Cenozoic evolution of deep ocean temperature from clumped isotope thermometry.

Characterizing past climate states is crucial for understanding the future consequences of ongoing greenhouse gas emissions. Here, we revisit the benchmark time series for deep ocean temperature across the past 65 million years using clumped isotope thermometry. Our temperature estimates from the deep Atlantic Ocean are overall much warmer compared with oxygen isotope-based reconstructions, highlighting the likely influence of changes in deep ocean pH and/or seawater oxygen isotope composition on classical oxygen isotope records of the Cenozoic. In addition, our data reveal previously unrecognized large swings in deep ocean temperature during early Eocene acute greenhouse warmth. Our results call for a reassessment of the Cenozoic history of ocean temperatures to achieve a more accurate understanding of the nature of climatic responses to tectonic events and variable greenhouse forcing.

[Real-life experiences with Brolucizumab in recalcitrant neovascular age-related macular degeneration]. / Erste Erfahrungen mit Brolucizumab bei neovaskulärer altersabhängiger Makuladegeneration und Therapierefraktärität unter der bisherigen Anti-VEGF-Therapie.

BACKGROUND: Pivotal clinical trials have proven brolucizumab to be a potent intravitreal anti-vascular endothelial growth factor (VEGF) drug in patients with neovascular age-related macular degeneration (nAMD). Therefore, it seems to be a promising drug also in patients with recalcitrant nAMD. This article presents the results of patients who were switched to brolucizumab due to persistent fluid under previous anti-VEGF treatment. METHODS: In this study 21 eyes were retrospectively analyzed in which treatment was switched to brolucizumab due to persistent intraretinal (IRF), subretinal (SRF) and/or sub-retinal pigment epithelium (sub-RPE fluid) fluid despite long-term anti-VEGF treatment. Functional and spectral domain optical coherence tomography (SD-OCT) data were investigated at diagnosis of nAMD (I), at switch to brolucizumab (II), 4 weeks after upload of brolucizumab (III) and at first reactivation of macular neovascularization (MNV, IV). RESULTS: There were no significant changes in fluid distribution between (I) and (II). After upload of brolucizumab (III) a significant reduction of central subfield retinal thickness (CSRT, p = 0.0001), SRF (p = 0.004) and sub-RPE fluid (p = 0.04), but no visual acuity improvement (p = 0.56) were observed. CONCLUSION: Intravitreal brolucizumab treatment can achieve significant reductions particularly of SRF and sub-RPE in patients refractory to previous anti-VEGF treatment. Future studies should further investigate the effects of brolucizumab in patients with recalcitrant nAMD.

Naturally occurring fire coral clones demonstrate a genetic and environmental basis of microbiome composition.

Coral microbiomes are critical to holobiont functioning, but much remains to be understood about how prevailing environment and host genotype affect microbial communities in ecosystems. Resembling human identical twin studies, we examined bacterial community differences of naturally occurring fire coral clones within and between contrasting reef habitats to assess the relative contribution of host genotype and environment to microbiome structure. Bacterial community composition of coral clones differed between reef habitats, highlighting the contribution of the environment. Similarly, but to a lesser extent, microbiomes varied across different genotypes in identical habitats, denoting the influence of host genotype. Predictions of genomic function based on taxonomic profiles suggest that environmentally determined taxa supported a functional restructuring of the microbial metabolic network. In contrast, bacteria determined by host genotype seemed to be functionally redundant. Our study suggests microbiome flexibility as a mechanism of environmental adaptation with association of different bacterial taxa partially dependent on host genotype.

[Treatment adherence and effectiveness of anti-Vascular Endothelial Growth Faktor(VEGF) treatment of diabetic macular edema in the clinical routine : Comparison between cooperative and unicentric organization of treatment]. / Therapieadhärenz und Effektivität bei der Anti-Vascular Endothelial Growth Faktor(VEGF)-Therapie des diabetischen Makulaödems im klinischen Alltag : Vergleich zwischen einer kooperativen und einer unizentrischen Organisation der Behandlung.

