Rise and fall of sea ice production in the Arctic Ocean's ice factories.

The volume, extent and age of Arctic sea ice is in decline, yet winter sea ice production appears to have been increasing, despite Arctic warming being most intense during winter. Previous work suggests that further warming will at some point lead to a decline in ice production, however a consistent explanation of both rise and fall is hitherto missing. Here, we investigate these driving factors through a simple linear model for ice production. We focus on the Kara and Laptev seas-sometimes referred to as Arctic "ice factories" for their outsized role in ice production, and train the model on internal variability across the Community Earth System Model's Large Ensemble (CESM-LE). The linear model is highly skilful at explaining internal variability and can also explain the forced rise-then-fall of ice production, providing insight into the competing drivers of change. We apply our linear model to the same climate variables from observation-based data; the resulting estimate of ice production over recent decades suggests that, just as in CESM-LE, we are currently passing the peak of ice production in the Kara and Laptev seas.

Multi-center planning study of radiosurgery for intracranial metastases through Automation (MC-PRIMA) by crowdsourcing prior web-based plan challenge study.

BACKGROUND: Planning radiosurgery to multiple intracranial metastases is complex and shows large variability in dosimetric quality among planners and treatment planning systems (TPS). This project aimed to determine whether autoplanning using the Muliple Brain Mets (AutoMBM) software can improve plan quality and reduce inter-planner variability by crowdsourcing results from prior international planning study. METHODS: Twenty-four institutions autoplanned with AutoMBM on a five metastases case from a prior international planning competition from which population statistics (means and variances) of 23 dosimetric metrics and resulting composite plan score (maximum score = 150) of other TPS (Eclipse, Monaco, RayStation, iPlan, GammaPlan, MultiPlan) were crowdsourced. Plan results of AutoMBM and each of the other TPS were compared using two sample t-tests for means and Levene's tests for variances. Plan quality of AutoMBM was correlated with the planner' experience and compared between academic and non-academic centers. RESULTS: AutoMBM produced plans with comparable composite plan score to GammaPlan, MultiPlan, Eclipse and iPlan (127.6 vs. 131.7 vs. 127.3 vs. 127.3 and 126.7; all p > 0.05) and superior to Monaco and RayStation (118.3 and 108.6; both p < 0.05). Inter-planner variability of overall plan quality was lowest for AutoMBM among all TPS (all p < 0.05). AutoMBM's plan quality did not differ between academic and non-academic centers and uncorrelated with planning experience (all p > 0.05). CONCLUSIONS: By plan crowdsourcing prior international plan challenge, AutoMBM produces high and consistent plan quality independent of the planning experience and the institution that is crucial to addressing the technical bottleneck of SRS to intracranial metastases.

[Susac Syndrome: A Diagnostic Chameleon]. / Susac-Syndrom: ein diagnostisches Chamäleon.

Susac's syndrome (SuS) is a rare, probably autoimmune endotheliopathy of the central nervous system, retina and inner ear. It is characterized by a clinical triad of encephalopathy, branch retinal artery occlusions (BRAOs) and sensorineural hearing loss. To date, more than 300 cases of SuS have been reported in the literature. However, SuS remains an under- and misdiagnosed entity in the clinical setting. This report presents an exemplary case of a patient, who was initially misdiagnosed with relapsing-remitting multiple sclerosis. At initial presentation, the patient did not demonstrate the complete clinical triad, and the interval between symptom onset and diagnosis was 4 months. Typical diagnostic features, which enabled the diagnosis of SuS were: a) MRI findings with T2-hyperintense snowball-like lesions of the corpus callosum and subcortical white matter and hyperintense lesions in diffusionweighted imaging with reduced apparent diffusion coefficient; b) BRAOs and vessel wall hyperfluorescence in fluorescein angiography and a significant thickness reduction of the inner retinal layers in optical coherence tomography; c) bilateral sensorineural hearing loss. The patient was aggressively treated with cyclophosphamide, rituximab, glucocorticoids and acetylsalicylic acid with a good response to therapy. This report draws attention to the need to take SuS into consideration in the differential diagnosis at the interface of neurological, psychiatric, ophthalmological and otorhinolaryngological disorders. As SuS may result in severe and persistent neurological deficits, an interdisciplinary collaboration is fundamental for the prompt diagnosis and initiation of adequate immunosuppressive treatment.

