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The hippocampus is the most prominent single region of interest (ROI) for the diagnosis and prediction of Alzheimer's disease (AD). However, its suitability in the earliest stages of cognitive decline, i.e., subjective cognitive decline (SCD), remains uncertain which warrants the pursuit of alternative or complementary regions. The amygdala might be a promising candidate, given its implication in memory as well as other psychiatric disorders, e.g. depression and anxiety, which are prevalent in SCD. In this 7 tesla (T) magnetic resonance imaging (MRI) study, we aimed to compare the contribution of volumetric measurements of the hippocampus, the amygdala, and their respective subfields, for early diagnosis and prediction in an AD-related study population.Participants from a longitudinal study were grouped into SCD (n = 29), mild cognitive impairment (MCI, n = 23), AD (n = 22) and healthy control (HC, n = 31). All participants underwent 7T MRI at baseline and extensive neuropsychological testing at up to three visits (baseline n = 105, 1-year n = 78, 3-year n = 39). Analysis of covariance (ANCOVA) was used to assess group differences of baseline volumes of the amygdala and the hippocampus and their subfields. Linear mixed models were used to estimate the effects of baseline volumes on yearly changes of a z-scaled memory score. All models were adjusted to age, sex and education.Compared to the HC group, individuals with SCD showed smaller amygdala ROI volumes (range across subfields -11% to -1%), but not hippocampus ROI volumes (-2% to 1%) except for the hippocampus-amygdala-transition-area (-7%). However, cross-sectional associations between baseline memory and volumes were smaller for amygdala ROIs (std. ß [95% CI] ranging between 0.16 [0.08; 0.25] and 0.46 [0.31; 0.60]) than hippocampus ROIs (between 0.32 [0.19; 0.44] and 0.53 [0.40; 0.67]). Further, the association of baseline volumes with yearly memory change in the HC and SCD groups was similarly weak for amygdala ROIs and hippocampus ROIs. In the MCI group, volumes of amygdala ROIs were associated with a relevant yearly memory decline [95% CI] ranging between -0.12 [-0.24; 0.00] and -0.26 [-0.42; -0.09] for individuals with 20% smaller volumes than the HC group. However, effects were stronger for hippocampus ROIs with a corresponding yearly memory decline ranging between -0.21 [-0.35; -0.07] and -0.31 [-0.50; -0.13].Volumes of amygdala ROIs, as determined by 7T MRI, might contribute to objectively and non-invasively identify patients with SCD, and thus aid early diagnosis and treatment of individuals at risk to develop dementia due to AD, however associations with other psychiatric disorders should be evaluated in further studies. The amygdala's value in the prediction of longitudinal memory changes in the SCD group remains questionable. Primarily in patients with MCI, memory decline over 3 years appears to be more strongly associated with volumes of hippocampus ROIs than amygdala ROIs.

Aquaporin-4 immunoglobulin-G positive (AQP4-IgGIn this cross-sectional study, clinically stable patients with AQP4-IgGHigher sGFAP concentrations were associated with thinner ganglion cell-inner plexiform layer (β (95% confidence interval (CI)) = -0.75 (-1.23 to -0.27), p = 0.007) and shallower fovea (average pit depth: β (95%CI) = -0.59 (-0.63 to -0.55), p = 0.020) in NMOSD non-ON eyes. Participants with pathological P100 latency had higher sGFAP (median [interquartile range]: 131.32 [81.10-179.34] vs. 89.50 [53.46-121.91] pg/ml, p = 0.024). In MOGAD, sGFAP was not associated with retinal structural or visual functional measures.The association of sGFAP with structural and functional markers of afferent visual system damage in absence of ON suggests that sGFAP may be a sensitive biomarker for chronic disease severity in clinically stable AQP4-IgG

