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Objective: Clinical rating scales often fail to capture the full spectrum of dystonic symptoms. Deep brain stimulation of the globus pallidus interna (GPi-DBS) effectively treats dystonia, but response variability necessitates a reliable biomarker. Intermuscular coherence (4-12 Hz) has been linked to abnormal activity in the cortico-basal ganglia-thalamo-cortical (CBGTC) loop and may serve as an objective measure of dystonia and GPi-DBS effectiveness., Methods: A retrospective cohort study included 12 dystonia patients undergoing GPi-DBS implantation. Clinical rating scales and a neurophysiological assessment were performed before and one year post-DBS. Coherence in the 4-12 Hz range was analyzed from electromyography (EMG) of antagonistic arm muscles. Comparisons were made between patients with and without arm dystonia, t-tests evaluated the differences between pre- and post-DBS, and correlations between coherence and clinical scales were performed., Results: Seven patients with arm dystonia appeared to have higher pre-operative intermuscular coherence compared to those without. Coherence was significantly decreased after GPi-DBS in the arm dystonia group. No strong correlations were found between coherence and clinical rating scales., Conclusion: Intermuscular coherence is present in dystonic muscles and decreases following GPi-DBS. Correlations with motor scores were inconclusive due to patient heterogeneity and ill-fitting clinical scales., Significance: Intermuscular coherence has potential to aid GPi-DBS patient selection and optimization but larger studies are needed to validate its use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data are available on NIRS regional cerebral tissue oxygen saturation (rSO 2 ) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO 2 values in patients with nontraumatic SAH with the occurrence of DCI and functional outcome at 2 months. In addition, the predictive value of NIRS rSO 2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, World Federation of Neurosurgical Societies after REsuscitation)., Methods: In this study, the rSO 2 distribution of patients with and without DCI after SAH was compared. The optimal cutoff points to predict DCI and outcome were assessed, and its predictive value was compared with the SAFIRE grade., Results: Of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve of 0.77 (95% confidence interval 0.62-0.92; P = 0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an area under the curve of 0.86 (95% confidence interval 0.74-0.98; P = 0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO 2 score is complementary to the SAFIRE grade., Conclusions: NIRS rSO 2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Automated detection of spikes and seizures has been a subject of research for several decades now. There have been important advances, yet automated detection in EMU (Epilepsy Monitoring Unit) settings has not been accepted as standard practice. We intend to implement this software at our EMU and so carried out a qualitative study to identify factors that hinder ('barriers') and facilitate ('enablers') implementation., Method: Twenty-two semi-structured interviews were conducted with 14 technicians and neurologists involved in recording and reporting EEGs and eight neurologists who receive EEG reports in the outpatient department. The study was reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ)., Results: We identified 14 barriers and 14 enablers for future implementation. Most barriers were reported by technicians. The most prominent barrier was lack of trust in the software, especially regarding seizure detection and false positive results. Additionally, technicians feared losing their EEG review skills or their jobs. Most commonly reported enablers included potential efficiency in the EEG workflow, the opportunity for quantification of EEG findings and the willingness to try the software., Conclusions: This study provides insight into the perspectives of users and offers recommendations for implementing automated spike and seizure detection in EMUs., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: During the surgical procedure of deep brain stimulation (DBS), insertion of an electrode in the subthalamic nucleus (STN) frequently causes a temporary improvement of motor symptoms, known as the microlesion effect (MLE). The objective of this study was to determine the correlation between the intraoperative MLE and the clinical effect of DBS., Materials and Methods: Thirty Parkinson's disease (PD) patients with Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) part III (MDS-UPDRS III) scores during bilateral STN-DBS implantation were included in this retrospective study. MDS-UPDRS III subscores (resting tremor, rigidity, and bradykinesia) of the contralateral upper extremity were used. During surgery, these subscores were assessed directly before and after insertion of the electrode. Also, these subscores were determined in the outpatient clinic after 11 weeks on average (on-stimulation). All assessments were performed in an off-medication state (at least 12 hours of medication washout)., Results: Postinsertion MDS-UPDRS motor scores decreased significantly compared to preinsertion scores (p < 0.001 for both hemispheres). The MLE showed a positive correlation with the clinical effect of DBS in both hemispheres (rho = 0.68 for the primarily treated hemisphere, p < 0.001, and rho = 0.59 for the secondarily treated hemisphere, p < 0.01)., Conclusion: The MLE has a clinically relevant correlation with the effect of DBS in PD patients. These results suggest that the MLE can be relied upon as evidence of a clinically effective DBS electrode placement., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment in advanced Parkinson's disease (PD). However, the clinical outcome after STN-DBS is variable. The aim of this study was to explore the coherence of antagonistic muscles measured with electromyography (EMG) as novel biomarker of STN-DBS efficacy in PD., Methods: EMG of bilateral wrist and upper arm antagonistic muscles of 21 PD patients was recorded during three standardized motor tasks. Patients were measured one day prior to DBS surgery (pre-DBS) and 6 months afterwards (post-DBS). Coherence analyses were performed on the antagonistic muscle pairs. Pearson correlations between intermuscular coherence and clinical performance were calculated., Results: Intermuscular