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The objective of this paper is to investigate the debonding behavior of the interface between continuously and discontinuously fiber reinforced thermoplastics using the climbing drum peel test. The study emphasizes on the importance of considering different climatic boundary conditions on the properties of thermoplastics. Specimens with varying moisture contents, from 0m.% up to above 6m.% are prepared and tested. It is observed that an increase in moisture content from 0m.% to 2m.% results in an increase of the fracture surface energy from 1.07·103J/m2 to 2.40·103J/m2 required to separate the two materials, but a further increase in moisture to 6.35m.% conversely results in a subsequent decrease of the required energy to 1.91·103J/m2. The study presents an explanatory model of increasing plasticization of the polymer due to increased polymer chain mobility, which results in more deformation energy being required to propagate the crack, which is corroborated in SEM investigations of the fracture surface. A further increase in humidity leads to polymer degradation due to hydrolysis, which explains the subsequent reduction of the fracture energy. The experimental set up is modeled numerically for the first time with cohesive surfaces, which could successfully reproduce the effective force-displacement curve in the experiment by varying the interface parameters in the model over an influence length, allowing the conclusion of a process induced variation in the interface properties over a specific consolidation length.

Background and purposeThe present study aimed to investigate whether cerebral microbleeds (CMB) are associated with vascular cognitive decline (VCD) already in the early course after ischemic stroke, and—if so—whether distinct cognitive domains are affected more preferentially by CMB.MethodsIn a prospective cohort study, cognitive performance was examined in 33 stroke patients showing ≥ 1 CMB on MRI. Matched for age, gender, clinical and radiological characteristics, 33 stroke survivors without CMB served as a control group. Neuropsychological testing was performed in both groups six months after the index event using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)-plus test battery.ResultsCMB-positive stroke patients showed more severe cognitive decline in mini mental state test compared to the control group (p = 0.024). Regarding the episodic memory, CMB-positive patients reached lower scores in Word-List-Learning- (p = 0.009) and the Word-List-Recognition-test (p = 0.006), whereas the findings in Word-List-Recall-test were similar in both groups. While semantic fluency is not more affected in CMB-positive than in CMB-negative patients, those with CMB reveal a significantly impaired phonemic fluency (p = 0.007). Concerning the visuospatial abilities, stroke patients with CMB showed restricted recall of recently learned visual information. Only slight differences between both groups were found in any test investigating the participants’ executive functions.ConclusionCognitive abilities are more severely impaired in CMB-positive stroke patients compared to CMB-free controls, whereby memory-associated functions are most affected. CMB might be associated with post-stroke cognitive decline, particularly with impaired memory and phonemic fluency.

BackgroundPatients with chronic kidney disease are at increased risk of stroke and frequently have cerebral microbleeds. Whether such patients also encounter an increased risk of recurrent stroke has not been firmly established. We aimed to determine whether impaired kidney function is associated with the risk of recurrent stroke, and microbleed presence, distribution and severity.MethodsWe used pooled data from the Microbleeds International Collaborate Network to investigate associations of impaired kidney function, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Our primary outcome was a composite of recurrent ischaemic stroke (IS) and intracranial haemorrhage (ICrH). Secondary outcomes included: (1) individual components of the primary outcome; (2) modification of the primary outcome by microbleed presence or anticoagulant use and (3) microbleed presence, distribution and severity.Results11 175 patients (mean age 70.7±12.6, 42% female) were included, of which 2815 (25.2%) had impaired kidney function. Compared with eGFR ≥60, eGFR <60 was associated with a higher risk of the primary outcome (adjusted HR, aHR 1.33 (95% CI 1.14 to 1.56), p<0.001) and higher rates of the recurrent IS (aHR 1.33 (95% CI 1.12 to 1.58)). Reduced eGFR was not associated with ICrH risk (aHR 1.07 (95% CI 0.70 to 1.60)). eGFR was also associated with microbleed presence (adjusted OR, aOR 1.14 (95% CI 1.03 to 1.26)) and severity (aOR 1.17 (95% CI 1.06 to 1.29)). Compared with having no microbleeds, eGFR was lower in those with strictly lobar microbleeds (adjusted mean difference (aMD) −2.10 mL/min/1.73 cm2 (95% CI −3.39 to −0.81)) and mixed microbleeds (aMD −2.42 (95% CI −3.70 to −1.15)), but not strictly deep microbleeds (aMD −0.67 (95% CI −1.85 to 0.51)).ConclusionsIn patients with IS or transient ischaemic attack, impaired kidney function was associated with a higher risk of recurrent stroke and higher microbleeds burden, compared with those with normal kidney function. Further research is needed to investigate potential additional measures for secondary prevention in this high-risk group.