[Retinovascular Findings in Susac's Syndrome]. / Retinovaskuläre Zeichen des Susac-Syndroms.

BACKGROUND: Susac syndrome is a vasculopathy affecting the central nervous system, retina and cochlea leading to the triad encephalopathy, branch retinal artery occlusions and hearing loss. To date, about 300 cases have been described in the literature. PATIENTS/METHODS: Three patients with confirmed Susac syndrome were evaluated for disease-specific retinal pathologies. In addition, the overall history of the disease is presented to put the ophthalmological pathology into context. RESULTS: All three cases showed a retinal occlusive microangiopathy with branch retinal artery occlusions. MRI imaging revealed snowball-like lesions of the corpus callosum in two of three cases. At the initial presentation not all criteria of the disease-specific triad encephalopathy, branch retinal artery occlusions, and hearing loss were fulfilled in the three patients. CONCLUSION: Interdisciplinary collaboration between neurologists, otorhinolaryngologists and ophthalmologists is mandatory to establish the diagnosis of the disease. The occurrence of the characteristic retinal pathology with small artery occlusions and a segmental vasculopathy should always lead to the differential diagnosis of Susac syndrome.

Thermotropic properties of phosphatidylcholine nanodiscs bounded by styrene-maleic acid copolymers.

Styrene-maleic acid copolymers (SMA) have been gaining interest in the field of membrane research due to their ability to solubilize membranes into nanodics. The SMA molecules act as an amphipathic belt that surrounds the nanodiscs, whereby the hydrophobic styrene moieties can insert in between the lipid acyl chains. Here we used SMA variants with different styrene-to-maleic acid ratio (i.e. 2:1, 3:1 and 4:1) to investigate how lipid packing in the nanodiscs is affected by the presence of the polymers and how it depends on polymer composition. This was done by analyzing the thermotropic properties of a series of saturated phosphatidylcholines in nanodiscs using laurdan fluorescence and differential scanning calorimetry. In all cases it was found that the temperature of the main phase transition (Tm) of the lipids in the nanodiscs is downshifted and that its cooperativity is strongly reduced as compared to the situation in vesicles. These effects were least pronounced for lipids in nanodiscs bounded by SMA 2:1. Unexpected trends were observed for the calorimetric enthalpy of the transition, suggesting that the polymer itself contributes, possibly by rearranging around the nanodiscs when the lipids adopt the fluid phase. Finally, distinct differences in morphology were observed for nanodiscs at relatively high polymer concentrations, depending on the SMA variant used. Overall, the results suggest that the extent of preservation of native thermodynamic properties of the lipids as well as the stability of the nanodiscs at high polymer concentrations is better for SMA 2:1 than for the other SMA variants.

High efficiency positron accumulation for high-precision magnetic moment experiments.

Positrons are accumulated within a Penning trap designed to make more precise measurements of the positron and electron magnetic moments. The retractable radioactive source used is weak enough to require no license for handling radioactive material, and the radiation dosage 1 m from the source gives an exposure several times smaller than the average radiation dose on the earth's surface. The 100 mK trap is mechanically aligned with the 4.2 K superconducting solenoid that produces a 6 T magnetic trapping field with a direct mechanical coupling.

