Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine

Development of ultra-pure NaI(Tl) detectors for the COSINE-200 experiment

The annual modulation signal observed by the DAMA experiment is a long-standing question in the community of dark matter direct detection. This necessitates an independent verification of its existence using the same detection technique. The COSINE-100 experiment has been operating with 106~kg of low-background NaI(Tl) detectors providing interesting checks on the DAMA signal. However, due to higher backgrounds in the NaI(Tl) crystals used in COSINE-100 relative to those used for DAMA, it was difficult to reach final conclusions. Since the start of COSINE-100 data taking in 2016, we also have initiated a program to develop ultra-pure NaI(Tl) crystals for COSINE-200, the next phase of the experiment. The program includes efforts of raw powder purification, ultra-pure NaI(Tl) crystal growth, and detector assembly techniques. After extensive research and development of NaI(Tl) crystal growth, we have successfully grown a few small-size (0.61$-$0.78 kg) thallium-doped crystals with high radio-purity. A high light yield has been achieved by improvements of our detector assembly technique. Here we report the ultra-pure NaI(Tl) detector developments at the Institute for Basic Science, Korea. The technique developed here will be applied to the production of NaI(Tl) detectors for the COSINE-200 experiment.Comment: 12 pages, 12 figure

Conservation and Diversity of Seed Associated Endophytes in Zea across Boundaries of Evolution, Ethnography and Ecology

Endophytes are non-pathogenic microbes living inside plants. We asked whether endophytic species were conserved in the agriculturally important plant genus Zea as it became domesticated from its wild ancestors (teosinte) to modern maize (corn) and moved from Mexico to Canada. Kernels from populations of four different teosintes and 10 different maize varieties were screened for endophytic bacteria by culturing, cloning and DNA fingerprinting using terminal restriction fragment length polymorphism (TRFLP) of 16S rDNA. Principle component analysis of TRFLP data showed that seed endophyte community composition varied in relation to plant host phylogeny. However, there was a core microbiota of endophytes that was conserved in Zea seeds across boundaries of evolution, ethnography and ecology. The majority of seed endophytes in the wild ancestor persist today in domesticated maize, though ancient selection against the hard fruitcase surrounding seeds may have altered the abundance of endophytes. Four TRFLP signals including two predicted to represent Clostridium and Paenibacillus species were conserved across all Zea genotypes, while culturing showed that Enterobacter, Methylobacteria, Pantoea and Pseudomonas species were widespread, with γ-proteobacteria being the prevalent class. Twenty-six different genera were cultured, and these were evaluated for their ability to stimulate plant growth, grow on nitrogen-free media, solubilize phosphate, sequester iron, secrete RNAse, antagonize pathogens, catabolize the precursor of ethylene, produce auxin and acetoin/butanediol. Of these traits, phosphate solubilization and production of acetoin/butanediol were the most commonly observed. An isolate from the giant Mexican landrace Mixteco, with 100% identity to Burkholderia phytofirmans, significantly promoted shoot potato biomass. GFP tagging and maize stem injection confirmed that several seed endophytes could spread systemically through the plant. One seed isolate, Enterobacter asburiae, was able to exit the root and colonize the rhizosphere. Conservation and diversity in Zea-microbe relationships are discussed in the context of ecology, crop domestication, selection and migration

A systematic review of frameworks for the interrelationships of mental health evidence and policy in low- and middle-income countries

Background: The interrelationships between research evidence and policy-making are complex. Different theoretical frameworks exist to explain general evidence–policy interactions. One largely unexplored element of these interrelationships is how evidence interrelates with, and influences, policy/political agenda-setting. This review aims to identify the elements and processes of theories, frameworks and models on interrelationships of research evidence and health policy-making, with a focus on actionability and agenda-setting in the context of mental health in low- and middle-income countries (LMICs). Methods: A systematic review of theories was conducted based on the BeHeMOTh search method, using a tested and refined search strategy. Nine electronic databases and other relevant sources were searched for peer-reviewed and grey literature. Two reviewers screened the abstracts, reviewed full-text articles, extracted data and performed quality assessments. Analysis was based on a thematic analysis. The included papers had to present an actionable theoretical framework/model on evidence and policy interrelationships, such as knowledge translation or evidence-based policy, specifically target the agenda-setting process, focus on mental health, be from LMICs and published in English. Results: From 236 publications included in the full text analysis, no studies fully complied with our inclusion criteria. Widening the focus by leaving out ‘agenda-setting’, we included ten studies, four of which had unique conceptual frameworks focusing on mental health and LMICs but not agenda-setting. The four analysed frameworks confirmed research gaps from LMICs and mental health, and a lack of focus on agenda-setting. Frameworks and models from other health and policy areas provide interesting conceptual approaches and lessons with regards to agenda-setting. Conclusion: Our systematic review identified frameworks on evidence and policy interrelations that differ in their elements and processes. No framework fulfilled all inclusion criteria. Four actionable frameworks are applicable to mental health and LMICs, but none specifically target agenda-setting. We have identified agenda-setting as a research theory gap in the context of mental health knowledge translation in LMICs. Frameworks from other health/policy areas could offer lessons on agenda-setting and new approaches for creating policy impact for mental health and to tackle the translational gap in LMICs

Meta-Analyses of the Effects of Habitual Running on Indices of Health in Physically Inactive Adults