Summary Background Pulmonary dysfunction and cardiovascular disease are major causes of impaired health status in later life, and co-development of these diseases has been reported. Aim To better understand the pathobiology involved in the co-development of these diseases. Methods We investigated the impact of pulmonary dysfunction on the development of cardiovascular disease among people aged ≥ 50 years in the English longitudinal study of ageing (ELSA). Hazard ratios were estimated by Cox proportional hazards regression models, with and without a time-dependent update of exposure and confounders. Pulmonary function was divided into three categories, with the least affected category as the reference. Results People with pulmonary dysfunction were at higher risk of developing cardiovascular disease than those with normal pulmonary function: the hazard ratio for pulmonary dysfunction versus healthy in the time-dependent crude analysis of model 1, adjusted for age, body mass index, sex, angina pectoris and heart arrhythmia, was 1.49 (95% confidence interval 1.2–1.9). The effect varied with the precise definition of pulmonary dysfunction and the subtype of the cardiovascular disease, and decreased after correction for some additional confounders but not after correction for inflammatory biomarkers. Conclusions A history of pulmonary disease increased the risk of developing cardiovascular disease, but inflammation did not seem to alter the effect of pulmonary dysfunction on cardiovascular disease development. This insight may lead to better understanding and treatment of cardiovascular comorbidities in pulmonary disease; it also indicates that the potentially beneficial effect of targeted anti-inflammatory drugs for pulmonary disease, in terms of reducing cardiovascular risk in these patients, may be limited.

Aims To estimate the prevalence of parental substance use disorder (PSUD) in the general population based on young adults’ reports adjusted for non-participation using register-based indicators of PSUD. Design A national sample survey study combined with a retrospective register-based study. Setting Denmark. Participants 10,414 young people (aged 15–25 years) invited to two national sample surveys in 2014 and 2015 (5,755 participants and 4,659 non-participants). Measurements A crude prevalence of PSUD was calculated based on participants’ reports. Parental data from medical, mortality, prescription, and treatment registers (from the young adults’ birth until the time of the surveys) were used to estimate a register-based prevalence of PSUD for both participants and non-participants. Differences between participants and non-participants were analysed using bivariate comparisons. Inverse probability weighting was used to adjust for bias due to non-participation. The crude prevalence of PSUD based on survey data was adjusted using the ratio of incidence proportion of the register-based PSUD compared with the survey-based PSUD. Findings A total of 731 (12.7%) of the 5,755 survey participants reported PSUD. Register-based PSUD was more common among non-participants (856/4,659; 18.4%) compared with participants (738/5,755; 12.8%, OR = 1.53, 95% CI 1.38–1.70). The adjusted estimate of the survey-based PSUD increased by 2.5 percentage points, from 12.7% to 15.2%. Conclusions In the absence of register data, youth-reported PSUD is likely to underestimate the number of young people experiencing PSUD.

Background Tuberosity repair in shoulder fracture prosthesis implantation still remains a challenge often leading to poor functional outcomes, despite a variety of materials and suggested suture patterns. We aimed to evaluate, which forces currently used suture and cerclage materials withstand and to assess whether they are useful with regard to stability of reconstruction of tuberosities and which failure modes they display. Material and methods Using sheep infraspinatus tendons with attached tuberosities three different suture materials (suture 1: Ethibond size 2; suture 2: Orthocord size 2; suture 3: Fiberwire size 5) and a 0.8 mm titanium cerclage wire were investigated. For each suture material as well as the cerclage wire 6 tests were carried out. A material testing machine was used to perform cyclic loading tests (20 mm/min, Fmin = 50 N, Fmax = 100 N, respectively after 50 cycles: Fmax + 50 N until failure). Outcome measures and thus comparison criteria were the maximum holding force, number of cycles reached, total elongation of the system (tendon and suture) and qualitative appraisal and documentation of the mechanism of failure. Results Overall average maximum forces between the fixation materials differed significantly (P = 0.003), especially suture 3 (braided polyethylene coating, non-resorbable polyfile UHMW core) displayed superior results in comparison to the cerclage wire (P = 0.016). Although, primary elongation of the cerclage technique was significantly lower compared to the suture materials (P = 0.002). All tests showed a high initial lengthening and caused incision-like defects in the bone or tendon and led to failure and huge displacement of the tuberosities. Discussion Currently used suture and cerclage materials have a limited usefulness for refixation of tuberosities due to an increased risk of obstruction for bony consolidation. Level of evidence Basic science, Biomechanics.