Retirada de implantes mamarios y corrección simultánea con colgajo dermoglandular inferior. Técnica de mastopexia con autoprótesis / Breast implant explantation and simultaneous correction with inferior dermoglandular flap authoprosthesis technique

Los cirujanos plásticos nos enfrentamos cada vez con más frecuencia en nuestra consulta a pacientes que desean o necesitan retirar sus implantes mamarios. Algunas de estas pacientes rechazan la idea de un reemplazo protésico, pero son exigentes con el resultado cosmético postoperatorio. Describimos la técnica empleada en 68 casos consecutivos y los resultados que hemos obtenido al tratar las secuelas en la mama tras la retirada de los implantes, fundamentalmente una disminución de volumen asociada a ptosis y excedente cutáneo. Esta técnica se basa en la extracción de los implantes y correccion mamaria simultanea con colgajo dermoglandular inferior que denominamos "autoprotesis" asociado a injerto graso simultáneo. Los resultados logran mejorar la forma, proyección y conificacion de la mama tras la retirada de los implantes, con un alto grado de satisfacción por parte de las pacientes (AU)

Plastic surgeons are frequently faced during consultation with patients who want or need breast implant explantation. Some of these patients reject the idea of a prosthetic replacement, but are demanding with the postoperative cosmetic result. We describe the technique used in 68 consecutive cases and our results to deal with breast alterations after breast implant explantation, leaving a decreased mammary volume, ptosis and a loosy cutaneous excedent. With this technique of explantation and simultaneous breast correction with de-epithelialized dermoglandular flap, "authoprosthesis", associated with simultaneous fat grafting, we can get a good result regarding the shape, projection and coning of the explanted breast, with high patient satisfaction (AU)

[Ultrahigh field MRI in context of neurological diseases]. / Ultrahochfeld-MRT im Kontext neurologischer Erkrankungen.

Ultrahigh field magnetic resonance imaging (UHF-MRI) has recently gained substantial scientific interest. At field strengths of 7 Tesla (T) and higher UHF-MRI provides unprecedented spatial resolution due to an increased signal-to-noise ratio (SNR). The UHF-MRI method has been successfully applied in various neurological disorders. In neuroinflammatory diseases UHF-MRI has already provided a detailed insight into individual pathological disease processes and elucidated differential diagnoses of several disease entities, e.g. multiple sclerosis (MS), neuromyelitis optica (NMO) and Susac's syndrome. The excellent depiction of normal blood vessels, vessel abnormalities and infarct morphology by UHF-MRI can be utilized in vascular diseases. Detailed imaging of the hippocampus in Alzheimer's disease and the substantia nigra in Parkinson's disease as well as sensitivity to iron depositions could be valuable in neurodegenerative diseases. Current UHF-MRI studies still suffer from small sample sizes, selection bias or propensity to image artefacts. In addition, the increasing clinical relevance of 3T-MRI has not been sufficiently appreciated in previous studies. Although UHF-MRI is only available at a small number of medical research centers it could provide a high-end diagnostic tool for healthcare optimization in the foreseeable future. The potential of UHF-MRI still has to be carefully validated by profound prospective research to define its place in future medicine.

[Retinovascular findings in Susac's syndrome]. / Retinovaskuläre Zeichen des Susac-Syndroms.

BACKGROUND: Susac syndrome is a vasculopathy affecting the central nervous system, retina and cochlea leading to the triad encephalopathy, branch retinal artery occlusions and hearing loss. To date, about 300 cases have been described in the literature. PATIENTS/METHODS: Three patients with confirmed Susac syndrome were evaluated for disease-specific retinal pathologies. In addition, the overall history of the disease is presented to put the ophthalmological pathology into context. RESULTS: All three cases showed a retinal occlusive microangiopathy with branch retinal artery occlusions. MRI imaging revealed snowball-like lesions of the corpus callosum in two of three cases. At the initial presentation not all criteria of the disease-specific triad encephalopathy, branch retinal artery occlusions, and hearing loss were fulfilled in the three patients. CONCLUSION: Interdisciplinary collaboration between neurologists, otorhinolaryngologists and ophthalmologists is mandatory to establish the diagnosis of the disease. The occurrence of the characteristic retinal pathology with small artery occlusions and a segmental vasculopathy should always lead to the differential diagnosis of Susac syndrome.

