Einfluss der thalamischen Stimulation auf das Gangbild von Patienten mit fortgeschrittenem Essentiellen Tremor

In dieser Studie wurde der Einfluss der tiefen Hirnstimulation im Thalamus auf das Gangbild von Patienten mit fortgeschrittenem Essentiellen Tremor (ET) untersucht. Vorherige Untersuchungen haben gezeigt, dass Patienten mit einem fortgeschrittenen ET nicht nur an einem Tremor der Hände leiden, sondern auch an einer Gangataxie mit Schwierigkeiten vor allem beim Seiltänzergang. Die tiefe Hirnstimulation im Thalamus ist eine therapeutische Option für ET-Patienten, die an einem medikamentös nicht mehr zufriedenstellend behandelbaren Tremor leiden. Während der positive Einfluss der tiefen Hirnstimulation auf die Handfunktion in vorangegangenen Studien bereits gezeigt werden konnte, ist der Einfluss auf die Gangstörung von ET-Patienten bisher unklar. Elf ET-Patienten wurden in drei unterschiedlichen Bedingungen untersucht: mit ausgeschalteter Stimulation (Stim OFF), mit eingeschalteter Stimulation (Stim ON) und mit supratherapeutischer Stimulation (Stim ST). Vorherige klinische Untersuchungen haben gezeigt, dass eine Erhöhung der Stimulationsparameter oberhalb der therapeutisch notwendigen Stimulationsparameter zu einer Verschlechterung der Handfunktion führen kann. In der Stim ST-Bedingung sollte also untersucht werden, ob dadurch eine Verschlechterung des Gangbildes provoziert werden kann. Zur Untersuchung des Einflusses der tiefen Hirnstimulation auf den Tremor von ET-Patienten haben wir eine modifizierte Version der Fahn-Tolosa-Marin Tremor Rating Scale (TRS) verwendet. Zur Charakterisierung des Einflusses auf die Ataxie haben wir die International Cooperative Ataxia Rating Scale (ICARS) angewendet. Das Gangbild von ET- Patienten wurde mit Hilfe der folgenden drei Paradigmen untersucht: 1. Normaler und Seiltänzergangs auf ebenem Boden, 2. Modifizierter Seiltänzergang auf dem Laufband, bei dem die Patienten sich an einer Querstange festhalten durften, 3. Normales Gehen auf dem Laufband. Die Laufbanduntersuchungen wurden mit Hilfe eines dreidimensionalen optokinetischen Systems analysiert. Als Vergleichsgruppe dienten zehn gesunde Kontrollpersonen im gleichen Alter wie die ET-Patienten. Die Untersuchung erbrachte folgende Ergebnisse: 1. In der Stim OFF-Bedingung zeigte sich in allen drei Gangparadigmen eine Gangataxie. Durch die Stim ON-Bedingung kam es zu einer Verbesserung der Ataxie, durch die Stim ST-Bedingung zu einer Verschlechterung. 2. Während des Seiltänzergangs auf ebenem Boden zeigten die Patienten in der Stim OFF und der Stim ST-Bedingung eine höhere Anzahl von Fehltritten und eine geringere Gehgeschwindigkeit als in der Stim ON-Bedingung. 3. Während des modifizierten Seiltänzergangs auf dem Laufband (Festhalten mit der Hand an der Stange) kam es in der Stim ON-Bedingung zu einer deutlichen Reduktion der räumlichen und zeitlichen Variabilität der Fußbewegungen, welche Werte von gesunden Kontrollpersonen erreichten. Hingegen zeigten sich in der Stim OFF und Stim ST-Bedingung deutlich erhöhte Werte für die räumliche und zeitliche Variabilität. Dies spricht für eine Verbesserung der Ataxie von Beinbewegungen in der Stim ON-Bedingung im Vergleich zur Stim OFF- und Stim ST-Bedingung. 4. Während des normalen Gehens auf dem Laufband kam es in der Stim ON-Bedingung im Vergleich zur Stim OFF- und Stim ST-Bedingung zu einer signifikanten Reduktion der Schrittweite, einem Anstieg des Verhältnisses zwischen Einbein- und Zweibeinstandphase, einer Zunahme der Gehgeschwindigkeit und der Exkursion im Fußgelenk. Dies spricht für eine Zunahme der Gangstabilität während eingeschalteter Stimulation im Vergleich zur Stim OFF- und Stim ST- Bedingung. 5. Eine Korrelation mit dem TRS zeigte, dass die Effekte auf das Gangbild unabhängig von dem Einfluss der tiefen Hirnstimulation auf den Tremor auftraten. Die Ergebnisse dieser Studie zeigen, dass die tiefe Hirnstimulation im Thalamus zu einer Verbesserung des Gangbilds von ET-Patienten in der Stim ON-Bedingung und zu einer Verschlechterung in der Stim ST-Bedingung führt. Die mutmaßlich zugrunde liegende zerebelläre Dysfunktion von ET-Patienten kann also durch die tiefe Hirnstimulation unabhängig von dem gleichzeitig bestehenden Tremor moduliert werden. Es wird diskutiert, dass die Stim ON- und Stim ST-Bedingung zwei unterschiedliche zerebrale Kreisläufe beeinflusst. In der Stim ON-Bedingung kommt es zu einer Beeinflussung der kortiko-thalamo-kortikalen Verbindung, in der Stim ST-Bedingung zu einer Beeinflussung der zerebello-thalamo-kortikalen Projektionen

