From subthalamic local field potentials to the selection of chronic deep brain stimulation contacts in Parkinson's disease - A systematic review

Background: Programming deep brain stimulation (DBS) of the subthalamic nucleus for optimal symptom control in Parkinson's Disease (PD) requires time and trained personnel. Novel implantable neurostimulators allow local field potentials (LFP) recording, which could be used to identify the optimal (chronic) stimulation contact. However, literature is inconclusive on which LFP features and prediction techniques are most effective. Objective: To evaluate the performance of different LFP-based physiomarkers for predicting the optimal (chronic) stimulation contacts.Methods: A literature search was conducted across nine databases, resulting in 418 individual papers. Two independent reviewers screened the articles based on title, abstract, and full text. The quality of included studies was assessed using a modified Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Results were categorised in four classes based on the predictive performance with respect to the a priori chance. Results: Twenty-five studies were included. Single-feature beta-band predictions demonstrated positive performance scores in 94 % of the outcomes. Predictions based on single non-beta-frequency features yielded positive scores in only 25 % of the outcomes, with positive results mainly for high frequency oscillations. Multi-feature predictions (e.g. machine learning) achieved accuracy scores within the two highest performance classes more often than single beta-based predictions (100 % versus 39 %). Conclusion: Predicting the optimal stimulation contact based on LFP recordings is feasible and can improve DBS programming efficiency in PD. Single beta-band predictions show more promising results than non-beta-frequency features alone, but are outperformed by multi-feature predictions. Future research should further explore multi-feature predictions for optimal contact identification.</p

Improving Health Literacy Responsiveness:A Randomized Study on the Uptake of Brochures on Doctor-Patient Communication in Primary Health Care Waiting Rooms

Presenting attractive and useful health education materials in waiting rooms can help improve an organization's health literacy responsiveness. However, it is unclear to what extent patients may be interested in health education materials, such as brochures. We conducted a three-week field study in waiting rooms of three primary care centers in Groningen. Three versions of a brochure on doctor-patient communication were randomly distributed, 2250 in total. One version contained six short photo stories, another version was non-narrative but contained comparable photos, and the third version was a traditional brochure. Each day we counted how many brochures were taken. We also asked patients (N = 471) to participate in a brief interview. Patients who consented (N = 390) were asked if they had noticed the brochure. If yes (N = 135), they were asked why they had or had not browsed the brochure, and why they had or had not taken it. Interview responses were categorized by two authors. Only 2.9% of the brochures were taken; no significant association with brochure version was found. Analysis of the interview data showed that the version with the photo narrative was noticed significantly more often than the non-narrative version or the traditional version. These results suggest that designing attractive and comprehensible health materials is not enough. Healthcare organizations should also create effective strategies to reach their target population

The Coax Dipole: A fully flexible coaxial cable dipole antenna with flattened current distribution for body imaging at 7 Tesla

Purpose: The coax dipole antenna, a flexible antenna for body imaging at 7T is presented. Similar to the high impedance coil, this coaxial cable antenna is fed on the central conductor and through gaps in the shield, the current passes to the outside of the antenna to generate B1 field. This could achieve more favorable current distributions and better adaptation to the body curvature. Methods: Finite difference time domain (FDTD) simulations are performed to optimize the positions of the gaps in the shield for a flat current profile. Lumped inductors are added to each end to reduce losses. The performance of a single antenna is compared to a fractionated dipole using B1 maps and MR thermometry. Finally, an array of eight coax dipoles is evaluated in simulations and used for in-vivo scanning. Results: An optimal configuration is found with gaps located at 10 cm from the center and inductor values of 28 nH. In comparison to the fractionated dipole antenna, in single antenna phantom measurements the coax dipole achieves similar B1 amplitude with 18% lower peak temperature. In simulations, the eight-channel array of coax dipoles improved B1 homogeneity by 18%, along with small improvements in transmit efficiency and specific absorption rate (SAR). MRI measurements on three volunteers show more consistent performance for the coax dipoles. Conclusion: The coax dipole is a novel antenna design with a flattened current distribution resulting in beneficial properties. Also, the flexible design of the coax dipoles allows better adaptation to the body curvature and can potentially be used for a wide range of imaging targets

Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Diabetic Macular Edema (BRDME):The BRDME Study, a Randomized Trial

Purpose: To generate conclusive evidence regarding the noninferiority of intravitreal bevacizumab compared with ranibizumab in patients with diabetic macular edema (DME). Design: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. Participants: Eligible patients were older than 18 years, diagnosed with type 1 or type 2 diabetes mellitus, with glycosylated hemoglobin of less than 12%, central area thickness of more than 325 μm, and visual impairment from DME with a best-corrected visual acuity (BCVA) between 24 letters and 78 letters. Methods: From June 2012 through February 2018, a total of 170 participants were randomized to receive 6 monthly injections of either 1.25 mg bevacizumab (n = 86) or 0.5 mg ranibizumab (n = 84). Main Outcome Measures: Primary outcome was change in BCVA from baseline to month 6 compared between the 2 treatment arms. The noninferiority margin was 3.5 letters. Results: The difference in mean BCVA between treatment arms was 1.8 letters in favor of ranibizumab after 6 months of follow-up; BCVA improved by 4.9±6.7 letters in the bevacizumab group and 6.7±8.7 letters in the ranibizumab group. The lower bound of the 2-sided 90% confidence interval (CI) was –3.626 letters, exceeding the noninferiority margin of 3.5 letters. Central area thickness decreased more with ranibizumab (138.2±114.3 μm) compared with bevacizumab (64.2±104.2 μm). In a post hoc subgroup analysis, participants with a worse BCVA at baseline (≤69 letters) improved by 6.7±7.0 letters with bevacizumab and 10.4±10.0 letters with ranibizumab, and central area thickness decreased significantly more in the ranibizumab arm of this subgroup compared with the bevacizumab arm. Participants with an initially better BCVA at baseline (≥70 letters) did not demonstrate differences in BCVA or OCT outcomes between treatment arms. Conclusions: Based on change in BCVA from baseline to month 6, the noninferiority of 1.25 mg bevacizumab to 0.5 mg ranibizumab was not confirmed. Only the subgroup of patients with a lower BCVA at baseline showed better visual acuity and anatomic outcomes with ranibizumab. Our study confirmed the potential differential efficacy of anti–vascular endothelial growth factor agents in the treatment of DME as well as the difference in response between patient groups with different baseline visual acuities

Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Retinal Vein Occlusion:The Bevacizumab to Ranibizumab in Retinal Vein Occlusions (BRVO) study, a Randomized Trial

PURPOSE: Comparing the efficacy of intravitreal injections of bevacizumab to ranibizumab in the treatment of macular edema (ME) resulting from retinal vein occlusion (RVO). DESIGN: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. The noninferiority margin was 4 letters. PARTICIPANTS: Patients with vision loss resulting from ME secondary to a branch or (hemi) central RVO who might benefit from anti-vascular endothelial growth factor treatment were eligible for participation. METHODS: From June 2012 through February 2018, 277 participants were randomized to receive injections of 1.25 mg bevacizumab (n = 139) or 0.5 mg ranibizumab (n = 138). The follow-up was 6 months with a monthly dosing interval. MAIN OUTCOME MEASURES: The primary outcome was a change in visual acuity from baseline at 6 months. Changes in the central area thickness and safety were studied as secondary outcomes. RESULTS: The mean visual acuity (±standard deviation) improved, with 15.3±13.0 letters for bevacizumab and 15.5±13.3 letters for ranibizumab after 6 months of monthly treatment. The lower limit of the 2-sided 90% confidence interval was -1.724 letters, which is within the noninferiority margin of 4 letters. Even in the branch and (hemi-)central RVO subgroups, minimal differences were found in visual acuity outcomes between treatment arms. Changes in central area thickness on OCT at 6 months did not differ significantly between treatment groups, with a decrease of 287.0±231.3 μm in the bevacizumab group and 300.8±224.8 μm in the ranibizumab group. Severe adverse events (SAEs) were also distributed equally over both treatment groups: 10 participants (7.1%) in the bevacizumab group and 13 participants (9.2%) in the ranibizumab group experienced SAEs. CONCLUSIONS: This study showed, based on the change in visual acuity, that bevacizumab is noninferior to ranibizumab for patients with ME resulting from RVO of either subtype when receiving monthly injections for a period of 6 months. In addition, anatomic and safety outcomes did not differ between treatment groups. Based on our findings, bevacizumab may be an effective alternative to ranibizumab

