Increased gravitational force reveals the mechanical, resonant nature of physiological tremor

Human physiological hand tremor has a resonant component. Proof of this is that its frequency can be modified by adding mass. However, adding mass also increases the load which must be supported. The necessary force requires muscular contraction which will change motor output and is likely to increase limb stiffness. The increased stiffness will partly offset the effect of the increased mass and this can lead to the erroneous conclusion that factors other than resonance are involved in determining tremor frequency. Using a human centrifuge to increase head-to-foot gravitational field strength, we were able to control for the increased effort by increasing force without changing mass. This revealed that the peak frequency of human hand tremor is 99% predictable on the basis of a resonant mechanism. We ask what, if anything, the peak frequency of physiological tremor can reveal about the operation of the nervous system.This work was funded by a BBSRC Industry Interchange Award to J.P.R.S. and R.F.R. C.J.O. was funded by BBSRC grant BB/I00579X/1. C.A.V. was funded by A∗Midex (Aix-Marseille Initiative of Excellence

Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review

Review Purpose: This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice. Findings: 34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. Summary: The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. Graphical Abstract: HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease

In vitro inhibition of Eimeria tenella invasion of epithelial cells by phytochemicals

Resistance to coccidiostats and possible future restrictions on their use raise the need for alternative methods of reducing coccidiosis in poultry. The aim of this study was to evaluate the effect of selected phytochemicals on Eimeria tenella sporozoite invasion in vitro. Four phytochemicals were selected on the basis that they reduce the virulence of Eimeria spp. and/or provide immune modulatory benefits to host cells: betaine, carvacrol, curcumin and Echinacea purpurea extract (EP). Madin–Darby bovine kidney (MDBK) cells were covered by medium containing phytochemicals at the highest concentration which was non-toxic to the cells. Salinomycin 50 μg/ml was positive control; negative control was medium only. E. tenella (Houghton strain) sporozoites were added to wells and after incubation for 2, 4 or 20 h at 37 °C, cells were fixed and stained with hematoxylin–eosin. Ten evenly spaced fields per well were photographed and the percentage of cells invaded by sporozoites was calculated and normalized to the control. At 2 h, carvacrol, curcumin and EP showed a significantly lower percentage of sporozoite invasion than the untreated control; in contrast, betaine treatment represented a significantly higher invasion percentage. Combining carvacrol with EP inhibited E. tenella invasion more effectively than applying the compounds individually, but the further addition of curcumin did not reduce invasion further. In conclusion, this study shows that invasion of MDBK epithelial cells by E. tenella sporozoites is inhibited in the presence of carvacrol, curcumin, or EP and enhanced by betaine. There may be potential for developing these phytochemicals as anti-coccidial feed or water additives for poultry

Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates

<div><p>Conventional control and eradication strategies for bovine tuberculosis (BTB) face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle.</p><p>Twenty-four mixed breed calves (<i>Bos taurus</i>) aged 4–6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live <i>M</i>. <i>bovis</i> BCG (Danish 1331), formalin-inactivated <i>M</i>. <i>bovis</i> BCG, heat-killed <i>M</i>. <i>bovis</i> or PBS/Montanide™ (control). Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live <i>M</i>. <i>bovis</i> BCG.</p><p>The animals in the heat-killed <i>M</i>. <i>bovis</i> group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed <i>M</i>. <i>bovis</i> group.</p><p>In conclusion, the parenteral heat-killed <i>M</i>. <i>bovis</i> vaccine proved to be clearly immunogenic in cattle in the present study, urging further evaluation of the vaccine in challenge studies using virulent <i>M</i>. <i>bovis</i> and assessment of vaccine efficacy in field conditions.</p></div