BACKGROUND: Intravitreal injection of anti-vascular endothelial growth factor (VEGF) is an established method for treatment of diabetic macular edema (DME); however, to ensure the best possible functional results continuous treatment of patients over a long period with regular control visits are necessary. The adherence of patients to the treatment is of great importance for success. METHODS: In order to make implementation of treatment easier for patients, an internet-based referral platform was established to enable the follow-up examination to be performed by an ophthalmologist using spectal domain optical coherence tomography (SD-OCT) close to the patients place of residence. Based on 50 patients the effectiveness of this cooperative treatment (IT-Cooperation) was compared to 50 patients who were controlled in the treatment center for DME patients over a period of 2 years. RESULTS: Patients in the IT-Cooperation group received an average of 6.3 injections in the first year of follow-up compared to the lower number of 5.2 injections for patients attending the treatment center. During the second year the average number of injections decreased to 2.7 (IT-Cooperation) and 2.4 (treatment center). Patients of the IT-Cooperation showed an average of 12.0 control visits in contrast to the average number of 9.6 visits (p < 0.01) for patients attending the treatment center in the first year of observation. This difference between the two groups was significant and was confirmed in the second year of follow-up with 8.3 visits in the IT-Cooperation group compared to 4.4 visits in the treatment center group (p < 0.01). CONCLUSION: The greater number of follow-up examinations close to the patient's place of residence for the IT-Cooperation group significantly improved the quality of treatment adherence in DME patients; however, intensive exchange of information between the ophthalmologist performing the control examinations and the treatment center where the injections were carried out is mandatory.

Tonic spinal cord stimulation as therapeutic option in Parkinson disease with axial symptoms: Effects on walking and quality of life.

Spinal cord stimulation (SCS) is an effective surgical therapy used for the treatment of chronic neuropathic pain. Tonic SCS is safe and improve not only gait disorders, motor symptoms, but also quality of life in Parkinson patients even with dopa-resistant symptoms with or without associated deep brain stimulation.

The association of frontal plane alignment to MRI-defined worsening of patellofemoral osteoarthritis: the MOST study.

OBJECTIVE: To determine the sex-specific relation of frontal plane alignment (FPA) to magnetic resonance imaging (MRI)-defined features of patellofemoral osteoarthritis, and also to tibiofemoral osteoarthritis and knee pain. METHOD: The Multicenter Osteoarthritis Study is cohort study comprised of individuals with or at risk of knee osteoarthritis. We determined the sex-specific dose-response relation of baseline FPA to MRI-defined patellofemoral and tibiofemoral structural worsening, and incident knee pain, over 7 years. RESULTS: In women only, greater varus alignment was associated with medial patellofemoral osteophytes (risk ratio [RR] 1.7 [95% CI 1.2, 2.6]) and valgus with lateral patellofemoral osteophytes (RR 1.9 [1.0, 3.6]). In men, greater varus increased risk for medial tibiofemoral cartilage worsening (RR 1.7 [1.1, 2.6]), and valgus for lateral tibiofemoral cartilage worsening (RR 1.8 [1.6, 2.2]). In women, findings were similar for tibiofemoral cartilage, but varus also increased risk for medial bone marrow lesions [BMLs] (RR 2.2 [1.6, 3.1]) and medial osteophytes (RR 1.8 [1.3, 2.5]), and valgus for lateral BMLs (RR 3.3 [2.2, 4.5]) and osteophytes (RR 2.0 [1.2, 3.2]). Varus increased risk of incident pain in men (RR 1.7 [1.4, 2.2]) and women (RR 1.3 [1.0, 1.6]), valgus did so in men only (RR 1.5 [1.1, 1.9]). CONCLUSION: FPA was associated with patellofemoral osteophyte worsening in women, though overall was more strongly associated with tibiofemoral than patellofemoral osteoarthritis feature worsening. FPA in women was more consistently associated with structural worsening, yet men had higher associations with incident pain.