PLoS One

Age-related macular degeneration (AMD) is a common, progressive multifactorial vision-threatening disease and many genetic and environmental risk factors have been identified. The risk of AMD is influenced by lifestyle and diet, which may be reflected by an altered metabolic profile. Therefore, measurements of metabolites could identify biomarkers for AMD, and could aid in identifying high-risk individuals. Hypothesis-free technologies such as metabolomics have a great potential to uncover biomarkers or pathways that contribute to disease pathophysiology. To date, only a limited number of metabolomic studies have been performed in AMD. Here, we aim to contribute to the discovery of novel biomarkers and metabolic pathways for AMD using a targeted metabolomics approach of 188 metabolites. This study focuses on non-advanced AMD, since there is a need for biomarkers for the early stages of disease before severe visual loss has occurred. Targeted metabolomics was performed in 72 patients with early or intermediate AMD and 72 control individuals, and metabolites predictive for AMD were identified by a sparse partial least squares discriminant analysis. In our cohort, we identified four metabolite variables that were most predictive for early and intermediate stages of AMD. Increased glutamine and phosphatidylcholine diacyl C28:1 levels were detected in non-advanced AMD cases compared to controls, while the rate of glutaminolysis and the glutamine to glutamate ratio were reduced in non-advanced AMD. The association of glutamine with non-advanced AMD corroborates a recent report demonstrating an elevated glutamine level in early AMD using a different metabolomics technique. In conclusion, this study indicates that metabolomics is a suitable method for the discovery of biomarker candidates for AMD. In the future, larger metabolomics studies could add to the discovery of novel biomarkers in yet unknown AMD pathways and expand our insights in AMD pathophysiology

Risultati preliminari delle indagini archeologiche ed etnografiche presso il sito di Togolok 1

Modern Turkmenistan is mainly constituted by a desert landscape, yet despite its harsh climate, cultures have been able to construct networks of water channels since the Bronze Age. This has resulted in a man-made landscape that integrates towns and villages. Extensive surveys and recent archaeological excavations have highlighted that between 2400 and 2100 BC (Namazga V period), the region of the Murghab alluvial fan was characterised by the development of complex urban societies. However, starting from the Late Bronze Age, a new group of mobile pastoralists appeared in the Murghab region and settled along the edges of the sedentary sites. Although their presence is well-attested both by survey and excavation data, their degree of interaction with the sedentary farmers is still debated. In modern Turkmenistan, semi-mobile shepherds continue to drive their cattle across the Murghab, using mobile camps for different months. This paper presents the preliminary results of the excavation of the sedentary site of Togolok 1, as well as the first ethnographic study of the mobile communities of the Murghab region

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Analysis of High Impedance Coils Both in Transmission and Reception Regimes

| openaire: EC/H2020/736937/EU//M-CUBETheory of a high impedance coil (HIC) - a cable loop antenna with a modified shield - is comprehensively discussed for MRI application in both transmitting and receiving regimes. Understanding a weakness of the previously reported HIC in transmitting regime, we suggest another HIC which is advantageous in both transmitting and receiving regimes compared to a conventional loop antenna. In contrast with the claim of previous works that the reported HICs are advantageous in transmission regime, we show only this HIC is a practical transceiver HIC. Using the perturbation approach and adding gaps to both shield and inner wire of the cable, we tune the resonance frequency to be suitable for ultra-high field (UHF) magnetic resonance imaging (MRI). These gaps reduce the quality factor of the enhanced HIC which makes its resonant frequency more stable with respect to different loadings. Our theoretical model and applicability of our HIC for MRI applications are verified by simulations. Using the theoretical model, we have designed and fabricated an array of three HICs operating at 298 MHz. The operation of the array has been experimentally studied in the presence of different phantoms used in ultrahigh field MRI and the results compared with those obtained for a conventional array.Peer reviewe