coherence during each of the different co-contraction tasks significantly correlated to UPDRS-III bradykinesia scores (p < 0.01). In other words, higher intermuscular coherence is associated with more severe PD symptoms. Moreover, coherence changes (pre-DBS - post-DBS coherence) correlated to clinical score changes after DBS (p < 0.01) and pre-DBS coherence correlated to this clinical score change as well (p < 0.01)., Conclusions: Higher pre-DBS coherence of antagonistic arm muscles is correlated to worsening of clinical PD state and higher intermuscular coherence predicts enhanced clinical improvement., Significance: We propose that pre-DBS intermuscular coherence could be developed into a predictor of STN-DBS clinical outcome. It could aid patient selection and adaptive stimulation algorithms for DBS., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Outbreaks of cattle lungworm disease (Dictyocaulus viviparus) are explosive and costly. The unpredictability of the disease often encourages farmers to apply blanket anthelmintic treatments to the herd, which impede the acquisition of immunity, increase the risk of drug resistance, and interfere with efforts to reduce anthelmintic use against ubiquitous gastrointestinal nematodes. Improving our understanding of the factors which lead to a high risk of infection with lungworm, (including climatic pressure), would support a more targeted management. We present GLOWORM-FL-DV, the first mathematical model of the free-living stages of D. viviparus. The ecology of D. viviparus is unique compared with other strongylid nematodes due to its relationship with Pilobilus spp. fungi, which enhance the transmission potential. The role of the fungi was therefore incorporated into the model framework, informed by laboratory observations of Pilobolus spp. development and sporulation. The thermal niche of D. viviparus was characterised based on published and laboratory observations. Mortality of parasitic larvae increased significantly below 0 o C, and larval development occurred above 1.4 o C, whereas the estimated minimum temperature for migration via Pilobolus spp. was 8.8 o C. Model predictions were compared with antibody levels in bulk milk tank samples collected at two-weekly intervals from eight dairy herds across Great Britain over two grazing seasons. The model predicted high levels of larval abundance on pasture 46 days (38-52 days) before a rise in antibody levels and 22-26 days before the onset of clinical signs. The model assesses the impact of climate and weather on lungworm larval availability at pasture and provides a framework for the development of a risk forecasting system. This could help to focus vigilance for clinical signs at high-risk times and facilitate the targeted use of anthelmintics to prevent outbreaks, in support of sustainable parasite control., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: We assessed whether automated detection software, combined with live observation, enabled reliable seizure detection using three commercial software packages: Persyst, Encevis and BESA., Methods: Two hundred and eighty-six prolonged EEG records of individuals aged 16-86 years, collected between August 2019 and January 2020, were retrospectively processed using all three packages. The reference standard included all seizures mentioned in the clinical report supplemented with true detections made by the software and not previously detected by clinical physiologists. Sensitivity was measured for offline review by clinical physiologists and software seizure detection, both in combination with live monitoring in an EMU setting, for all three software packages at record and seizure level., Results: The database contained 249 seizures in 64 records. The sensitivity of seizure detection was 98% for Encevis and Persyst, and 95% for BESA, when a positive results was defined as detection at least one of the seizures occurring within an individual record. When positivity was defined as recognition of all seizures, sensitivity was 93% for Persyst, 88% for Encevis and 84% for BESA. Clinical physiologists' review had a sensitivity of 100% at record level and 98% at seizure level. The median false positive rate per record was 1.7 for Persyst, 2.4 for BESA and 5.5 for Encevis per 24 h., Conclusion: Automated seizure detection software does not perform as well as technicians do. However, it can be used in an EMU setting when the user is aware of its weaknesses. This assessment gives future users helpful insight into these strengths and weaknesses. The Persyst software performs best., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: We assessed three commercial automated spike detection software packages (Persyst, Encevis and BESA) to see which had the best performance., Methods: Thirty prolonged EEG records from people aged at least 16 years were collected and 30-minute representative epochs were selected. Interictal epileptiform discharges (IEDs) were marked by three human experts and by all three software packages. For each 30-minutes selection and for each 10-second epoch we measured whether or not IEDs had occurred. We defined the gold standard as the combined detections of the experts. Kappa scores, sensitivity and specificity were estimated for each software package., Results: Sensitivity for Persyst in the default setting was 95% for 30-minute selections and 82% for 10-second epochs. Sensitivity for Encevis was 86% (30-minute selections) and 61% (10-second epochs). The specificity for both packages was 88% for 30-minute selections and 96%-99% for the 10-second epochs. Interrater agreement between Persyst and Encevis and the experts was similar than between experts (0.67-0.83 versus 0.63-0.67). Sensitivity for BESA was 40% and specificity 100%. Interrater agreement (0.25) was low., Conclusions: IED detection by the Persyst automated software is better than the Encevis and BESA packages, and similar to human review, when reviewing 30-minute selections and 10-second epochs. This findings may help prospective users choose a software package., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa., Study Design and Setting: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption., Results: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0)., Conclusion: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The pathophysiology of vasovagal syncope (VVS) is reviewed, focusing on hemodynamic aspects. Much more is known about orthostatic than about emotional