Corrección de la mama tuberosa solo conimplantes anatómicos / Tuberous breast correction only with anatomical implants

Las mamas tuberosas, denominadas así por Rees y Aston, y también llamadas hernias del complejo areolar (Bass), Snoopy deformity (Gruber), mamas tubulares (Williams), hipoplasia del polo inferior (Brink) o mamas de base estrecha (Puckett), son una malformacion en el desarrollo del volumen mamario en los cuadrantes inferiores con hernia areolar secundaria (placa areolar y músculo mamilar débiles), areola ancha y protruida (en la mitad de los casos), ascenso del surco submamario, mamas hipotróficas y raramente hipertróficas, con asimetrías en las dos terceras partes de las pacientes. Presentamos la estrategia quirúrgica adecuada para resolver esta patología utilizando solo implantes anatómicos de gel cohesivo sin necesidad de tallar colgajos glandulares. De esta manera, disminuimos la morbilidad quirúrgica, ofreciendo resultados estables y con alta satisfaccion por parte de las pacientes (AU)

Tuberous breasts, denominated like this by Rees and Aston, and also called areolar complex hernia by Bass, Snoopy deformity by Gruber, tubular breasts by Williams, inferior pole hypoplasia by Brink, tight base breasts by Puckett, are a malformation of breast with inferior quadrants alteration that produce an areolar herniation and protrusion (in fifty per cent of the cases), and elevation of the infamammary fold; they are rarely hypertrophic and with asymmetries in two thirds of the patients. Authors present the surgical strategy to solve this pathology just using high cohesive silicone gel anatomical implants without needing of glandular flap tailoring. By this way, surgical morbidity is diminished offering stable results and high patient satisfaction (AU)

[Diagnosis and monitoring of multiple sclerosis: the value of optical coherence tomography]. / Diagnostik und Verlaufsbeurteilung der Multiplen Sklerose: Stellenwert der optischen Kohärenztomographie.

Besides the relapse rate and neurological examination, magnetic resonance imaging (MRI) plays a key role in multiple sclerosis (MS) monitoring. However, MRI is costly and even in Germany not always readily available. Additionally, routine MRI scans are not sensitive enough regarding differentiation between demyelination and neurodegeneration and show a discrepancy between lesion load and the degree of disability. In contrast, optical coherence tomography (OCT) is a validated non-invasive method for the quantification of neurodegenerative processes in the retina, as they appear in MS and other neurological diseases. The OCT is inexpensive, easy to handle and highly reproducible. Additionally, it is well tolerated and thus represents a promising tool for monitoring of neurodegenerative disorders. This article describes in detail the OCT technique and its usefulness for both diagnosis and monitoring of MS.

[Vitamin D and multiple sclerosis : the role for risk of disease and treatment]. / Vitamin D und Multiple Sklerose : Der Stellenwert für das Erkrankungsrisiko und die Behandlung.

In addition to its important role in bone metabolism and calcium homeostasis an increasing number of beneficial effects are being attributed to vitamin D. Because of its suggested immunomodulatory capacity vitamin D deficiency or disturbance in the vitamin D metabolism might be a risk factor for the development of autoimmune diseases, such as multiple sclerosis; but supplementation with vitamin D might also be a therapeutic option. Substantial epidemiologic evidence indicates an association between vitamin D levels and risk of multiple sclerosis, suggesting vitamin D to be one of the long searched environmental factors for the development of this most common chronic inflammatory disease of the central nervous system. Less consistent are the available data for modification of the disease course in already established multiple sclerosis.This review highlights possible interactions between vitamin D and multiple sclerosis and focuses on its putative involvement in the pathogenesis and its possible role for treatment of multiple sclerosis. In particular the as yet insufficiently investigated therapeutic aspect is currently being addressed in several high quality clinical trials.

A brief review of Susac syndrome.