Humoral immune response after different SARS-CoV-2 vaccination regimens

Results After the first vaccination, the prevalence of IgG directed against the (trimeric) SARS-CoV-2 S-protein and its receptor binding domain (RBD) varied from 55-95% (AZD1222) to 100% (BNT162b2), depending on the vaccine regimen and the SARS-CoV-2 antigen used. The booster vaccination resulted in 100% seroconversion and the occurrence of highly avid IgG, which is directed against the S-protein subunit 1 and the RBD, as well as VNA against VOC B.1.1.7, while anti-NP IgGs were not detected. The results of the three anti-SARS-CoV-2 IgG tests showed an excellent correlation to the VNA titres against this VOC. The agreement of cVNT and sVNT results was good. However, the sVNT seems to overestimate non- and weak B.1.1.7-neutralising titres. The anti-SARS-CoV-2 IgG concentrations and the B.1.1.7-neutralising titres were significantly higher after heterologous vaccination compared to the homologous AZD1222 scheme. If VOC B.1.617.2 was used as antigen, significantly lower VNA titres were measured in the cVNT, and three (33.3%) vector vaccine recipients had a VNA titre < 1:10. Conclusions Heterologous SARS-CoV-2 vaccination leads to a strong antibody response with anti-SARS-CoV-2 IgG concentrations and VNA titres at a level comparable to that of a homologous BNT162b2 vaccination scheme. Irrespective of the chosen immunisation regime, highly avid IgG antibodies can be detected just 2 weeks after the second vaccine dose indicating the development of a robust humoral immunity. The reduction in the VNA titre against VOC B.1.617.2 observed in the subgroup of 26 individuals is remarkable and confirms the immune escape of the delta variant

Kinetics of Nucleo- and Spike Protein-Specific Immunoglobulin G and of Virus-Neutralizing Antibodies after SARS-CoV-2 Infection

Kinetics of neutralizing antibodies and immunoglobulin G (IgG) against the nucleo (N) or spike (S) proteins of severe acute respiratory syndrome coronavirus type2 (SARS-CoV-2) were studied in patients up to 165 days after PCR diagnosis of infection. Two immunoassays were selected out of eight IgG or total antibody tests by comparing their specificities and sensitivities. Sensitivities were calculated with convalescent sera from 26 PCR-confirmed cases, of which 76.9% had neutralizing antibodies (>1:10). Stored sera collected during the summer 2018 (N = 50) and winter seasons 2018/2019 (N = 50) were included to demonstrate the test specificities. IgG kinetics, avidities, and virus-neutralizing capacities were recorded over up to 165 days in eleven patients and five individuals from routine diagnostics. Sensitivities, specificities, and diagnostic accuracies ranged between 80.8-96.3%, 96.0-100%, and 93.7-99.2%, respectively. Nearly all results were confirmed with two different SARS-CoV-2-specific immunoblots. Six (54.4%) patients exhibited stable N-specific IgG indices over 120 days and longer; three of them developed IgG of high avidity. The S-specific IgG response was stable in ten (91.0%) patients, and eight (72.7%) had neutralizing antibodies. However, the titers were relatively low, suggesting that sustained humoral immunity is uncertain, especially after outpatient SARS-CoV-2 infection