VVS, probably because the former can be studied using a tilt table test (TTT). Recent advances made it possible to quantify the relative contributions of the three factors that control blood pressure: heart rate (HR), stroke volume (SV) and total peripheral resistance (TPR). Orthostatic VVS starts with venous pooling, reflected in a decrease of SV. This is followed by cardioinhibition (CI), which is a decrease of HR that accelerates the ongoing decrease of BP, making the start of CI a literal as well as fundamental turning point. The role of hormonal and other humoral factors, respiration and of psychological influences is reviewed in short, leading to the conclusion that a multidisciplinary approach to the study of the pathophysiology of VVS may yield new insights., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Although various determinants of exercise limitation in Fontan patients have been studied, most research has been performed in patients who underwent different surgical procedures with differing haemodynamic characteristics. The aim of the current study was to evaluate non-invasively measured cardiovascular parameters and their influence on exercise performance in paediatric Fontan patients with an extracardiac conduit and moderate-good systolic ventricular function., Methods: Fontan patients, between 8 and 18 years of age, with moderate to good systolic ventricular function and an extracardiac conduit were included. Exercise performance and cardiovascular assessment, comprising echocardiography, aortic stiffness measurement and ambulatory measurement of cardiac autonomous nervous activity were performed on the same day. Healthy subjects served as controls., Results: Thirty-six Fontan patients (age 14.0 years) and thirty-five healthy subjects (age 12.8 years) were included. Compared to controls, Fontan patients had reduced diastolic ventricular function and increased arterial stiffness. No differences were found in heart rate (HR) and cardiac parasympathetic nervous activity. In Fontan patients, maximal as well as submaximal exercise capacity was impaired, with the percentage of predicted capacity ranging between 54 and 72%. Chronotropic competence, however, was good with a peak HR of 174 (94% of predicted). Lower maximal and submaximal exercise capacity was correlated with a higher HR at rest, higher pulse wave velocity of the aorta and a lower ratio of early and late diastolic flow velocity., Conclusion: Contemporary paediatric Fontan patients have an impaired exercise capacity with preserved chronotropic competence. Exercise performance correlates with heart rate at rest, diastolic function and aortic stiffness., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

An expert committee was formed to reach consensus on the use of Tilt Table Testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous ones. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to perform (1) additional provocation tests, such as the active standing test carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO 2 or neuro-endocrine tests; (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and improve quality of life. We implemented the European Society of Cardiology (ESC) 2018 syncope guidelines at the Emergency Departments (ED) and established Syncope Units in five Dutch hospitals. We evaluated the implementation process by identifying factors that hinder ('barriers') and facilitate ('facilitators') the implementation., Methods and Results: We conducted, recorded and transcribed semi-structured interviews with 19 specialists and residents involved in syncope care from neurology, cardiology, internal medicine and emergency medicine. Two researchers independently classified the reported barriers and facilitators, according to the framework of qualitative research (Flottorp), which distinguished several separate fields ('levels'). Software package Atlas.ti was used for analysis. We identified 31 barriers and 22 facilitators. Most barriers occurred on the level of the individual health care professional (e.g. inexperienced residents having to work with the guideline at the ED) and the organizational context (e.g. specialists not relinquishing preceding procedures). Participants reported most facilitators at the level of innovation (e.g. structured work-flow at the ED). The multidisciplinary Syncope Unit was welcomed as useful solution to a perceived need in clinical practice., Conclusion: Implementing ESC syncope guidelines at the ED and establishing Syncope Units facilitated a structured multidisciplinary work-up for syncope patients. Most identified barriers related to the individual health care professional and the organizational context. Future implementation of the multidisciplinary guideline should be tailored to address these barriers., Competing Interests: Declaration of Competing Interest MG, LvBV, FJdL, ECAK, BdG and MB report no disclosures relevant to the manuscript. SYGP received lecture fees from Spaarne Gasthuis hospital and Medtronic. MEWH received speakers fees from Biotronik and Medtronic. JGvD has received lecture fees from Medtronic. RDT has received fees for lectures from Medtronic, UCB, and Novartis. RDT has received consultancy fees from Theravarance and Arvelle. RDT receives research support from the Dutch National Epilepsy Fund, The Netherlands Organisation for Health Research and Development (ZonMW), NUTS Ohra Fund, Medtronic, Christelijke Vereniging voor de Verpleging van Lijders aan Epilepsie, The Netherlands., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of diagnostic difficulties. Improving the differentiation would have an important impact on patients and families in view of better prediction of disease progression., Objective: To investigate whether several new non-invasive autonomic tests are beneficial in discriminating between PAF and MSA., Methods: Patients and controls underwent two tests examining the autonomic innervation of the skin (Sudoscan and water-induced skin wrinkling) and one test measuring retinal nerve fiber layer thickness in the eye., Results: The skin vasomotor tests yielded differences between the disease and control groups, but did not discriminate between PAF and MSA. No differences in retinal nerve fiber layer thickness were found between the groups., Conclusion: The tests applied in this study may help to confirm autonomic failure but did not support the differential diagnosis between PAF and MSA., (Copyright © 2021. Published by Elsevier B.V.)