Regulatory agencies overseeing the labor market often rely on worker complaints to target their enforcement resources. This system might be counterproductive if the workers at risk of poor working conditions also face high barriers to complain. We examine the implications of complaint-based enforcement in the context of the U.S. Occupational Safety and Health Administration (OSHA). We provide descriptive evidence that Hispanic workers face higher barriers to complain: workplaces with large shares of Hispanic workers have higher injury rates but issue fewer complaints to OSHA. We show that workers' willingness to complain causally affects the job hazards they face. At workplaces with large shares of Hispanic workers, counties’ participation in an immigration enforcement program reduced complaints to OSHA, but increased injuries. Our results highlight that using complaints to direct regulatory enforcement can exacerbate existing inequalities when workers face differential barriers to complain.

Highlights • Injury to major white matter pathways during language-area associated glioma surgery often results in permanent aphasia. • DTI-based tractography of language pathways allows to correlate individual tract injury profiles with functional outcome. • Infiltration of the AF is particularly associated with functional deterioration. • The temporo-parieto-occipital junction and the temporal stem were confirmed as pivotal functional nodes. • Standardized DTI-based tractography can help to determine the individual aphasia risk profile before surgery., Objectives Injury to major white matter pathways during language-area associated glioma surgery often leads to permanent loss of neurological function. The aim was to establish standardized tractography of language pathways as a predictor of language outcome in clinical neurosurgery. Methods We prospectively analyzed 50 surgical cases of patients with left perisylvian, diffuse gliomas. Standardized preoperative Diffusion-Tensor-Imaging (DTI)-based tractography of the 5 main language tracts (Arcuate Fasciculus [AF], Frontal Aslant Tract [FAT], Inferior Fronto-Occipital Fasciculus [IFOF], Inferior Longitudinal Fasciculus [ILF], Uncinate Fasciculus [UF]) and spatial analysis of tumor and tracts was performed. Postoperative imaging and the resulting resection map were analyzed for potential surgical injury of tracts. The language status was assessed preoperatively, postoperatively and after 3 months using the Aachen Aphasia Test and Berlin Aphasia Score. Correlation analyses, two-step cluster analysis and binary logistic regression were used to analyze associations of tractography results with language outcome after surgery. Results In 14 out of 50 patients (28%), new aphasic symptoms were detected 3 months after surgery. The preoperative infiltration of the AF was associated with functional worsening (cc = 0.314; p = 0.019). Cluster analysis of tract injury profiles revealed two areas particularly related to aphasia: the temporo-parieto-occipital junction (TPO; temporo-parietal AF, middle IFOF, middle ILF) and the temporal stem/peri-insular white matter (middle IFOF, anterior ILF, temporal UF, temporal AF). Injury to these areas (TPO: OR: 23.04; CI: 4.11 – 129.06; temporal stem: OR: 21.96; CI: 2.93 – 164.41) was associated with a higher-risk of persisting aphasia. Conclusions Tractography of language pathways can help to determine the individual aphasia risk profile pre-surgically. The TPO and temporal stem/peri-insular white matter were confirmed as functional nodes particularly sensitive to surgical injuries.

Oral anticoagulation (OAC) substantially reduces stroke risk in patients with atrial fibrillation (AF) at risk for stroke. Whether non-vitamin K-dependent oral anticoagulants (NOACs) improve OAC use in stroke prevention requires investigation.To investigate temporal trends of OAC use in patients with known AF pre-stroke, we retrospectively analyzed records of 6,803 stroke patients admitted in 2003-2004 (n=1,496), 2008-2010 (n=1,638) or 2013-2015 (n=3,669) to the Charité-Universitätsmedizin Berlin, Germany. Adjusted regression models were used to identify factors associated with OAC use.Of 1,209 AF patients (mean age 79 years, 55.9% female) with given indication for OAC according to the CHADS2/CHA2DS2-VASc score, 484 (40.0%) were anticoagulated prior to the index stroke, 458 (37.9%) received antiplatelets and 236 (19.5%) had no antithrombotic medication. Compared to 2003-2004 and 2008-2010, there was a higher rate of pre-admission OAC in 2013-2015 (28.2% vs. 49.6%, p