Development of SARS-CoV-2 Specific IgG and Virus-Neutralizing Antibodies after Infection with Variants of Concern or Vaccination

The humoral immunity after SARS-CoV-2 infection or vaccination was examined. Convalescent sera after infection with variants of concern (VOCs: B.1.1.7, n = 10; B.1.351, n = 1) and sera from 100 vaccinees (Pfizer/BioNTech, BNT162b2, n = 33; Moderna, mRNA-1273, n = 11; AstraZeneca, ChAdOx1 nCoV-19/AZD1222, n = 56) were tested for the presence of immunoglobulin G (IgG) directed against the viral spike (S)-protein, its receptor-binding domain (RBD), the nucleoprotein (N) and for virus-neutralizing antibodies (VNA). For the latter, surrogate assays (sVNT) and a Vero-cell based neutralization test (cVNT) were used. Maturity of IgG was determined by measuring the avidity in an immunoblot (IB). Past VOC infection resulted in a broad reactivity of anti-S IgG (100%), anti-RBD IgG (100%), and anti-N IgG (91%), while latter were absent in 99% of vaccinees. Starting approximately two weeks after the first vaccine dose, anti-S IgG (75-100%) and particularly anti-RBD IgG (98-100%) were detectable. After the second dose, their titers increased and were higher than in the convalescents. The sVNT showed evidence of VNA in 91% of convalescents and in 80-100%/100% after first/second vaccine dose, respectively. After the second dose, an increase in VNA titer and IgGs of high avidity were demonstrated by cVNT and IB, respectively. Re-vaccination contributes to a more robust immune response

Gait ataxia in essential tremor is differentially modulated by thalamic stimulation

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Metabolite Ratios as Quality Indicators for Pre-Analytical Variation in Serum and EDTA Plasma

In clinical diagnostics and research, blood samples are one of the most frequently used materials. Nevertheless, exploring the chemical composition of human plasma and serum is challenging due to the highly dynamic influence of pre-analytical variation. A prominent example is the variability in pre-centrifugation delay (time-to-centrifugation; TTC). Quality indicators (QI) reflecting sample TTC are of utmost importance in assessing sample history and resulting sample quality, which is essential for accurate diagnostics and conclusive, reproducible research. In the present study, we subjected human blood to varying TTCs at room temperature prior to processing for plasma or serum preparation. Potential sample QIs were identified by Ultra high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) based metabolite profiling in samples from healthy volunteers (n = 10). Selected QIs were validated by a targeted MS/MS approach in two independent sets of samples from patients (n = 40 and n = 70). In serum, the hypoxanthine/guanosine (HG) and hypoxanthine/inosine (HI) ratios demonstrated high diagnostic performance (Sensitivity/Specificity > 80%) for the discrimination of samples with a TTC > 1 h. We identified several eicosanoids, such as 12-HETE, 15-(S)-HETE, 8-(S)-HETE, 12-oxo-HETE, (±)13-HODE and 12-(S)-HEPE as QIs for a pre-centrifugation delay > 2 h. 12-HETE, 12-oxo-HETE, 8-(S)-HETE, and 12-(S)-HEPE, and the HI- and HG-ratios could be validated in patient samples

‘Bonkers but good!’ – Using illustration-based interview methods to understand land management and conservation visions