Background: Beta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson's disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed., Methods: To determine the acute effectiveness and side-effect profile of aDBS in PD compared to conventional continuous DBS (cDBS) and no stimulation (NoStim), years after DBS implantation, 13 PD patients undergoing battery replacement were pseudo-randomised in a crossover fashion, into three conditions (NoStim, aDBS or cDBS), with a 2-min interval between them. Patient videos were blindly evaluated using a short version of the Unified Parkinson's Disease Rating Scale (subUPDRS), and the Speech Intelligibility Test (SIT)., Results: Mean disease duration was 16 years, and the mean time since DBS-implantation was 6.9 years. subUPDRS scores (11 patients tested) were significantly lower both in aDBS (p=<.001), and cDBS (p = .001), when compared to NoStim. Bradykinesia subscores were significantly lower in aDBS (p = .002), and did not achieve significance during cDBS (p = .08), when compared to NoStim. Two patients demonstrated re-emerging tremor during aDBS. SIT scores of patients who presented stimulation-induced dysarthria significantly worsened in cDBS (p = .009), but not in aDBS (p = .407), when compared to NoStim. Overall, stimulation was applied 48.8% of the time during aDBS., Conclusion: Beta-based aDBS is effective in PD patients with bradykinetic phenotypes, delivers less stimulation than cDBS, and potentially has a more favourable speech side-effect profile. Patients with prominent tremor may require a modified adaptive strategy., Competing Interests: Declaration of competing interest PB is a consultant with Medtronic., (Copyright © 2020. Published by Elsevier Inc.)

Background: Colorectal carcinoma (CRC) has a worldwide incidence of 1.4 million patients and a large share in cancer-related mortality. After curative treatment, the risk of recurrence is 30-65%. Early detection may result in curative treatment. However, current follow-up (FU) examinations have low sensitivity ranging from 49 to 85% and are associated with high costs. Therefore, the search for a new diagnostic tool is justified. Analysis of volatile organic compound in exhaled air through an electronic nose (eNose) is a promising new patient-friendly diagnostic tool. We studied whether the eNose under investigation, the Aeonose™, is able to detect local recurrence or metastases of CRC., Methods: In this cross-sectional study we included 62 patients, all of whom underwent curative treatment for CRC in the past 5 years. Thirty-six of them had no metastases and 26 had extraluminal local recurrence or metastases of CRC, detected during FU. Breath testing was performed and machine learning was used to predict extraluminal recurrences or metastases, and based on the receiver operating characteristics (ROC)-curve both sensitivity and specificity were calculated., Results: The eNose identified extra luminal local recurrences or metastases of CRC with a sensitivity and specificity of 0.88 (CI 0.69-0.97) and 0.75 (CI 0.57-0.87), respectively, with an overall accuracy of 0.81., Discussion: This eNose may be a promising tool in detecting extraluminal local recurrences or metastases in the FU of curatively treated CRC. However, a well-designed prospective study is warranted to show its accuracy and predictive value before it can be used in clinical practice., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

In the Netherlands it is common to nourish the coastline with sand from the seabed. Foredunes are replenished with sand from the beach and can be transported further into the dune area. We investigated whether nourishment material alters the phosphorus (P) content of dune soil and the nitrogen (N):P ratio of dune vegetation in two areas: a mega sand nourishment with fixed foredunes (SE) and a traditional sand nourishment with dynamic foredunes (NWC). Four zones were considered: beach (zone 1), frontal foredunes (zone 2), foredunes crest (zone 3) and inner dunes (zone 4). We estimated the characteristics of fine (< 250-μm) and coarse (250-2000 μm) sand. Total P, P speciation and available P of SE and NWC were similar until zone 4. Zone 1-3 consisted mainly of coarse sand, whereas the sand in zone 4 was finer with higher amounts at NWC. Iron (Fe) bound P was comparable for fine and coarse sand in zone 1-3, but high contents were present in zone 4. In zone 1-3, calcium (Ca) bound P was mainly found in the fine fraction, which was abundant in the coarse fraction of zone 4. After a period of 4 years, the effect of dynamic dunes on P fractions and dune plant species was not apparent yet, although inblowing sand mainly consisted of fine sand with high contents of Ca-bound P. This may change over time, especially in dynamic dunes with higher eolian activity of fine sand. Consequently, pH buffering of the soil may increase because of a higher Ca‑carbonate content, which leads to decreased solubility of Ca-bound P and low P availability for the vegetation. Both low P availability and high buffering capacity are known environmental factors that facilitate endangered dune plant species., Competing Interests: Declaration of competing interest Potential conflicts do not exist., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Benzimidazoles (BZ) have been the anthelmintic of choice for controlling Nematodirus battus infections since their release in the 1950s. Despite heavy reliance on this single anthelmintic drug class, resistance was not identified in this nematode until 2010 (Mitchell et al., 2011). The study aimed to explore the prevalence of BZ-resistance mutations in N. battus from UK sheep flocks using deep amplicon sequencing and pyrosequencing platforms. Based on evidence from other gastrointestinal nematodes, resistance in N. battus is likely to be conferred by single nucleotide polymorphisms (SNP) within the β-tubulin isotype 1 locus at codons 167, 198 and 200. Pyrosequencing and deep amplicon sequencing assays were designed to identify the F167Y (TTC to TAC), E198A (GAA to GCA) and F200Y (TTC to TAC) SNPs. Nematodirus battus populations from 253 independent farms were analysed by pyrosequencing; 174 farm populations were included in deep amplicon sequencing and 170 were analysed using both technologies. F200Y was the most prevalent SNP identified throughout the UK, in 12-27% of the populations tested depending on assay, at a low overall individual frequency of 2.2 ± 0.6% (mean ± SEM, based