The present study is a comprehensive experimental investigation of the uncertainties in the mechanical response of short fibre-reinforced composites. The reference material investigated is a short glass fibre-reinforced phenolic resin matrix material, manufactured in a thermoset injection-moulding process. The mechanical material response was investigated in experiments on three different scales, considering ISO-size, miniature, and micro tensile samples. Further to the tensile experiments, compressive and shear tests were performed on macroscopic samples. Experiments on breadboard samples featuring more complex stress and deformation states complete the study. The injection-moulding process was found to control the basic fibre orientation. However, the nominal local fibre orientation distribution is superimposed with a pronounced local uncertainty. This microstructural uncertainty strongly affects the uncertainty in the local mechanical properties as well as variations between samples taken from identical positions in different but nominally identical plates.

Disentangling shallow‐water bulk carbonate carbon isotope archives into primary and diagenetic components is a notoriously difficult task and even diagenetically screened records often provide chemostratigraphic patterns that significantly differ from global signals. This is mainly caused by the polygenetic nature of shallow‐water carbonate substrates, local carbon cycle processes causing considerable neritic–pelagic isotope gradients and the presence of hiatal surfaces resulting in extremely low carbonate preservation rates. Provided here is an in‐depth petrographic and geochemical evaluation of different carbonate phases of a mid‐Cretaceous (Barremian–Aptian) shallow‐water limestone succession (Jabal Madar section) deposited on the tropical Arabian carbonate platform in Oman. The superposition of stable isotope signatures of identified carbonate phases causes a complex and often noisy bulk carbon isotope pattern. Blocky sparite cements filling intergranular pores and bioclastic voids evidence intermediate to (arguably) deep burial diagenetic conditions during their formation, owing to different timing or differential faulting promoting the circulation of fluids from variable sources. In contrast, sparite cements filling sub‐vertical veins reveal a rock‐buffered diagenetic fluid composition with an intriguing moderate enrichment in 13C, probably due to fractionation during pressure release in the context of the Miocene exhumation of the carbonate platform under study. The presence of abundant, replacive dedolomite in mud‐supported limestone samples forced negative carbon and oxygen isotope changes that are either associated with the thermal breakdown of organic matter in the deep burial realm or the expulsion of buried meteoric water in the intermediate burial realm. Notwithstanding the documented stratigraphically variable and often facies‐related impact of different diagenetic fluids on the bulk‐rock stable isotope signature, the identification of diagenetic end‐members defined δ13C and δ18O threshold values that allowed the most reliable ‘primary’ bulk carbon isotope signatures to be extracted. Most importantly, this approach exemplifies how to place regional shallow‐water stable isotope patterns with evidence for a complex multi‐stage diagenetic history into a supraregional or even global context. This study exemplifies how to extract stratigraphically meaningful global carbon cycle fluctuations out of deep‐time shallow‐water bulk carbonate carbon isotope archives that show evidence for a complex multi‐stage diagenetic alteration. Based on a detailed sedimentological, petrographic (CL microscopy) and geochemical (δ13C, δ18O, 87Sr/86Sr, major and trace elements) approach, δ13C and δ18O threshold values are defined, which in turn allowed filtering the diagenetically least altered and thus most reliable ‘primary’ bulk carbon isotope signatures.

