain observed network structure on the basis of community-level stability or persistence, such correlative studies have reached minimal consensus. Here we demonstrate that nested interaction networks could emerge as a consequence of an optimization principle aimed at maximizing the species abundance in mutualistic communities. Using analytical and numerical approaches, we show that because of the mutualistic interactions, an increase in abundance of a given species results in a corresponding increase in the total number of individuals in the community, as also the nestedness of the interaction matrix. Indeed, the species abundances and the nestedness of the interaction matrix are correlated by an amount that depends on the strength of the mutualistic interactions. Nestedness and the observed spontaneous emergence of generalist and specialist species occur for several dynamical implementations of the variational principle under stationary conditions. Optimized networks, while remaining stable, tend to be less resilient than their counterparts with randomly assigned interactions. In particular, we analytically show that the abundance of the rarest species is directly linked to the resilience of the community. Our work provides a unifying framework for studying the emergent structural and dynamical properties of ecological mutualistic networks.Comment: 10 pages, 4 figure

Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study

Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state

Early Warning Signals for Critical Transitions: A Generalized Modeling Approach

Critical transitions are sudden, often irreversible, changes that can occur in a large variety of complex systems; signals that warn of critical transitions are therefore highly desirable. We propose a new method for early warning signals that integrates multiple sources of information and data about the system through the framework of a generalized model. We demonstrate our proposed approach through several examples, including a previously published fisheries model. We regard our method as complementary to existing early warning signals, taking an approach of intermediate complexity between model-free approaches and fully parameterized simulations. One potential advantage of our approach is that, under appropriate conditions, it may reduce the amount of time series data required for a robust early warning signal

DYRK1A genetic variants are not linked to Alzheimer's disease in a Spanish case-control cohort

<p>Abstract</p> <p>Background</p> <p>As dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has been implicated in the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain, and the development of neurofibrillary tangles, we examined the contribution of this gene to the susceptibility for AD.</p> <p>Methods</p> <p>We examined genetic variations of DYRK1A by genotyping haplotype tagging SNPs (htSNPs) (rs11701483, rs2835740, rs1137600, rs2835761, rs2835762, rs2154545 and rs8132976) in a group of 634 Spanish AD cases and 733 controls.</p> <p>Results</p> <p>There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by APOE ε4 allele.</p> <p>Conclusion</p> <p>Our negative findings in the Spanish population argue against the hypothesis that DYRK1A genetic variations are causally related to AD risk. Still, additional studies using different sets of patients and control subjects deserve further attention, since supporting evidence for association between DYRK1A gene and AD risk in the Japanese population exists.</p

Worldwide diagnostic reference levels for single-photon emission computed tomography myocardial perfusion imaging: findings from INCAPS.

OBJECTIVES: This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). BACKGROUND: Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset. METHODS: Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data. RESULTS: The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m-labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions. CONCLUSIONS: This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs

Bootstrapping Q Methodology to Improve the Understanding of Human Perspectives.

Q is a semi-qualitative methodology to identify typologies of perspectives. It is appropriate to address questions concerning diverse viewpoints, plurality of discourses, or participation processes across disciplines. Perspectives are interpreted based on rankings of a set of statements. These rankings are analysed using multivariate data reduction techniques in order to find similarities between respondents. Discussing the analytical process and looking for progress in Q methodology is becoming increasingly relevant. While its use is growing in social, health and environmental studies, the analytical process has received little attention in the last decades and it has not benefited from recent statistical and computational advances. Specifically, the standard procedure provides overall and arguably simplistic variability measures for perspectives and none of these measures are associated to individual statements, on which the interpretation is based. This paper presents an innovative approach of bootstrapping Q to obtain additional and more detailed measures of variability, which helps researchers understand better their data and the perspectives therein. This approach provides measures of variability that are specific to each statement and perspective, and additional measures that indicate the degree of certainty with which each respondent relates to each perspective. This supplementary information may add or subtract strength to particular arguments used to describe the perspectives. We illustrate and show the usefulness of this approach with an empirical example. The paper provides full details for other researchers to implement the bootstrap in Q studies with any data collection design