on pyrosequencing results). Four out of the five populations with high frequencies (>20%) of the F200Y mutation were located in NW England. The F167Y SNP was identified, for the first time in this species, in four of the populations tested at a low frequency (1.2% ± 0.01), indicating the early emergence of the mutation. E198A or E198L were not identified in any of the isolates. Results obtained were comparable between both techniques for F200Y (Lins' CCC, r c  = 0.96) with discrepancies being limited to populations with low frequencies. The recent emergence of resistance in this species will provide a unique opportunity to study the early stages of anthelmintic resistance within a natural setting and track its progress in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To compare the efficacy of a medetomidine constant rate infusion (CRI) with a detomidine CRI for standing sedation in horses undergoing high dose rate brachytherapy., Study Design: Randomized, controlled, crossover, blinded clinical trial., Animals: A total of 50 horses with owner consent, excluding stallions., Methods: Each horse was sedated with intravenous acepromazine (0.02 mg kg -1 ), followed by an α 2 -adrenoceptor agonist 30 minutes later and then by butorphanol (0.1 mg kg -1 ) 5 minutes later. A CRI of the same α 2 -adrenoceptor agonist was started 10 minutes after butorphanol administration and maintained for the treatment duration. Treatments were given 1 week apart. Each horse was sedated with detomidine (bolus dose, 10 μg kg -1 ; CRI, 6 μg kg -1 hour -1 ) or medetomidine (bolus dose, 5 μg kg -1 ; CRI, 3.5 μg kg -1 hour -1 ). If sedation was inadequate, a quarter of the initial bolus of the α 2 -adrenoceptor agonist was administered. Heart rate (HR) was measured via electrocardiography, and sedation and behaviour evaluated using a previously published scale. Between treatments, behaviour scores were compared using a Wilcoxon signed-rank test, frequencies of arrhythmias with chi-square tests, and HR with two-tailed paired t tests. A p value <0.05 indicated statistical significance., Results: Total treatment time for medetomidine was longer than that for detomidine (p = 0.04), and ear movements during medetomidine sedation were more numerous than those during detomidine sedation (p = 0.03), suggesting there may be a subtle difference in the depth of sedation. No significant differences in HR were found between treatments (p ≥ 0.09). Several horses had arrhythmias, with no difference in their frequency between the two infusions., Conclusions and Clinical Relevance: Medetomidine at this dose rate may produce less sedation than detomidine. Further studies are required to evaluate any clinical advantages to either drug, or whether a different CRI may be more appropriate., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Finding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients., Methods: EEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4-12 Hz) and beta band (13-30 Hz) peak coherences were studied., Results: Dystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3-10), TWSTRS: 22%, median 6.8 (IQR 4-9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit., Conclusions: Peak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity., Significance: IMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To outline the current knowledge of (sub)cortical oscillations in Parkinson's Disease (PD) and dystonia, and to quantitatively summarize the results of direct comparisons of local oscillatory power between both diseases in the resting state, without medication or stimulation, in both the low-frequency (LF, ±4-12 Hz) and beta (±13 to ∼30 Hz) range., Methods: Eight relevant studies were included. Recordings from 127 dystonia-, and 144 PD-patient hemispheres were analyzed. Ratios of LF and beta power between diseases were obtained., Results: Beta oscillations in dystonia were lower when compared to beta oscillations in PD, ratio = 0.72, Z = 3.56, p = 0.0004, 95% CI [0.60, 0.86]. Subgroup analyses showed significant differences only in the GPi, whilst conflicting evidence was shown in the STN. LF oscillations in PD were lower when compared to LF oscillations in dystonia, ratio = 0.77, Z = 2.45, p = 0.01, 95% CI [0.63, 0.95]. Subgroup analyses showed significant differences in the GPi and the STN, but not in the M1., Conclusions: LF and beta oscillations are present in the resting-state motor network of both PD and dystonia patients. However, the power distribution of those oscillations differs between diseases., Significance: This meta-analysis provides high-level evidence which supports the presence of exaggerated oscillations across the parkinsonian/dystonic motor networks., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Introduction: Clinical response to deep brain stimulation (DBS) strongly depends on the appropriate placement of the electrode in the targeted structure. Postoperative MRI is recognized as the gold standard to verify the DBS-electrode position in relation to the intended anatomical target. However, intraoperative computed tomography (iCT) might be a feasible alternative to MRI., Materials and Methods: In this prospective noninferiority study, we compared iCT with postoperative MRI (24-72 hours after surgery) in 29 consecutive patients undergoing placement of 58 DBS electrodes. The primary outcome was defined as the difference in Euclidean distance between lead tip coordinates as determined on both imaging modalities, using the lead tip depicted on MRI as reference. Secondary outcomes were difference in radial error and depth, as well as difference in accuracy relative to target., Results: The mean difference between the lead tips was 0.98 ± 0.49 mm (0.97 ± 0.47 mm for the left-sided electrodes and 1.00 ± 0.53 mm for the right-sided electrodes). The upper confidence interval (95% CI, 0.851 to 1.112) did not exceed the noninferiority margin established. The average radial error between lead tips was 0.74 ± 0.48 mm and the average depth error was determined to be 0.53 ± 0.40 mm. The linear Deming regression indicated a good agreement between both imaging modalities regarding accuracy relative to target., Conclusions: Intraoperative CT is noninferior to MRI for the verification of the DBS-electrode position. CT and MRI have their specific benefits, but both should be considered equally suitable for assessing accuracy., (© 2019 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.)