Probiotic or synbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults.

The gut microbiota contributes to host energy metabolism, and altered gut microbiota has been associated with obesity-related metabolic disorders. We previously reported that a probiotic alone or together with a prebiotic controls body fat mass in healthy overweight or obese individuals in a randomised, double-blind, placebo controlled clinical study (ClinicalTrials.gov NCT01978691). We now aimed to investigate whether changes in the gut microbiota may be associated with the observed clinical benefits. Faecal and plasma samples were obtained from a protocol compliant subset (n=134) of participants from a larger clinical study where participants were randomised (1:1:1:1) into four groups: (1) placebo, 12 g/d microcrystalline cellulose; (2) Litesse® Ultra™ polydextrose (LU), 12 g/day; (3) Bifidobacterium animalis subsp. lactis 420™ (B420), 1010 cfu/d in 12 g microcrystalline cellulose; (4) LU+B420, 1010 cfu/d of B420 in 12 g/d LU for 6 months of intervention. The faecal microbiota composition and metabolites were assessed as exploratory outcomes at baseline, 2, 4, 6 months, and +1 month post-intervention and correlated to obesity-related clinical outcomes. Lactobacillus and Akkermansia were more abundant with B420 at the end of the intervention. LU+B420 increased Akkermansia, Christensenellaceae and Methanobrevibacter, while Paraprevotella was reduced. Christensenellaceae was consistently increased in the LU and LU+B420 groups across the intervention time points, and correlated negatively to waist-hip ratio and energy intake at baseline, and waist-area body fat mass after 6 months treatment with LU+B420. Functional metagenome predictions indicated alterations in pathways related to cellular processes and metabolism. Plasma bile acids glycocholic acid, glycoursodeoxycholic acid, and taurohyodeoxycholic acid and tauroursodeoxycholic acid were reduced in LU+B420 compared to Placebo. Consumption of B420 and its combination with LU resulted in alterations of the gut microbiota and its metabolism, and may support improved gut barrier function and obesity-related markers.

[The heart catheter table is not the operating table : Intraindividual comparison of pulmonary artery pressures]. / Der Herzkathetertisch ist nicht der OP-Tisch : Intraindividueller Vergleich der pulmonalarteriellen Druckwerte.

BACKGROUND: Patients undergoing cardiac surgery need extensive and invasive monitoring, which needs to be individually adapted for each patient and requires a diligent risk-benefit analysis. The use of a pulmonary artery catheter (PAC) seems to be justifiable in certain cases; therefore, the preoperative diagnosis of pulmonary hypertension represents an indication for perioperative monitoring with PAC in the S3 guidelines of the German Society for Anesthesiology and Intensive Care Medicine (DGAI). In many cases, however, this preoperative diagnosis cannot be confirmed intraoperatively. OBJECTIVE: We wanted to find out whether this is just an impression or whether there actually are significant differences between preoperative, intraoperative and postoperative pulmonary artery pressures. MATERIAL AND METHODS: After obtaining ethical approval, we retrospectively compared the pulmonary pressures of cardiac surgery patients with an elevated pulmonary pressure during preoperative right heart catheterization with those obtained intraoperatively and postoperatively by means of a PAC. All patients with a preoperatively documented pulmonary artery pressure of 40 mmHg or above and an intraoperative use of a PAC during a 4-year period were included. Exclusion criteria were intracardiac shunts, cardiogenic shock, emergency procedures, pulmonary hypertension of non-cardiac origin and a time span of more than 1 year between right heart catheterization and surgery. We included 90 patients. RESULTS: In the whole group and in the subgroups (according to diagnosis, time elapsed between heart catheterization and operation and pulmonary pressure), there were significant differences between preoperative and intraoperative pulmonary and systemic pressures. Systemic and pulmonary artery pressures were significantly higher during preoperative catheterization than intraoperatively. The systemic systolic pressure/systolic pulmonary pressure ratio, however, remained constant. The intraoperative and postoperative systemic and pulmonary artery pressures showed no significant differences. As a normal ejection fraction does not exclude heart failure with preserved ejection fraction and as we did not have any information on this condition, we did not group the patients according to the ejection fraction. CONCLUSION: An elevated pulmonary pressure obtained preoperatively during right heart catheterization is not indicative of an elevated pulmonary pressure either intraoperatively or postoperatively. There are various explanations for the differences (e.g., different physiological and pathophysiological settings, such as sedation with potential hypercapnia versus anesthesia with vasodilation when measured; newly prescribed medication coming into effect between the right heart catheterization and surgery; intraoperative positioning). Even though the inherent risks of a PAC seem to be low, we recommend refraining from using a PAC in patients with a once documented elevated pulmonary pressure by default. As an alternative we suggest estimating the pulmonary pressure by transesophageal echocardiography (TEE) as an aid to decide whether the patient will benefit from the use of a PAC. Especially if it is not possible to identify tricuspid valve regurgitation for determining the peak gradient, it is helpful to check for additional signs of pulmonary hypertension. But we also have to bear in mind that in the postoperative period only a PAC can provide continuous measurement of pulmonary pressure.