BACKGROUND: In order to implement running to promote physical activity, it is essential to quantify the extent to which running improves health. OBJECTIVE: The aim was to summarise the literature on the effects of endurance running on biomedical indices of health in physically inactive adults. DATA SOURCES: Electronic searches were conducted in October 2014 on PubMed, Embase, CINAHL, SPORTDiscus, PEDro, the Cochrane Library and LILACS, with no limits of date and language of publication. STUDY SELECTION: Randomised controlled trials (with a minimum of 8 weeks of running training) that included physically inactive but healthy adults (18–65 years) were selected. The studies needed to compare intervention (i.e. endurance running) and control (i.e. no intervention) groups. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors evaluated study eligibility, extracted data, and assessed risk of bias; a third author resolved any uncertainties. Random-effects meta-analyses were performed to summarise the estimates for length of training and sex. A dose-response analysis was performed with random-effects meta-regression in order to investigate the relationship between running characteristics and effect sizes. RESULTS: After screening 22,380 records, 49 articles were included, of which 35 were used to combine data on ten biomedical indices of health. On average the running programs were composed of 3.7 ± 0.9 sessions/week, 2.3 ± 1.0 h/week, 14.4 ± 5.4 km/week, at 60–90 % of the maximum heart rate, and lasted 21.5 ± 16.8 weeks. After 1 year of training, running was effective in reducing body mass by 3.3 kg [95 % confidence interval (CI) 4.1–2.5], body fat by 2.7 % (95 % CI 5.1–0.2), resting heart rate by 6.7 min(−1) (95 % CI 10.3–3.0) and triglycerides by 16.9 mg dl(−1) (95 % CI 28.1–5.6). Also, running significantly increased maximal oxygen uptake (VO(2max)) by 7.1 ml min(−1) kg(−1) (95 % CI 5.0–9.1) and high-density lipoprotein (HDL) cholesterol by 3.3 mg dl(−1) (95 % CI 1.2–5.4). No significant effect was found for lean body mass, body mass index, total cholesterol and low-density lipoprotein cholesterol after 1 year of training. In the dose-response analysis, larger effect sizes were found for longer length of training. LIMITATIONS: It was only possible to combine the data of ten out the 161 outcome measures identified. Lack of information on training characteristics precluded a multivariate model in the dose-response analysis. CONCLUSIONS: Endurance running was effective in providing substantial beneficial effects on body mass, body fat, resting heart rate, VO(2max), triglycerides and HDL cholesterol in physically inactive adults. The longer the length of training, the larger the achieved health benefits. Clinicians and health authorities can use this information to advise individuals to run, and to support policies towards investing in running programs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40279-015-0359-y) contains supplementary material, which is available to authorized users

From Mendel’s discovery on pea to today’s plant genetics and breeding

In 2015, we celebrated the 150th anniversary of the presentation of the seminal work of Gregor Johann Mendel. While Darwin’s theory of evolution was based on differential survival and differential reproductive success, Mendel’s theory of heredity relies on equality and stability throughout all stages of the life cycle. Darwin’s concepts were continuous variation and “soft” heredity; Mendel espoused discontinuous variation and “hard” heredity. Thus, the combination of Mendelian genetics with Darwin’s theory of natural selection was the process that resulted in the modern synthesis of evolutionary biology. Although biology, genetics, and genomics have been revolutionized in recent years, modern genetics will forever rely on simple principles founded on pea breeding using seven single gene characters. Purposeful use of mutants to study gene function is one of the essential tools of modern genetics. Today, over 100 plant species genomes have been sequenced. Mapping populations and their use in segregation of molecular markers and marker–trait association to map and isolate genes, were developed on the basis of Mendel's work. Genome-wide or genomic selection is a recent approach for the development of improved breeding lines. The analysis of complex traits has been enhanced by high-throughput phenotyping and developments in statistical and modeling methods for the analysis of phenotypic data. Introgression of novel alleles from landraces and wild relatives widens genetic diversity and improves traits; transgenic methodologies allow for the introduction of novel genes from diverse sources, and gene editing approaches offer possibilities to manipulate gene in a precise manner

LOW-COST TELEMETRY USING FREQUENCY HOPPING AND THE TRF6900™ TRANSCEIVER1

International Telemetering Conference Proceedings / October 21, 2002 / Town & Country Hotel and Conference Center, San Diego, CaliforniaThe ISM bands have opened up new opportunities for telemetry using spread-spectrum communications. A low-cost frequency-hopping radio is described here for the 900 MHz ISM band that can be programmed with a wide range of hop and data rates. The ‘C6201 DSP from TI is used to control the frequency and data rate of the TI TRF6900 transceiver chip using a custom interface of the 6201 EVM board to the serial I/O on the 6900 evaluation board.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

Cine-MRI assessment of cardiac function in mice anesthetized with ketamine/xylazine and isoflurane

Since small-animal MRI generally requires anesthesia, the effect of the anesthetic regimen on the explored organ(s) has to be taken into account for study interpretation. In this work, we assess the influence of ketamine/xylazine and isoflurane anesthesia on left-ventricular (LV) function in the mouse in vivo by cine-MRI. Three groups of animals were anesthetized with ketamine/xylazine (n = 13) and two different concentrations of isoflurane (1.25%, n = 12 and 2.00%, n = 12) delivered in O2/N2O mix. Long- and short-axis cine-MRI was performed to measure end-diastolic volume, stroke volume, ejection fraction and LV wall thickness. Ketamine/xylazine significantly reduced heart rate, cardiac output and wall thickness, but increased stroke volume and end-diastolic volume compared with both isoflurane groups. No differences across all groups were observed in ejection fraction or systolic wall thickening. Breath rate under isoflurane was significantly lower and concentration dependent, whereas heart function was independent of concentration in all measured parameters. These findings are in agreement with echocardiography and catheterization studies. Isoflurane is advantageous for MR studies because it better maintains cardiac function. Taking into account previously obtained myocardial perfusion measurements, isoflurane concentration should, however, be maintained at the minimum required for a stable sleep even if cardiac function is unaffected by higher isoflurane concentrations