Від коваріацій до каузальності. Відкриття структур залежностей у даних

Проаналізовано сучасну методологію виводу каузальних моделей та структур систем імовірнісних залежностей із статистичних даних пасивних спостережень. Висвітлено можливості, проблеми, застереження та обмеження методів індуктивної ідентифікації каузальних відношень в апараті марковських властивостей та баєсових мереж. Виділено кілька ступенів каузальних моделей згідно з рівнем їх обґрунтованості та адекватності джерелу даних. Сформульовано статистичний паттерн, який зводить обґрунтування висновку про каузальний характер зв’язку двох змінних до тестування набору статистичних фактів (не)залежності.Проанализирована современная методология вывода каузальных моделей и структур систем вероятностных зависимостей из статистических данных пассивных наблюдений. Освещены возможности, проблемы, оговорки и ограничения методов индуктивной идентификации каузальных отношений в аппарате марковских свойств и байесовых сетей. Выделены несколько ступеней каузальных моделей согласно уровню их обоснованности и адекватности источнику данных. Сформулирован статистический паттерн, который сводит обоснование вывода о каузальном характере связи двух переменных к тестированию набора статистических фактов (не)зависимости.The current methodology of output casual models and structures of systems of probabilistic dependencies of stafistical data of passive observation is analysed. The problems, features, traps and limitations of the methods of the inductive identification of casual relation in the unit of marcov properties and bayesias nets are highlighted. Several stages of casual models according to the level of their validity and adequacy of the data source are emphasized. The statistical pattern, which brings the justification of a finding about casual nature of the connections between two variables to the test of a set of statistical facts of (in)dependency is formulated

Microstructural brain injury in post-concussion syndrome after minor head injury

Introduction: After minor head injury (MHI), post-concussive symptoms commonly occur. The purpose of this study was to correlate the severity of post-concussive symptoms in MHI patients with MRI measures of microstructural brain injury, namely mean diffusivity (MD) and fractional anisotropy (FA), as well as the presence of microhaemorrhages. Methods: Twenty MHI patients and 12 healthy controls were scanned at 3 T using diffusion tensor imaging (DTI) and high-resolution gradient recalled echo (HRGRE) T2*-weighted sequences. One patient was excluded from the analysis because of bilateral subdural haematomas. DTI data were preprocessed using Tract Based Spatial Statistics. The resulting MD and FA images were correlated with the severity of post-concussive symptoms evaluated with the Rivermead Postconcussion Symptoms Questionnaire. The number and location of microhaemorrhages were assessed on the HRGRE T2*-weighted images. Results: Comparing patients with controls, there were no differences in MD. FA was decreased in the right temporal subcortical white matter. MD was increased in association with the severity of post-concussive symptoms in the inferior fronto-occipital fasciculus (IFO), the inferior longitudinal fasciculus and the superior longitudinal fasciculus. FA was reduced in association with the severity of post-concussive symptoms in the uncinate fasciculus, the IFO, the internal capsule and the corpus callosum, as well as in the parietal and frontal subcortical white matter. Microhaemorrhages were observed in one patient only. Conclusions: The severity of post-concussive symptoms after MHI was significantly correlated with a reduction of white matter integrity, providing evidence of microstructural brain injury as a neuropathological substrate of the post-concussion syndrome

Clinical practice of language fMRI in epilepsy centers: a European survey and conclusions by the ESNR Epilepsy Working Group

Purpose: To assess current clinical practices throughout Europe with respect to acquisition, implementation, evaluation, and interpretation of language functional MRI (fMRI) in epilepsy patients. Methods: An online survey was emailed to all European Society of Neuroradiology members (n = 1662), known associates (n = 6400), and 64 members of European Epilepsy network. The questionnaire featured 40 individual items on demographic data, clinical practice and indications, fMRI paradigms, radiological workflow, data post-processing protocol, and reporting. Results: A total of 49 non-duplicate entries from European centers were received from 20 countries. Of these, 73.5% were board-certified neuroradiologists and 69.4% had an in-house epilepsy surgery program. Seventy-one percent of centers performed fewer than five scans per month for epilepsy. The most frequently used paradigms were phonemic verbal fluency (47.7%) and audi

The Rotterdam Scan Study: design and update up to 2012

Neuroimaging plays an important role in etiologic research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to unravel causes of neurological disease by performing neuroimaging in a population-based longitudinal setting. In 1995 and 1999 random subsets of the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. We also describe the imaging protocol and post-processing techniques, and highlight the main findings to date. Finally, we make recommendations for future research, which will also be the main focus of investigation in the Rotterdam Scan Study