Dose calculation and verification of the Vero gimbal tracking treatment delivery.

The Vero linear accelerator delivers dynamic tumor tracking (DTT) treatment using a gimbal motion. However, the availability of treatment planning systems (TPS) to simulate DTT is limited. This study aims to implement and verify the gimbal tracking beam geometry in the dose calculation. Gimbal tracking was implemented by rotating the reference CT outside the TPS according to the ring, gantry, and gimbal tracking position obtained from the tracking log file. The dose was calculated using these rotated CTs. The geometric accuracy was verified by comparing calculated and measured film response using a ball bearing phantom. The dose was verified by comparing calculated 2D dose distributions and film measurements in a ball bearing and a homogeneous phantom using a gamma criterion of 2%/2 mm. The effect of implementing the gimbal tracking beam geometry in a 3D patient data dose calculation was evaluated using dose volume histograms (DVH). Geometrically, the gimbal tracking implementation accuracy was <0.94 mm. The isodose lines agreed with the film measurement. The largest dose difference of 9.4% was observed at maximum tilt positions with an isocenter and target separation of 17.51 mm. Dosimetrically, gamma passing rates were >98.4%. The introduction of the gimbal tracking beam geometry in the dose calculation shifted the DVH curves by 0.05%-1.26% for the phantom geometry and by 5.59% for the patient CT dataset. This study successfully demonstrates a method to incorporate the gimbal tracking beam geometry into dose calculations. By combining CT rotation and MU distribution according to the log file, the TPS was able to simulate the Vero tracking treatment dose delivery. The DVH analysis from the gimbal tracking dose calculation revealed changes in the dose distribution during gimbal DTT that are not visible with static dose calculations.

Influence of fracture stability on Staphylococcus epidermidis and Staphylococcus aureus infection in a murine femoral fracture model.

Fracture-related infection (FRI) is a major complication in surgically fixed fractures. Instability of the fracture after fixation is considered a risk factor for infection; however, few experimental data are available confirming this belief. To study whether stable fractures led to higher infection clearance, mouse femoral osteotomies were fixed with either stable or unstable fixation and the surgical site was contaminated with either Staphylococcus epidermidis (S. epidermidis)or Staphylococcus aureus (S. aureus)clinical isolates. Infection progression was assessed at different time points by quantitative bacteriology, total cell counts in spleen and lymph node and histological analysis. Operated, non-inoculated mice were used as controls. Two inbred mouse strains (C57BL/6 and BALB/c) were included in the study to determine the influence of different host background in the outcome. Stable fixation allowed a higher proportion of C57BL/6 mice to clear S. epidermidis inoculation in comparison to unstable fixation. No difference associated with fixation type was observed for BALB/c mice. Inoculation with S. aureus resulted in a more severe infection for both stable and unstable fractures in both mouse strains; however, significant osteolysis around the screws rendered the stable group functionally unstable. Our results suggested that fracture stability could have an influence on S. epidermidis infection, although host factors also played a role. No differences were observed when using S. aureus, due to a more severe infection, leading to osteolysis and loss of stability in both groups. Further studies are required in order to address the biological features underlying the differences observed.