Susac syndrome was named after J.O. Susac who first described the syndrome in 1979. It is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. It mainly occurs in young women. This underdiagnosed disease needs to be considered in the differential diagnosis of a broad variety of disorders. In Susac syndrome, autoimmune processes leading to damage and inflammation-related occlusion of the microvessels in brain, retina, and inner ear are thought to play a causal role. The diagnosis is based primarily on the clinical presentation, the documentation of branch retinal artery occlusion by fluorescence angiography, and characteristic findings on cerebral MRI, that help in distinguishing Susac syndrome from other inflammatory entities, like multiple sclerosis. Antiendothelial cell antibodies could be detected in some patients. Patients are successfully treated with immunosuppression, however, the best regimen still needs to be defined. As a result of the rarity of the disease, controlled therapeutic trials are missing so far. In this review, we want to demonstrate the clinical features, natural history, treatment, and clinical course of Susac syndrome, illustrated by a typical case history.

[Susac syndrome: an interdisciplinary challenge]. / Susac-Syndrom : Eine interdisziplinäre Herausforderung.

Susac syndrome, named after John Susac, the first to describe this condition, is characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. Although certainly a rare disease, Susac syndrome needs to be considered in the differential diagnosis of a broad variety of diseases. The pathogenesis is not yet clear. Autoimmune processes leading to damage and inflammation-related occlusion of the microvessels in brain, retina, and inner ear are thought to play a causal role. The diagnosis is based primarily on the clinical presentation, the documentation of branch retinal artery occlusion by fluorescence angiography, and characteristic findings on cerebral MRI. Usually, immunosuppressive therapy is required, though controlled therapy trials are missing so far. The intention of this review article is to raise awareness of this disease among neurologists, psychiatrists, ophthalmologists, and ENT specialists as a high number of unreported cases probably exists. Accordingly, the focus is on the clinical presentation and the diagnostic approach.

Fatigue in multiple sclerosis is closely related to sleep disorders: a polysomnographic cross-sectional study.

BACKGROUND: Sleep disorders can cause tiredness. The relationship between sleep disorders and fatigue in patients with multiple sclerosis (MS) has not yet been investigated systematically. OBJECTIVE: To investigate the relationship between fatigue and sleep disorders in patients with MS. METHODS: Some 66 MS patients 20 to 66 years old were studied by overnight polysomnography. Using a cut-off point of 45 in the Modified Fatigue Impact Scale (MFIS), the entire cohort was stratified into a fatigued MS subgroup (n=26) and a non-fatigued MS subgroup (n=40). RESULTS: Of the fatigued MS patients, 96% (n=25) were suffering from a relevant sleep disorder, along with 60% of the non-fatigued MS patients (n=24) (p=0.001). Sleep-related breathing disorders were more frequent in the fatigued MS patients (27%) than in the non-fatigued MS patients (2.5%). Significantly higher MFIS values were detected in all (fatigued and non-fatigued) patients with relevant sleep disorders (mean MFIS 42.8; SD 18.3) than in patients without relevant sleep disorders (mean MFIS 20.5; SD 17.0) (p<0.001). Suffering from a sleep disorder was associated with an increased risk of fatigue in MS (odds ratio: 18.5; 95% CI 1.6-208; p=0.018). CONCLUSION: Our results demonstrate a clear and significant relationship between fatigue and sleep disorders.

Poor PASAT performance correlates with MRI contrast enhancement in multiple sclerosis.

BACKGROUND: Cognitive impairment is increasingly recognized as relevant clinical feature in multiple sclerosis (MS). We applied the Paced Auditory Serial Addition Test (PASAT), a recommended screening tool for cognitive dysfunction in MS, to investigate the relationship between cognitive performance and the presence of gadolinium (Gd)-enhancing lesions on brain MRI. METHODS: In this longitudinal correlational research study, 75 patients with relapsing-remitting MS (48 women and 27 men, mean age 36 years, mean disease duration 5 years, mean Expanded Disability Status Scale [EDSS] 1.7) without clinical signs of a relapse underwent 2 MRI measurements (number and volume of T1 contrast-enhancing lesions and of T2 lesions) and clinical examinations (EDSS and Multiple Sclerosis Functional Composite [MSFC]) with a mean interscan interval of 10 weeks. Patients were divided into 3 groups: A (n = 38), Gd on 1 scan; B (n = 12), Gd on both scans; and C (n = 25), Gd on neither scan. RESULTS: In group A, PASAT was better at the Gd-negative time point (p = 0.002), whereas the other MSFC subscores remained unchanged. Subgroup analysis confirmed the finding in patients with a Gd-positive scan first, whereas this was not the case for patients with a Gd-negative scan first, presumably owing to the small sample size of this subgroup. In groups B and C, there was no difference between both time points regarding MSFC and its subscores. EDSS remained stable in all groups during the investigation. CONCLUSIONS: Paced Auditory Serial Addition Test performance is affected by the appearance of Gd enhancement as surrogate marker of inflammatory activity in otherwise physically stable patients with multiple sclerosis, which may indicate that Gd enhancement causes a diffuse impairment of cerebral connectivity with a negative impact on cognitive functioning.

ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis.

Escalation therapy with mitoxantrone (MX) in highly active multiple sclerosis is limited by partially dose-dependent side-effects. Predictors of therapeutic response may result in individualized risk stratification and MX dosing. ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux. Here, we investigated the role of ABC-gene single nucleotide polymorphisms (SNPs) for clinical MX response, corroborated by experimental in vitro and in vivo data. Frequencies of ABCB1 2677G>T, 3435C>T and five ABCG2-SNPs were analysed in 832 multiple sclerosis patients (Germany, Spain) and 264 healthy donors. Using a flow-cytometry-based in vitro assay, MX efflux in leukocytes from individuals with variant alleles in both ABC-genes (designated genotype ABCB1/ABCG2-L(ow), 22.2% of patients) was 37.7% lower than from individuals homozygous for common alleles (ABCB1/ABCG2-H(igh), P < 0.05, 14.8% of patients), resulting in genotype-dependent MX accumulation and cell death. Addition of glucocorticosteroids (GCs) inhibited MX efflux in vitro. ABC-transporters were highly expressed in leukocyte subsets, glial and neuronal cells as well as myocardium, i.e. cells/tissues potentially affected by MX therapy. In vivo significance was further corroborated in experimental autoimmune encephalomyelitis in Abcg2(-/-) animals. Using a MX dose titrated to be ineffective in wild-type animals, disease course and histopathology in Abcg2(-/-) mice were strongly ameliorated. Retrospective clinical analysis in MX monotherapy patients (n = 155) used expanded disability status scale, relapse rate and multiple sclerosis functional composite as major outcome parameters. The clinical response rate [overall 121 of 155 patients (78.1%)] increased significantly with genotypes associated with decreasing ABCB1/ABCG2-function [ABCB1/ABCG2-H 15/24 (62.5%) responders, ABCB1/ABCG2-I(ntermediate) 78/98 (79.6%), ABCB1/ABCG2-L 28/33 (84.8%), exact Cochran-Armitage test P = 0.039]. The odds ratio for response was 1.9 (95% CI 1.0-3.5) with each increase in ABCB1/ABCG2 score (from ABCB1/ABCG2-H to -I-, and -I to -L). In 36 patients with severe cardiac or haematological side effects no statistically relevant difference in genotype frequency was observed. However, one patient with biopsy proven cardiomyopathy only after 24 mg/m2 MX exhibited a rare genotype with variant, partly homozygous alleles in 3 ABC-transporter genes. In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis. Combined MX/GC-treatment warrants further investigation.

Early mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis.

Mitoxantrone is an anthracenedione antineoplastic agent approved as an escalating immunotherapy for multiple sclerosis. Owing to structural similarity with other anthracyclines, cardiotoxicity is a severe side effect of mitoxantrone. The risk of mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis increases with cumulative doses >100 mg/m(2) body surface area (BSA). However, the effect of mitoxantrone on cardiac function in the early phase of treatment with cumulative doses <100 mg/m(2) BSA is unclear. The present report concerns four patients with a temporary and considerable decrease in left ventricular ejection fraction (LVEF) and with additional echocardiographic findings of diastolic dysfunction after only one or two doses of mitoxantrone. The risk of cardiotoxicity at low doses of mitoxantrone is highlighted.