Abstract Introduction Glomerular hyperfiltration has previously been associated with cardiovascular events and mortality but has scarcely been investigated in patients with stroke. Patients and methods We used pooled data from an individual patient data meta-analysis of prospective, cohort studies of stroke or TIA populations. For this analysis, we included participants from study sites that collected estimated glomerular filtration rate (eGFR) at stroke presentation. Using Cox proportional hazards regression, we investigated the risk of death, any stroke and vascular death according to glomerular hyperfiltration, defined as having an eGFR greater than the age- and sex-adjusted 95th percentile. We also investigated these outcomes according to eGFR as a continuous variable, modelled using fractional polynomials. Results A total of 11,175 patients (mean age 70.7 years, 42% female) were included in the analysis, 554 (4.9%) with hyperfiltration. Compared to the normofiltration group (absence of hyperfiltration and eGFR ≥ 60 mL/min/1.73 m2), the hyperfiltration group had a higher rate of all-cause death, 147 per 1000 person-years (95% CI, 119–180) vs 61 (95% CI, 57–66). Compared to normofiltration, hyperfiltration was independently associated with the risk of death from any cause (adjusted hazard ratio [HR] 1.76; 95% CI, 1.46–2.11; P < .001) and the risk of vascular death (adjusted HR 1.68; 95% CI, 1.29–2.17; P < .001). There were non-linear associations of eGFR with risk of death and vascular death, with increasing risk at both low and high eGFR (Pnon-linearity < .001 for both). Discussion and conclusion Glomerular hyperfiltration was associated with a 76% increased risk of death and a 68% increased risk of vascular death in multivariable models adjusted for age, sex and comorbidities. Glomerular hyperfiltration may be associated with adverse health outcomes, specifically in patients with ischaemic stroke. Further research is needed to confirm these findings. Graphical Abstract Graphical Abstract

Surgical intervention is advised in patients with multiple endocrine neoplasia type-1 (MEN-1) and nonfunctioning pancreatic neuroendocrine tumors (PanNETs) with a size ≥20 mm. Functioning PanNETs, such as in patients with endogenous hyperinsulinemic hypoglycemia (EHH) due to (one or multiple) insulinomas, should be treated surgically independent of size. Preoperative localization of insulinomas is critical for surgery. To evaluate the feasibility and sensitivity of 68Ga-DOTA-exendin-4 positron emission tomography (PET)/CT in the detection of clinically relevant lesions in patients with MEN-1 and EHH in combination with MRI. Post hoc subgroup analysis of a larger prospective imaging study with 52 patients with EHH. Six of 52 consecutive patients with EHH and genetically proven MEN-1 mutation were included. All patients received one 68Ga-DOTA-exendin-4 PET/CT and one MRI scan within 3 to 4 days. Thereafter, surgery was performed based on all imaging results. Lesion-based sensitivity of PET/CT and MRI for detection of clinically relevant lesions was calculated. Readers were unaware of other results. The reference standard was surgery with histology and treatment outcome. True positive (i.e., clinically relevant lesions) was defined as PanNETs ≥20 mm or insulinoma. In six patients, 37 PanNETs were confirmed by histopathology. Sensitivity (95% CI) in the detection of clinically relevant lesions for combined PET/CT plus MRI, MRI, and PET/CT was 92.3% (64% to 99.8%), 38.5% (13.9% to 68.4%), and 84.6% (54.6% to 98.1%), respectively (P = 0.014 for the comparison of PET/CT plus MRI vs MRI). Postsurgery, EHH resolved in all patients. 68Ga-DOTA-exendin-4 PET/CT is feasible in patients with MEN-1 and EHH. The combination with MRI is superior to MRI alone in the detection of insulinomas and may guide the surgical strategy.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors, mainly localized in the gastrointestinal system. What characterizes NENs is the expression of hormone receptors on the tumor cell surface, making them accessible for diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides. Somatostatin receptors subtype-two (SST2) play an important role in NENs since they are overexpressed and homogeneously distributed at the surface of the majority of NENs. Accordingly, targeting SST2 for diagnostic and therapeutic purposes has been established. Current research aims at upregulating its expression by epigenetic treatment or improving its targeting via use of alternative radioligands. In addition, recent data suggest a future role of SST antagonists as a diagnostic tool and a potential therapeutic option. Another promising target is the glucagon-like peptide-1 (GLP-1) receptor. Targeting GLP-1R using exendin-4 (GLP-1 analogue) has a high sensitivity for the localization of the often SST2-negative sporadic insulinomas and insulinomas in the context of multiple endocrine neoplasia type-1. Further options for patients with insufficient expression of SST2 involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4), which have been evaluated for potential theranostic approach in symptomatic NENs or dedifferentiated tumors. Recently, new targets such as the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs. Finally, minigastrin – a ligand targeting the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut neuroendocrine tumors – may improve future management of these diseases with currently limited therapeutic options. This review summarises the current approaches and future challenges of diagnostic and therapeutic evaluations in neuroendocrine neoplasms.