Current diagnostic methods for detecting the presence or absence of Dictyocaulus viviparus in dairy herds, are insensitive when based on detection of antibody levels in bulk tank milk (BTM). Here we present a novel technique to confirm the presence of the parasite based on a pooled-milk sample from 10 randomly selected first - lactation heifers (FLH). This study was run in two parts. First, a longitudinal study was performed to look at infection dynamics in milk samples across the grazing season using a prototype ELISA developed by Svanova (Boehringer-Ingelheim, Uppsala). We identified that mean ODR values in milk samples from FLH was significantly higher than that for older cows (0.13 versus 0.07 respectively, p < 0.001) suggesting that samples from the FLH cohort should be pooled to produce the test. Second, the pooled - milk test was evaluated on a cross-sectional survey of UK dairy herds (n = 25 grazing and n = 25 zero-grazing herds) to evaluate test performance under field conditions. The optical density ratio (ODR) cut-off value for our pooled-milk test using 10 FLH milk samples was optimal at a value of 0.16. Pooling 10 FLH samples created a sensitivity and specificity of 66.7% and 95.5% respectively. In comparison, whole-herd BTM samples had a maximum sensitivity of 37.5% and specificity of 63.6% at an ODR cut-off of 0.18. The area under the curve according to receiver-operative-characteristic (ROC) analysis was high for the 10-heifer test (0.87) but poor for the whole herd BTM testing (0.45). This study provides a more sensitive diagnostic test strategy for the screening of D.viviparus in dairy herds. Testing herds at the end of a grazing season would facilitate the planning of effective control measures, such as the use of the lungworm vaccination or strategic deworming, for the following grazing season. This may prove to be a useful test strategy for the diagnosis of a variety of parasitic diseases of livestock., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are established treatment option in Parkinson's disease (PD). If DBS does not provide the desired effect, re-operation to the alternative target is a treatment option, but data on the effect of re-operation are scarce., Objectives: The objective of this study is to evaluate the clinical effect of re-operation the alternative target after failure of initial STN or GPi DBS for Parkinson's disease., Materials and Methods: We descriptively analyzed the baseline characteristics, the effect of initial surgery and re-operation of eight NSTAPS (Netherlands SubThalamic and Pallidal Stimulation) patients and six previously published cases that underwent re-operation to a different target., Results: In the NSTAPS cohort, two of the eight patients showed more than 30% improvement of off-drug motor symptoms after re-operation. The initial DBS leads of these patients were off target. In the cases from the literature, 30% off-drug motor improvement was seen in all three patients re-operated from GPi to STN and none of the three patients re-operated from STN to GPi. Only one of the three cases from the literature where any improvement was seen with the operation had a confirmed on target lead location after the first surgery, while the other two patients did not undergo post-operative imaging after the first surgery., Conclusions: Re-operation to a different target due to lack of effect appears to have a limited chance of leading to objective improvement if the leads were correctly placed during initial surgery., (© 2017 International Neuromodulation Society.)