Background Common carotid artery intima-media thickness (CCA-IMT) is an established marker for atherosclerosis. The role of triglycerides in CCA-IMT remains controversial. We sought to determine if elevated fasting and post-challenge triglycerides are associated with CCA-IMT. Methods All acute ischemic stroke patients who participated in the Berlin "Cream & Sugar" study in the Charite Virchow and Charite Mitte Campuses between January 2009 and January 2014 and underwent carotid artery ultrasound studies were eligible for inclusion. A combined oral glucose and triglyceride tolerance test was performed 3–7 days after first ever ischemic stroke. Patients were classified according to triglyceride metabolism—namely, (1) patients reaching a maximum triglyceride levels 3 h post-challenge ("fast metabolizers," n = 37), (2) patients with increasing triglycerides 4 (medium metabolizers, n = 64), and (3) 5 h post-challenge ("slow metabolizers," n = 44; 13 missing). Results We included 158 patients (34% female; mean age 63 years, SD 14). Absolute non-fasting triglyceride levels were positively associated with CCA-IMT. A final multiple regression model revealed that older age, more severe strokes, and higher levels of fasting triglycerides were significantly and independently associated with higher mean CCA-IMT. Older age, higher waist-to-hip ratio, and higher levels of thyroid-stimulating hormone were independently associated with higher maximum CCA-IMT. Conclusion Fasting triglycerides but not post-challenge triglycerides associate with CCA-IMT. An oral fat challenge may not add information on atherosclerotic status in ischemic stroke patients. Clinical Trial Registration Information: The Berlin "Cream & Sugar" study is registered with EudraCT (2009-010356-97) and clinicaltrials.gov (NCT 01378468).

The present study focuses on the influence of longitudinal and charge weld seams on the possibility for their non-destructive testing in extruded profiles. For this, aluminum and magnesium alloys were extruded at different extrusion conditions using porthole dies and prepared for non-destructive testing. First, the electrical conductivity of profiles containing charge welds was measured on two measuring paths over the length of the profile and correlated to the respective mechanical properties and microstructures. Second, detailed measurements on specimens taken from similar profiles were done in order to evaluate and compare the detectability of longitudinal weld seams for different alloys.

Introduction Rehabilitation of cognitive deficits has been voted ‘#1 research priority’ for patients suffering from stroke ( Saunders et al., 2014 ). Aerobic fitness training may modulate cognitive performance either by enhancing neuroplasticity or by increasing brain oxygenation. The majority of studies in this area have focused on motor function; its effect on cognitive performance is not well understood yet. The current study therefore aims to evaluate the influence of aerobic fitness intervention on cognitive functions in subacute stroke patients, and tries to elucidate the mechanisms underlying this effect. Methods The endpoint-blinded multicenter trial Physical Activity in Subacute Stroke ( Floel et al., 2014 ) (NCT01953549) randomized 194 patients (5–45 days post stroke, Barthel-Index ⩽ 65) to receive either a 4 week aerobic fitness intervention (PHYS) or a relaxation program (RELAX) of equal length. 100 patients additionally received an MRI pre and post intervention (Biomarkers and Perfusion – Training-Induced changes after Stroke (BAPTISe), NCT01954797). Image acquisition included T1 MPRAGE (1 mm isovoxel), Resting State fMRI (3 × 3v4 mm × 150 scans, TR = 2.3 s) and DTI (64 directions plus 9 × B0, 2.3 mm isovoxel). Cognition was assessed via neuropsychological tests (MoCA, Trail Making Test Part A & B (TMT)) in all patients pre and post intervention and 6 months poststroke. Statistical modeling accounted for age, functional ambulation and center effects. Results In 70/190 BAPTISe patients (60 PHYS, 49 RELAX, median 70 yrs, median NIHSS 9), T1-weighted images were available for Baseline and post intervention. Mean (standard deviation) Hippocampus volume was 3.5 (0.6) mm3 for the left and 3.6 (0.5) mm3 for the right hemisphere respectively. MoCA sum score and TMT A and B changed significantly ( p 0.001 ) between pre and post intervention across groups, but did not differ significantly between groups. 6 months post-stroke PHYS group showed a significant better outcome in MoCA sum score ( p 0.01 ) compared to the RELAX group. Further analyses on mechanisms underlying this findings are ongoing. Discussion Aerobic fitness training during the rehabilitation phase of subacute stroke patients shows some indication of improving cognitive recoverys but not immediately following the intervention. Analyses on underlying mechanisms including lesion location and lesion volume are ongoing, and will be presented on the DGKN 2018.