Purpose Benign insulinomas are the most prevalent cause of endogenous hyperinsulinaemic hypoglycaemia (EHH) in adults, and because of their small size are difficult to localise. The purpose of the study was to test the diagnostic accuracy and clinical impact of glucagon-like peptide-1 receptor (GLP-1R) PET/CT using 68 Ga-DOTA-exendin-4 in consecutive adult patients referred for localisation of insulinomas. The results were compared with 111 In-DOTA-exendin-4 SPECT/CT, study-MRI and previously performed external CT and/or MRI (prior external CT/MRI). Methods We prospectively enrolled patients with neuroglycopenic symptoms due to EHH. GLP-1R PET/CT, SPECT/CT and study-MRI were performed in a randomised, crossover order within 3–4 days. The reference standard was surgery with histology and treatment outcome. Results From January 2014 until March 2017, 52 patients were recruited. All imaging and invasive procedures before recruitment identified suspicious lesions in 46.2% of patients. GLP-1R PET/CT, SPECT/CT and study-MRI detected suspicious lesions in 78.8%, 63.5% and 63.4% of patients, respectively. In 38 patients, conclusive histology was available for final analysis. Accuracy (95% confidence interval) for PET/CT, SPECT/CT, study-MRI and prior external CT/MRI was 93.9% (87.8–97.5%), 67.5% (58.1–76.0%), 67.6% (58.0–76.1%) and 40.0% (23.9–57.9%), respectively (all P values < 0.01, except comparison of SPECT/CT and study-MRI with a P value = 1.0). Impact on clinical management was 42.3%, 32.7% and 33.3% for PET/CT, SPECT/CT and study-MRI, respectively. Percentage reading agreement was 89.5%, 75.7%, and 71.1% for PET/CT, SPECT/CT and study-MRI, respectively. Conclusion 68 Ga-DOTA-exendin-4 PET/CT performed significantly better than 111 In-DOTA-exendin-4 SPECT/CT and MRI in the localisation of benign insulinomas and should be considered in patients where localisation fails with CT/MRI ( ClinicalTrials.gov , NCT02127541).

Understanding the history of the Greenland Ice Sheet (GrIS) is critical for determining its sensitivity to warming and contribution to sea level; however, that history is poorly known before the last interglacial. Most knowledge comes from interpretation of marine sediment, an indirect record of past ice-sheet extent and behavior. Subglacial sediment and rock, retrieved at the base of ice cores, provide terrestrial evidence for GrIS behavior during the Pleistocene. Here, we use multiple methods to determine GrIS history from subglacial sediment at the base of the Camp Century ice core collected in 1966. This material contains a stratigraphic record of glaciation and vegetation in northwestern Greenland spanning the Pleistocene. Enriched stable isotopes of pore-ice suggest precipitation at lower elevations implying ice-sheet absence. Plant macrofossils and biomarkers in the sediment indicate that paleo-ecosystems from previous interglacial periods are preserved beneath the GrIS. Cosmogenic 26Al/10Be and luminescence data bracket the burial of the lower-most sediment between <3.2 ± 0.4 Ma and >0.7 to 1.4 Ma. In the upper-most sediment, cosmogenic 26Al/10Be data require exposure within the last 1.0 ± 0.1 My. The unique subglacial sedimentary record from Camp Century documents at least two episodes of ice-free, vegetated conditions, each followed by glaciation. The lower sediment derives from an Early Pleistocene GrIS advance. 26Al/10Be ratios in the upper-most sediment match those in subglacial bedrock from central Greenland, suggesting similar ice-cover histories across the GrIS. We conclude that the GrIS persisted through much of the Pleistocene but melted and reformed at least once since 1.1 Ma.