Vibration exercise (VE) has been suggested as an effective training for improving muscle strength and coordination. However, the underlying physiological adaptation processes are not yet fully understood, limiting the development of safe and effective exercise protocols. To better understand the neuromuscular responses elicited by VE, we aimed at investigating the acute effects of superimposed vibration on the Hoffmann reflex (H-reflex), measured after fatiguing exercise. Twenty-five volunteers performed four isometric contractions of the right Flexor Carpi Radialis (FCR) with baseline load at 80% of their maximal voluntary contraction (MVC), both with no vibration and with superimposed vibration at 15, 30, and 45 Hz. Fatigue was estimated by MVC test and estimation of electromyographic spectral compression. H-reflex suppression was estimated as the relative decrease after exercise. Our results show that fatiguing exercise determined a decrease in H-reflex amplitude compared to rest condition while vibration determined a lower H-reflex suppression as compared to no vibration. The superimposition of 30-Hz vibration determined the largest acute reduction in force generating capacity (36 N, p < 0.05) and the lowest H-reflex suppression (20%, p < 0.05). These results suggest VE to be particularly suitable in rehabilitation programs for rapid restoration of muscle form and function after immobilization periods., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: There is an ongoing search for conditions that induce spontaneous subarachnoid hemorrhage (SAH). The seasonal pattern of SAH is shown in a large meta-analysis of the literature, but its explanation remains undecided. There is a clear need for sound meteorologic data to further elucidate the seasonal influence on SAH. Because of the stable and densely monitored atmospheric situation in the north of the Netherlands, we reviewed our unique cohort on the seasonal incidence of SAH and the association between SAH and local atmospheric changes., Methods: Our observational cohort study included 1535 patients with spontaneous SAH admitted to our neurovascular center in the north of the Netherlands between 2000 and 2015. Meteorologic data could be linked to the day of the ictus. To compare SAH incidences over the year and to test the association with meteorologic conditions, incidence rate ratios (IRRs) with corresponding 95% confidence intervals (CIs) were used, calculated by Poisson regression analyses., Results: Atmospheric pressure variations were significantly associated with aneurysmal SAH. In particular, the pressure change on the second and third day before the ictus was independently correlated to a higher incidence of aneurysmal SAH (IRR, 1.11; 95% CI, 1.00-1.23). The IRR for aneurysmal SAH in July was calculated 0.67 (95% CI, 0.49-0.92) after adjustment for temperature and atmospheric pressure changes., Conclusions: Atmospheric pressure variations are a delayed trigger for aneurysmal SAH. Also, a significantly decreased incidence of aneurysmal SAH was noted in July., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation (DBS) is an established treatment for refractory essential tremor (ET). Initially, the target of choice was the thalamic ventralis intermedius nucleus (VIM). However, the zona incerta (ZI) has been suggested as a superior target. Both targets are considered safe and effective, but a direct comparison between these targets is lacking., Methods: We analyzed a single-center cohort of 44 patients with ET treated with DBS between 1998 and 2017, targeting the VIM and/or ZI. Patient-reported outcome on the Washington Heights-Inwood Genetic Study of Essential Tremor rating scale, adverse events, and stimulation-induced side effects were assessed., Results: Patient-reported outcome of ZI DBS (-2.2 ± 1.2; 18 patients with 28 electrodes) was superior to VIM DBS (-1.2 ± 1.4; 10 patients with 19 electrodes) (P < 0.01). There was no difference in adverse events between implantations in VIM (45%) and ZI (46%). Dysarthria stimulation-induced side effects were significantly more often reported after VIM DBS (P = 0.01), whereas visual stimulation-induced side effects occurred more often after ZI DBS (P = 0.04)., Conclusions: In this study, ZI DBS was superior to VIM DBS in terms of patient-reported effectiveness. There was a comparable number of complications between both targets. This finding further supports ZI over VIM as the principal DBS target in essential tremor., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To examine the relation between depressive symptoms and outcome of carpal tunnel release (CTR)., Methods: Prospective study in a general hospital with data collection at baseline and 3 and 12 months after CTR. We quantified depressive symptoms using the Center for Epidemiologic Studies Depression (CES-D) scale and performed multivariable analyses on 2 outcome measures: (1) carpal tunnel syndrome (CTS) symptoms (Boston Carpal Tunnel Questionnaire [BCTQ]) and (2) palmar pain, focusing on preoperative CES-D and BCTQ score, sex, age, alcohol use, diabetes, and severity of nerve conduction abnormalities., Results: We included 227 patients. Before surgery, patients with depression had a higher BCTQ score than patients without depression. After 1 year, depressed patients had a higher BCTQ score and more palmar pain. The CES-D decreased by a median of 2 points from baseline to 1 year. This correlated with the decrease in BCTQ score. Multivariable analyses showed that preoperative depression had a small but statistically significant influence on palmar pain, but not on postoperative BCTQ score., Conclusions: Depression is not an independent predictor of residual CTS symptoms 1 year after CTR. Depressive symptoms in patients with CTS decrease after CTR, along with a decrease in CTS symptoms. The nature of this relationship is unknown. Patients with CTS and depression may expect a somewhat higher degree of palmar pain after CTR, the clinical relevance of which is small., Type of Study/level of Evidence: Prognostic II., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Neonatal Brachial Plexus Palsy (NBPP) may lead to permanent impairment of arm function. As NBPP occurs when central motor programs develop, these may be ill-formed. We studied elbow flexion and motor imagery with fMRI to search for abnormal motor programming. We compared the cortical activity of adults with conservatively treated NBPP to that of healthy individuals stratified for hand dominance, using fMRI BOLD tasks of elbow flexion and motor imagery of flexion. Additionally, resting-state networks and regional gray matter volume were studied. Sixteen adult NBPP patients (seven men; median age 29 years) and sixteen healthy subjects (seven men, median age 27 years) participated. Cortical activation was significantly higher in patients during flexion imagery compared to healthy individuals and it increased with lesion extent and muscle weakness. The contralateral and ipsilateral premotor cortex, and the contralateral motor cortex showed stronger activity during imagined flexion in the right-handed NBPP subjects compared to healthy individuals. Activity patterns during actual flexion did not differ between groups. No differences in resting-state network connectivity or gray matter amount were found between the groups. NBPP affected imagined but not actual elbow flexion, suggesting an impairment of motor planning which would indicate abnormal motor programming in NBPP., (Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)