X-autosome and X-Y Translocations in Female Carriers: X-chromosome Inactivation Easily Detectable by 5-ethynyl-2-deoxyuridine (EdU).

Here we report one new case each of an X-autosome translocation (maternally derived), and an X-Y-chromosome translocation. Besides characterizing the involved breakpoints and/or imbalances in detail by molecular cyto-genetics, also skewed X-chromosome inactivation was determined on single cell level using 5-ethynyl-2-deoxyuridine (EdU). Thus, we confirmed that the recently suggested EdU approach can be simply adapted for routine diagnostic use. The latter is important, as only by knowing the real pattern of the skewed X-chromosome inactivation, correct interpretation of obtained results and subsequent reliable genetic counseling, can be done.

Histamine receptor 2 modifies iNKT cell activity within the inflamed lung.

BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGalCer or OCH) to invariant natural killer T (iNKT) cells. RESULTS: Famotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM-induced airway diseases were more severe in H2 R-deficient animals. Flow cytometric analysis of lung tissue from H2 R-deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGalCer-stimulated iNKT cells from H2 R-deficient mice secreted higher levels of IL-4, IL-5, and GM-CSF. In vivo, αGalCer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment, and cytokine production in H2 R-deficient or famotidine-treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2 R-deficient (CD1d-/- H2 R-/- ) animals normalized the lung response to HDM. CONCLUSION: The deliberate activation of H2 R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d-mediated presentation of lipid antigens to iNKT cells is contributing to the pathology.

[Visual acuity in anti-VEGF therapy for AMD : Can specific characteristics in the SD-OCT help?] / Visusprognose bei der Anti-VEGF-Therapie der AMD : Können spezifische Charakteristika im SD-OCT weiterhelfen?

BACKGROUND: The efficacy of anti-VEGF therapy in exudative AMD has been established in several large clinical trials using a fixed injection regimen as well as a SD-OCT-based PRN regimen. In these studies, after the first three injections, an increase of the mean visual acuity was observed, which could be stabilized with constant treatment for up to 24 months. However, the specific course of the visual acuity is very different between individuals. The aim of the present study was to correlate specific initial SD-OCT parameters with the course of visual acuity in order to characterize factors that may be important for the individual visual prognosis. PATIENTS AND METHODS: In a prospective case study, the visual course and SD-OCT changes of 156 patients with minimum follow-up of 12 months (mean 80.1 months) were analysed. Visual acuity (LogMar) was investigated at regular intervals and correlated with specific SD-OCT parameters (foveal thickness, height of sub-retinal fluid or presence of associated PED, presence of intra-retinal cysts, length of IS/OS break, choroidal thickness). RESULTS: The initial increase in visual acuity could be stabilized over time. This effect was associated with a decrease in foveal retinal thickness, which also persisted over time. While sub-retinal fluid, presence of PED, and choroidal thickness showed no prognostic relevance for the change in visual acuity, the presence of more advanced central retinal thickness, of intra-retinal cysts or a longer break in the IS/OS junction were associated with a less favourable development of visual acuity. CONCLUSION: In the present study, the presence of more advanced central retinal thickness, of intra-retinal cysts or a larger IS/OS break correlated significantly with a worse visual prognosis. These might be clinical signs for more extensive pre-existing intra-retinal changes. Further analysis and new diagnostic tools may prove this and may result in specific additive neuroprotective or regenerative therapeutic approaches in exudative AMD.