Introduction Recently, growing interest emerged in the enhancement of human potential by means of non-invasive brain stimulation. In particular, anodal transcranial direct current stimulation (atDCS) has been shown to exert beneficial effects on motor and higher cognitive functions. However, the majority of transcranial direct current stimulation (tDCS) studies have assessed effects of single stimulation sessions that are mediated by transient neural modulation. Studies assessing the impact of multiple stimulation sessions on learning that may induce long-lasting behavioural and neural changes are scarce and have not yet been accomplished in the language domain in healthy individuals. Method The present study probed the potential of atDCS to enhance language learning over multiple days by employing an explicit word learning paradigm. Forty healthy young participants were randomized to learning with either simultaneous atDCS or sham stimulation ( N = 20/group; comparable regarding demographic variables and neurocognitive status). All participants acquired a novel vocabulary (familiar and novel object picture – non-word pairs) over five consecutive days. Two memory tasks (free recall; forced choice recognition tasks) were administered immediately after each training session. A one week follow-up tested the maintenance of learning success. Results Linear mixed effects model analysis revealed superior learning during atDCS compared to sham stimulation for both familiar and novel objects. atDCS yielded a steeper learning curve and significantly more pronounced learning at the end of the training during the recall task. During the recognition task, the atDCS group reached ceiling levels earlier and overall learning success was greater. For both tasks, beneficial atDCS effects were maintained during the follow-up assessment. Conclusions The present study provides direct evidence that atDCS administered during multiple learning sessions facilitates language learning and that effects are maintained over time. This study contributes important novel information about the extent of stimulation effects in the healthy brain, thereby highlighting the potential of atDCS to enhance language recovery after stroke.

The aim of this study was to evaluate whether a computer-based 3-item version (Alcohol Use Disorders Identification Test–Consumption [AUDIT-C]) of the Alcohol Use Disorders Identification Test (AUDIT) identifies alcohol use disorder (AUD) in the same patients as the full 10-item version in 809 women and 747 men in an anesthesiology preoperative assessment clinic. According to cutoffs used (AUDIT: 5–8 points, AUDIT-C: 4–6 points), rate of disagreement (AUDIT-positive and AUDIT-C-negative or vice versa) ranged between 4% and 31% (men) and between 4% and 19% (women). In male patients, 15% were positive for both the AUDIT (≥8 points) and the AUDIT-C (≥6 points), 7% were positive for AUDIT-C only, and 4% were positive for AUDIT only. In female patients, using cutoffs of 5 more points (AUDIT) and 4 or more points (AUDIT-C), 16% were positive for both versions, 9% were positive for AUDIT-C only, and 2% were positive for AUDIT only. The AUDIT and AUDIT-C seem to identify AUD in differing patients.

This study focused on the extrusion of hybrid sheet metals. Co-extrusion of profiles having sheet metals as reinforcing elements are a promising alternative to the more common rotation-symmetric composite rods or wire reinforced profiles. The influence of non-rotation-symmetric die geometry was investigated by extruding aluminum alloy billets with three different types of sheet metals as core material and the aluminum alloy (AlMgSi1 EN AW-6082) as sleeve material. The hybrid sheet metals were analyzed by non-destructive testing using ultrasonic testing and X-ray inspection. The steel (DC 06) and the titanium (titanium grade 1) cores fractured during extrusion, while the magnesium alloy core (AZ31) showed a uniform deformation. A new deformation mode in co-extrusion has been found for the titanium grade 1 core which most likely fractured due to a combination of tensile and shear stresses caused by the material flow of the non-symmetrical cross-section of the profile. The DC 06 core predominantly fractured due to tensile stresses. Microstructural analysis showed a decrease in thickness for all cores, with AZ31 showing the highest reduction and DC 06 the lowest. It was found that no intermetallic phases occurred having a DC 06 or titanium grade 1 core. However, EDX line scans indicated the start of diffusion processes at the interphase of EN AW-6082 and DC 06. An intermetallic phase could be observed for the specimens having an AZ31 core, EDX line scans showed this to be the Al 3 Mg 2 (β) phase. The experimental results state that special constraints have to be taken into consideration, especially concerning material flow of the sleeve material, when extruding hybrid sheet metals with reinforcements of higher strength sheet metal cores.