The acetylcholine muscarinic M 1 receptor has been implicated in both psychosis and cognition. Post-mortem research has shown reduced muscarinic M 1 receptor density in 25% of chronic patients with schizophrenia. It is unknown whether reduced M 1 receptor density is related to cognitive symptoms of psychosis. We investigated the role of the M 1 receptor in separate cognitive domains in subjects with a psychotic disorder using a muscarinic M 1 antagonist as an acute pharmacological challenge. 33 young subjects with a psychotic disorder and 30 gender, age and IQ matched healthy controls were enrolled. All participants completed a comprehensive cognitive test battery twice: once after placebo and once after oral administration of 4mg. biperiden (M 1 antagonist). The order of drug administration was counterbalanced. Biperiden significantly negatively influenced both verbal (p< 0.001 and p=0.032) and visual learning and memory (p=0.028) in both groups. A medication x group interaction effect was found for reasoning and problem solving (p=0.005). No main or interaction effects were found for other cognitive domains. These results provide further in-vivo evidence that the M 1 receptor is involved in cognitive functioning, particularly verbal and visual memory processes. Lack of differential effects of biperiden between psychotic subjects and healthy controls may suggest that decreased M 1 receptor density is only present in chronic, older schizophrenia patients. However, it remains possible that differential effects of biperiden would be present in more severe cognitive impaired subjects with psychosis after several doses of biperiden instead of a single administration., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Objective: Tinnitus is a common entity that may lead to severe impairment in quality of life. An adequate treatment modality for severe tinnitus is currently lacking. Neurostimulation of the auditory tract may serve as a promising adjunct in tinnitus treatment. The aim is to investigate the effect of direct stimulation on the cochleovestibular nerve for intractable tinnitus., Methods: This study was conducted at the University Medical Center Groningen, The Netherlands. We studied 10 patients with severe, unilateral, intractable tinnitus, who were implanted with a cuff electrode around the cochleovestibular nerve between 2001 and 2013. All patients had preoperative ipsilateral hearing loss. Tinnitus Handicap Inventory (THI) scores and audiometric values were collected. Treatment success was determined based on the self-assessment of satisfactory usage by each patient., Results: The mean preoperative tinnitus duration was 8.0 ± 5.9 years. The preoperative THI score was 71 ± 18 points. During mean follow-up of 49 months, the mean THI reduction was 24 ± 26 points (P = 0.02). Treatment was regarded successful in 6 patients (60%). In these patients, tinnitus did not disappear, but transformed into a more bearable sound. In 4 patients, transient complications occurred, and 1 patient experienced permanent vertigo postoperatively. Furthermore, hearing deterioration was a result of implantation in 86% of the patients., Conclusions: Direct neurostimulation resulted in treatment success in a small majority of the patients, with a significant decrease in THI score. However, because of a high risk of additional hearing damage, this technique seems not viable for patients with moderate hearing loss., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this paper, we reflect on the implications for science, policy and practice of the recently introduced concept of Nature-Based Solutions (NBS), with a focus on the European context. First, we analyse NBS in relation to similar concepts, and reflect on its relationship to sustainability as an overarching framework. From this, we derive a set of questions to be addressed and propose a general framework for how these might be addressed in NBS projects by funders, researchers, policy-makers and practitioners. We conclude that: To realise their full potential, NBS must be developed by including the experience of all relevant stakeholders such that 'solutions' contribute to achieving all dimensions of sustainability. As NBS are developed, we must also moderate the expectations placed on them since the precedent provided by other initiatives whose aim was to manage nature sustainably demonstrates that we should not expect NBS to be cheap and easy, at least not in the short-term., (Copyright © 2016 British Geological Survey, NERC. Published by Elsevier B.V. All rights reserved.)

Background: In deep brain stimulation (DBS), accurate placement of the lead is critical. Target definition is highly dependent on visual recognition on magnetic resonance imaging (MRI). We prospectively investigated whether the 7-T MRI enabled better visualization of targets and led to better placement of leads compared with the 1.5-T and the 3-T MRI., Methods: Three patients with PD (mean, 55 years) were scanned on 1.5-, 3-, and 7-T MRI before surgery. Tissue contrast and signal-to-noise ratio were measured. Target coordinates were noted on MRI and during surgery. Differences were analyzed with post-hoc analysis of variance., Results: The 7-T MRI demonstrated a significant improvement in tissue visualization (P < 0.005) and signal-to-noise ratio (P < 0.005). However, no difference in the target coordinates was found between the 7-T and the 3-T MRI., Conclusions: Although the 7-T MRI enables a significant better visualization of the DBS target in patients with PD, we found no clinical benefit for the placement of the DBS leads., (Copyright © 2016 Elsevier Inc. All rights reserved.)