Forest biodiversity studies conduct Visions help to understand common ground and tensions among citizens and stakeholders, supporting inclusive land management and conservation solutions to the climate emergency and biodiversity crisis. With careful design and sufficient resource, it is possible to bring together communities and other stakeholders to share perspectives and deliberate desired futures, identifying more acceptable alternatives and avoiding costly delays. We evaluated researcher and participant experiences of illustration-based interviews to understand land management visions using four studies in Scotland, The Netherlands and Spain. These studies used STREAMLINE, a visual mixed-method interview format using thematic illustrated canvases designed to provide an inclusive and creative framing for participants to contemplate their desired future. Participants enjoyed the informal visual format, which reduced pressure, increased comfort through the research process, and helped their thinking and reflection about complex topics. They also valued being listened to and having the opportunity to share their views. Researchers appreciated the ability to triangulate rich qualitative data with a variety of quantitative measure through the mixed-method format and the flexibility to adapt the canvases to suit their research aims. Positive participant experience made facilitation easier and was stimulating for the researchers. The credibility and legitimacy of illustration-based interviews will ultimately depend on specific research design-decisions and testing, which can make the approach more resource intensive than conventional interviews. While organisal barriers should be considered realistically, illustration-based interviews can have high saliency by providing useful and usable insights that strengthen land management policy and planning. Inclusive Conservation Participatory planning Governance Visions Visual methods Participatory methods d across Europe use a multitude of forestry terms, often inconsistently. This hinders the comparability across studies and makes the assessment of the impacts of forest management on biodiversity highly context-dependent. Recent attempts to standardize forestry and stand description terminology mostly used a top-down approach that did not account for the perspectives and approaches of forest biodiversity experts. This work aims to establish common standards for silvicultural and vegetation definitions, creating a shared conceptual framework for a consistent study on the effects of forest management on biodiversity. We have identified both strengths and weaknesses of the silvicultural and vegetation information provided in forest biodiversity studies. While quantitative data on forest biomass and dominant tree species are frequently included, information on silvicultural activities and vegetation composition is often lacking, shallow, or based on broad and heterogeneous classifications. We discuss the existing classifications and their use in European forest biodiversity studies through a novel bottom-up and top-driven review process, and ultimately propose a common framework. This will enhance the comparability of forest biodiversity studies in Europe, and puts the basis for effective implementation and monitoring of sustainable forest management policies. The standards here proposed are potentially adaptable and applicable to other geographical areas and could be extended to other forest interventions.publishedVersio

‘Bonkers but good!’ – Using illustration-based interview methods to understand land management and conservation visions

Visions help to understand common ground and tensions among citizens and stakeholders, supporting inclusive land management and conservation solutions to the climate emergency and biodiversity crisis. With careful design and sufficient resource, it is possible to bring together communities and other stakeholders to share perspectives and deliberate desired futures, identifying more acceptable alternatives and avoiding costly delays. We evaluated researcher and participant experiences of illustration-based interviews to understand land management visions using four studies in Scotland, The Netherlands and Spain. These studies used STREAMLINE, a visual mixed-method interview format using thematic illustrated canvases designed to provide an inclusive and creative framing for participants to contemplate their desired future. Participants enjoyed the informal visual format, which reduced pressure, increased comfort through the research process, and helped their thinking and reflection about complex topics. They also valued being listened to and having the opportunity to share their views. Researchers appreciated the ability to triangulate rich qualitative data with a variety of quantitative measure through the mixed-method format and the flexibility to adapt the canvases to suit their research aims. Positive participant experience made facilitation easier and was stimulating for the researchers. The credibility and legitimacy of illustration-based interviews will ultimately depend on specific research design-decisions and testing, which can make the approach more resource intensive than conventional interviews. While organisational barriers should be considered realistically, illustration-based interviews can have high saliency by providing useful and usable insights that strengthen land management policy and planning

Laser power stabilization for improved ablation depth uniformity

Due to low heat deposition into the surrounding material, ps-lasers are well suited for a precise ablation of micro structures. However, to obtain constant removal rates the laser parameters as well as the environmental conditions need to be kept stable. For our investigations we used a frequency tripled ps-laser operating at 355 nm. Without any additional power stabilization system, long term micro structuring processes of OFE-copper typically resulted in depth variations of about +/- 10 % which are strongly correlated with detected laser power fluctuations. The developed system for laser power stabilization takes advantage of the linear polarized radiation of our laser source. With a fast photoelectric detector the power fluctuations are measured. A specifically designed feedback control system turns a half wave plate mounted in a piezo driven rotation stage to decouple fluctuating power fractions via a polarizing beam splitter. We demonstrate a nearly constant laser power at the work piece. Substantially improved ablation depth uniformity is verified by a profilometric analysis of directly ablated diffractive structures