[Compliance of age related macular degeneration patients undergoing anti-VEGF therapy : Analysis and suggestions for improvement]. / Compliance von Patienten mit altersabhängiger Makuladegeneration unter Anti-VEGF-Therapie : Analyse und Verbesserungsvorschläge.

BACKGROUND: Activity-based treatment regimens with anti-vascular endothelial growth factor (anti-VEGF) are currently the gold standard for treatment of exudative age-related macular degeneration (nAMD). Whereas injection frequencies of approximately seven injections in the first year and six in the second year are expected with a pro re nata (PRN) regimen, retrospective real life observations have recorded significantly reduced numbers of injections. This study was carried out to investigate the reasons for the reduction in follow-up control appointments and to find out whether a telemedicine network could influence the motivation and compliance for regular control examinations and treatment. MATERIAL AND METHODS: The patient collective included 210 eyes from 191 patients with nAMD treated by anti-VEGF therapy in 2010 and 2011. The activity-based anti-VEGF treatment, control examinations and treatment intervals were performed according to the guidelines over a mean follow-up of 2 years. In another collective of 100 eyes from 100 patients with treatment of nAMD 2 groups were observed: 1 group with patients for whom control examinations were carried out close to home including an online transmission of the results to the treating retinal center and another group in which the patients had to be examined in the treatment center. RESULTS: After 140 weeks 50 % of the patients in the first collective regularly attended control examinations and after 1 year the number was 79 %. After 2 years the probability of continuous supervision is given for only 62 % of the patients, whereas in 38 % the treatment was terminated. Of these patients treatment was terminated in 8 % due to valid criteria, whereas in 30 % of the patients the termination was unintentional. The main reason (38 %) for an unintentional termination of examination and treatment was the frequent and long journey. Patients in the second collective had a significantly higher compliance with respect to the control examinations (p < 0.001) and number of injections (p = 0.02) over the period of nearly 2 years due to the introduction of electronic transmission of images. CONCLUSION: A long-term therapy of nAMD in the clinical routine can be achieved by a close relationship with the ophthalmologist, continuous follow-up controls and therapy cycles. A close telemedical networking between the ophthalmologist and the treatment center can lead to better patient compliance. Furthermore, the construction of such platforms represents a challenge not only for the treatment of nAMD but also for other diseases.

An exploratory study investigating the metabolic activity and local cytokine profile in patients with melanoma treated with pazopanib and paclitaxel.

BACKGROUND: There is a medical need for new drugs in patients with BRAF wild-type metastatic melanoma. Pazopanib is a multitarget tyrosine kinase inhibitor with antitumour and antiangiogenic activity. OBJECTIVES: The primary aim was to investigate the metabolic response to pazopanib monotherapy and pazopanib plus paclitaxel in patients with BRAF wild-type melanoma. Secondary end points were the early cytokine and chemokine profiles and histological findings. METHODS: Pazopanib (400 mg twice daily) was administered orally from days 1 to 10 and from days 14 to 70. An intravenous infusion with paclitaxel (150 mg m-2 body surface) was administered on days 14, 35 and 56. Metabolic response evaluation was performed before treatment, after treatment with pazopanib (day 10) and after treatment with pazopanib and paclitaxel (day 70). Skin biopsy of metastatic tissue for chemokine and cytokine expression analysis and histology and immunohistochemistry (CD68, CD163) evaluation, and blood samples were taken at the same time points. RESULTS: Two patients failed screening and 17 were dosed. Of 67 adverse events, nine (13%) were grade 3 or 4. Five of 14 evaluable patients had a partial metabolic response at day 10 under pazopanib monotherapy. The response rate at day 70 under combined pazopanib-paclitaxel treatment was 0%. Immunohistochemistry revealed an increase of M2-like macrophages in nonresponders compared with responders. We observed a significant upregulation of five cytokines (CXCL1, CXCL2, CXCL13, CCL22 and SPP1) in responding vs. nonresponding lesions. Overall, the median progression-free survival was 70 days (range 5-331), which did not differ significantly between responders (148 days) and nonresponders (70 days, P = 0·17). CONCLUSIONS: In this patient population pazopanib efficacy was limited. Response is associated with low M2-like macrophage density and increased expression of several chemokines.

A double barrier memristive device.

We present a quantum mechanical memristive Nb/Al/Al2O3/NbxOy/Au device which consists of an ultra-thin memristive layer (NbxOy) sandwiched between an Al2O3 tunnel barrier and a Schottky-like contact. A highly uniform current distribution for the LRS (low resistance state) and HRS (high resistance state) for areas ranging between 70 µm2 and 2300 µm2 were obtained, which indicates a non-filamentary based resistive switching mechanism. In a detailed experimental and theoretical analysis we show evidence that resistive switching originates from oxygen diffusion and modifications of the local electronic interface states within the NbxOy layer, which influences the interface properties of the Au (Schottky) contact and of the Al2O3 tunneling barrier, respectively. The presented device might offer several benefits like an intrinsic current compliance, improved retention and no need for an electric forming procedure, which is especially attractive for possible applications in highly dense random access memories or neuromorphic mixed signal circuits.

[OCT Angiography - Is this the Future for Macular Diagnosis?]. / OCT-Angiografie - ist dies die Zukunft der makulären Diagnostik?

Recent developements in OCT technology using high speed acquisition and calculation of consecutive scans (SSADA = split spectrum amplitude decorrelation algorithm) have resulted in the possibility to demonstrate retinal and choroidal vessels in the macula. This new technology of "OCT angiography" thus allows the non-invasive and rapid (within seconds) reconstruction of the three-dimensional structure of the retinal and choroidal vascularisation. There are still limitations caused by movement artefacts, superposition of superficial retinal vessels at the RPE level or insufficient three-dimensional imaging, but the first experience with this new method and especially the correlations with the current standard diagnostic procedure fluorescein angiography shows that especially for vascular changes which are predominantly in one retinal layer (e.g., the inner retina) like in diabetic retinopathy or retinal vein occlusions, a very good correlation can be seen. Also in MacTel type 2 patients the proposed vascular changes in the deeper capillary network of the retina can be visualised very well with OCT angiography. In contrast, more three-dimensional vascular changes like the neovascular complex in exsudative AMD need a more sophisticated diagnostic analysis strategy, which has still to be developed. However, the first experience also demonstrates that fluorescein angiographic differentiation can also be seen in OCT angiography. In addition, the new technology gives additional information about the choroidal and outer retinal changes in these pathologies, which may result in a better understanding of the underlying pathologies.

PALEOCEANOGRAPHY. A warm and poorly ventilated deep Arctic Mediterranean during the last glacial period.

Changes in the formation of dense water in the Arctic Ocean and Nordic Seas [the "Arctic Mediterranean" (AM)] probably contributed to the altered climate of the last glacial period. We examined past changes in AM circulation by reconstructing radiocarbon ventilation ages of the deep Nordic Seas over the past 30,000 years. Our results show that the glacial deep AM was extremely poorly ventilated (ventilation ages of up to 10,000 years). Subsequent episodic overflow of aged water into the mid-depth North Atlantic occurred during deglaciation. Proxy data also suggest that the deep glacial AM was ~2° to 3°C warmer than modern temperatures; deglacial mixing of the deep AM with the upper ocean thus potentially contributed to the melting of sea ice, icebergs, and terminal ice-sheet margins.

Implementation of Mock Competency Skill Assessments to Improve Student Outcomes.

A primary responsibility for nurse educators is to provide students with theoretical knowledge and clinical skills for professional nursing. In this study, laboratory faculty developed a creative pedagogical strategy to reduce nursing student stress during assessment of skill performance. Mock competencies were structured so that students participated in peer-to-peer evaluations in simulated competency assessments. The purpose of this study was to determine whether this pedagogical strategy had an impact on first-round pass rates for skills competency assessments.